TUBERCULOSIS
(Diagnosis, Diagnostics, Immunodiagnosis,
Immunodiagnostics, Pathogenesis, Vaccines & Drugs)
ABSTRACT
1441. Al-Marri
MR. Kirkpatrick MB. Erythrocyte
sedimentation rate in childhood tuberculosis: is it still worthwhile?.
International Journal of Tuberculosis & Lung Disease. 4(3):237-9, 2000 Mar.
Abstract
OBJECTIVE: To evaluate the utility of the erythrocyte
sedimentation rate (ESR) in the diagnosis
of childhood tuberculosis. DESIGN: Data were
collected retrospectively from the Qatar National Tuberculosis (TB) Registry for children (birth to 14 years of
age) from 1983 to 1996. The diagnosis
of active tuberculosis was based on positive sputum cultures (or histology) or an abnormal chest radiograph
that responded to anti-tuberculosis
chemotherapy. RESULTS: Of 144 childhood TB patients, 68 (47%) had an ESR documented at the time of
diagnosis. Twenty-two children (33%)
had a normal ESR (<10 mm/hour) and 46 children (67%) had an elevated ESR (> or =10 mm/hour) at the time of
diagnosis. Culture positive and
symptomatic children had significantly higher ESR values than
culture negative and asymptomatic
children, respectively, at the time of
diagnosis. There was no significant difference in ESR values for
children with extrapulmonary versus
pulmonary disease, and likewise no significant
correlation between either age or size of tuberculin skin test
reactivity and ESR values. CONCLUSION:
Although an elevated ESR may be expected in
children with tuberculosis, this study found that one-third of
children with TB had a normal ESR at
the time of diagnosis, and consequently there
would seem to be little value in using ESR as a diagnostic test for childhood
tuberculosis.
1442. Amaral
L. Kristiansen JE. Phenothiazines: an
alternative to conventional therapy for the initial management of suspected
multidrug resistant tuberculosis. A call for
studies. [Review] [26 refs] International Journal of Antimicrobial
Agents. 14(3):173-6, 2000 Apr.
Abstract
Increased frequency of multidrug resistant strains of
Mycobacterium tuberculosis results from
inappropriate treatment and lack of patient
compliance. The Center for Disease Control/American Thoracic Society (CDC/ATS) guidelines issued for the
management of newly diagnosed cases of
tuberculosis (TB) will not be totally effective regardless of adherence
to the guidelines and patient cooperation. The long interim period between the
diagnosis of TB and confirmation of antibiotic susceptibility contributes to
the infection rate. Consequently, the use of an adjuvant that is known to
inhibit all encountered multidrug resistant strains of M. tuberculosis may be
helpful until antibiotic susceptibility is known. Phenothiazines such as
chlorpromazine, methdilazine and thioridazine are effective against strains of
M. tuberculosis in vitro and in vivo. It is recommended that studies be
designed and conducted for the purpose of managing new cases of TB that emanate
from areas known to harbour multidrug
resistant strains of M. tuberculosis, with phenothiazines as adjuvants to the regimen recommended by the
CDC/ATS guidelines until antibiotic
susceptibility is defined. Because the normal maximum period for obtaining conventional antibiotic
susceptibility results is less than 7
or 8 weeks, the probability of serious side effects from the use of a phenothiazine is remote. [References: 26]
1443. Arend
SM. Andersen P. van Meijgaarden KE. Skjot RL.
Subronto YW. van Dissel JT.
Ottenhoff TH. Detection of active tuberculosis infection by T cell
responses to early-secreted antigenic target 6-kDa protein and culture filtrate
protein 10. Journal of Infectious Diseases.
181(5):1850-4, 2000 May.
Abstract
The purified protein derivative (PPD) skin test has no predictive
value for tuberculosis (TB) in
Mycobacterium bovis bacillus Calmette-Guerin
(BCG)-vaccinated individuals because of cross-reactive responses to nonspecific constituents of PPD. T cell
responses to early-secreted antigenic
target 6-kDa protein (ESAT-6) and the newly identified culture filtrate protein 10 (CFP-10), 2 proteins
specifically expressed by M.
tuberculosis (MTB) but not by BCG strains, were evaluated. Most TB patients responded to ESAT-6 (92%) or CFP-10
(89%). A minority of BCG-vaccinated
individuals responded to both ESAT-6 and CFP-10, their history being consistent with latent
infection with MTB in the presence of
protective immunity. No responses were found in PPD-negative controls.
The sensitivity and specificity of the
assay were 84% and 100%, respectively,
at a cutoff of 300 pg of interferon-gamma/mL. These data indicate
that ESAT-6 and CFP-10 are promising antigens
for highly specific immunodiagnosis of
TB, even in BCG-vaccinated individuals.
1444. Arend
SM. Geluk A. van Meijgaarden KE. van
Dissel JT. Theisen M. Andersen P.
Ottenhoff TH. Antigenic equivalence of human T-cell responses to
Mycobacterium tuberculosis-specific
RD1-encoded protein antigens ESAT-6 and culture filtrate protein 10 and to mixtures of synthetic peptides.
Infection & Immunity.
68(6):3314-21, 2000 Jun.
Abstract
The early secreted antigenic target 6-kDa protein (ESAT-6) and
culture filtrate protein 10 (CFP-10)
are promising antigens for reliable
immunodiagnosis of tuberculosis. Both antigens are encoded by RD1,
a genomic region present in all strains
of Mycobacterium tuberculosis and M.
bovis but lacking in all M. bovis bacillus Calmette-Guerin vaccine strains. Production and purification of
recombinant antigens are laborious and
costly, precluding rapid and large-scale testing. Aiming to develop alternative diagnostic reagents, we have
investigated whether recombinant ESAT-6
(rESAT-6) and recombinant CFP-10 (rCFP-10) can be replaced with corresponding mixtures of overlapping
peptides spanning the complete amino
acid sequence of each antigen. Proliferation of M.
tuberculosis-specific human T-cell
lines in response to rESAT-6 and rCFP-10 and that in response to the corresponding peptide mixtures were
almost completely correlated (r = 0.96,
P < 0.0001 for ESAT-6; r = 0.98, P < 0.0001 for CFP-10). More importantly, the same was found when gamma
interferon production by peripheral
blood mononuclear cells in response to these stimuli was analyzed (r = 0.89, P < 0.0001 for
ESAT-6; r = 0.89, P < 0.0001 for
CFP-10). Whole protein antigens and the peptide mixtures resulted
in identical sensitivity and
specificity for detection of infection with M.
tuberculosis. The peptides in each mixture contributing to the
overall response varied between
individuals with different HLA-DR types.
Interestingly, responses to CFP-10 were significantly higher in the presence of HLA-DR15, which is the major
subtype of DR2. These results show that
mixtures of synthetic overlapping peptides have potency equivalent to that of whole ESAT-6 and
CFP-10 for sensitive and specific
detection of infection with M. tuberculosis, and peptides have the advantage of faster production at lower
cost.
1445. Arora
SK. Kumar B. Sehgal S. Development of a polymerase chain reaction dot-blotting
system for detecting cutaneous tuberculosis. British Journal of
Dermatology. 142(1):72-6, 2000 Jan.
Abstract
For a definitive diagnosis of cutaneous tuberculosis the
demonstration of mycobacteria is
essential, but this is generally not possible in skin lesions. Routinely available techniques have poor sensitivity and
are time consuming, therefore, delaying
the institution of timely therapy. The high
sensitivity and speed of polymerase chain reaction (PCR) for the
detection of infectious agents has
prompted investigators to use this technique for the detection of Mycobacterium tuberculosis in body fluids such as cerebrospinal fluid or pleural fluid. In the
present study, PCR was used to examine
punch biopsy specimens from the affected skin of 10 patients with clinical diagnoses of tuberculosis
verrucosa cutis, lupus vulgaris,
scrofuloderma, papulonecrotic tuberculide and erythema induratum. A control group of 20 patients included individuals
having skin manifestations with
definite clinical diagnoses other than cutaneous tuberculosis, such as leprosy, fungal mycetoma, chronic bullous
disease of childhood and pemphigus
vulgaris. The PCR amplified products were dot
hybridized with a probe which was random prime labelled with 32P.
The results were compared with routine
microbiological and histological
findings. Among the test group, six of 10 (60%) were positive for M.
tuberculosis by PCR, although their histopathology showed non-specific chronic inflammation with no definite
diagnosis. Microbiological
investigations, including acid-fast bacillus smear and culture,
were positive in a single case of
scrofuloderma. All patients in the control
group were negative by PCR for M. tuberculosis. The data indicate that
the combination of dot hybridization
with PCR markedly increased the
sensitivity and specificity of PCR. This may be a useful tool in the diagnosis of tuberculosis when conventional
methods fail.
1446. Baron
JH. Inflammatory bowel disease up to 1932. Mount Sinai Journal of
Medicine. 67(3):174-89, 2000 May.
Abstract
Inflammatory bowel diseases have been a major interest of
generations of Mount Sinai Hospital
gastroenterologists. Although clinical descriptions of diarrhea with or without blood go back thousands of years,
clear distinctions between enteritis
and ulcerative colitis were possible only
in the 19th century. At that time, many case reports were published of,
in retrospect, classical regional
enteritis. The term "ulcerative colitis" dates from 1888; the introduction of the electric sigmoidoscope
soon after made it possible to make
proper diagnosis of ulcerative colitis and
distinguish it from infective dysentery, membranous mucous or
catarrhal colitis, and nervous
diarrhea. Doctors at The Mount Sinai Hospital adopted this diagnostic approach in the 1870s and 1880s, and were
particularly interested in patients
with tuberculosis-like ileocecal disease without tubercle bacilli. Articles were written by Weiner in 1914,
Moschcowitz and Wilensky in 1923 and
1927, and Goldfarb and Suissman in 1931. Dr. A.A. Berg, in 1925, encouraged his assistant Leon Ginzburg to conduct
a study of the inflammatory
granulomatous diseases of the bowel, when Ginzburg and Gordon Oppenheimer were working in Dr. Paul
Klemperer's laboratory. Initial reports
came in 1927 and 1928, but Ginzburg and Oppenheimer "in conjunction with Dr. Burrill B. Crohn"
presented a definitive paper,
"Non-specific Granulomata of the Intestine," on May 2, 1932,
to the American Gastro-Enterological
Association. On May 13, 1932, Dr. Crohn
presented a paper on "Terminal Ileitis" to the American
Medical Association; this was published
later that year with the title "Regional
Ileitis: A Pathologic and Chronic Entity," under the authorship of
Crohn, Ginzburg and Oppenheimer.
1447. Bastian
I. Rigouts L. Van Deun A. Portaels F.
Directly observed treatment, short-course strategy and multidrug-resistant
tuberculosis: are any modifications required?. Bulletin of the World Health
Organization. 78(2):238-51, 2000.
Abstract
Multidrug-resistant tuberculosis (MDRTB) should be defined as
tuberculosis with resistance to at least isoniazid and rifampicin because these
drugs are the cornerstone of short-course chemotherapy, and combined
isoniazid and rifampicin resistance
requires prolonged treatment with second-line agents. Short-course chemotherapy
is a key ingredient in the tuberculosis control strategy known as directly
observed treatment, short-course (DOTS). For populations in which
multidrug-resistant tuberculosis is endemic, the outcome of the standard
short-course chemotherapy regimen remains uncertain. Unacceptable failure rates
have been reported and resistance to additional agents may be induced. As a consequence
there have been calls for well-functioning DOTS programmes to provide
additional services in areas with high rates of multidrug-resistant
tuberculosis. These "DOTS-plus for
MDRTB programmes" may need to modify all five elements of the DOTS strategy: the treatment may need to be
individualized rather than
standardized; laboratory services may need to provide facilities for on-site culture and antibiotic susceptibility
testing; reliable supplies of a wide
range of expensive second-line agents would
have to be supplied; operational studies would be required to
determine the indications for and
format of the expanded programmes; financial and technical support from international organizations and Western
governments would be needed in addition
to that obtained from local governments.
1448. Becerra MC.
Bayona J. Freeman J. Farmer PE.
Kim JY. Redefining MDR-TB transmission 'hot spots'. International
Journal of Tuberculosis & Lung Disease.
4(5):387-94, 2000 May.
Abstract
Halting further spread of
multidrug-resistant tuberculosis (MDR-TB)
requires both new resources and a renewed
discussion of priority setting
informed by estimates of the existing burden
of this disease. The 1997
report of the first phase of the global
survey by the World Health
Organization (WHO) and the International
Union Against Tuberculosis and
Lung Disease (IUATLD) uses the indicator of
the proportion of TB cases
that are MDR-TB to identify MDR-TB 'hot
spots'. We sought to refine the
definition of MDR-TB transmission 'hot
spots'. For this purpose, we
obtained estimates of two additional
indicators for regions where data are
available: MDR-TB incidence per 100,000
population per year, and expected
numbers of new patients with MDR-TB per
year. There is generally much
agreement in the three indicators
considered, and some differences also
appear. We conclude that it is useful, when
defining indicators of MDR-TB
transmission 'hot spots', to include
estimates of underlying TB incidence
rates and of absolute numbers of MDR-TB
cases. Estimating the force of
morbidity of MDR-TB in a population is
important for comparing this burden
across settings with very different
underlying TB incidence rates;
estimating the absolute number of MDR-TB
patients will be critical for
planning the delivery of directly observed
MDR-TB therapy and the rational
procurement of second-line drugs. Through
this exercise, we aim to
initiate discussion about improved methods
of quantifying and comparing
current MDR-TB transmission 'hot spots' that
require intervention.
1449. Benakappa
A. Benakappa N. Benakappa DG. Management of
tuberculosis. Indian Journal of
Pediatrics. 62(5):557-63, 1995 Sep-Oct.
Abstract
Tuberculosis is a common disease in children
but it is highly mismanaged.
It is bound to be triggered off by HIV
infection in the near future. The
importance of HIV and TB has become apparent
from the high incidence of
disease caused by mycobacteria in AIDS
patients. The injudicious use of
needles and syringes should be discouraged
in high HIV prevalence
countries. Multiple drug resistant
tuberculosis is emerging as one of the
most important problems in medical history.
It is often created by health
workers who administer anti-TB drugs improperly.
The diagnostic aspects
and treatment are discussed.
1450. Bleed
D. Dye C. Raviglione MC. Dynamics and control of the global tuberculosis
epidemic. [Review] [42 refs] Current Opinion in Pulmonary Medicine. 6(3):174-9, 2000 May.
Abstract
Studies of disease burden have reaffirmed
that tuberculosis is among the
top 10 causes of death in the world. The
tuberculosis epidemic in most
countries could eventually be brought under
control by implementing the
World Health Organization's (WHO) directly
observed therapy, short course
(DOTS) strategy, although tuberculosis
linked to human immunodeficiency
virus (HIV) in Africa and
multidrug-resistant tuberculosis (MDR-TB) in the
former Soviet Union urgently demand
adaptations and extensions of DOTS.
Most high-incidence countries have achieved
treatment success rates
approaching the WHO 85% target in pilot
projects. In the long term, we may
have better diagnostics, drugs, and vaccines
to control the disease; for
the next 5 years, the central problem in
global tuberculosis control is to
expand DOTS coverage in high-incidence
countries. Improved case finding
and diagnosis, coupled with best-practice
short-course chemotherapy, could
quickly and dramatically cut the number of
years of healthy life lost due
to tuberculosis, especially by preventing
death. [References: 42]
1451. Bungay
HK. Adams RF. Morris CM. Haggett
PJ. Traill ZC. Gleeson FV.
Cutting needle biopsy in the diagnosis of clinically suspected
non-carcinomatous disease of the lung. British Journal of Radiology. 73(868):349-55, 2000 Apr.
Abstract
Most patients referred for lung biopsy have
a focal lesion that is likely
to be a carcinoma, and fine needle
aspiration is usually sufficient to
confirm the diagnosis. When
non-carcinomatous disease is suspected, tissue
architecture is important and potential
diagnostic techniques include
percutaneous cutting needle biopsy (CNB). We
retrospectively reviewed 37
CNBs performed for clinically suspected
non-carcinomatous disease;
recording the biopsy result, final
diagnosis, radiological nature of the
pulmonary abnormality, distance from the
pleura of the lesion biopsied and
biopsy complications. 9 patients had a
single pulmonary nodule/mass; 13
had multiple nodules/masses; 8 had a lobar
consolidation/mass; and 7 had
multifocal consolidation. The lesion abutted
the pleura in 31 cases, lying
within 1 cm in the other 6 cases. The minor
complication rate was 14%,
with no major complications. Specific
malignant diagnoses were made in 9
patients, and specific benign in 23, in all
of whom clinicoradiological
follow-up was concordant. CNB did not yield
a specific diagnosis in five
patients, including two lymphomas and one
case of unsuspected tuberculosis
in which the sample was not cultured. The
overall accuracy of CNB was
32/37 (86%). CNB is a safe and accurate
means of achieving a tissue
diagnosis for patients with peripheral
pulmonary parenchymal disease
thought not to represent carcinoma.
1452. Bustamante-Montes
LP. Escobar-Mesa A. Borja-Aburto VH. Gomez-Munoz A.
Becerra-Posada F. Predictors of death from pulmonary tuberculosis: the
case of Veracruz, Mexico. International Journal of Tuberculosis & Lung
Disease. 4(3):208-15, 2000 Mar.
Abstract
OBJECTIVES: To identify factors
(particularly social, economic and
cultural), associated with the risk of death
from pulmonary tuberculosis
in Mexico. METHODS: A case-control study of
patients receiving medical
attention from the official health services
of Veracruz, Mexico. Cases
were deaths from pulmonary tuberculosis in
1993. Controls were survivors
randomly selected from the State
Tuberculosis Case Registry. Next of kin
provided information for both cases and
controls. RESULTS: Multivariate
analysis of 161 cases and 161 controls showed an increased risk of
dying
for those patients who withdrew from
treatment (odds ratio [OR] = 3.52),
who were refused medical attention during
some period of time in any
health center (OR = 4.45), and who had a
concomitant disease at the time
of diagnosis (OR = 2.62). A linear trend
with age was observed (OR = 1.02
per year), as well as a lower risk for those
patients who were compliant
with treatment and optimistic about
surviving the disease (OR = 0.17). The
risk of death was not associated with the
presence of a health care unit
in the town, time spent to get to the health
center, or the residence of a
patient in an urban area. CONCLUSIONS: These
findings indicate that deaths
due to tuberculosis in this area are not
related to the geographical
distribution of health services but to
delays in treatment after the onset
of disease and to the low adherence of
patients to the treatment regimen.
1453. Chanteau
S. Rasolofo V. Rasolonavalona T. Ramarokoto H. Horn
C. Auregan G. Marchal G. 45/47 kilodalton (APA) antigen
capture and antibody detection assays for the diagnosis of tuberculosis.
International Journal of Tuberculosis & Lung Disease. 4(4):377-83, 2000 Apr.
Abstract
SETTING: APA complex (45/47 kDa) is an
antigen specifically excreted by
Mycobacterium tuberculosis and could
therefore be a good candidate for
diagnosis. OBJECTIVES: To develop three APA
immunocapture ELISA assays
using monoclonal antibodies (Mabs) and one
IgG anti-APA ELISA test, and to
determine their usefulness for the diagnosis
of tuberculosis in
Madagascar. DESIGN: For the Ag assays, 23
negative sputum and serum
samples and 64 pairs of sputum and serum
from active smear-positive
patients (PTM+) were tested. For antibody
assay, 116 negative controls,
143 PTM+ and 54 extra-pulmonary tuberculosis
patients were tested.
RESULTS: The sensitivities of the APA
antigen detection assays were low
(less than 40%) for a specificity of 95.6%,
using either monoclonal
antibodies or clinical specimens. The
anti-APA serology was more sensitive
(76.9% for PTM+ patients) but less specific
(73.2%). Due to their poor
predictive values, these tests cannot be
recommended for the routine
diagnosis of tuberculosis in Madagascar.
1454. Char
G. Morgan OS. Tuberculous
encephalopathy. A rare complication of pulmonary tuberculosis. West Indian
Medical Journal. 49(1):70-2, 2000 Mar.
Abstract
A case of tuberculous encephalopathy, a rare
form of neuro-tuberculosis,
is reported in a 16-year-old girl who had
pulmonary tuberculosis and
extensive cerebral demyelination. The
clinical, laboratory and
pathological features of this entity are
highlighted and the pathogenesis
discussed.
1455. Churchyard
GJ. Corbett EL. Kleinschmidt I. Mulder D. De Cock KM.
Drug-resistant
tuberculosis in South African gold miners: incidence and associated factors. International Journal of
Tuberculosis & Lung Disease.
4(5):433-40, 2000 May.
Abstract
SETTING: A gold mining company in the Free State Province of South
Africa.
OBJECTIVE: To document the incidence of and
factors associated with
drug-resistant tuberculosis (TB) in South
African gold miners. DESIGN:
Review of Mycobacterium tuberculosis drug
susceptibility records for the
period from 1 July 2023 to 30 June 1997.
RESULTS: Over the study period,
2241 miners had culture-positive M.
tuberculosis pulmonary disease where
isolates were tested for drug susceptibility
to the four primary
anti-tuberculosis drugs. The proportions of
primary and acquired drug
resistance were respectively 7.3% and 14.3%
for isoniazid and 1.0% and
2.8% for resistance to at least isoniazid
and rifampicin (multidrug
resistance). Resistance to streptomycin and
ethambutol was uncommon, and
rifampicin monoresistance was rare. No
significant factors for primary
drug resistance were identified. Patients
with retreatment pulmonary TB
who failed primary TB treatment (versus
cure) were significantly more
likely to have TB with resistance to any TB
drug or MDR (odds ratios
respectively 9.82, 95%CI 2.97-33.5, and
18.74, 95%CI 1.76-475). Human
immunodeficiency virus (HIV) infection was
not significantly associated
with primary or acquired drug resistance,
and there was no trend of
increasing resistance over time. CONCLUSION: Anti-tuberculosis
drug
resistance has remained stable despite the
HIV epidemic and increasing TB
rates. Directly observed therapy may have
contributed to containing the
level of drug resistance. Adherence to and
completion of treatment are
essential to prevent drug resistance and
treatment failure, including in
situations with high HIV prevalence.
1456. Delogu
G. Howard A. Collins FM. Morris SL.
DNA vaccination against tuberculosis: expression of a ubiquitin-conjugated
tuberculosis protein enhances antimycobacterial immunity. Infection &
Immunity. 68(6):3097-102, 2000 Jun.
Abstract
Genetic immunization is a promising new
technology for developing vaccines
against tuberculosis that are more effective.
In the present study, we
evaluated the effects of intracellular
turnover of antigens expressed by
DNA vaccines on the immune response induced
by these vaccines in a mouse
model of pulmonary tuberculosis. The
mycobacterial culture filtrate
protein MPT64 was expressed as a chimeric
protein fused to one of three
variants of the ubiquitin protein (UbG, UbA,
and UbGR) known to
differentially affect the intracellular
processing of the coexpressed
antigens. Immunoblot analysis of cell
lysates of in vitro-transfected
cells showed substantial differences in the
degradation rate of
ubiquinated MPT64 (i.e., UbG64 < UbA64
< UbGR64). The specific immune
response generated in mice correlated with
the stability of the
ubiquitin-conjugated antigen. The UbA64 DNA
vaccine induced a weak humoral
response compared to UbG64, and a mixed
population of interleukin-4
(IL-4)- and gamma interferon
(IFN-gamma)-secreting cells. Vaccination with
the UbGR64 plasmid generated a strong Th1
cell response (high IFN-gamma,
low IL-4) in the absence of a detectable
humoral response. Aerogenic
challenge of vaccinated mice with
Mycobacterium tuberculosis indicated
that immunization with both the UbA64- and
UbGR64-expressing plasmids
evoked an enhanced protective response
compared to the vector control. The
expression of mycobacterial antigens from
DNA vaccines as fusion proteins
with a destabilizing ubiquitin molecule (UbA
or UbGR) shifted the host
response toward a stronger Th1-type immunity
which was characterized by
low specific antibody levels, high numbers
of IFN-gamma-secreting cells,
and significant resistance to a tuberculous
challenge.
1457. Divya
Jyothi M. Garg SK. Singh NB. Mechanisms involved in protective
immune response generated by secretory proteins of Mycobacterium habana against
experimental tuberculosis. Scandinavian Journal of Immunology. 51(5):502-10, 2000 May.
Abstract
Live mycobacteria secrete a number of unique
proteins early in their
multiplication which are important for both
the pathogenesis and the
stimulation of specific host responses. We
have investigated the
mechanisms by which the host mounts immune
response against tuberculosis
after vaccination with secretory proteins
(SP) of a vaccine candidate
Mycobacterium habana TMC 5135. Mice
vaccinated with SP of 10th day growth
of M. habana, either alone or emulsified in
Freund's incomplete adjuvant
(FIA) possessed antituberculous resistance
and cellular immune responses
against M. tuberculosis H37Rv. These
proteins induced a significant
cutaneous delayed type hypersensitivity
response in guinea pigs vaccinated
with heat killed M. tuberculosis H37Rv,
which was equivalent to that
observed with a standard purified protein
derivative (PPD). The
splenocytes of these guinea pigs have shown
higher proliferative response
after stimulation with SP than with PPD. The
SP + FIA immunization has
been found to exert maximum prophylactic
effect by potentiating both the
oxygen dependent arms and enzymatic
activities of macrophages. Macrophages
from mice vaccinated with SP of M. habana
produced enhanced levels of
interleukin(IL)-2, interleukin-12 and
interferon(IFN)-gamma. The
protective as well as cell mediated immune
responses were upregulated in
SP immunized animals when compared to whole
cell (M. habana) vaccinated
animals. SDS-PAGE of SP from M. habana
showed the prominent bands of 60,
32, 31 and 30 kDa. Furthermore, the western
analysis of SP with pulmonary
tuberculosis patient's serum has revealed
the presence of immunoreactive
antigens of 36, 35, 33/32 kDa. Overall study
demonstrated that the
secretory antigens released by actively
growing M. habana bacilli could
activate different arms of effective immune
response.
1458. Doherty
TM. Andersen P. Tuberculosis vaccines:
developmental work and the future. [Review] [74 refs] Current Opinion in Pulmonary Medicine. 6(3):203-8, 2000 May.
Abstract
The last year in tuberculosis vaccine
research has witnessed the initial
flowering of the benefits promised by the
tuberculosis genome sequencing
product. Although the real benefits in terms
of clinical treatments are
yet to be realized, genomics is making its
presence felt in the rapid
identification and expression of proteins
with vaccine potential from
Mycobacterium tuberculosis, the definition
of species-specific antigens
for diagnostic use, and the construction of
a variety of novel living
vectors for vaccination. At the same time,
the recent increase in work on
animal models with more direct applicability
to the situations likely to
be encountered in human vaccine trials are
providing the basic
underpinnings needed for the assessment of
these new vaccines.
[References: 74]
1459. Donald
PR. Childhood tuberculosis. [Review] [39 refs] Current Opinion in Pulmonary
Medicine. 6(3):187-92, 2000 May.
Abstract
Childhood tuberculosis will reflect the
incidence of cavitating pulmonary
tuberculosis in adults and will consequently
be encountered most
frequently in those areas with a high
incidence of tuberculosis. Problem
areas include our continuing inability to
confirm the diagnosis of
tuberculosis in many children, the
escalating interaction of the human
immunodeficiency virus (HIV) pandemic and
tuberculosis, which is now
evident with greater frequency in childhood,
and the scarcity of data
relating to antituberculosis therapy in
childhood, which necessitates
reliance on adult studies in many cases.
This review highlights several
options for obtaining material for culture
of Mycobacterium tuberculosis
in children, aspects of tuberculin testing,
which remains one of the
cornerstones supporting a diagnosis of
tuberculosis in childhood, the
potential importance of therapeutic drug
monitoring in problem cases, new
data giving epidemiologic and clinical
details of the interaction of HIV
infection and tuberculosis in children, and
studies describing the
epidemiology of tuberculosis in the
developed and developing world.
[References: 39]
1460. Elis
A. Mulchanov I. Radnay J.
Shapiro H. Lishner M. The
diagnostic significance of polyclonal lymphocytosis in pleural effusions. New Zealand Medical Journal. 113(1104):56-8, 2000 Feb 25.
Abstract
AIM: To evaluate the diagnostic contribution
and clinical relevance of
analysing subpopulations of lymphocytes in
pleural effusions. METHODS:
Forty patients (age >60 years) with newly
diagnosed, polyclonal,
lymphocyte-rich pleural effusions were
evaluated. The following data were
collected: demographic characteristics,
associated diseases, fluid type,
fluid white blood cells count, differential
morphology and
immunephenotyping, and final diagnosis.
RESULTS: Of the 33 patients for
whom biochemical data were available, 18 had
exudative effusion, while 15
had transudate. Thirty-three fluids
contained mostly T cells and only one
was B-cell rich. (The lymphocytes of five
patients with malignant
epithelial cells in the effusion were not
subtyped.) Thirty-two of the 33
T-cell rich fluids contained mainly CD4+
lymphocytes. The most common
causes of pleural effusion were congestive
heart failure (17 patients) and
epithelial malignant diseases (eight
patients), while none of the patients
had tuberculosis. Since most effusions were
CD4+ rich, no correlation
could be detected between lymphocyte
subtyping and diagnosis or the
biochemical type of the fluids. Congestive
heart failure was significantly
associated with transudates, while malignant
diseases correlated with
exudates. CONCLUSIONS: Most patients with
pleural polyclonal
lymphocytosis, especially those with
transudates, have congestive heart
failure. The presence of exudative,
lymphocyte-rich effusion is an
indication for further evaluation, since it
is most commonly associated
with malignancy. The clinical value of
lymphocyte subtyping is low and
this procedure should not be used routinely.
1461. Espinal
MA. Kim SJ. Suarez PG. Kam KM. Khomenko AG. Migliori GB. Baez J.
Kochi A. Dye C. Raviglione MC. Standard short-course
chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6 countries
[see comments]. JAMA. 283(19):2537-45, 2000 May 17.
Abstract
CONTEXT: No large-scale study has
investigated the impact of
multidrug-resistant tuberculosis (TB) on the
outcome of standard
short-course chemotherapy under routine
countrywide TB control program
conditions in the World Health
Organization's (WHO) directly observed
treatment short-course strategy for TB
control. OBJECTIVE: To assess the
results of treatment with first-line drugs
for patients enrolled in the
WHO and the International Union Against
Tuberculosis and Lung Disease's
global project on drug-resistance
surveillance. DESIGN AND SETTING:
Retrospective cohort study of patients with
TB in the Dominican Republic,
Hong Kong Special Administrative Region
(People's Republic of China),
Italy, Ivanovo Oblast (Russian Federation),
the Republic of Korea, and
Peru. PATIENTS: New and retreatment TB cases
who received short-course
chemotherapy with isoniazid, rifampicin,
pyrazinamide, and either
ethambutol or streptomycin between 1994 and
1996. MAIN OUTCOME MEASURE:
Treatment response according to WHO
treatment outcome categories (cured;
died; completed, defaulted, or failed
treatment; or transferred). RESULTS:
Of the 6402 culture-positive TB cases
evaluated, 5526 (86%) were new cases
and 876 (14%) were retreatment cases. A
total of 1148 (20.8%) new cases
and 390 (44.5%) retreatment cases were drug
resistant, including 184 and
169 cases of multidrug-resistant TB,
respectively. Of the new cases 4585
(83%) were treated successfully, 138 (2%)
died, and 151 (3%) experienced
short-course chemotherapy failure. Overall,
treatment failure (relative
risk [RR], 15.4; 95% confidence interval
[CI], 10.6-22.4; P<.001) and
mortality (RR, 3.73; 95% CI, 2.13-6.53;
P<.001) were higher among new
multidrug-resistant TB cases than among new
susceptible cases. Even in
settings using 100% direct observation,
cases with multidrug resistance
had a significantly higher failure rate than
those who were susceptible
(9/94 [10%] vs 8/1410 [0.7%]; RR, 16.9; 95%
CI, 6.6-42.7; P<.001).
Treatment failure was also higher among
patients with any rifampicin
resistance (n=115) other than multidrug resistance
(RR, 5.48; 95% CI,
3.04-9.87; P<.001), any isoniazid
resistance (n=457) other than multidrug
resistance (RR, 3. 06; 95% CI, 1.85-5.05;
P<.001), and among patients with
TB resistant to rifampicin only (n=76) (RR,
5.47; 95% CI, 2.68-11.2;
P<.001). Of the retreatment cases, 497
(57%) were treated successfully, 51
(6%) died, and 124 (14%) failed short-course
chemotherapy treatment.
Failure rates among retreatment cases were
higher in those with
multidrug-resistant TB, with any isoniazid
resistance other than multidrug
resistance, and in cases with TB resistant
to isoniazid only. CONCLUSIONS:
These data suggest that standard
short-course chemotherapy, based on
first-line drugs, is an inadequate treatment
for some patients with
drug-resistant TB. Although the directly
observed treatment short-course
strategy is the basis of good TB control,
the strategy should be modified
in some settings to identify drug-resistant
cases sooner, and to make use
of second-line drugs in appropriate treatment
regimens. JAMA.
2000;283:2537-2545
1462.
Faerman M. Jankauskas R. Paleopathological and
molecular evidence of human bone tuberculosis in Iron Age Lithuania.
Anthropologischer Anzeiger.
58(1):57-62, 2000 Mar.
Abstract
Skeletal remains of two individuals, showing
lesions suggestive of bone
tuberculosis, from the archaeological sites
of Marvele and Sukioniai in
Lithuania were analyzed at the DNA level.
The diagnosis of bone
tuberculosis was confirmed in the remains
from Marvele by amplifiying a
245-bp fragment of a repetitive insertion
element-like sequence (IS 6110)
of Mycobacterium tuberculosis DNA. This is
direct evidence for the
presence of tuberculosis in Lithuania at the
beginning of the first
millennium AD. The individual from Sukioniai
was found to be
tuberculosis-negative. No PCR product was
obtained for the 245-bp target
sequence or for a smaller 123-bp DNA
fragment specific for Mycobacterium
tuberculosis. However, amplifiable ancient
DNA appeared to be present in
the
examined specimen as was shown by the results of the DNA-based sex
identification, which indicated, consistent
with the bone morphology, a
male individual.
1463. Furin
JJ. Becerra MC. Shin SS.
Kim JY. Bayona J. Farmer PE. Effect of administering
short-course, standardized regimens in individuals infected with drug-resistant
Mycobacterium tuberculosis strains. European Journal of Clinical Microbiology
& Infectious Diseases. 19(2):132-6, 2000 Feb.
Abstract
Presented here are the cases of three
siblings with multidrug-resistant
tuberculosis who demonstrated increased
antituberculous-drug resistance
during the periods in which they received
standard regimens of directly
observed, short-course chemotherapy that
were administered before the
susceptibility patterns of their
Mycobacterium tuberculosis isolates had
been checked. More specifically, they
acquired resistance to drugs they
received as part of ineffective standard
treatment and retreatment
regimens. Development of antituberculous-drug
resistance through
inadvertent, inadequate therapy appears to
be the most likely explanation
for the increased resistance seen in these
three patients.
1464.
No Abstract
1465. Garay
JE. Analysis of a simplified concentration sputum smear technique for pulmonary
tuberculosis diagnosis in rural hospitals. Tropical Doctor. 30(2):70-2, 2000
Apr.
Abstract
Rural hospitals in Africa face the challenge
of an increasing number of
pulmonary tuberculosis (PTB) cases, much of
it related with the AIDS
pandemic. The main diagnostic tool in these
hospitals is the direct sputum
smears. Sensitivity of direct sputum smears
is low, especially in cases of
AIDS related PTB. Several concentration
methods have been described but
none is routinely used in Zimbabwe.
Fluorescence microscopy of auramine
stained samples increases sensitivity and
saves laboratory time but it is
not an appropriate technique for rural
African hospitals. In a rural
hospital of southwest Zimbabwe, we studied
the sensitivity and
appropriateness of a simplified
concentration method. The sensitivity
against culture was significantly higher
with the concentration method
(80%) than with the classical direct smear
method (57%). However, when
sputum is not adequate (with high number of
squamous epithelial cells,
meaning upper airway origin), the
sensitivity of this method is low. A
combination of both methods is proposed to
increase the sensitivity of PTB
diagnosis in rural hospitals.
1466. Glickman
MS. Cox JS. Jacobs WR Jr. A novel mycolic acid cyclopropane synthetase is
required for coding, persistence, and virulence of Mycobacterium tuberculosis.
Molecular Cell. 5(4):717-27, 2000 Apr.
Abstract
Colonial morphology of pathogenic bacteria
is often associated with
virulence. For M. tuberculosis, the
causative agent of tuberculosis (TB),
virulence is correlated with the formation
of serpentine cords, a
morphology that was first noted by Koch. We
identified a mycobacterial
gene, pcaA, that we show is required for
cording and mycolic acid
cyclopropane ring synthesis in the cell wall
of both BCG and M.
tuberculosis. Furthermore, we show that
mutants of pcaA fail to persist
within and kill infected mice despite normal
initial replication. These
results indicate that a novel member of a
family of cyclopropane
synthetases is necessary for lethal chronic
persistent M. tuberculosis
infection and define a role for
cyclopropanated lipids in bacterial
pathogenesis.
1467. Grange
JM. Zumla A. Advances in the management
of tuberculosis: clinical trials and beyond. [Review] [23 refs] Current Opinion
in Pulmonary Medicine. 6(3):193-7, 2000
May.
Abstract
Modern short-course treatment for
tuberculosis is highly effective and
cost-effective, yet the disease remains a
leading cause of suffering and
death. The problem has been exacerbated in
recent years by the human
immunodeficiency virus (HIV) pandemic and
the increasing prevalence of
multidrug-resistant tuberculosis.
Improvements in diagnosis, vaccination,
chemoprophylaxis, and therapy are thus
urgently needed. Molecular
techniques are facilitating the development
of rapid and sensitive
diagnostic tests and the rational approach
to the production of new
vaccines. New forms of treatment are being investigated
and there is also
considerable emphasis on optimizing the
deployment of the available
treatment regimens. This has resulted in the
World Health Organization's
five-point directly observed therapy, short
course (DOTS) strategy and
proposed modifications (DOTS-plus) for the
management of
multidrug-resistant (MDR) tuberculosis.
Despite these advances, it is
becoming abundantly clear that the failure
to control tuberculosis is a
direct consequence of the gross inequities
in the distribution of wealth
and health care provision worldwide, which
do not allow for putting
advances in the management of tuberculosis
into practice. The control of
tuberculosis will therefore require
attention to justice and human rights
as well as greatly increased technical and
financial support from the
developed nations. [References: 23]
1468.
No Abstract
1469. Gurunathan
S. Klinman DM. Seder RA. DNA vaccines: immunology,
application, and optimization*. [Review] [244 refs] Annual Review of Immunology. 18:927-74, 2000.
Abstract
The development and widespread use of
vaccines against infectious agents
have been a great triumph of medical
science. One reason for the success
of currently available vaccines is that they
are capable of inducing
long-lived antibody responses, which are the principal agents of
immune
protection against most viruses and
bacteria. Despite these successes,
vaccination against intracellular organisms
that require cell-mediated
immunity, such as the agents of tuberculosis,
malaria, leishmaniasis, and
human immunodeficiency virus infection, are
either not available or not
uniformly effective. Owing to the
substantial morbidity and mortality
associated with these diseases worldwide, an
understanding of the
mechanisms involved in generating long-lived
cellular immune responses has
tremendous practical importance. For these
reasons, a new form of
vaccination, using DNA that contains the
gene for the antigen of interest,
is under intensive investigation, because it
can engender both humoral and
cellular immune responses. This review
focuses on the mechanisms by which
DNA vaccines elicit immune responses. In
addition, a list of potential
applications in a variety of preclinical
models is provided. [References:
244]
1470. Hadley M.
Maher D. Community involvement in tuberculosis control: lessons from
other health care programmes. [Review] [46 refs] International Journal of
Tuberculosis & Lung Disease.
4(5):401-8, 2000 May.
Abstract
Decentralising tuberculosis control measures
beyond health facilities by
harnessing the contribution of the community
could increase access to
effective tuberculosis care. This review of
community-based health care
initiatives in developing countries gives
examples of the lessons for
community contribution to tuberculosis
control learned from health care
programmes. Sources of information were
Medline and Popline databases and
discussions with community health experts.
Barriers to success in
tuberculosis control stem from biomedical,
social and political factors.
Lessons are relevant to the issues of
limited awareness of tuberculosis
and the benefits of treatment, stigma,
restricted access to drugs,
case-finding and motivation to continue
treatment. The experience of other
programmes suggests potential for an
expansion of both formal and informal
community involvement in tuberculosis
control. Informal community
involvement includes delivery of messages to
encourage tuberculosis
suspects to come forward for treatment and
established tuberculosis
patients to continue treatment. A wide range
of community members provide
psychological and logistic support to
patients to complete their
treatment. Lessons from formal community
involvement indicate that
programmes should focus on ensuring that
treatment is accessible. This
activity could be combined with a variety of
complementary activities:
disseminating messages to increase awareness
and promote adherence,
tracing patients who interrupt treatment,
recognising adverse effects, and
case detection. Programmes should generally
take heed of existing
political and cultural structures in
planning community-based tuberculosis
control programmes. Political support, the
support of health professionals
and the community are vital, and planning
must involve or stem from the
patients themselves. [References: 46]
1471. Hendrickson
RC. Douglass JF. Reynolds LD. McNeill PD. Carter D. Reed
SG. Houghton RL. Mass
spectrometric identification of mtb81, a novel serological marker for
tuberculosis. Journal of Clinical Microbiology. 38(6):2354-61, 2000 Jun.
Abstract
We have used serological proteome analysis
in conjunction with tandem mass
spectrometry to identify and sequence a
novel protein, Mtb81, which may be
useful for the diagnosis of tuberculosis
(TB), especially for patients
coinfected with human immunodeficiency virus
(HIV). Recombinant Mtb81 was
tested by an enzyme-linked immunosorbent
assay to detect antibodies in 25
of 27 TB patients (92%) seropositive for HIV
as well as in 38 of 67
individuals (57%) who were TB positive
alone. No reactivity was observed
in 11 of 11 individuals (100%) who were HIV
seropositive alone. In
addition, neither sera from purified protein
derivative (PPD)-negative (0
of 29) nor sera from healthy (0 of 45) blood
donors tested positive with
Mtb81. Only 2 of 57 of PPD-positive
individuals tested positive with
Mtb81. Sera from individuals with
smear-positive TB and seropositive for
HIV but who had tested negative for TB in
the 38-kDa antigen
immunodiagnostic assay were also tested for
reactivity against Mtb81, as
were sera from individuals with lung cancer
and pneumonia. Mtb81 reacted
with 26 of 37 HIV(+) TB(+) sera (70%) in
this group, compared to 2 of 37
(5%) that reacted with the 38-kDa antigen.
Together, these results
demonstrate that Mtb81 may be a promising
complementary antigen for the
serodiagnosis of TB.
1472. Heymann
SJ. Brewer TF. Ettling M. Effectiveness and cost of rapid
and conventional laboratory methods for Mycobacterium tuberculosis
screening.Source Public Health
Reports. 112(6):513-23, 1997 Nov-Dec.
Abstract
OBJECTIVE: Because delay in the diagnosis of
tuberculosis (TB) contributes
to the spread of disease and the associated
mortality risk, the authors
examined the effectiveness and cost of
recent advances in methods of
diagnosing TB and testing for drug
susceptibility, comparing these rapid
methods to traditional approaches. METHODS:
Decision analysis was used to
compare newer rapid and older nonrapid
methods for diagnosing TB and
testing for drug susceptibility. The average
time to diagnosis, average
time to treatment, average mortality, and
cost of caring for patients
evaluated for TB were compared. RESULTS:
Using a combination of solid
medium and broth cultures, nucleic acid
probes for identification, and
radiometric broth drug susceptibility
testing would lead to diagnosis on
average 15 days faster and to appropriate
therapy on average five days
sooner than methods currently employed by
many U.S. laboratories. The
average mortality would drop by five
patients per 1000 patients evaluated
(31%) and the average cost per patient would
drop by $272 (18%).
CONCLUSIONS: In this era of cost
containment, it is important to
incorporate test sensitivity and specificity
when evaluating technologies.
Tests with higher unit costs may lead to
lower medical expenditures when
diagnostic accuracy and speed are improved.
U.S. laboratories should
employ available rapid techniques for the
diagnosis of TB.
1473. Hudson
CP. Wood R. Maartens G. Diagnosing HIV-associated tuberculosis: reducing
costs and diagnostic delay.
International Journal of Tuberculosis & Lung Disease. 4(3):240-5, 2000 Mar.
Abstract
SETTING: University-affiliated hospital in
South Africa. OBJECTIVE: To
assess the time to diagnosis and the yield
and laboratory cost of
diagnostic procedures in human
immunodeficiency virus (HIV) associated
tuberculosis. DESIGN: Cohort study.
PATIENTS: Adult HIV-infected patients
with newly-diagnosed tuberculosis admitted
over a 2-year period. RESULTS:
A total of 141 admissions fulfilled the case
definition. Sputum smear
yield (43% overall) correlated strongly with
chest radiograph appearance
but not with CD4+ lymphocyte count. Sputum
smear yield was approximately
40% per sample sent, resulting in a high
cumulative yield when > or =
three samples were sent. Smear of sputum or
wide needle lymph node
aspirates were the most cost-effective
diagnostic methods. Significant
diagnostic delay occurred in sputum
smear-negative patients. Most patients
with sputum smear-negative tuberculosis had
either pleural effusions or
lymphadenopathy. Lymph
node biopsy had a high diagnostic yield even in
patients with symmetrical nodes, but was
under-utilised in this group.
There was unnecessary expenditure on
cultures, with many patients having
several positive cultures. CONCLUSION:
Repeated sputum smear examination
produces a high cumulative yield in
HIV-associated tuberculosis.
Considerable savings in laboratory
utilisation and bed occupancy would
have been made if a streamlined diagnostic
approach with greater use of
lymph node aspirate and early pleural or
lymph node biopsy had been
followed.
1474. Jasmer
RM. Edinburgh KJ. Thompson A.
Gotway MB. Creasman JM. Webb WR.
Huang
L.Clinical and radiographic predictors of the etiology of pulmonary nodules in
HIV-infected patients. Chest.
117(4):1023-30, 2000 Apr.
Abstract
STUDY OBJECTIVES: To determine the etiology
and the clinical and
radiographic predictors of the etiology of
pulmonary nodules in a group of
HIV-infected patients. DESIGN: Retrospective
analysis. SETTING: A large
urban hospital in San Francisco, CA.
PATIENTS: HIV-infected patients
evaluated at San Francisco General Hospital
from June 1, 1993, through
December 31, 1997, having one or more
pulmonary nodules on chest CT. Main
outcome measures: Three physicians reviewed
medical records for clinical
data and final diagnoses. Three chest
radiologists blinded to clinical
data reviewed chest CTs. Univariate and
multivariate analyses were
performed to determine clinical and
radiographic predictors of having an
opportunistic infection and the specific
diagnoses of bacterial pneumonia
and tuberculosis. RESULTS: Eighty seven of
242 patients (36%) had one or
more pulmonary nodules on chest CT. Among
these 87 patients, opportunistic
infections were the underlying etiology in
57 patients; bacterial
pneumonia (30 patients) and tuberculosis (14
patients) were the most
common infections identified. Multivariate
analysis identified fever,
cough, and size of nodules < 1 cm on
chest CT as independent predictors of
having an opportunistic infection.
Furthermore, a history of bacterial
pneumonia, symptoms for 1 to 7 days, and
size of nodules < 1 cm on CT
independently predicted a diagnosis of
bacterial pneumonia; a history of
homelessness, weight loss, and
lymphadenopathy on CT independently
predicted a diagnosis of tuberculosis.
CONCLUSIONS: In HIV-infected
patients having one or more pulmonary
nodules on chest CT scan,
opportunistic infections are the most common
cause. Specific clinical and
radiographic features can suggest particular
opportunistic infections.
1475. Jerant
AF. Bannon M. Rittenhouse S. Identification and management of tuberculosis [see
comments]. American Family Physician.
61(9):2667-78, 2681-2, 2000 May 1.
Abstract
Although the resurgence of tuberculosis in
the early 1990s has largely
been controlled, the risk of contracting
this disease remains high in
homeless persons, recent immigrants and
persons infected with the human
immunodeficiency virus (HIV). Purified
protein derivative testing should
be targeted at these groups and at persons
with known or suspected
exposure to active tuberculosis. Most
patients with latent tuberculosis
are treated with isoniazid administered
daily for nine months. In patients
with active tuberculosis, the initial
regimen should include four drugs
for at least two months, with subsequent
therapy determined by
mycobacterial sensitivities and clinical
response. To avoid harmful drug
interactions, regimens that do not contain
rifampin may be employed in
HIV-infected patients who are taking
protease inhibitors or nonnucleoside
reverse transcriptase inhibitors. To
maximize compliance and minimize the
emergence of mycobacterial drug resistance,
family physicians should
consider using directly observed therapy in
all patients with
tuberculosis.
1476. Jindal
SK. Gupta D. Algorithm for diagnosing
pulmonary fibrosis in tropical countries. [Review] [44 refs] Current Opinion in
Pulmonary Medicine. 4(5):294-9, 1998
Sep.
Abstract
An algorithm for diagnosis of pulmonary
fibrosis in the tropical countries
has been developed on the basis of the
common causes of fibrosis, and the
availability and feasibility of different
diagnostic techniques in those
countries. First, it is important to exclude
common diseases such as the
atypical or occult forms of bronchiectasis,
pulmonary tuberculosis, and
chronic bronchitis, which often overshadow
interstitial pulmonary
fibrosis. A good history and physical
examination supplemented with chest
radiography and simple lung function tests
are generally enough to narrow
down the list of causes of diffuse lung
disease to interstitial pulmonary
fibrosis. The real difficulty lies in
identifying the idiopathic or "lone"
forms from the secondary forms of pulmonary
fibrosis. High-resolution CT
is helpful in a large number of patients.
Transbronchial lung biopsy is
performed in a select population of
patients. Open surgical or
thoracoscopy guided biopsy is the gold
standard, but is rarely required.
[References: 44]
1477. Joshi
S. Malik S. Kandoth PW. Diagnostic and therapeutic evaluation of
bronchoscopy. Indian Journal of Pediatrics.
62(1):83-7, 1995 Jan-Feb.
Abstract
The diagnostic and therapeutic efficacy of
bronchoscopy was determined in
85 children. The major indications were
foreign body removal in younger
patients and evaluation of tracheobronchial
pathology in older children.
Foreign body was commonly isolated in the
toddlers and even in the elder
age group (19%) as well as in those with
suspected ingestion (44%).
Groundnut was the predominant foreign body
and right bronchus was the most
frequent site. Tracheobronchitis (27%),
bronchiectasis (13%) endobronchial
tuberculosis (9.4%) and mucus plug (3%) were
the other frequent findings.
Bronchography was performed in 16 patients
and it confirmed the diagnosis
in 75% of the cases. Minor complications
were encountered in 8% of
patients. In the present study bronchoscopy
yielded definite results in
83% and in many, including those with normal
findings it guided further
management.
1478.
Kakkar S. Kapila K.
Singh MK. Verma K. Tuberculosis
of the breast. A cytomorphologic study. Acta Cytologica. 44(3):292-6, 2000 May-Jun.
Abstract
OBJECTIVE: Extrapulmonary tuberculosis
occurring in the breast is rare
despite the fact that 1-2 billion people
worldwide suffer from
tuberculosis. The aim of this study was to
examine the cytomorphology of
breast tuberculosis (breast TB) and to
review the literature. STUDY
DESIGN: Old records from the Cytopathology
Laboratory, All India Institute
of Medical Sciences, were reviewed from
January 1980 to December 1998.
Cases of breast TB where a cytologic
diagnosis was rendered or a
histologic diagnosis with prior fine needle
aspiration cytology (FNAC) was
available were selected. These slides were
reviewed for determining the
cytologic findings. RESULTS: One hundred
sixty cases of breast TB were
included in the study. Six males and 154
females with a clinical suspicion
of carcinoma had undergone FNA that was
reported as TB. The majority of
the patients (111) were in the reproductive
age group, 21-40 years. Of the
160 cases, 118 (73.75%) had cytomorphology
diagnostic of
tuberculosis--epithelioid cell granulomas
with caseous necrosis. Eleven of
the remaining 42 cases were positive for
acid-fast bacilli (AFB) on
Ziehl-Neelsen (ZN) staining, while 31 cases
were confirmed to be
tubercular on histology. ZN staining was
done in 44 cases, and AFB were
demonstrated in only 38.6% of cases.
CONCLUSION: Up to 73% of breast TB
can be confidently diagnosed when both
epithelioid cell granulomas and
necrosis are present. Also, the possibility
that a woman in the
reproductive age group who presents with a
palpable lump in the breast may
have
tuberculosis must be kept in mind, especially as the incidence of
breast TB may increase in the future with
the global spread of AIDS.
1479. Kamath
AT. Groat NL. Bean AG. Britton WJ.
Protective effect of DNA immunization against mycobacterial infection is
associated with the early emergence of interferon-gamma (IFN-gamma)-secreting
lymphocytes. Clinical & Experimental Immunology. 120(3):476-82, 2000 Jun.
Abstract
The development of more effective
anti-tuberculosis (TB) vaccines would
contribute to the global control of TB.
Understanding the activated/memory
T cell response to mycobacterial infection
and identifying immunological
correlates of protective immunity will
facilitate the design and
assessment of new candidate vaccines. Therefore,
we investigated the
kinetics of the CD4+ T cell response and
IFN-gamma production in an
intravenous challenge model of Mycobacterium
bovis bacille Calmette-Guerin
(BCG) before and after DNA immunization.
Activated/memory CD4+ T cells,
defined as CD44hiCD45RBlo, expanded
following infection, peaking at 3-4
weeks, and decreased as the bacterial load
fell. Activated/memory CD4+ T
cells were the major source of IFN-gamma and
the level of antigen-specific
IFN-gamma-secreting lymphocytes, detected by
ELISPOT, paralleled the
changes in bacterial load. To examine the
effects of a DNA vaccine, we
immunized mice with a plasmid expressing the
mycobacterial secreted
antigen 85B (Ag85B). This led to a
significant reduction in mycobacteria
in the liver, spleen and lung. This
protective effect was associated with
the rapid emergence of antigen-specific
IFN-gamma-secreting lymphocytes
which were detected earlier, at day 4, and
at higher levels than in
infected animals immunized with a control
vector. This early and increased
response of IFN-gamma-secreting T cells may
serve as a correlate of
protective immunity for anti-TB vaccines.
1480. Khare
MD. Sharland M. Pulmonary
manifestations of pediatric HIV infection. [Review] [26 refs] Indian Journal of
Pediatrics. 66(6):895-904, 1999
Nov-Dec.
Abstract
Vertically acquired HIV infection is
becoming increasingly common in
India. The main clinical manifestations of
HIV in childhood are growth
failure, lymphadenopathy, chronic cough and
fever, recurrent pulmonary
infections, and persistent diarrhoea.
Pulmonary disease is the major cause
of morbidity and mortality in pediatric
AIDS, manifesting itself in more
than 80% of cases. The most common causes
are Pneumocystis carinii
pneumonia (PCP), lymphocytic interstitial
pneumonitis (LIP), recurrent
bacterial infections which include bacterial
pneumonia and tuberculosis.
The commonest AIDS diagnosis in infancy is
PCP, presenting in infancy with
tachypnea, hypoxia, and bilateral opacification
on chest-X-ray (CXR).
Treatment is with cotrimoxazole. LIP
presents with bilateral
reticulonodular shadows on CXR. It may be
asymptomatic in the earlier
stages, but children develop recurrent
bacterial super infections, and can
progress to bronchiectasis. LIP is a good
prognostic sign in children with
HIV infection in comparison to PCP. HIV
should be considered in children
with recurrent bacterial pneumonia,
particularly with a prolonged or
atypical course, or a recurrence after standard
treatment. Pulmonary TB is
common in children with HIV, but little data
is available to guide
treatment decisions. Much can be done to
prevent PCP and bacterial
infections with cotrimoxazole prophylaxis
and appropriate immunisations,
which may reduce hospital admissions and
health care costs. [References:
26]
1481.
Khatri GR. Frieden TR. The status and prospects of
tuberculosis control in India [see comments]. International Journal of
Tuberculosis & Lung Disease.
4(3):193-200, 2000 Mar.
Abstract
SETTING: India, where much of the global
strategy for tuberculosis control
was established, but where, every year,
there are an estimated 2 million
cases of tuberculosis. OBJECTIVE: To
describe the policies, initial
results, and lessons learned from
implementation of a Revised National
Tuberculosis Control Programme using the
principles of DOTS (Directly
Observed Treatment, Short-course). DESIGN: A
Revised National Tuberculosis
Control Programme (RNTCP) was designed and
implemented starting in 1993.
With funding from the Government of India,
State Governments, the World
Bank and bilateral donors, regular supply of
drugs and logistics was
ensured. Persons with chest symptoms who
attend health facilities are
referred to microscopy centres for
diagnosis. Diagnosed cases are
categorized as per World Health Organization
guidelines, and treatment is
given by direct observation. Systematic
recording and cohort reporting is
done. RESULTS: From October 1993 through
mid-1999, 146,012 patients were
put on treatment in the programme. The
quality of diagnosis was improved,
with the ratio of smear-positive to
smear-negative patients being
maintained at 1:1. Case detection rates
varied greatly between project
sites and correlated with the percentage of
patients who were
smear-positive among those examined for
diagnosis, suggesting
heterogeneous disease rates. Treatment
success was achieved in 81% of new
smear-positive patients, 82% of new
smear-negative patients, 89% of
patients with extra-pulmonary tuberculosis,
and 70% of re-treatment
patients. CONCLUSION: The RNTCP has
successfully treated approximately 80%
of patients in 20 districts of 15 states of
India. Treatment success rates
are more than double and death rates are
less than a seventh those of the
previous programme. Starting in late 1998,
the programme began to scale up
and now covers more than 130 million people.
Maintaining the quality of
implementation during the expansion phase is
the next challenge.
1482.
Krause KH.
Professional phagocytes: predators and prey of microorganisms. [Review] [13 refs] Schweizerische Medizinische
Wochenschrift. Journal Suisse de Medecine.
130(4):97-100, 2000 Jan 29.
Abstract
Phagocytosis is an ancient cellular function.
However, professional
phagocytes have evolved only in higher
organisms, where they play an
important role in host defence. Professional
phagocytes are capable of
engulfing relatively large microorganisms
and killing them with a
combination of various microbicidal systems.
Crucial killing mechanisms of
phagocytes include superoxide generation by
phagocyte NADPH oxidase and
release of microbicidal proteins through
exocytosis of performed granules.
Phagocytes are also able to interfere with
microbial growth through
alteration of the phagosomal ionic
environment (acidification, iron
depletion). While the microbicidal
mechanisms of phagocytes are extremely
efficient and capable of killing most
microorganisms, pathogenic
microorganisms have developed mechanisms to
resist phagocytes.
Microorganisms capable of surviving within
phagocytes are rare, but
represent very successful pathogens, such as
Mycobacterium tuberculosis.
Other pathogens, such as S. aureus, have
developed strategies to evade
phagocytosis. How microorganisms are
phagocytosed and killed, and why
certain pathogens resist these mechanisms,
are crucial questions for an
understanding of the pathogenesis of
infectious diseases and the
development of innovative treatment
approaches. [References: 13]
1483.
Kuaban C. Bercion R.
Jifon G. Cunin P. Blackett KN. Acquired anti-tuberculosis drug
resistance in Yaounde, Cameroon. International Journal of Tuberculosis &
Lung Disease. 4(5):427-32, 2000 May.
Abstract
SETTING: Tuberculosis centre of Hopital
Jamot, Yaounde, Cameroon.
OBJECTIVES: To determine the prevalence of
acquired resistance (ADR) to
the main anti-tuberculosis drugs, and to
identify risk factors associated
with its occurrence in Yaounde. DESIGN: A total
of 111 previously treated
adults admitted consecutively to the
tuberculosis centre with sputum
smear-positive pulmonary tuberculosis
between June 1996 and July 1997 were
included in the study. Information on
potential risk factors for ADR was
obtained from each patient, and human
immunodeficiency virus (HIV)
serostatus was determined. Drug
susceptibility testing to the main
anti-tuberculosis drugs was performed on
cultures of Mycobacterium
tuberculosis complex isolated from sputum
samples of each patient by the
indirect proportion method. All patients
whose isolates tested resistant
to at least one anti-tuberculosis drug were
defined as having ADR.
RESULTS: Growth of M. tuberculosis complex
was obtained from sputum
specimens of 98 (88.3%) of the 111 patients
studied; 57 (58.2%) of these
were resistant to at least one
anti-tuberculosis drug. Resistance to
isoniazid was the most common (54.1%),
followed by resistance to
rifampicin (27.6%), streptomycin (25.5%) and
ethambutol (12.2%). Multidrug
resistance was observed in 27 (27.6%) of the
cases. In a multivariate
logistic regression analysis, ADR was
significantly associated only with
monotherapy use in previous tuberculosis
treatment(s) (P = 0.03).
CONCLUSION: The rate of ADR of M.
tuberculosis is quite high in Yaounde.
Acquired resistance to rifampicin alone or
in combination with isoniazid
is also high. Monotherapy in previous
anti-tuberculosis treatment(s) is a
significant predictor of ADR in previously
treated patients in Yaounde.
These results underscore the urgent need for
the re-establishment of a
tuberculosis control programme, using the
DOTS strategy, in Cameroon.
1484. Kwiatkowski
D. Genetic dissection of the molecular pathogenesis of severe infection. [Review]
[61 refs] Intensive Care Medicine. 26
Suppl 1:S89-97, 2000.
Abstract
A fundamental question for the intensivist
is why some individuals but not
others succumb to life-threatening
infection. A growing body of evidence
indicates that both the risk of acquiring
infection and the risk of
developing severe complications are
determined by host genetic factors.
These include a number of single gene
defects with devastating
consequences, e. g. interferon-gamma
receptor mutations that lead to fatal
infections with ubiquitous mycobacteria, but
such examples are relatively
rare. Of greater importance for routine
clinical practice is the
potentially vast number of genetic variants
with subtle effects on the
regulation or function of specific
immunological, physiological and
metabolic mediators. Such polygenic traits
do not obey simple patterns of
familial segregation seen for monogenic
disorders, and their clinical
investigation is further complicated by the
environmental variability of
infectious exposure. Recent advances in this
field have therefore largely
stemmed from hospital-based case-controlled
studies that have uncovered
disease associations with specific DNA
polymorphisms in candidate gene
regions. For example, tumour necrosis factor
polymorphisms have been
associated with susceptibility to malaria
and other infections; chemokine
receptor polymorphisms with susceptibility
to HIV; natural
resistance-associated macrophage protein 1
with tuberculosis; and mannose
binding lectin polymorphisms with
meningococcal disease. A much greater
number of genetic associations will emerge
as the full extent of human
genomic diversity becomes known. The
challenge for clinical investigators
is to generate an epidemiological framework
for population- and
family-based association studies, which is
sufficiently robust to exclude
population artifacts and sufficiently
powerful to be able to dissect true
disease-causing polymorphisms from linked
genetic markers. In the long
term this approach promises to identify host
mediators that are critical
for pathogenesis and immunity and to yield
molecular insights into the
complex processes of human gene regulation.
This information is likely to
be of considerable value in designing more
effective approaches to the
treatment and prevention of life-threatening
infectious disease.
[References: 61]
1485.
Lee NH. Choi EH.
Lee WS. Ahn SK. Tuberculous
cellulitis. Clinical & Experimental Dermatology. 25(3):222-3, 2000 May.
Abstract
We report a case of cutaneous tuberculosis
presenting as cellulitis. The
patient was a 63-year-old Korean woman who
also had diabetes mellitus and
a 20-year-history of oral corticosteroid
medication prescribed for
arthralgia. In addition, she had had
pulmonary tuberculosis 20-year
previously for which she received systemic
treatment for 1 year. Her
clinical cellulitis failed to respond to
antibiotic therapy. Subsequent
investigations, using histopathology and
polymerase chain reaction,
established an alternative diagnosis of
cutaneous tuberculosis. The skin
eruption cleared after treatment with
isoniazid, rifampicin, ethambutol
and pyrazinamide. This case represents a
most unusual presentation of
tuberculosis in the skin. The atypical
features may reflect the patient's
general medical state.
1486. Lu
W. Cheng P. Chen S. HSP60, HSP70 in the pathogenesis of Kawasaki disease:
implication and action. Journal of
Tongji Medical University. 18(3):145-8, 1998.
Abstract
HSP60, HSP70 in plasma of 11 cases of
Kawasaki diseases (KD) and 23
healthy children were determined. The two
groups were controlled for age.
Determination of HSP60, HSP70 was conducted
in lymphocytes of 14 cases of
KD and 26 healthy children. The results were
compared with those of 12
patients with febrile diseases and 10
patients with tuberculosis. Our
results showed that except a significant
difference in plasma HSP70 found
between acute phase and convalescent phase
of KD (P < 0.01), no
significant difference was found in HSP60,
HSP70 among all groups (P >
0.05). The differences in HSP60, HSP70 in
lymphocytes were relatively
obvious among all groups. The levels of
HSP60, HSP70 in acute phase of KD
were significantly higher than those in
convalescent phase or in healthy
controls (P < 0.01). The levels of HSP60
in KD were significantly higher
than those of patients with febrile
diseases. HSP60 of KD children was
significantly lower than those of children
with tuberculosis (P < 0.01).
The findings showed that HSP60, HSP70 might
contribute to the pathogenesis
of KD. Determination of HSP60, HSP70 in
lymphocytes is of help in the
diagnosis of KD.
1487.
MacIntyre CR. Ansari MZ.
Carnie J. Hart WG. No evidence
for multiple-drug prophylaxis for tuberculosis compared with isoniazid alone in
Southeast Asian refugees and migrants: completion and compliance are major
determinants of effectiveness. Preventive Medicine. 30(5):425-32, 2000 May.
Abstract
BACKGROUND: The use of multiple-drug prophylaxis
for tuberculosis (TB) has
not been shown to be more effective than
prophylaxis with isoniazid alone.
The boundary between inactive pulmonary TB
(class 4 TB) and
culture-negative "active"
pulmonary TB (class 3 TB) is often unclear, as
is the intention to treat such patients as a
preventive measure or as a
curative measure. METHODS: We compared the
effectiveness of single drug
preventive therapy with isoniazid to the
effectiveness of multiple drug
preventive therapy for patients with asymptomatic,
inactive TB, in a
retrospective cohort study of 984 Southeast
(SE) Asian migrants and
refugees who received prophylaxis between
1978 and 1980. RESULTS: The rate
of TB developing in this cohort was 122 per
100,000 person-years. There
was no significant difference in development
of TB between people who
received isoniazid only and those who
received multiple drugs. The only
significant predictor of TB was
noncompletion of prophylaxis [relative
risk (RR) = 62, 95% confidence interval (CI)
= 20-194]. Subgroup analysis
on people who had completed therapy showed
noncompliance as a significant
predictor of TB (RR = 16, 95% CI = 1.4-179).
The risk of noncompletion (RR
= 4.7, 95% CI = 2.37-9.39, P < 0.0001)
and noncompliance (RR = 2.2, 95% CI
= 1.03-4.7, P = 0.03) was higher for
patients who received multiple drugs
compared with isoniazid alone. Multiple-drug
therapy cost 30 times more
than isoniazid alone. CONCLUSIONS: We did
not find evidence in support of
the empirical practice of giving multiple
drugs for prevention of TB. This
practice is also more costly and more likely
to result in noncompliance
and adverse drug reactions.
1489. Mahadevan
S. Clinical utility of serodiagnosis of tuberculosis. [Review] [33 refs] Indian
Journal of Pediatrics. 64(1):97-103,
1997 Jan-Feb.
Abstract
The use of TB-ELISA tests as a diagnostic
tool offer a lot of scope in
early diagnosis of serious forms of
childhood tuberculosis. The
characteristics of these tests have improved
with the availability of
purified and recombinant antigens and
competition assays using monoclonal
antibodies. Lower antibody titres to M.
tuberculosis specific antigens in
children and the presence of 'natural
exposure' antibodies make the
interpretation of these tests difficult at
times. Caution must be
exercised in interpreting their results due
to problems inherent on
currently available methods of
TB-immunodiagnosis. The selection of best
combination of antigens for serology,
prospective clinical trials
comparing success rate of serology with the
standard different diagnostic
procedures are required. [References: 33]
1490. Martin
E. Kamath AT. Triccas JA. Britton WJ.
Protection against virulent Mycobacterium avium infection following DNA vaccination
with the 35-kilodalton antigen is accompanied by induction of gamma
interferon-secreting CD4(+) T cells. Infection & Immunity. 68(6):3090-6, 2000 Jun.
Abstract
Mycobacterium avium is an opportunistic
pathogen that primarily infects
immunocompromised individuals, although the
frequency of M. avium
infection is also increasing in the
immunocompetent population. The
antigen repertoire of M. avium varies from
that of Mycobacterium
tuberculosis, with the immunodominant 35-kDa
protein being present in M.
avium and Mycobacterium leprae but not in
members of the M. tuberculosis
complex. Here we show that a DNA vector
encoding this M. avium 35-kDa
antigen (DNA-35) induces protective immunity
against virulent M. avium
infection, and this protective effect
persists over 14 weeks of infection.
In C57BL/6 mice, DNA vaccines expressing the
35-kDa protein as a
cytoplasmic or secreted protein, both
induced strong T-cell gamma
interferon (IFN-gamma) and humoral immune
responses. Furthermore, the
antibody response was to conformational
determinants, confirming that the
vector-encoded protein had adopted the
native conformation. DNA-35
immunization resulted in an increased
activated/memory CD4(+) T-cell
response, with an accumulation of CD4(+)
CD44(hi) CD45RB(lo) T cells and
an increase in antigen-specific IFN-gamma
production. The protective
effect of the DNA-35 vectors against M.
avium infection was comparable to
that of vaccination with Mycobacterium bovis
BCG and significantly greater
than that for previous treated infection
with M. avium. These results
illustrate the importance of the 35-kDa
protein in the protective response
to M. avium infection and indicate that DNA
vaccination successfully
promotes a sustained level of protection
during chronic M. avium
infection.
1491. McLellan
DG. Philips KB. Corbett CE.
Bronze MS. Sternal osteomyelitis caused by mycobacterium tuberculosis:
case report and review of the literature. [Review] [31 refs] American Journal
of the Medical Sciences. 319(4):250-4,
2000 Apr.
Abstract
Sternal osteomyelitis caused by
Mycobacterium tuberculosis is rare; since
the advent of modern antituberculous
therapy, a limited number of detailed
cases have been reported. Most patients were
relatively young, free of
underlying disease, and lived in a country
in which tuberculosis is
endemic. The disease presented indolently
with sternal pain and swelling.
Extrasternal disease is detectable in less
than half. Diagnosis was based
on histologic examination of infected
tissues and mycobacterial cultures.
Most patients recovered after surgical
debridement and combination drug
therapy. Tuberculous sternal osteomyelitis
should be considered in
patients with sternal pain and swelling.
[References: 31]
1492. Miller
RF. Howling SJ. Reid AJ.
Shaw PJ. Pleural effusions in patients with AIDS. Sexually Transmitted
Infections. 76(2):122-5, 2000 Apr.
Abstract
OBJECTIVE: To describe the range of
pathology causing pleural effusions in
HIV infected patients with acute respiratory
episodes and to attempt to
identify whether any associated radiological
abnormalities enabled
aetiological discrimination. METHODS:
Prospective study of chest
radiographs of 58 consecutive HIV infected
patients with pleural effusion
and their microbiological, cytological, and
histopathological diagnoses.
RESULTS: A specific diagnosis was made in
all cases. Diagnoses were
Kaposi's sarcoma, 19 patients;
para-pneumonic effusion, 16 patients;
tuberculosis, eight patients; Pneumocystis
carinii pneumonia, six
patients; lymphoma, four patients; pulmonary
embolus, two patients; and
heart failure, aspergillus/leishmaniasis,
and Cryptococcus neoformans, one
case each. Most effusions (50/58) were
small. Bilateral effusions were
commoner in Kaposi's sarcoma (12/19) and
lymphoma (3/4) than in
para-pneumonic effusion (3/16). Concomitant
interstitial parenchymal
shadowing did not aid discrimination. A
combination of bilateral
effusions, focal air space consolidation,
intrapulmonary nodules, and/or
hilar lymphadenopathy suggests Kaposi's
sarcoma. Unilateral effusion with
focal air space consolidation suggests
para-pneumonic effusion if
intrapulmonary nodules are absent: if
miliary nodules and/or mediastinal
lymphadenopathy are detected, this suggests
tuberculosis. CONCLUSIONS: A
wide variety of infectious and malignant
conditions cause pleural
effusions in HIV infected patients, the most
common cause in this group
was Kaposi's sarcoma. The presence of additional
radiological
abnormalities such as focal air space
consolidation, intrapulmonary
nodules, and mediastinal lymphadenopathy
aids aetiological discrimination.
1493. Morris
S. Kelley C. Howard A. Li Z. Collins F. The immunogenicity of single and
combination DNA vaccines against
tuberculosis. Vaccine.
18(20):2155-63, 2000 Apr 14.
Abstract
DNA immunization is a promising new approach
for the development of novel
tuberculosis vaccines. In this study, the
immune responses following the
administration of single and combination
tuberculosis DNA vaccines were
evaluated. Single DNA vaccines encoding the
MPT-63 and MPT-83 tuberculosis
antigens evoked partial protection against
an aerogenic challenge with M.
tuberculosis Erdman in the mouse model of
pulmonary tuberculosis.
Immunization with a multivalent combination
DNA vaccine (containing the
ESAT-6, MPT-64, MPT-63, and KatG constructs)
generated immune responses
that indicated an absence of antigenic
competition since antigen-specific
cell-mediated and humoral responses were
detected to each component of the
mixture. More importantly, the combination
vaccine elicited a strong
protective response relative to the
protection evoked by live BCG vaccine.
1494. Morrison
WI. Bourne FJ. Cox DR.
Donnelly CA. Gettinby G. McInerney
JP. Woodroffe R. Pathogenesis
and diagnosis of infections with Mycobacterium bovis in cattle. Independent Scientific Group on
Cattle TB. Veterinary Record.
146(9):236-42, 2000 Feb 26.
Abstract
In last week's Veterinary Record, members of
the Independent Scientific
Group on Cattle TB discussed the approach
they are adopting in attempting
to develop sustainable strategies for
controlling bovine tuberculosis in
cattle (VR, February 19, pp 207-210). In
this second, complementary
article, they consider the extent to which
efforts to control the disease
may be constrained by limitations in current
testing procedures.
1496. Mustafa
AS. Shaban FA. Abal AT.
Al-Attiyah R. Wiker HG. Lundin KE.
Oftung F. Huygen K.
Identification and HLA restriction of naturally derived Th1-cell epitopes from
the secreted Mycobacterium tuberculosis antigen 85B recognized by
antigen-specific human CD4(+) T-cell lines. Infection & Immunity. 68(7):3933-40, 2000 Jul.
Abstract
Antigen 85B (Ag85B/MPT59) is a major
secreted protein from Mycobacterium
tuberculosis which is a promising candidate
antigen for inclusion in novel
subunit vaccines against tuberculosis (TB).
The present study was
undertaken to map naturally derived T-cell
epitopes from M. tuberculosis
Ag85B in relation to major
histocompatibility complex (MHC) class II
restriction. Antigen-specific CD4(+) T-cell
lines were established from
HLA-typed TB patients and Mycobacterium
bovis BCG vaccinees by stimulation
of peripheral blood mononuclear cells with
purified Ag85B in vitro. The
established T-cell lines were then tested
for proliferation and gamma
interferon (IFN-gamma) secretion in response
to 31 overlapping synthetic
peptides (18-mers) covering the entire
sequence of the mature protein. The
results showed that the epitopes recognized
by T-cell lines from TB
patients were scattered throughout the Ag85B
sequence whereas the epitopes
recognized by T-cell lines from BCG
vaccinees were located toward the
N-terminal part of the antigen. The T-cell
epitopes represented by
peptides p2 (amino acids [aa] 10 to 27), p3
(aa 19 to 36), and p11 (aa 91
to 108) were frequently recognized by
antigen-specific T-cell lines from
BCG vaccinees in both proliferation and
IFN-gamma assays. MHC restriction
analysis demonstrated that individual T-cell
lines specifically recognized
the complete Ag85B either in association
with one of the self HLA-DRB1,
DRB3, or DRB4 gene products or nonspecifically
in a promiscuous manner. At
the epitope level, panel studies showed that
peptides p2, p3, and p11 were
presented to T cells by HLA-DR-matched as
well as mismatched allogeneic
antigen-presenting cells, thus representing
promiscuous epitopes. The
identification of naturally derived peptide epitopes from the M.
tuberculosis Ag85B presented to Th1 cells in
the context of multiple
HLA-DR molecules strongly supports the
relevance of this antigen to
subunit vaccine design.
1497. Mwandumba
HC. Squire SB. Fully intermittent
dosing with drugs for tuberculosis. [Review] [1 refs] Cochrane Database of
Systematic Reviews [computer file].
(2):CD000970, 2000.
Abstract
BACKGROUND: The number of people infected
with tuberculosis continues to
rise world-wide. Rifampicin-containing
treatment regimens can achieve high
cure rates. Intermittent drug treatment
delivered in the community has the
potential to improve adherence to treatment.
OBJECTIVES: The objective of
this review was to compare the effectiveness
of rifampicin-containing
short-course chemotherapy regimens, given
two or three times a week, with
similar regimens given daily in patients
with pulmonary tuberculosis.
SEARCH STRATEGY: We searched the Cochrane
Infectious Diseases Group trials
register, the Cochrane Controlled Trials
Register, Medline, and reference
lists of articles. We contacted experts in
the field. SELECTION CRITERIA:
Randomised and quasi-randomised trials of
any multi-drug regimen
containing rifampicin in patients with
confirmed pulmonary tuberculosis.
Treatment had to be given up to three times
a week for up to nine months,
with any initial daily dosing period not
more than one month, and was
compared to daily dosing throughout for the
same period. DATA COLLECTION
AND ANALYSIS: Two reviewers independently
assessed trial eligibility and
quality. MAIN RESULTS: One trial involving
399 patients was included. The
trial compared treatment three times per
week with daily treatment for six
months. There was no difference in cure rate
(198 out of 199 people in the
intermittent group compared to all 200 in
the daily group), but 5 patients
relapsed in the group receiving intermittent
therapy compared to one in
the group receiving the daily regimen. REVIEWER'S
CONCLUSIONS: There is
not enough evidence to assess the
equivalence of effect between fully
intermittent, rifampicin-containing
short-course chemotherapy and similar
daily therapy in patients with pulmonary
tuberculosis. Larger randomised
studies are required to establish the
effectiveness of fully intermittent,
short-course chemotherapy. [References: 1]
1498. Osann
KE. Lowery JT. Schell MJ. Small cell lung cancer in women:
risk associated with smoking, prior respiratory disease, and occupation. Lung
Cancer. 28(1):1-10, 2000 Apr.
Abstract
Small cell carcinoma of the lung (SCLC)
occurs most frequently in heavy
smokers, yet exhibits a lesser predominance
among men than other
smoking-associated lung cancers. Incidence
rates have increased more
rapidly in women than men and at a faster
rate among women than other cell
types. To investigate the importance of
smoking and other risk factors, a
case-control study of SCLC in women was
conducted. A total of 98 women
with primary SCLC and 204 healthy controls,
identified by random-digit
dialing and frequency matched for age,
completed telephone interviews.
Data collected include demographics, medical
history, family cancer
history, residence history, and lifetime
smoking habits. Odds ratios (ORs)
and 95% confidence intervals (95% CI) were
calculated using logistic
regression analysis. Risk for small cell
carcinoma in women is strongly
associated with current use of cigarettes.
Ninety-seven of 98 cases had
smoked cigarettes; 79% of cases were current
smokers and 20% were former
smokers at the time of diagnosis compared to
13% current and 34% former
smokers among controls. The ORs associated
with smoking are 108.7 (95% CI
14.8-801) for ever-use of cigarettes, 278.9
(95% CI 37.0-2102) for current
smoking, and 31.5 (95% CI 4. 1-241) for
former smoking. Risk increases
steeply with pack-years of smoking and
decreases with duration of smoking
cessation. After adjusting for age,
education, and lifetime smoking
history, medical history of
physician-diagnosed respiratory disease
including chronic bronchitis, emphysema,
pneumonia, tuberculosis, asthma,
and hay fever is not associated with a
significant increase in lung cancer
risk. Employment in blue collar, service, or
other high risk occupations
is associated with a two to three-fold
non-significant increase in risk
for small cell carcinoma after adjusting for
smoking.
1499. Ozates
M. Ozkan U. Kemaloglu S. Hosoglu
S. Sari I. Spinal subdural tuberculous
abscess. Spinal Cord. 38(1):56-8, 2000
Jan.
Abstract
OBJECTIVES: Spinal subdural abscess is rare
and only 48 cases have been
described to date. In this report, we
present an additional spinal
subdural tuberculous abscess. METHOD:
Tuberculous meningitis was diagnosed
with clinical and laboratory findings in a
45-year-old man. A spinal
subdural abscess was demonstrated using MRI.
Presence of the abscess was
revealed by surgical intervention. The
diagnosis was confirmed by
pathological examination. RESULTS: The
patient had been treated for
tuberculous meningitis 2 years previously.
The disease recurred when
anti-tuberculous therapy was prematurely
discontinued. During the second
treatment, the patient also underwent a
ventriculo-peritoneal shunt
operation for hydrocephalus. Dizziness and
weakness of both legs developed
after the postoperative period. Spinal MRI
showed a spinal subdural
abscess as a iso-intense mass with spinal
cord in the T1 and T2 weighted
images, ring like enhancement and
compression on the spinal cord at T3-T4
level. The patient underwent surgery and the
abscess was drained.
CONCLUSION: Tuberculosis may cause a spinal
subdural abscess and although
it is a rare disorder, when encountered MRI
is very useful in the
diagnosis.
1500. Pereira
Arias-Bouda LM. Nguyen LN. Ho LM.
Kuijper S. Jansen HM. Kolk
AH. Development of antigen detection assay for diagnosis of tuberculosis
using sputum samples. Journal of
Clinical Microbiology. 38(6):2278-83,
2000 Jun.
Abstract
The rising incidence of tuberculosis
worldwide means an increasing burden
on diagnostic facilities, so tests simpler
than Ziehl-Neelsen staining are
needed. Such tests should be objective,
reproducible, and have at least as
good a detection limit as 10(4) bacteria/ml.
A capture enzyme-linked
immunosorbent assay (ELISA) was developed
for detection of
lipoarabinomannan (LAM) in human sputum
samples. As a capture antibody, we
used a murine monoclonal antibody against
LAM, with rabbit antiserum
against Mycobacterium tuberculosis as a
source of detector antibodies. The
sensitivity of the capture ELISA was
evaluated by using purified LAM and
M. tuberculosis whole cells. We were able to
detect 1 ng of purified
LAM/ml and 10(4) M. tuberculosis whole
cells/ml. LAM could also be
detected in culture filtrate of a 3-week-old
culture of M. tuberculosis.
The culture filtrate contained approximately
100 microgram of LAM/ml. The
detection limit in sputum pretreated with
N-acetyl-L-cysteine and
proteinase K was 10(4) M. tuberculosis whole
cells per ml. Thirty-one
(91%) of 34 sputum samples from 18
Vietnamese patients with tuberculosis
(32 smear positive and 2 smear negative)
were positive in the LAM
detection assay. In contrast, none of the 25
sputum samples from 21
nontuberculous patients was positive. This
specific and sensitive assay
for the detection of LAM in sputum is
potentially useful for the diagnosis
of tuberculosis.
1501. Portillo-Gomez
L. Morris SL. Panduro A. Rapid and efficient detection of extra-pulmonary
Mycobacterium tuberculosis by PCR
analysis. International Journal of Tuberculosis & Lung Disease. 4(4):361-70, 2000 Apr.
Abstract
SETTING: The diagnosis of extra-pulmonary
tuberculosis (EPTB) remains an
important clinical problem, primarily
because of the inadequate
sensitivity of conventional bacteriologic
methods for detecting
Mycobacterium tuberculosis in
extra-pulmonary specimens. OBJECTIVE: To
evaluate whether a IS6110-based polymerase
chain reaction (PCR) method can
be utilized to detect M. tuberculosis in
non-pulmonary specimens. DESIGN:
Specimens from 286 Mexican patients with a
presumptive clinical diagnosis
of EPTB were prospectively examined by
Ziehl-Neelsen staining,
mycobacterial culture on Lowenstein-Jensen
slants, and by PCR. The DNA for
PCR was extracted by the buffer lysis method
and phenol-guanidine
thiocyanate-chloroform. Primers that amplify
a 200 bp fragment from the
insertion-like M. tuberculosis sequence
element IS6110 were utilized.
RESULTS: Our results demonstrate that this
PCR method is highly specific
(100%) for identifying M. tuberculosis from
a variety of specimens
including cerebrospinal fluid (CSF), pleural
fluid, ascitic fluid,
pericardial fluid, urine, and lymph node
exudate. Moreover, the
sensitivity of PCR for detecting M.
tuberculosis in CSF (94%), pleural
fluid (94%), ascitic fluid and other
extrapulmonary specimens (93%)
greatly exceeds the sensitivity of
conventional smear and culture methods.
CONCLUSION: These results demonstrate that
PCR can be a highly specific
and sensitive aid in the detection of M.
tuberculosis from extra-pulmonary
specimens.
1502.
Pottumarthy
S. Wells VC. Morris AJ. A comparison
of seven tests for serological diagnosis of tuberculosis. Journal of Clinical
Microbiology. 38(6):2227-31, 2000 Jun.
Abstract
Seven serological tests, two
immunochromatographic tests, ICT Tuberculosis
and RAPID TEST TB, and five enzyme-linked
immunosorbent assays,
TUBERCULOSIS IgA EIA, PATHOZYME-TB complex,
PATHOZYME-MYCO IgG,
PATHOZYME-MYCO IgA, and PATHOZYME-MYCO IgM,
were evaluated simultaneously
with 298 serum samples from three groups of
individuals: 44 patients with
active tuberculosis, 204 controls who had
undergone the Mantoux test (89
Mantoux test-positive and 115 Mantoux
test-negative controls), and 50
anonymous controls. The sensitivities of the
tests with sera from patients
with active tuberculosis were poor to
modest, ranging from 16 to 57%. All
the tests performed equally with sera from
subgroups of those with active
tuberculosis, those with pulmonary (33
patients) versus extrapulmonary (11
patients) disease, and those who were smear
positive (24 patients) versus
smear negative (12 patients) (P > 0.05).
The specificities of the tests
ranged from 80 to 97% with sera from the
Mantoux test controls and 62 to
100% with sera from the anonymous controls.
The TUBERCULOSIS IgA EIA had
the highest sensitivity (57%) with sera from
patients with active
tuberculosis, with a high specificity of 93% with sera from the
Mantoux
test controls, but a very poor specificity
of 62% with sera from the
anonymous controls. Overall, ICT
Tuberculosis followed by PATHOZYME-MYCO
IgG had the best performance characteristics,
with sensitivities of 41 and
55%, respectively, with sera from patients
with active tuberculosis and
specificities of 96 and 89%, respectively,
with sera from the Mantoux test
controls and 88 and 90%, respectively, with
sera from the anonymous
controls. By combining all the test results,
a maximum sensitivity of 84%
was obtained, with reciprocal drops in
specificities to 55 and 42% for the
Mantoux test controls and anonymous
controls, respectively. The best
combination was that of ICT Tuberculosis and
PATHOZYME-MYCO IgG, with a
sensitivity of 66% and a specificity of 86%
for the Mantoux test controls
and a sensitivity and specificity of 78% for
the anonymous controls. While
a negative result by any one of these tests
would be useful in helping to
exclude disease in a population with a low
prevalence of tuberculosis, a
positive result may aid in clinical decision
making when applied to
symptomatic patients being evaluated for
active tuberculosis.
1503. Poveda
F. Camacho J. Arnalich F. Codoceo
R. del Arco A. Martinez-Hernandez P.
Circulating cytokine concentrations in tuberculosis and other chronic bacterial infections. Infection. 27(4-5):272-4, 1999.
Abstract
Cytokines are a group of hormone-like
polypeptides that play a variety of
regulatory roles in host defense against
infection. Because of the
possible different involvement of these
mediators in bacterial infections
and tuberculosis, enzyme immunoassay was
used to measure comparatively the
plasma levels of the proinflammatory
cytokines interleukin-1 beta
(IL-1beta), tumor necrosis factor alpha
(TNF-alpha), interleukin-6 (IL-6)
and interferon gamma (IFN-gamma) in 25
immunocompetent patients divided
into two groups: in 12 patients clinical and
microbiological diagnosis
showed a chronic bacterial infection and 13
patients had pleuropulmonar
tuberculosis. After resolution of the
infectious disorders (> or = 3
months), these measurements were repeated
for each patient. High levels of
IL-1b, TNF-alpha and IL-6 were observed at
study entry, but no significant
difference was found between the groups. In
contrast, plasma levels (mean
+/- SEM) of IFN-gamma were significantly
higher in patients with
tuberculosis when compared with the
bacterial group (0.753 +/- 0.201 vs
0.325 +/- 0.105 IU/ml; P = 0.020). This
different pattern of plasma
proinflammatory cytokines could be ascribed
to a prevaling role of the
mediators of so-called Th-1 immune response
(IFN-gamma) in host defense
against infection with Mycobacterium
tuberculosis.
1504. Rameshkumar
K. Tuberculous lymphadenitis in children--role of fine needle aspiation cytology. Journal of the Association of
Physicians of India. 47(10):976-9, 1999 Oct.
Abstract
OBJECTIVES: Tuberculosis in children remains
misdiagnosed, underdiagnosed
or paradoxically overtreated as a result of
diagnostic difficulties and
non-specific manifestations such as
lymphadenopathy. The aims of the study
were, i) To assess the efficiency of fine
needle aspiration cytology
(FNAC) in comparison to histology to
determine the prevalence of
tuberculosis in lymph nodes, ii) To compare
the cytological and
histopathological features of
lymphadenopathy in children to adults, iii)
To analyse the clinical significance of the
results in the context of
diagnosis. MATERIAL AND METHODS: The
biopsies of lymph nodes obtained
during the seven year period from January
1989 to December 1995 and the
lymph nodes on which fine needle aspiration
cytology was done during the
period, January 1990 to December 1995 were
included for the study.
Hemotoxylin and Eosin stain was used for
basic evaluation of the
histopathologic features. A grading system
of 0 to 5+ was used to assess
the smears to categorise them into diagnostic
groups. RESULTS: Among 1396
lymph node biopsies submitted for evaluation
of non-neoplastic conditions
54.12% (741) showed tuberculosis, in which
children constituted 9.04%. A
higher incidence of 68.61% was observed on
FNAC. Both on cytology and
histology, a necrotizing type of
inflammation was observed more in
children, which indicated hypersensitivity.
CONCLUSION: FNAC was found to
be a useful adjunct diagnostic technique
especially in children, but the
need to develop a sensitive and easily
available method to diagnose in
asymptomatic and high risk children still
persists. Selection of patients
with lymphadenopathy for more than three
weeks is important, as otherwise
nonspecific changes and acute inflammatory
changes are likely to interfere
with the diagnosis.
1505. Roring
S. Hughes MS. Skuce RA. Neill SD.
Simultaneous detection and strain differentiation of Mycobacterium bovis
directly from bovine tissue specimens by spoligotyping. Veterinary
Microbiology. 74(3):227-36, 2000 Jun 1.
Abstract
Culture of Mycobacterium bovis is used
routinely to support field
diagnosis of bovine tuberculosis; however,
this method is slow. Rapid
detection and strain-typing of M. bovis
directly from 37 lesioned bovine
lymph node specimens was performed by the
polymerase chain reaction (PCR)
based method, spoligotyping. Mycobacterial
DNA was extracted from the
specimens using a nucleic acid sequence
capture technique. Two sets of
specimens were tested, the first set
comprising 16 decontaminated tissue
homogenates from lesioned lymph node
specimens which had been processed
for BACTEC culture and a second set of 21
non-decontaminated lesioned
lymph node specimens. Both sets of specimens
had been frozen before
analysis. Sequence capture PCR enabled
detection and strain-typing of M.
bovis directly from 15 of the 16
decontaminated homogenates and all 21 of
the non-decontaminated tissues. Four
spoligotype (ST) patterns were
obtained from each set; ST1, ST2, ST3 and
ST16 were detected in the
decontaminated specimens and ST1, ST2, ST11
and ST14 in the
non-decontaminated specimens. For both sets
of specimens, ST1 was the
predominant strain type detected. ST
patterns obtained from the BACTEC
cultures of the decontaminated specimens
were in agreement with those
obtained directly from the tissue. The
sensitivity of detection by
sequence capture-PCR compared very
favourably with that of BACTEC culture.
ST patterns were obtained directly from
tissues of 34 of the 35 culture
positive specimens and the two culture
negative specimens. DNA extraction
from the 21 non-decontaminated specimens
involved an initial stomaching
treatment. An assessment of sequence capture
on both liquid alone and
liquid and tissue homogenate combined,
following stomaching, indicated
that PCR was less successful on the liquid
component alone.
1506. Rossi
MC. Gori A. Zehender G. Marchetti
G. Ferrario G. De Maddalena C. Catozzi L. Bandera A.
Esposti AD. Franzetti F. A
PCR-colorimetric microwell plate hybridization assay for detection of Mycobacterium tuberculosis and M. avium from
culture samples and
Ziehl-Neelsen-positive smears. Journal of Clinical Microbiology. 38(5):1772-6, 2000 May.
Abstract
Differentiation between Mycobacterium tuberculosis
and M. avium is
essential for the treatment of mycobacterial
infections. We have developed
an easy and rapid detection assay for the
diagnosis of mycobacterial
diseases. This is a PCR-hybridization assay
based on selective
amplification of a 16S rRNA gene sequence
using pan-Mycobacterium primers
followed by hybridization of the
amplification products to biotinylated M.
tuberculosis and M. avium-specific probes. A
total of 55 mycobacterial
isolates were tested. For all isolates, results
concordant with those of
conventional identification methods were
obtained. Moreover, we developed
a method for extraction of DNA from
Ziehl-Neelsen-positive smears which
allows the recovery of intact target DNA in
our PCR-hybridization assay.
Our method was able to confirm all culture
results for 59
Ziehl-Neelsen-positive smears from clinical
specimens (35 sputum, 11 lymph
node biopsy, 6 stool, 4 pus, 2 urine, and 1
pericardial fluid specimens).
These data suggest that our PCR-hybridization
assay, which is simple to
perform and less expensive than commercial
probe methods, may be suitable
for the identification of M. tuberculosis
and M. avium. It could become a
valuable alternative approach for the
diagnosis of mycobacterial
infections when applied directly to DNA
extracted from
Ziehl-Neelsen-positive smears as well.
1507. Salajka
F. Mezensky L. Pokorny A. Commercial polymerase chain
reaction test (Amplicor set) in the diagnosis of smear-negative pulmonary
tuberculosis from sputum and bronchoalveolar
lavage. Monaldi Archives for Chest Disease. 55(1):9-12, 2000 Feb.
Abstract
The study presents experience with
polymerase chain reaction (PCR) in the
diagnosis of tuberculosis (TB) and compares
the results obtained in sputum
and bronchoalveolar lavage fluid (BALF). A
total of 1,097 samples from 846
smear-negative patients with suspected TB
was examined using PCR and
culture during a period of 40 months. TB was
the final diagnosis in 160
patients, based on the evidence of
mycobacteria in 90 patients and on
clinical criteria in the remaining 70. The
PCR test had high specificity
(98% and 99%, respectively) but poor
sensitivity (37% and 34%,
respectively) regardless of whether sputum
or BALF was examined.
Surprisingly, the sensitivity of culture
(44% and 35% in sputum and BALF,
respectively) was higher than that of PCR in
this group. The contribution
of BAL to establishing the diagnosis of
tuberculosis was rather limited,
yet substantial in some patients. The results
obtained in this study were
compared with the results published in the
literature, and it was
concluded that further clinical studies are
necessary to establish an
appropriate role for the polymerase chain
reaction in the diagnosis of
tuberculosis.
1508. Scarparo
C. Piccoli P. Rigon A. Ruggiero G. Scagnelli M. Piersimoni C. Comparison
of enhanced Mycobacterium tuberculosis amplified direct test with COBAS AMPLICOR Mycobacterium
tuberculosis assay for direct detection of Mycobacterium tuberculosis complex
in respiratory and extrapulmonary
specimens. Journal of Clinical
Microbiology. 38(4):1559-62, 2000 Apr.
Abstract
The new Roche COBAS AMPLICOR Mycobacterium
tuberculosis Assay was compared
to the Gen-Probe enhanced Mycobacterium tuberculosis
Amplified Direct Test
(AMTDII). A total of 486 specimens (296
respiratory and 190
extrapulmonary) collected from 323 patients
were tested in parallel with
both assays. Results were compared with
those of acid-fast staining and
culture, setting the combination of culture
and clinical diagnosis as the
"gold standard." After resolution
of discrepant results, the sensitivity,
specificity, and positive and negative
predictive values for AMTDII were
85.7, 100, 100, and 90.4% for respiratory
specimens and 82.9, 100, 100,
and 95. 5% for extrapulmonary specimens,
respectively. The corresponding
values for AMPLICOR were 94.2, 100, 100, and
96.6% for respiratory
specimens and 85, 100, 100, and 96.1% for
extrapulmonary specimens,
respectively. No significant differences
were observed between the results
of both assays or, within each one, between
respiratory and extrapulmonary
specimens. The difference between AMTDII and
AMPLICOR sensitivities was
related to the presence of inhibitory
samples, which the former assay,
lacking an internal amplification control
(IAC), could not detect. The
overall inhibition rate for the AMPLICOR
assay was 3.9% (19 specimens). It
is concluded that, although both
amplification assays proved to be rapid
and specific for the detection of M.
tuberculosis complex in clinical
samples, AMPLICOR, by a completely automated
amplification and detection
procedure, was shown to be particularly
feasible for a routine laboratory
setting. Finally, AMTDII is potentially an
excellent diagnostic technique
for both respiratory and extrapulmonary
specimens, provided that an IAC is
included with the assay.
1509. Sethi
GR. Batra V. Bronchiectasis: causes and
management. Indian Journal of Pediatrics.
67(2):133-9, 2000 Feb.
Abstract
Bronchiectasis is a condition representing
abnormal and permanent
dilatation and distortion of medium sized
bronchi, usually accompanied by
destruction of the airway wall. Post
inflammatory bronchiectasis remains
very common in the developing countries as a
sequel to pulmonary
tuberculosis, whooping cough, and severe
measles (among other causes).
Cystic fibrosis is the most common cause of
generalized bronchiectasis in
developed countries. Symptoms primarily are
chronic cough and
expectoration of foul smelling sputum.
Bronchography was, until recently,
the investigation of choice for the
diagnosis of bronchiectasis and the
gold standard against which the current best
imaging technique HRCT (high
resolution computed tomography) has been
compared. Treatment includes
prompt attention to acute exacerbations,
management of airway secretions
and control of airway hyperreactivity.
Treatment is aimed at the non
progression of the disease and complete cure
if possible. The role of
surgical therapy has evolved from early
curative resection for all
patients to a more palliative approach.
Patients with advanced generalized
bronchiectasis should be considered for lung
transplantation.
1510. Silva
CL. Lowrie DB. Identification and
characterization of murine cytotoxic T cells that kill Mycobacterium tuberculosis. Infection &
Immunity. 68(6):3269-74, 2000 Jun.
Abstract
As we seek to develop and evaluate new
vaccines against tuberculosis, it
is desirable that we understand the
mechanisms of protective immunity in
our models. Adoptive transfer of protection
with hsp65-specific T-cell
clones from infected or vaccinated mice into
naive mice had indicated that
cytotoxic T cells can make a major
contribution to protection. We
characterized 28 CD4(+) CD8(-) and 28 CD4(-)
CD8(+) hsp65-specific T-cell
clones derived from infected or vaccinated
mice. Half of the CD4(+) CD8(-)
and 64% of the CD4(-) CD8(+) clones were
cytotoxic. Cytotoxicity was
associated with high expression of CD44 and
gamma interferon production.
Most (86%) of the cytotoxic CD4(+) CD8(-)
clones lysed target cells via
the Fas-FasL pathway, and most (83%) of the
cytotoxic CD4(-) CD8(+) clones
lysed target cells via cytotoxic granules.
Only the clones using the
granule-mediated pathway caused substantial
loss of viability of virulent
Mycobacterium tuberculosis during lysis of
infected macrophages, and the
degree of killing closely correlated with
the availability of granule
marker enzyme activity. Granule-mediated
cytotoxicity thus may have a key
role in protection against tuberculosis by
delivering mycobactericidal
granule contents.
1511. Silva
CL. The potential use of heat-shock
proteins to vaccinate against mycobacterial
infections. [Review] [43 refs] Microbes & Infection. 1(6):429-35, 1999 May.
Abstract
Over the last few years, some of our
experiments in which mycobacterial
heat-shock protein (HSP) antigens were
presented to the immune system as
if they were viral antigens have had a
significant impact on our
understanding of protective immunity against
tuberculosis. They have also
markedly enhanced the prospects for new
vaccines. We now know that the
mycobacterial HSP65 antigen can confer
protection equal to that from live
BCG vaccine in mice. [References: 43]
1512. Singh
KK. Muralidhar M. Kumar A.
Chattopadhyaya TK. Kapila
K. Singh MK. Sharma SK. Jain NK.
Tyagi JS. Comparison of in house polymerase chain reaction with
conventional techniques for the detection of Mycobacterium tuberculosis DNA in
granulomatous lymphadenopathy. Journal of Clinical Pathology. 53(5):355-61, 2000 May.
Abstract
AIMS: To evaluate the usefulness of the devR
based polymerase chain
reaction (PCR) in the detection of
Mycobacterium tuberculosis in lymph
node aspirates and tissues of lymphadenitis
and to compare PCR with
conventional diagnostic techniques. SUBJECTS
AND METHODS: Coded specimens
of fine needle aspirates and biopsies from
22 patients with tuberculous
lymphadenitis, 14 patients with
non-tubercular lymphadenitis, and nine
patients with granulomatous lymphadenitis
were processed and subjected to
analysis by PCR, smear microscopy, M
tuberculosis culture, histology, and
cytology. RESULTS: Tuberculous lymphadenitis
was correctly diagnosed by
PCR in 18 patients, by culture in five
patients, by histology in 13
patients, and by cytology in seven patients.
PCR gave two false positive
results in 14 patients with non-tubercular
lymphadenitis. The sensitivity
of the conventional techniques was
significantly higher with biopsies (17
of 22 specimens; 77%) than with fine needle
aspirates (nine of 22
specimens; 41%). However, the sensitivity of
PCR was not significantly
higher with biopsies (68%) in comparison
with fine needle aspirates (55%).
The sensitivity of either biopsy PCR or fine
needle aspirate PCR was not
significantly different from that of either
histology combined with
culture or cytology combined with culture.
The overall combined
specificity of PCR was 86%. Mycobacterium
tuberculosis DNA was detected in
six of nine patients with granulomatous
lymphadenitis. CONCLUSION: PCR is
the most sensitive single technique
available to date for the
demonstration of M tuberculosis in specimens
derived from patients with a
clinical suspicion of tuberculous
lymphadenitis. The value of PCR lies in
its use as an adjunct test in the diagnosis
of tuberculous lymphadenitis,
particularly in those patients where
conventional methods fail. Because
fine needle aspiration is not an invasive
procedure, it is the procedure
of choice, and PCR should be performed
initially on these samples.
Excisional biopsy histology and PCR should
be recommended only for
patients in whom fine needle aspirate PCR is
negative or when there is
discrepancy with the clinical impression.
1513.
Singh NP. Parija SC. The value of fluorescence
microscopy of auramine stained sputum smears for the diagnosis of pulmonary
tuberculosis. Southeast Asian Journal of Tropical Medicine & Public
Health. 29(4):860-3, 1998 Dec.
Abstract
Laboratory diagnosis of pulmonary
tuberculosis rests on the
bacteriological examination of sputum smears
stained by the Ziehl-Neelsen
(ZN) method for acid fast bacilli (AFB). In
the present study, we have
compared light microscopy of ZN stained
smears with that of fluorescence
microscopy of sputum smears stained by
auramine-phenol flurochrome dye for
detection of AFB in sputum specimens. Sputum
specimens from a total of
2,600 clinically suspected and diagnosed
cases of pulmonary tuberculosis
were examined by both the methods. Sputum
specimens from a total of 1,104
patients were found to be positive for AFB.
These included sputa from 975
(37.5%) patients positive for AFB by both ZN
and auramine staining methods
and sputa from an additional 129 (4.96%)
patients positive for AFB by
auramine staining only. Thus auramine
staining of sputum smears in
comparison to that of ZN staining is a
better method of sputum microscopy
for demonstration of AFB in sputum
specimens. Fluorescence microscopy is
relatively more sensitive and has the added
advantage of allowing a large
number of sputum specimens to be examined in
a given time, in laboratories
equipped with a fluorescent microscope.
1514. Singh
S. Cherian RS. George B.
Nair S. Srivastava A. Unusual
extra-axial central nervous system involvement of non-Hodgkin's lymphoma:
magnetic resonance imaging. Australasian Radiology. 44(1):112-4, 2000 Feb.
Abstract
The MR imaging findings in a patient with
non-Hodgkin's lymphoma with
unusual involvement of the sella, pituitary
stalk and left parasellar
region are reported here. On the basis of
the MR imaging findings, the
initial differential diagnosis included
invasive pituitary adenoma, a
granulomatous lesion and en plaque
meningioma. Trans-sphenoidal biopsy of
the sellar mass showed chronic inflammatory
changes and the patient was
initially treated for tuberculosis. Because
follow-up imaging showed the
lesion to be progressive, a biopsy was done
of an enlarged right inguinal
lymph node. This revealed non-Hodgkin's
lymphoma.
1515. Stone
DS. Health surveillance for health care workers. A vital role for the
occupational and environmental health nurse. [Review] [33 refs] AAOHN
Journal. 48(2):73-9, 2000 Feb.
Abstract
Health surveillance for the general health
care worker includes
surveillance for immunity to infectious
diseases such as measles, mumps,
rubella, varicella, and hepatitis B. Post
exposure surveillance for
bloodborne pathogens includes HIV, hepatitis
B, and hepatitis C. Periodic
surveillance of specialty practice areas as
mandated by OSHA include
workers exposed to lasers, radiation,
formaldehyde, ethylene oxide,
hazardous drugs, anesthetic gases, and
tuberculosis. [References: 33]
1516. Strohmeier
GR. Fenton MJ. Roles of
lipoarabinomannan in the pathogenesis of tuberculosis. [Review] [63 refs] Microbes & Infection. 1(9):709-17, 1999 Jul.
Abstract
Tuberculosis is a worldwide public health
threat caused by Mycobacterium
tuberculosis. All mycobacteria express a
unique cell envelope glycolipid,
lipoarabinomannan, which can be released at
sites of infection.
Lipoarabinomannan is a potential virulence
factor which can bind to
leukocytes and modulate immune responses.
Here, we provide an overview of
the interactions of mycobacteria and
lipoarabinomannan with immune cells.
[References: 63]
1517. Swaminathan
S. Umadevi P. Shantha S. Radhakrishnan
A. Datta M. Sero diagnosis of tuberculosis in children using two ELISA kits.
Indian Journal of Pediatrics.
66(6):837-42, 1999 Nov-Dec.
Abstract
The diagnosis of childhood tuberculosis is
based on circumstantial
evidence in the absence of a gold standard
in the majority of cases.
Sero-diagnosis offers scope for an early
diagnosis in a variety of
clinical conditions and is simple to
perform. A number of mycobacterial
antigens have been used for antibody
detection assays and several are
available as kits in the market. This study
was done to evaluate the value
of antibody detection kits (ELISA) against
the A60 antigen and 38 kDa
antigen of Mycobacterium tuberculosis in the
diagnosis of childhood
tuberculosis at the outpatient department of
the Institute of Social
Paediatrics, Government Stanley Hospital in
collaboration with
Tuberculosis Research Centre, Chennai.
Thirty five children with pulmonary
tuberculosis, 7 with TB lymphadenitis and 22
healthy controls were
studied. In addition to routine
investigations including gastric lavage
for AFB culture, serum antibodies against
the A60 and 38 kDa antigens were
assayed using commercially available ELISA
kits. With A60, IgM serum
levels were positive in 74% of pulmonary TB
cases, 57% of TB lymphadenitis
cases and 50% of controls. A60 IgG was
positive in 17% of pulmonary TB,
86% of TB lymphadenitis and 14% of controls.
The 38 kDa IgG antibody was
positive in 37% of pulmonary and 86% of TB
lymphadenitis cases and 27% of
controls. Among 10 culture confirmed cases,
A60 IgM was positive in 8, A60
IgG in 3 and 38 kDa IgG in 5 patients. The
sensitivity of the tests ranged
between 29% and 71% and specificity between
50% and 86%. Although the
numbers are small, the results suggest that
serodiagnosis using the
currently available antigens of M.
tuberculosis is unlikely to be a
confirmatory test for tuberculosis in
children.
1518. Swingler
GH. Chest radiography in ambulatory children with acute lower respiratory infections: effective tuberculosis case-finding?.
Annals of Tropical Paediatrics.
20(1):11-5, 2000 Mar.
Abstract
A study was performed to determine the
proportion of ambulatory children
with acute lower respiratory infections in
whom clinical management was
changed by findings on routine chest
radiography that suggested
tuberculosis. The children studied were aged
between 2 and 59 months and
met the World Health Organization's case
definition for pneumonia. They
lived in an area with a very high prevalence
of tuberculosis. Exclusion
criteria included a cough of more than 14
days' duration and a history of
a current household contact with active
tuberculosis. Twelve (4.4%) of 273
children had radiological findings
suggesting tuberculosis, nine of which
were suspected mediastinal lymphadenopathy.
Eight children were further
investigated for tuberculosis: seven of them
did not require treatment for
tuberculosis and one was lost to follow-up.
It is concluded that chest
radiography in ambulatory children with
acute lower respiratory infections
of less than 14 days' duration and not in
contact with active tuberculosis
does not result in a meaningful increase in
the diagnosis of tuberculosis.
1519. van
Pinxteren LA. Ravn P. Agger EM.
Pollock J. Andersen P. Diagnosis
of tuberculosis based on the two specific antigens ESAT-6 and CFP10. Clinical
& Diagnostic Laboratory Immunology.
7(2):155-60, 2000 Mar.
Abstract
Tests based on tuberculin purified protein
derivative (PPD) cannot
distinguish between tuberculosis infection,
Mycobacterium bovis BCG
vaccination, or exposure to environmental
mycobacteria. The present study
investigated the diagnostic potential of two
Mycobacterium
tuberculosis-specific antigens (ESAT-6 and
CFP10) in experimental animals
as well as during natural infection in
humans and cattle. Both antigens
were frequently recognized in vivo and in
vitro based on the induction of
delayed-type hypersensitivity responses and
the ability to induce gamma
interferon production by lymphocytes,
respectively. The combination of
ESAT-6 and CFP10 was found to be highly
sensitive and specific for both in
vivo and in vitro diagnosis. In humans, the
combination had a high
sensitivity (73%) and a much higher
specificity (93%) than PPD (7%).
1520. Walker
D. McNerney R. Mwembo MK.
Foster S. Tihon V. Godfrey-Faussett P. An incremental cost-effectiveness analysis of the first,
second and third sputum examination in
the diagnosis of pulmonary tuberculosis. International Journal of Tuberculosis
& Lung Disease. 4(3):246-51,
2000 Mar.
Abstract
SETTING: St. Francis Hospital in Katete
District, Eastern Province,
Zambia. OBJECTIVE: To compare the
incremental cost-effectiveness of
examining serial sputum smears for screening
suspects for pulmonary
tuberculosis at a rural district hospital in
Zambia. DESIGN: An
incremental cost-effectiveness analysis of
serial sputum smear
examinations for diagnosing pulmonary
tuberculosis based on laboratory
results collected during 1997 and 1998 in a
rural district hospital in
Zambia. The cost analysis took a health
service provider perspective, and
used the ingredients approach. The
cost-effectiveness is expressed in
terms of the incremental cost per
tuberculosis case diagnosed. Relevant
information was obtained from various
sources, including administrative
records, interviews and direct observation.
RESULTS: Of a total of 166
acid-fast bacilli positive suspects who had
three sputum smears examined
sequentially, 128 (77.1%) were found on the
first smear, a further 25
(15%) on the second smear and 13 (7.9%)
additional cases were identified
on the third smear. The economic analysis
shows that the incremental cost
of performing a third test, having already
done two, increases rapidly
with only a small gain in terms of
additional cases of tuberculosis
identified. CONCLUSION: A policy of
examining two samples should be
considered in resource-poor settings, if the
remaining steps of the
national diagnostic algorithm can be adhered
to with respect to
smear-negative suspects.
1521. Ward
BJ. Vaccine adverse events in the new millennium: is there reason for concern?
[see comments]. [Review] [62 refs] Bulletin of the World Health
Organization. 78(2):205-15, 2000.
Abstract
As more and more infectious agents become
targets for immunization
programmes, the spectrum of adverse events
linked to vaccines has been
widening. Although some of these links are
tenuous, relatively little is
known about the immunopathogenesis of even
the best characterized
vaccine-associated adverse events (VAAEs).
The range of possible use of
active immunization is rapidly expanding to
include vaccines against
infectious diseases that require cellular
responses to provide protection
(e.g. tuberculosis, herpes viral
infections), therapeutic vaccines for
chronic infections (e.g. human
immunodeficiency virus (HIV) infection,
viral hepatitis B and C), and vaccines
against non-infectious conditions
(e.g. cancer, autoimmune diseases). Less
virulent pathogens (e.g.
varicella, rotavirus in the developed world)
are also beginning to be
targeted, and vaccine use is being justified
in terms of societal and
parental "costs" rather than in
straightforward morbidity and mortality
costs. In the developed world the paediatric
immunization schedule is
becoming crowded, with pressure to
administer increasing numbers of
antigens simultaneously in ever simpler
forms (e.g. subcomponent, peptide,
and DNA vaccines). This trend, while
attractive in many ways, brings
hypothetical risks (e.g. genetic
restriction, narrowed shield of
protection, and loss of randomness), which
will need to be evaluated and
monitored. The available epidemiological and
laboratory tools to address
the issues outlined above are somewhat limited.
As immunological and
genetic tools improve in the years ahead, it
is likely that we shall be
able to explain the immunopathogenesis of
many VAAEs and perhaps even
anticipate and avoid some of them. However,
this will only happen if the
human and financial resources needed for
monitoring and studying vaccine
safety stay in step with the accelerating
pace of vaccine development.
Failure to make such a commitment would put
all immunization programmes at
risk. [References: 62]
1522. Warren
JR. Bhattacharya M. De Almeida KN. Trakas K. Peterson
LR. A minimum 5.0 ml of sputum improves
the sensitivity of acid-fast smear for
Mycobacterium tuberculosis. American Journal of Respiratory &
Critical Care Medicine. 161(5):1559-62, 2000 May.
Abstract
Detection of acid-fast bacilli (AFB) by
sputum smear supports treatment
decisions with pulmonary tuberculosis (TB),
but smear sensitivity for
Mycobacterium tuberculosis is only
approximately 45 to 75%. In an effort
to increase sensitivity, smears were
prepared using a minimum sputum
volume of 5.0 ml. Sensitivity of smears
during a 39-mo period (n = 1,849)
using >/= 5.0 ml of sputum was 92. 0%,
significantly greater (p < 0.001)
than a sensitivity of 72.5% in a previous
24-mo period (n = 3,486) when
all specimens were processed regardless of
volume. All new cases of TB (n
= 18) were smear-positive with >/= 5.0 ml
of sputum before treatment, and
all were receiving antituberculosis drugs at
hospital discharge. In
contrast, significantly fewer new cases of
TB (14 of 26, p = 0.002) were
positive before treatment when smears were
prepared using sputum of any
volume, and significantly fewer of these new
TB cases (18 of 26, p = 0.03)
were receiving treatment at hospital
discharge. The eight cases without
treatment were smear-negative. These results
indicate that acid-fast smear
using >/= 5.0 ml of sputum increases
sensitivity for M. tuberculosis and
accelerates treatment of TB.
1523.
Wilkinson D. Drugs
for preventing tuberculosis in HIV infected persons. [Review] [6 refs] Cochrane Database of Systematic
Reviews [computer file].
(2):CD000171, 2000.
Abstract
BACKGROUND: People with HIV have a increased
risk of developing
tuberculosis. Preventive therapy may help
prevent progression of
tuberculosis infection to disease.
OBJECTIVES: The objective of this
review was to assess the effects of
preventive therapy with
anti-tuberculosis drugs in people with HIV
infection. SEARCH STRATEGY: The
Cochrane Infectious Diseases Group trials
register, the Cochrane
Controlled Trials Register, Medline, Embase
and reference lists of
articles were searched. Researchers in the
field were contacted. SELECTION
CRITERIA: Randomised trials of
anti-tuberculosis drugs in people with HIV
infection but without evidence of active
tuberculosis. DATA COLLECTION AND
ANALYSIS: One reviewer assessed eligibility
and trial quality. Study
authors were contacted for additional
information. MAIN RESULTS: Six
trials were included. Compared to placebo,
preventive therapy was
associated with a lower incidence of active
tuberculosis (relative risk
0.54, 95% confidence interval 0.39 to 0.76).
Risk of death (relative risk
0.96, 95% confidence interval 0.82 to 1.13)
was not significantly
different in the two groups. Incidence of
tuberculosis was reduced in
people with a positive tuberculin skin test
(relative risk 0.24, 95%
confidence interval 0.14 to 0.40), but was
not significantly lower in
those with a negative skin test (relative
risk 0.87, 95% confidence
interval 0.56 to 1.36). Similarly death was
less frequent in those with a
positive skin test who received preventive
therapy (relative risk 0.77,
95% confidence interval 0.58 to 1.03), but
this difference was not
observed among those with a negative skin
test (relative risk 1.07, 95%
confidence interval 0.88 to 1.30). Each
regimen (isoniazid alone,
isoniazid plus rifampicin, isoniazid plus
rifampicin plus pyrazinamide,
rifampicin plus pyrazinamide) had similar
protective effects against
active tuberculosis for people with positive
skin tests. REVIEWER'S
CONCLUSIONS: Preventive therapy appears to
be effective in reducing
incidence of tuberculosis, and death from
tuberculosis in HIV infected
adults with a positive tuberculin skin test,
at least in the short to
medium term. [References: 6]
1524. Willcox
PA. Drug-resistant tuberculosis. [Review] [49 refs] Current Opinion in
Pulmonary Medicine. 6(3):198-202, 2000
May.
Abstract
There is increasing concern in many countries
about the problem of
drug-resistant tuberculosis, particularly so
because no new classes of
drugs have been developed for the treatment
of tuberculosis since the
1960s. Although drug resistance is thought
to be fairly common in some
countries and rare in others, the global
extent of this condition is not
precisely known. This problem is currently
being investigated by a
combined initiative of the World Health
Organization and the International
Union Against Tuberculosis and Lung Disease.
Recently, there have been
advances in the understanding of the genetic
basis of drug-resistant
tuberculosis. With the sequencing of the
whole genome of Mycobacterium
tuberculosis, the possibility of new targets
for drug development has
emerged. For the present, however, cure
rates on average remain modest,
and nonadherence with chemotherapy remains a
major problem. Drug
resistance is a man-made problem and efforts
to prevent it through
directly observed therapy, short course are
essential. [References: 49]
1525.
Yencha MW. Linfesty R.
Blackmon A. Laryngeal tuberculosis. [Review] [15 refs] American Journal
of Otolaryngology. 21(2):122-6, 2000 Mar-Apr.
Abstract
Since the introduction of antituberculous
medications, the incidence of
laryngeal tuberculosis (TB) has decreased
and remains stable. However,
with the incidence of TB increasing, mainly
caused by the acquired
immunodeficiency syndrome epidemic, the
incidence of laryngeal involvement
may be on the rise. The main presenting
symptom of laryngeal TB is
dysphonia. The diagnosis is confirmed with
the identification of
granulomatous inflammation, caseating
granulomas, and acid-fast bacilli on
histopathologic examination of biopsied
laryngeal tissue. However, making
the diagnosis difficult can be the presence
of pseudoepitheliomatous
hyperplasia, which mimics squamous cell
carcinoma. Treatment is primarily
with antituberculous medications with
surgery reserved for those cases of
airway compromise. Laryngeal complications
can occur; thus, long-term
follow-up is recommended. We report a case
of laryngeal TB in a human
immunodeficiency virus-negative patient and
review the literature.
[References: 15]
1526. Zedtwitz-Liebenstein
K. Podesser B. Peck-Radosavljevic M. Graninger W. Intestinal tuberculosis presenting as fever of unknown origin in
a heart transplant patient. Infection. 27(4-5):289-90, 1999.
Abstract
Patients undergoing transplantation have an
increased risk of developing
infections such as tuberculosis,
Pneumocystis carinii pneumonia, Candida
infections or cytomegalovirus infections
because of their
immunosuppressive therapy with cyclosporin
A, azathioprine and steroids.
Mycobacterial infection is well recognized
as a complication in the
immunocompromised host but diagnosis and
therapy are very difficult.
1884. Authors
Anonymous.
Title
Update: Nucleic acid amplification tests for
tuberculosis.
Source
MMWR - Morbidity & Mortality Weekly
Report. 49(26):593-4, 2000 Jul 7.
Abstract
On September 30, 1999, the Food and Drug
Administration approved a
reformulated Amplified Mycobacterium
Tuberculosis Direct Test (MTD)
(Gen-Probe, San Diego, California) for
detection of Mycobacterium
tuberculosis in acid-fast bacilli (AFB)
smear-positive and smear-negative
respiratory specimens from patients
suspected of having tuberculosis (TB).
MTD and one other nucleic acid amplification
(NAA) test, the Amplicor
Mycobacterium Tuberculosis Test (Amplicor)
(Roche Diagnostic Systems,
Inc., Branchburg, New Jersey), previously
had been approved for the direct
detection of M. tuberculosis in respiratory
specimens that have positive
AFB smears. This notice updates the original
summary published in 1996 (1)
and provides suggestions for using and
interpreting NAA test results for
managing patients suspected of having TB.
The appropriate number of
specimens to test with NAA will vary
depending on the clinical situation,
the prevalence of TB, the prevalence of
nontuberculous mycobacteria (NTM),
and laboratory proficiency (2,3). Based on
available information, the
following algorithm is a reasonable approach
to NAA testing of respiratory
specimens from patients with signs or
symptoms of active pulmonary TB for
whom a presumed diagnosis has not been
established.
1885.
Authors
Ardito F.
Sanguinetti M. Sechi L. Posteraro B. Masucci L. Fadda G.
Zanetti S.
Title
Comparison of the mycobacteria growth
indicator tube with radiometric and
solid culture for isolation of mycobacteria
from clinical specimens and
susceptibility testing of Mycobacterium
tuberculosis.
Source
New Microbiologica. 23(2):151-8, 2000 Apr.
Abstract
We compared the mycobacteria growth
indicator tube (MGIT) system with the
BACTEC 460 TB and Loewenstein-Jensen (LJ)
systems for the recovery of
mycobacteria (acid-fast bacilli [AFB]) from
600 clinical specimens. A
total of 50 AFB (32 Mycobacterium
tuberculosis complex, 10 M. avium
complex, 3 M. gordonae, 3 M. xenopi, 1 M.
terrae and 1 M. fortuitum) were
detected. MGIT recovered 50 isolates of AFB
(100% sensitivity), and BACTEC
460 TB and LJ recovered 49 (98% sensitivity)
and 19 (38% sensitivity) AFB
isolates, respectively. The mean times to
detect mycobacteria were 10, 10
and 25 days for MGIT, BACTEC 460, and LJ
slants. All isolates of M.
tuberculosis complex were tested for
susceptibility to streptomycin,
isoniazid, rifampin, and ethambutol with the
MGIT and BACTEC 460 TB. Both
systems yielded identical susceptibility
data with different mean times to
report (5.38 days for MGIT versus 7.33 days
for BACTEC 460 TB, P<0.05).
The results suggest that MGIT is equivalent
to BACTEC 460 TB in its
ability to support the growth of
mycobacteria, but significantly more
efficient than LJ. MGIT may also be used for
susceptibility testing of
primary antituberculosis drugs.
1886.
Authors
Barnes PF.
Wizel B.
Title
Type 1 cytokines and the pathogenesis of
tuberculosis [editorial;
comment].
Source
American Journal of Respiratory &
Critical Care Medicine. 161(6):1773-4,
2000 Jun.
1887.
Authors
Braibant M.
Gilot P. Content J.
Title
The ATP binding cassette (ABC) transport
systems of Mycobacterium
tuberculosis. [Review] [114 refs]
Source
FEMS Microbiology Reviews. 24(4):449-67, 2000 Oct.
Abstract
We have undertaken the inventory and
assembly of the typical subunits of
the ABC transporters encoded by the complete
genome of Mycobacterium
tuberculosis. These subunits, i.e. the
nucleotide binding domains (NBDs),
the membrane-spanning domains (MSDs) and the
substrate binding proteins
(SBPs), were identified on the basis of
their characteristic stretches of
amino acids and/or conserved structure. A
total of 45 NBDs present in 38
proteins, of 47 MSDs present in 44 proteins and
of 15 SBPs were found to
be encoded by M. tuberculosis. Analysis of
transcriptional clusters and
searches of homology between the identified
subunits of the transporters
and proteins characterized in other
organisms allowed the reconstitution
of at least 26 complete (including at least
one NBD and one MSD) and 11
incomplete ABC transporters. Sixteen of them
were unambiguously classified
as importers whereas 21 were presumed to be
exporters. By searches of
homology with already known transporters
from other organisms, potential
substrates (peptides, macrolides,
carbohydrates, multidrugs, antibiotics,
iron, anions) could be attributed to 30 of
the ABC transporters identified
in M. tuberculosis. The ABC transporters
have been further classified in
nine different sub-families according to a
tree obtained from the
clustering of their NBDs. Contrary to
Escherichia coli and similarly to
Bacillus subtilis, there is an equal
representation of extruders and
importers. Many exporters were found to be
potentially implicated in the
transport of drugs, probably contributing to
the resistance of M.
tuberculosis to many antibiotics.
Interestingly, a transporter (absent in
E. coli and in B. subtilis) potentially
implicated in the export of a
factor required for the bacterial attachment
to the eukaryotic host cells
was also identified. In comparison to E.
coli and B. subtilis, there is an
under-representation of the importers (with
the exception of the phosphate
importers) in M. tuberculosis. This may
reflect the capacity of this
bacterium to synthesize many essential
compounds and to grow in the
presence of few external nutrients. The
genes encoding the ABC
transporters occupy about 2.5% of the genome
of M. tuberculosis.
[References: 114]
1888.
Authors
Brennan MJ.
Title
Moving new vaccines for tuberculosis through
the regulatory process.
Source
Clinical Infectious Diseases. 30 Suppl 3:S247-9, 2000 Jun.
Abstract
The development of novel vaccines for the
prevention of tuberculosis is an
area of intense interest for scientific
researchers, public health
agencies, and pharmaceutical manufacturers.
Development of effective new
vaccines directed against tuberculosis for
use in target populations will
require close cooperation among several
different international
organizations, including regulatory agencies
responsible for evaluating
the safety and effectiveness of new
biologics for human use.
1889.
Authors
Casal M.
Ruiz P. Herreras A.
Title
Study of the in vitro susceptibility of M.
tuberculosis to ofloxacin in
Spain. Spanish Study Group of M.
tuberculosis resistance.
Source
International Journal of Tuberculosis &
Lung Disease. 4(6):588-91, 2000
Jun.
Abstract
The aim of this study was to determine the
proportion of antituberculosis
ofloxacin resistance among Mycobacterium
tuberculosis strain isolates in
Spain. Over a period of one month, 213 M.
tuberculosis strains collected
from 14 different hospitals were studied,
including strains both
susceptible and resistant to primary
antituberculosis drugs. In 28.1% of
the strains, a minimum inhibitory
concentration (MIC) for ofloxacin of
0.25 microg/ml was obtained; in 43.6% the
MIC was 0.5 microg/ml; in 22.06%
it was 1 microg/ml; and in 6.1% it was >
or =2 microg/ml. Ofloxacin
currently seems to be an effective
antimicrobial in vitro against
susceptible or multiresistant strains of M.
tuberculosis in human
immunodeficiency virus (HIV)-negative or
HIV-positive patients in Spain.
1890.
Authors
Castellano I. Gomez-Martino JR.
Hernandez T. Mateos L. Arguello C.
Title
Hemophagocytic syndrome as an unusual form
of presentation of tuberculosis
in a hemodialysis patient: case report and
review of the literature.
[Review] [22 refs]
Source
American Journal of Nephrology. 20(3):214-6, 2000 May-Jun.
Abstract
We present an unusual manifestation of
tuberculosis in a patient on
hemodialysis. A 73-year-old woman was
admitted to our hospital with a
picture of fever, dyspnea and weight loss.
She had chronic renal failure
and had started periodic hemodialysis 5
years before. Fifteen days after
admission, she began with pancytopenia,
abnormal liver function and
coagulopathy. A bone marrow aspiration was
made 1 week later showing
macrophage elements with phagocytic
activity. Eight weeks later, bone
marrow culture in Lowenstein media confirmed
the presence of tuberculosis.
After the beginning of antituberculosis
therapy, the laboratory
disturbances disappeared and the clinical situation
improved. We think
that fever of unknown origin and
pancytopenia in patients on maintenance
hemodialysis must lead to an early bone
marrow biopsy or aspiration since
after the diagnosis a specific therapy can
cure the disease. Copyright
2000 S. Karger AG, Basel [References: 22]
1891.
Authors
Chambers MA. Vordermeier H. Whelan
A. Commander N. Tascon R.
Lowrie
D.
Hewinson RG.
Title
Vaccination of mice and cattle with plasmid
DNA encoding the Mycobacterium
bovis antigen MPB83.
Source
Clinical Infectious Diseases. 30 Suppl 3:S283-7, 2000 Jun.
Abstract
A scientific review of bovine tuberculosis
in Great Britain has concluded
that the development of a cattle vaccine
holds the best prospect for
long-term disease control. Recent reports of
successful DNA vaccination
against Mycobacterium tuberculosis in small
animal models have raised the
possibility of using a similar strategy to
produce vaccines against
Mycobacterium bovis infection in cattle. To
test this possibility, BALB/c
mice were immunized with DNA encoding the M.
bovis antigen MPB83. The mice
responded to vaccination with a mixed
IgG1/IgG2a response to the antigen
and were protected from intravenous
challenge with virulent M. bovis to a
similar extent as those vaccinated with
bacille Calmette-Guerin. The
immunogenicity of the DNA vaccine in cattle
was tested, after having
established that DNA encoding MPB83 was
immunogenic and elicited
protective immunity in mice. In these
studies, vaccinated animals had
strong proliferative responses to MPB83.
1892.
Authors
Coetsier C.
Vannuffel P. Blondeel N. Denef JF.
Cocito C. Gala JL.
Title
Duplex PCR for differential identification
of Mycobacterium bovis, M.
avium, and M. avium subsp. paratuberculosis
in formalin- fixed
paraffin-embedded tissues from cattle.
Source
Journal of Clinical Microbiology. 38(8):3048-54, 2000 Aug.
Abstract
We previously isolated and sequenced two
genomic segments of Mycobacterium
avium subsp. paratuberculosis, namely, f57,
a species-specific sequence,
and the p34 gene, coding for a 34-kDa
antigenic protein. Comparison of
sequences upstream of the p34 open reading
frame (us-p34) from M. avium
subsp. paratuberculosis and M. tuberculosis
showed a 79-base deletion in
M. tuberculosis. Sequence analysis of the
p34 genes in another two
species, M. bovis (strain BCG) and M. avium
(strain D4), confirmed the
differences observed between tuberculous and
nontuberculous species. A
duplex diagnostic PCR strategy based on
coamplification of nonhomologous
us-p34 and species-specific f57 sequences
was therefore developed. Duplex
PCR yielded three different patterns,
specific either for tuberculous
bacilli (M. tuberculosis, M. bovis, and M.
africanum), for both
nontuberculous mycobacteria M. avium and M.
intracellulare, or for M.
avium subsp. paratuberculosis. The
specificity of this single-step
DNA-based assay was assessed on DNA from
cultured mycobacterial strains,
as well as on a panel of formalin-fixed and
paraffin-embedded tissues from
cattle. Molecular assay results from
tissular DNA were compared to
conventional bacteriological and
histological test results, including
those obtained by Ziehl-Neelsen staining on
tissue biopsy specimens.
Molecular discrimination was successful and
confirmed the value of duplex
us-p34 and f57 sequence amplification for
differential diagnosis of
tuberculosis, paratuberculosis, or
infections caused by other members of
the M. avium complex.
1893.
Authors
Coler RN.
Skeiky YA. Ovendale PJ. Vedvick TS.
Gervassi L. Guderian J.
Jen S.
Reed SG. Campos-Neto A.
Title
Cloning of a Mycobacterium tuberculosis gene
encoding a purifed protein
derivative protein that elicits strong
tuberculosis-specific delayed-type
hypersensitivity.
Source
Journal of Infectious Diseases. 182(1):224-33, 2000 Jul.
Abstract
The purified protein derivative (PPD) skin
test has been used for the
diagnosis of tuberculosis for more than 75
years. However, the test lacks
specificity because all mycobacteria share
antigens present in PPD.
Therefore, sensitization with nontuberculous
pathogenic or with
environmental nonpathogenic mycobacteria can
lead to positive skin tests.
This communication describes a novel PPD
protein present only in
tuberculous complex mycobacteria. A
recombinant protein was obtained and
named DPPD on the basis of the first 4 amino
acids of its N-terminus
sequence. DPPD elicited delayed-type
hypersensitivity (DTH) in 100% of
Mycobacterium tuberculosis-infected guinea
pigs but in no animals
sensitized with several organisms
representative of all members of the
Mycobacterium genus. Preliminary results
indicate that DPPD induces strong
and specific DTH in humans. This work points
to the definition of a single
recombinant M. tuberculosis protein that may
be an alternative to the PPD
test.
1894.
Authors
Collins DM.
Title
New tuberculosis vaccines based on
attenuated strains of the Mycobacterium
tuberculosis complex.
Source
Immunology & Cell Biology. 78(4):342-8, 2000 Aug.
Abstract
The world urgently needs a better
tuberculosis vaccine. Bacille
Calmette-Guerin (BCG), an attenuated strain
of Mycobacterium bovis, has
been very widely used as a vaccine for many
years but has had no major
effect on reducing the incidence of
tuberculosis. A number of alternative
living and non-living vaccines are being
investigated. Live vaccine
candidates include genetically modified
forms of BCG, genetically
attenuated strains of the Mycobacterium
tuberculosis complex and
genetically engineered vaccinia virus and
Salmonella strains. Non-living
vaccine candidates include killed
mycobacterial species, protein subunits
and DNA vaccines. One requirement for
acceptance of any new vaccine will
be a favourable comparison of the protection
it induces relative to BCG in
a range of animal models, some of which may
need further development.
Molecular genetic techniques are now
available that enable production of
live attenuated strains of the M.
tuberculosis complex with vaccine
potential. In the first of two broadly
different approaches that are being
used, large numbers of mutants are produced
by transposon mutagenesis or
illegitimate recombination and are screened
for properties that correlate
with attenuation. In the second approach,
putative genes that may be
required for virulence are identified and
subsequently inactivated by
allelic exchange. In both approaches,
mutants that are attenuated need to
be identified and subsequently tested for
their vaccine efficacy in animal
models. Many mutants of the M. tuberculosis
complex have now been produced
and the vaccine properties of a substantial
number will be assessed in the
next 3 years.
1895.
Authors
Comstock GW.
Title
Simple, practical ways to assess the
protective efficacy of a new
tuberculosis vaccine. [Review] [18 refs]
Source
Clinical Infectious Diseases. 30 Suppl 3:S250-3, 2000 Jun.
Abstract
There is strong evidence that tuberculin
sensitivity cannot be used to
evaluate the efficacy of different strains
of bacille Calmette-Guerin
(BCG). For identifying efficacious strains
of BCG and evaluating
candidates for new vaccines, the best method
is a randomized trial. Simple
trials in which newborns would be vaccinated
with new and old vaccines in
alternate years could demonstrate which
vaccine was the better.
[References: 18]
1896.
Authors
de La Rosa JM. Escobedo M.
Title
Tuberculosis and other infectious diseases
in the adolescent immigrant.
[Review] [23 refs]
Source
Adolescent Medicine. 11(2):453-66, 2000 Jun.
Abstract
Adolescent medicine physicians are
frequently the initial contact for
adolescents newly arriving in the U.S. and
it is important that they
recognize the needs of their patients. The
adolescent immigrant may be
encountered in a school-based health
setting, private practice, community
health center, or other health care
settings. This article begins with a
review of the categories of immigrants
comprising the adolescent
population. It gives an extensive review of
tuberculosis among
Mexican-American adolescents, detailing
history, epidemiology, diagnosis,
social factors, and treatment modalities. It
further delineates the impact
of Mexican tuberculosis control strategies
on the practice of medicine in
the U.S., and outlines preventive,
diagnostic, and therapeutic strategies
that should be followed in the adolescent
immigrant. This article also
reviews viral hepatitis in its multiple
forms and its impact on the
adolescent immigrant. It concludes by
delineating prevention practices
required for the adolescent immigrant and
summarizes the interventions an
initial contact physician should undertake
upon encountering such
adolescents. [References: 23]
1897.
Authors
DeBarber AE. Mdluli K. Bosman M. Bekker LG.
Barry CE 3rd.
Title
Ethionamide activation and sensitivity in
multidrug-resistant
Mycobacterium tuberculosis.
Source
Proceedings of the National Academy of
Sciences of the United States of
America.
97(17):9677-82, 2000 Aug 15.
Abstract
Ethionamide (ETA) is an important component
of second-line therapy for the
treatment of multidrug-resistant
tuberculosis. Synthesis of radiolabeled
ETA and an examination of drug metabolites
formed by whole cells of
Mycobacterium tuberculosis (MTb) have
allowed us to demonstrate that ETA
is activated by S-oxidation before
interacting with its cellular target.
ETA is metabolized by MTb to a
4-pyridylmethanol product remarkably
similar in structure to that formed by the
activation of isoniazid by the
catalase-peroxidase KatG. We have
demonstrated that overproduction of
Rv3855 (EtaR), a putative regulatory protein
from MTb, confers ETA
resistance whereas overproduction of an
adjacent, clustered monooxygenase
(Rv3854c, EtaA) confers ETA
hypersensitivity. Production of EtaA appears
to be negatively regulated by EtaR and
correlates directly with [(14)C]ETA
metabolism, suggesting that EtaA is the
activating enzyme responsible for
thioamide oxidation and subsequent toxicity.
Coding sequence mutations in
EtaA were found in 11 of 11
multidrug-resistant MTb patient isolates from
Cape Town, South Africa. These isolates
showed broad cross-resistance to
thiocarbonyl containing drugs including ETA,
thiacetazone, and
thiocarlide.
1898.
Authors
Dillinger TL. Barriga P. Escarcega
S. Jimenez M. Salazar Lowe D.
Grivetti LE.
Title
Food of the gods: cure for humanity? A
cultural history of the medicinal
and ritual use of chocolate.
Source
Journal of Nutrition. 130(8S Suppl):2057S-72S, 2000 Aug.
Abstract
The medicinal use of cacao, or chocolate,
both as a primary remedy and as
a vehicle to deliver other medicines,
originated in the New World and
diffused to Europe in the mid 1500s. These
practices originated among the
Olmec, Maya and Mexica (Aztec). The word
cacao is derived from Olmec and
the subsequent Mayan languages (kakaw); the
chocolate-related term
cacahuatl is Nahuatl (Aztec language),
derived from Olmec/Mayan etymology.
Early colonial era documents included
instructions for the medicinal use
of cacao. The Badianus Codex (1552) noted
the use of cacao flowers to
treat fatigue, whereas the Florentine Codex
(1590) offered a prescription
of cacao beans, maize and the herb
tlacoxochitl (Calliandra anomala) to
alleviate fever and panting of breath and to
treat the faint of heart.
Subsequent 16th to early 20th century
manuscripts produced in Europe and
New Spain revealed >100 medicinal uses
for cacao/chocolate. Three
consistent roles can be identified: 1) to
treat emaciated patients to gain
weight; 2) to stimulate nervous systems of
apathetic, exhausted or feeble
patients; and 3) to improve digestion and
elimination where
cacao/chocolate countered the effects of
stagnant or weak stomachs,
stimulated kidneys and improved bowel
function. Additional medical
complaints treated with chocolate/cacao have
included anemia, poor
appetite, mental fatigue, poor breast milk
production,
consumption/tuberculosis, fever, gout,
kidney stones, reduced longevity
and poor sexual appetite/low virility.
Chocolate paste was a medium used
to administer drugs and to counter the taste
of bitter pharmacological
additives. In addition to cacao beans,
preparations of cacao bark, oil
(cacao butter), leaves and flowers have been
used to treat burns, bowel
dysfunction, cuts and skin irritations.
1899.
Authors
Donald PR.
Title
Preventing tuberculosis in childhood.
[Review] [20 refs]
Source
Indian Journal of Pediatrics. 67(5):383-5, 2000 May.
Abstract
Almost half of the cases of tuberculosis
requiring treatment may arise in
children. The strategies to control
tuberculosis in developing countries
remain firmly focussed upon adults who are
smear positive. The prevention
of tuberculosis in childhood has two
aspects: prevention of infection and
management of infection once it has
occurred. The steps for prevention of
infection include early diagnosis of adults
with tuberculosis who are
culture positive but not yet smear positive.
Use of ultraviolet lighting
or at least large windows and ventilation in
the area where patients are
kept may reduce the infection rate. An
appropriate regimen and supervised
chemoprophylaxis to ensure good compliance may
be an important step
towards control of tuberculosis infection.
[References: 20]
1900.
Authors
Dye C.
Williams BG.
Title
Criteria for the control of drug-resistant
tuberculosis.
Source
Proceedings of the National Academy of
Sciences of the United States of
America.
97(14):8180-5, 2000 Jul 5.
Abstract
Antibiotic resistance is a growing
impediment to the control of infectious
diseases worldwide, tuberculosis (TB) being
among them. TB kills two
million people each year and foci of multidrug-resistant
TB (MDR-TB) have
been identified in Eastern Europe, Africa,
Asia, and Latin America. A
critical question for health policy is
whether standardized short-course
chemotherapy for TB, based on cheap
first-line drugs, can prevent and
reverse the spread of drug resistance. Here
we use mathematical modeling,
in conjunction with treatment results from
six countries, to show that
best-practice short-course chemotherapy is
highly likely to bring strains
resistant to either of the two key drugs
isoniazid and rifampicin under
control and to prevent the emergence of
MDR-TB. However, it is not certain
to contain MDR-TB once it has emerged,
partly because cure rates are too
low. We estimate that approximately 70% of
prevalent, infectious MDR-TB
cases should be detected and treated each
year, and at least 80% of these
cases should be cured, in order to prevent
outbreaks of MDR-TB. Poor
control programs should aim to increase case
detection and cure rates
together for three reasons: (i) these
variables act synergistically; (ii)
when either is low, the other cannot succeed
alone; and (iii) the
second-line drugs needed to raise MDR-TB
cure rates are few and extremely
costly. We discuss the implications of these
results for World Health
Organization policy on the management of
antibiotic resistance.
1901.
Authors
Edwards RJ.
David KM. Crockard HA.
Title
Management of tuberculomas of the
craniovertebral junction.
Source
British Journal of Neurosurgery. 14(1):19-22, 2000 Feb.
Abstract
Tuberculosis of the craniovertebral junction
is extremely rare. However,
recent evidence suggests that the incidence
of this condition may be
increasing in the United Kingdom. The
diagnosis is often difficult despite
advances in imaging using MRI. CT guided
biopsy of lesions often yields
inconclusive results. The transoral approach
to the anterior
craniovertebral junction provides excellent
access to this region with a
low operative morbidity and mortality,
enabling biopsy of lesions and
decompression of the neuraxis. Management of
secondary atlantoaxial
instability, regarding both timing and
method of stabilization, is
controversial. We report two cases of
tuberculomas of the craniovertebral
junction, that illustrate the role of
transoral surgery in both diagnosis
and treatment of this condition. Previous
management strategies are
reviewed and future recommendations are
presented.
1902.
Authors
Gennaro ML.
Title
Immunologic diagnosis of tuberculosis.
[Review] [30 refs]
Source
Clinical Infectious Diseases. 30 Suppl 3:S243-6, 2000 Jun.
Abstract
Evaluation of new vaccines against
tuberculosis requires diagnostic tools
for accurately identifying asymptomatic
individuals infected with
Mycobacterium tuberculosis and persons with
active tuberculosis. This
article discusses limitations of current
methods for the immunologic
diagnosis of latent infection and active
disease and presents novel
approaches to developing skin tests and
serodiagnostic assays based on
"cocktails" of multiple antigens
of M. tuberculosis. [References: 30]
1903.
Authors
Ginsberg AM.
Title
A proposed national strategy for
tuberculosis vaccine development.
Source
Clinical Infectious Diseases. 30 Suppl 3:S233-42, 2000 Jun.
Abstract
The global tuberculosis epidemic causes
approximately 5% of deaths
worldwide. Despite recent concerted and
largely successful tuberculosis
control efforts, the incidence of
tuberculosis in the United States
remains 74-fold higher than the stated elimination
goal of <1 case per
million population by the year 2010. Current
bacille Calmette-Guerin
vaccines, although efficacious in preventing
extrapulmonary tuberculosis
in young children, have shown widely
variable efficacy in preventing adult
pulmonary tuberculosis, confound skin test
screening, and are not
recommended for use in the United States.
The Advisory Council for
Elimination of Tuberculosis recently stated
that tuberculosis would not be
eliminated from the United States without a
more effective vaccine. Recent
scientific advances have created
unprecedented opportunity for
tuberculosis vaccine development. Therefore,
members of the broad
tuberculosis research and control
communities have recently created and
proposed a national strategy, or blueprint,
for tuberculosis vaccine
development, which is presented here.
1904.
Authors
Glassroth J.
Title
Clinical considerations in designing trials
of vaccines for tuberculosis.
Source
Clinical Infectious Diseases. 30 Suppl 3:S229-32, 2000 Jun.
Abstract
Despite remarkable strides in the treatment
of tuberculosis, the disease
continues to be a major public health
problem in many parts of the world,
a situation that is projected to remain
unchanged for years into the
future. The development of a highly
effective vaccine could substantially
reduce the magnitude of the tuberculosis
problem. A tuberculosis vaccine
could theoretically prevent initial
infection by Mycobacterium
tuberculosis and enhance host response to prevent
the progression from
infection to disease or even to augment
response to treatment in cases of
established disease. Assessment of candidate
vaccines will require
clinical trials. This article suggests how
traditional end points of
morbidity and mortality, a number of newer
measures of disease impact, and
surrogate markers of tuberculous infection
and disease might be used in
such studies.
1905.
Authors
Gupta A.
Kumar V. Xess A. Sharma HP.
Shahi SK.
Title
Role of enzyme linked immunosorbent assay in
the diagnosis of suspected
cases of genito urinary tuberculosis.
Source
Indian Journal of Pathology &
Microbiology. 42(3):307-9, 1999 Jul.
Abstract
The aim of study was evaluation of the
utility of ELISA test using A60
Antigen for rapid diagnosis of Genitourinary
Tuberculosis in various age
groups. ELISA test based on mycobacterial
antigen A60 (Anda biological,
France) was used to estimate specific IgG
antibodies in the sera of fifty
four suspected cases of Genito urinary
tuberculosis. (GUT)Sera of 30
montoux negative healthy adults (age/sex
matched) were taken as control by
detecting IgG anti bodies to A60 antigen. It
was concluded from this study
that IgM was positive in 87.0% of cases.
1906.
Authors
Hermon-Taylor J. Bull TJ. Sheridan
JM. Cheng J. Stellakis ML. Sumar
N.
Title
Causation of Crohn's disease by
Mycobacterium avium subspecies
paratuberculosis [see comments] [comment].
[Review] [369 refs]
Source
Canadian Journal of Gastroenterology. 14(6):521-39, 2000 Jun.
Abstract
Mycobacterium avium subspecies
paratuberculosis (MAP) is a member of the M
avium complex (MAC). It differs genetically
from other MAC in having 14 to
18 copies of IS900 and a single cassette of
DNA involved in the
biosynthesis of surface carbohydrate. Unlike
other MAC, MAP is a specific
cause of chronic inflammation of the
intestine in many animal species,
including primates. The disease ranges from
pluribacillary to
paucimicrobial, with chronic granulomatous
inflammation like leprosy in
humans. MAP infection can persist for years
without causing clinical
disease. The herd prevalence of MAP
infection in Western Europe and North
America is reported in the range 21% to 54%.
These subclinically infected
animals shed MAP in their milk and onto
pastures. MAP is more robust than
tuberculosis, and the risk that is conveyed
to human populations in retail
milk and in domestic water supplies is high.
MAP is harboured in the
ileocolonic mucosa of a proportion of normal
people and can be detected in
a high proportion of full thickness samples
of inflamed Crohn's disease
gut by improved culture systems and IS900
polymerase chain reaction if the
correct methods are used. MAP in Crohn's
disease is present in a
protease-resistant nonbacillary form, can
evade immune recognition and
probably causes an immune dysregulation. As
with other MAC, MAP is
resistant to most standard antituberculous
drugs. Treatment of Crohn's
disease with combinations of drugs more active
against MAC such as
rifabutin and clarithromycin can bring about
a profound improvement and,
in a few cases, apparent disease
eradication. New drugs as well as
effective MAP vaccines for animals and
humans are needed. The problems
caused by MAP constitute a public health
issue of tragic proportions for
which a range of remedial measures are
urgently needed. [References: 369]
1907.
Authors
Horsburgh CR Jr.
Title
A large, simple trial of a tuberculosis
vaccine.
Source
Clinical Infectious Diseases. 30 Suppl 3:S213-6, 2000 Jun.
Abstract
Although there are no new tuberculosis
vaccines currently available, it is
possible to estimate the infrastructure
needed for efficacy trials of such
a vaccine. A randomized, placebo-controlled
vaccine strategy for
community-wide vaccination of adults is
proposed: a large, simple trial
with recipients stratified at enrollment by
human immunodeficiency virus
serologic status and purified protein
derivative-skin test status. The
outcome, tuberculous disease, would be
assessed by community-wide
surveillance. Such a trial could be carried
out in populations in
developed countries where the annual
incidence of tuberculous disease is
>100 cases per 100,000 persons and in
developing countries where the
incidence is >400 per 100,000 persons. In
developed countries, enrollment
of 14,600-80,000 persons would be needed,
depending on the initial
assumptions; in developing countries,
enrollment would be 4400-27,000
persons. Readiness for tuberculosis vaccine
efficacy trials will require
epidemiological field studies to identify
potential trial sites and
investment in local diagnostic,
surveillance, and data management
capabilities.
1908.
Authors
Jain AK.
Jena A. Dhammi IK.
Title
Correlation of clinical course with magnetic
resonance imaging in
tuberculous myelopathy.
Source
Neurology India. 48(2):132-9, 2000 Jun.
Abstract
Sixty cases of spinal tuberculosis with
neurological deficit treated with
'middle path regimen' were analysed and
therapeutic response was
correlated with the magnetic resonance
imaging (MRI) observations.
Tuberculous lesions were found to be more
extensive than seen on plain
X-ray in 60% of the cases. MRI showed the
involvement of one or both
pedicles in nearly 90% of the cases, in
addition to the vertebral body
lesion as seen in the X-rays. The patients
showing predominantly
extradural collection of fluid with
relatively preserved cord size, and
MRI evidence of myelitis/oedema, improved
neurologically with treatment.
The myelomalacia of cord was found to be a
poor prognostic sign for neural
recovery. The magnitude of thinning of cord
did not always correlate with
severity of neural deficit, however,
thinning of cord in association with
myelomalacia carried a bad prognosis. The
complete neural recovery is not
expected in patients with syrinx formation
proximal or distal to the
diseased spine, either with antitubercular
drugs or after mechanical
decompression. MRI changes in dura-subarachnoid
complex suggesting
arachnoiditis generally correlated with poor
neural recovery. MRI provided
a reliable guide to the level and extent of
surgical decompression, and
prognostication of the outcome of
therapeutic measures.
1909.
Authors
Jeyakumar D.
Title
A case of primary drug resistant
tuberculosis.
Source
Medical Journal of Malaysia. 55(2):129-31, 2000 Jun.
Abstract
A young man presented with primary
multi-drug resistant tuberculosis. The
institution of second-line regimes with insufficient
efficacy due to
clinical inexperience, unreliable
sensitivity reports and the
inavailability of second-line drugs led to
the development of an organism
that was resistant to ten anti-tuberculous
drugs. Accurate sensitivity
testing done in an overseas laboratory
enabled the institution of a
six-drug regimen that has resulted in
clinical cure.
1910.
Authors
Jones PB.
Parrish NM. Houston TA. Stapon A.
Bansal NP. Dick JD.
Townsend CA.
Title
A new class of antituberculosis agents.
Source
Journal of Medicinal Chemistry. 43(17):3304-14, 2000 Aug 24.
Abstract
Long-chain lipid envelopes are
characteristic of mycobacteria such as
those that cause tuberculosis and leprosy.
Inhibition of fatty acid
synthesis or elongation is a strategy
demonstrated to be clinically
effective against M. tuberculosis. A new
class of compounds designed to
inhibit the beta-ketoacyl synthase reaction
of fatty acid synthesis has
been developed. Of >30 compounds
described, the most active were
acetamides containing alkylsulfonyl
substituents. Inhibitory activities
were acutely sensitive to net charge, chain
length, and degree of
unsaturation. The most active compound 5
(alkyl = C(10)) contained a
single methylene spacer between the sulfone
and carboxamide and exhibited
an MIC of 0.75-1.5 &mgr;g/mL, comparable
to first-line antituberculosis
drugs. These compounds are species-specific,
exhibiting no significant
activity against bacterial species other
than M. tuberculosis and closely
related strains. The synthesis, biological
activity, and specificity of
these compounds are described.
1911.
Authors
Kakkar N.
Sharma M. Ray P. Sethi S.
Kumar S.
Title
Evaluation of E test for susceptibility
testing of Mycobacterium
tuberculosis to primary anti tubercular
drugs.
Source
Indian Journal of Medical Research. 111:168-71, 2000 May.
Abstract
BACKGROUND & OBJECTIVES: Antimicrobial
susceptibility tests for
tuberculosis take weeks and delayed therapy
can lead to an increase in
disease incidence. The E test is a new concept for minimum
inhibitory
concentrations (MIC) determinations for
antimicrobial agents that is based
on a predefined antibiotic gradient on a
plastic strip calibrated with a
continuous logarithmic MIC scale covering 15
two-fold dilutions. The
present study was undertaken to evaluate E
test strips for susceptibility
testing of Mycobacterium tuberculosis.
METHODS: Twenty five clinical
isolates of M. tuberculosis were tested for
the four first line
antitubercular drugs by E test and were
compared with standard proportion
method. The inoculum turbidity was adjusted
to McFarland 3.0 standard and
agar plates (Middle brook 7H11 agar) were
inoculated and preincubated (37
degrees C in 7-10% CO2) for 24 h after which
time, the E test strips were
placed on the agar surface which were
incubated under same conditions. The
MIC was interpreted as the point at which
the ellipse intersected the 'E
test' strip as described in E test technical
guide. RESULTS: Of the 25
strains, susceptibility as determined by
both methods for isoniazid (INH),
rifampin, ethambutol and streptomycin was
found in 22 (88%), 20 (80%), 24
(96%) and 18 (72%) strains respectively.
Agreement between E test and
proportion method was 96 per cent for INH,
92 per cent for rifampin and
100 per cent for ethambutol and streptomycin
each. However, sensitivity
could be predicted after 7-10 days by E test
and exact MIC could also be
determined. INTERPRETATION &
CONCLUSIONS: E test method was found to be
rapid, accurate, reliable and easy to
perform. It can be employed for
routine susceptibility testing for
antitubercular drugs.
1912.
Authors
Karia K.
Mathur SK.
Title
Tuberculous cold abscess simulating
pancreatic pseudocyst.
Source
Journal of Postgraduate Medicine. 46(1):33-4, 2000 Jan-Mar.
Abstract
A patient with a peripancreatic lymph node
tuberculosis mimicking
pancreatic pseudocyst is reported, which was
diagnosed on exploration to
be a tuberculous cold abscess. The patient
responded to antituberculous
drugs after drainage of the cold abscess.
1913.
Authors
Klein DL.
Title
From pertussis to tuberculosis: what can be
learned?. [Review] [37 refs]
Source
Clinical Infectious Diseases. 30 Suppl 3:S302-8, 2000 Jun.
Abstract
Following the introduction of whole-cell
pertussis vaccines into the
general population, the number of cases of
Bordetella pertussis disease
declined dramatically. As disease incidence
declined, the public's concern
for pertussis as a national health problem
gradually waned. However, a
shift in paradigm occurred, and various
groups and the media began to
voice their concerns regarding adverse
events associated with whole-cell
vaccines. These events provided an impetus
for the expedited development
of safer and as efficacious subunit
acellular vaccines. Effective public
health leadership, public advocacy,
scientific ingenuity, and
collaborative interactions between
government, academia, and industry
culminated in the licensure of acellular
pertussis vaccines. In this
article, emphasis is placed on
conceptualizing how a national public
health agenda was implemented that allowed
better insight into various
public health concerns related to the
development and use of acellular
pertussis vaccines, concerns that were
eventually translated into concrete
actions. Knowledge of the environment in
which this occurred may play a
major role in relating the pertussis
experience to tuberculosis vaccine
development. [References: 37]
1914.
Authors
Kwon KS.
Oh CK. Jang HS. Lee CW.
Jun ES.
Title
Detection of mycobacterial DNA in cervical
granulomatous lymphadenopathy
from formalin-fixed, paraffin-embedded
tissue by PCR.
Source
Journal of Dermatology. 27(6):355-60, 2000 Jun.
Abstract
Cervical tuberculous lymphadenitis is the
most common form of inflammatory
neck mass in Korea. The diagnosis of
tuberculosis requires proof of the
presence of Mycobacterium tuberculosis by
acid-fast staining or bacterial
growth in culture. However, these are often
difficult in cervical
tuberculous lymphadenitis. The aim of this
study was to investigate the
value of the polymerase chain reaction (PCR)
technique for detection of
mycobacteria in routinely processed tissue
sections of cervical
granulomatous lymphadenopathy. In this
retrospective study, twenty
formalin-fixed, paraffin-embedded biopsy
specimens from clinically and/or
histopathologically diagnosed cervical
granulomatous lymphadenopathy were
analyzed for mycobacterial DNA by PCR. Two
different primers to amplify
mycobacterial-common 383-base pair (bp) DNA
and Mycobacterium
tuberculosis-complex-specific 123-bp DNA
were used. Positive PCR products
were sequenced directly.
Mycobacterial-common DNA (383-bp positive) was
found in 10 of the 20 cases. Among them, 7
cases were PCR positive with
both primer sets. These seven cases can be
considered as tuberculosis. The
other three cases indicated possible
atypical mycobacteriosis. PCR is a
useful technique for the demonstration of
mycobacterial DNA fragments in
patients with clinically suspected cervical
tuberculous lymphadenitis who
have acid fast-negative histology and/or
unsuccessful mycobacterial
cultures.
1915.
Authors
Lazarus A.
Sanders J.
Title
Management of tuberculosis. Choosing an
effective regimen and ensuring
compliance. [Review] [20 refs]
Source
Postgraduate Medicine. 108(2):71-4, 77-9, 83-4, 2000 Aug.
Abstract
Management of active TB requires a team
approach. All patients newly
diagnosed with TB should be tested for HIV
infection. Currently available
anti-TB drug regimens are well tolerated and
highly effective. Directly
observed therapy has shown improved survival
and decline in the rate of
new cases of active TB. In suspected or
proven drug-resistant TB, the
regimen should be individualized in
consultation with a specialist
experienced in MDR TB. Primary care
physicians play a pivotal role in
reducing morbidity and emergence of drug
resistance through early
diagnosis and prompt initiation of an
effective regimen under directly
observed therapy. [References: 20]
1916.
Authors
Li JY.
Lo ST. Ng CS.
Title
Molecular detection of Mycobacterium
tuberculosis in tissues showing
granulomatous inflammation without
demonstrable acid-fast bacilli.
Source
Diagnostic Molecular Pathology. 9(2):67-74, 2000 Jun.
Abstract
Early diagnosis of tuberculosis (TB) is
important for early medical
intervention and prevention of spread of the
bacteria. It is not uncommon
to
observe granulomatous inflammation but without demonstrable acid-fast
bacilli (AFB) on Ziehl-Neelsen (ZN) staining
in tissues sent for
histologic examination, and the definitive
diagnosis of TB cannot be made
because no concurrent tissue is sent for TB
culture. In this study, the
authors explored the feasibility of using
polymerase chain reaction (PCR)
for early detection of Mycobacterium
tuberculosis (Mtb) in formalin-fixed,
paraffin-embedded tissues where a definite
diagnosis of TB cannot be made.
One hundred fifteen patients (131 paraffin
blocks of biopsy specimens)
with granulomatous inflammation but
ZN-negative for AFB were studied. DNA
was extracted from paraffin sections and
amplified by PCR with the IS6110
primers (specific for the Mtb complex) and
the specific 122-base pairs
(bp) PCR product was detected by agarose gel
electrophoresis. Sixty-eight
of the 115 (59%) patients were TB-PCR
positive, thus enabling definite
diagnosis of TB in significant numbers of
these patients in 3 days. The
authors conclude that molecular diagnosis by
PCR is useful for early
detection of TB in histologic material where
morphologic features are
suggestive but not confirmatory because of
negative staining for AFB.
1917.
Authors
Lietman T.
Blower SM.
Title
Potential impact of tuberculosis vaccines as
epidemic control agents.
[Review] [24 refs]
Source
Clinical Infectious Diseases. 30 Suppl 3:S316-22, 2000 Jun.
Abstract
We use 2 simple mathematical models (one a
preexposure vaccine model and
the other a postexposure vaccine model) to
provide general insight into
the effects of vaccination on tuberculosis
epidemics. We discuss how these
models can be used as health policy tools:
to identify which vaccines are
"equivalent," to design control
strategies, and to predict the
epidemiological impact of different
vaccination strategies. Our results
show that even moderately effective vaccines
could have a significant
effect on reducing tuberculosis epidemics if
they can be coupled with
moderate to high treatment rates. We suggest
that both preexposure and
postexposure tuberculosis vaccines can be
used to help eliminate
tuberculosis in developing countries. In
developed countries, only a
preexposure vaccine (used in combination
with a high level of treatment)
would be necessary to eliminate
tuberculosis. [References: 24]
1918.
Authors
Long R.
Title
Drug-resistant tuberculosis. [Review] [31
refs]
Source
CMAJ.
163(4):425-8, 2000 Aug 22.
Abstract
Globally the proportion of tuberculosis
cases caused by drug-resistant
strains is increasing. Interruptions in the
drug supply, improper drug
prescription and nonadherence to treatment
protocols promote drug
resistance through mechanisms that are now
well understood. The treatment
of tuberculosis must take into account the
possibility of drug resistance
and include at least 2 drugs, preferably 3,
to which the isolate is proven
or anticipated to be susceptible.
[References: 31]
1919.
Authors
Louie M.
Louie L. Simor AE.
Title
The role of DNA amplification technology in
the diagnosis of infectious
diseases. [Review] [81 refs]
Source
CMAJ.
163(3):301-9, 2000 Aug 8.
Abstract
Nucleic acid amplification and detection
methods developed in the past
decade are useful for the diagnosis and
management of a variety of
infectious diseases. The most widely used of
these methods is the
polymerase chain reaction (PCR). PCR assays
can detect rapidly and
accurately the presence of fastidious and
slow-growing microorganisms,
such as Chlamydia, mycoplasmas,
mycobacteria, herpesviruses and
enteroviruses, directly from clinical
specimens. Commercial PCR assays for
the diagnosis of tuberculosis and genital C.
trachomatis infection are now
routinely used in many diagnostic
laboratories. Assays have also been
developed that can detect antimicrobial
resistance and are used to
identify the cause of infection by organisms
that cannot be cultivated.
The value of viral load measurement by
nucleic acid amplification in the
management of patients with HIV infection or
hepatitis C has also been
well established. However, evaluations of
this technology for rapid
microbial diagnosis have generally been
limited by small samples, and the
cost of these assays may be as high as
Can$125 per test. As nucleic acid
amplification methods continue to evolve,
their role in the diagnosis and
management of patients with infectious
diseases and their impact on
clinical outcomes will become better
defined. [References: 81]
1920.
Authors
Martin G.
Lazarus A.
Title
Epidemiology and diagnosis of tuberculosis.
Recognition of at-risk
patients is key to prompt detection.
[Review] [20 refs]
Source
Postgraduate Medicine. 108(2):42-4, 47-50, 53-4, 2000 Aug.
Abstract
The increasing incidence of TB and HIV
infection and the emergence of drug
resistance worldwide poses a major threat,
particularly in developing
nations. In an era with an increasing number
of Americans living with HIV
infection or with immunosuppression
associated with chemotherapy or organ
transplants, the possibility of primary M
tuberculosis and of unusual
clinical and radiographic presentations of
reactivation disease is
becoming more common. The primary care
physician plays a crucial role in
recognizing high-risk patients and
initiating prompt isolation and
evaluation. [References: 20]
1921.
Authors
Matsuyama W. Hashiguchi T. Matsumuro
K. Iwami F. Hirotsu Y. Kawabata
M.
Arimura K. Osame M.
Title
Increased serum level of vascular
endothelial growth factor in pulmonary
tuberculosis.
Source
American Journal of Respiratory &
Critical Care Medicine. 162(3 Pt
1):1120-2, 2000 Sep.
Abstract
Pulmonary tuberculosis, one of the
granulomatous diseases, has few
serological markers for its activity.
Recently, an increased serum level
of vascular endothelial growth factor (VEGF)
was detected in patients with
Crohn's disease, also a granulomatous
disease. We hypothesized that VEGF
might be associated with the pathogenesis of
pulmonary tuberculosis. We
investigated the serum level of VEGF in 43
patients with active pulmonary
tuberculosis, 29 patients with old
tuberculosis, and 25 patients with
acute bronchitis. We were able to examine
the serum VEGF levels every 3 mo
for a period of 6 mo in seven patients with
active pulmonary tuberculosis.
We examined the presence of VEGF in the
resected lungs of three patients
with active pulmonary tuberculosis by
immunohistochemistry. The serum
levels of VEGF were significantly higher in
patients with active pulmonary
tuberculosis than in patients with old
tuberculosis and acute bronchitis.
The decrease in titer of serum VEGF
paralleled the clinical improvement of
patients with pulmonary tuberculosis.
Immunohistochemical staining of the
resected lungs demonstrated the presence of
VEGF in alveolar macrophages
surrounding the lesion. Therefore, VEGF may
be associated with the
pathogenesis of pulmonary tuberculosis.
1922.
Authors
McMurray DN.
Title
A nonhuman primate model for preclinical
testing of new tuberculosis
vaccines. [Review] [10 refs]
Source
Clinical Infectious Diseases. 30 Suppl 3:S210-2, 2000 Jun.
Abstract
Nonhuman primates appear to have significant
advantages over conventional
laboratory animals in terms of modeling
pulmonary tuberculosis for
purposes of vaccine evaluation. Primates are
quite susceptible to
infection by the aerosol route, develop a
humanlike disease, exhibit
antigen-induced T lymphocyte reactivity both
in vitro and in vivo, and can
be protected quite effectively by bacille
Calmette-Guerin vaccination.
There are fewer than a dozen published
studies of experimental
tuberculosis in primates, and all of the
available data on the response of
primates to vaccination have been generated
in rhesus monkeys (Macaca
mulatta). There have been no modern
immunologic studies of primate
tuberculosis. Thus, responses to
tuberculosis vaccines in primates are
only minimally characterized, and much
additional baseline work remains to
be done before the responses to new vaccines
can be placed in the proper
biological context. [References: 10]
1923.
Authors
McNab BD.
Marciniuk DD. Alvi RA. Tan L.
Hoeppner VH.
Title
Twice weekly isoniazid and rifampin
treatment of latent tuberculosis
infection in Canadian plains Aborigines.
Source
American Journal of Respiratory &
Critical Care Medicine. 162(3 Pt
1):989-93, 2000 Sep.
Abstract
Six months of twice weekly directly observed
isoniazid and rifam-picin
treatment of latent tuberculosis (TB)
infection was implemented to improve
the outcome of treatment. A total of 591
infected aborigines without
previous tuberculosis or treatment of latent
TB infection received twice
weekly isoniazid and rifampicin for 6 mo from
1992 to 1995. The outcome
was compared with 403 infected aborigines
without previous tuberculosis or
treatment of latent TB infection who
received self-administered isoniazid
daily for 1 yr from 1986 to 1989. Of
patients, 487 (82%) completed the
twice weekly 6-mo regimen compared with 77
(19%) who completed the daily
12-mo regimen. The main reason for
incomplete treatment was default. Both
groups were followed over a 6-yr period. The
rate of tuberculosis in the
twice-weekly isoniazid and rifampicin-treated
patients was 0.9/1,000
patient-years compared with 9/1,000
patient-years in the daily
isoniazid-treated patients. The rate of side
effects was higher for
directly observed treatment patients,
136/1,000 patient-years of drugs,
compared with 39/ 1,000 patient-years for
self-administered treatment
patients. Life-threatening side effects such
as skin allergic reactions
and hepatitis were the same in both groups.
A regimen of 52 doses of
directly observed twice weekly isoniazid and
rifampicin is an effective
and well-tolerated regimen to improve the
outcome of the treatment of
latent tuberculosis infection in a
population with a high rate of default
with daily self-administered isoniazid.
1924.
Authors
Means-Markwell M. O'Neil KM.
Title
Prevention of tuberculosis. Vigilance and
infection control strategies are
mainstays of efforts. [Review] [15 refs]
Source
Postgraduate Medicine. 108(2):87-90, 93-6, 2000 Aug.
Abstract
Until a vaccine is available, efforts to
control the spread of TB will
continue to rely on the effective use of our
currently available tools and
the diligence of primary care physicians.
Rapid diagnosis, directly
observed therapy, public health and
infection control measures, and
appropriate preventive therapy remain the
mainstays of TB control.
Physicians in the primary care setting,
particularly those serving
long-term-care institutions or other
high-risk populations, need to be
keenly aware of the possibility of TB in
their patient population and of
the methods available in their community for
preventing its spread.
[References: 15]
1925.
Authors
Moussa OM.
Eraky I. El-Far MA. Osman HG.
Ghoneim MA.
Title
Rapid diagnosis of genitourinary
tuberculosis by polymerase chain reaction
and non-radioactive DNA hybridization.
Source
Journal of Urology. 164(2):584-8, 2000 Aug.
Abstract
OBJECTIVE: To establish a polymerase chain
reaction (PCR) assay for the
rapid detection and identification of
mycobacteria in urine, and to assess
the value of such assay in routine
laboratory diagnosis of genitourinary
tuberculosis. MATERIALS AND METHODS: Urine
specimens from 1000 patients
with clinical suspicion of urinary
tuberculosis were examined. Two assays
for the detection and identification of
Mycobacterium tuberculosis (M.
tuberculosis) complex and mycobacteria other
than tuberculosis (MOTT) by
non-radioactive DNA hybridization of
PCR-product were applied. The first
assay used PCR primers and probe derived
from M. tuberculosis
species-specific DNA insertion sequence,
IS6110. The second utilized
mycobacterium genus-specific sequence
encoding ribosomal ribonucleic acid
(16S rRNA). The results obtained by PCR were
compared with those obtained
by standard microbiological methods,
acid-fast bacilli (AFB) stain and
culture. RESULTS: Compared with cultures,
the sensitivity of AFB staining
was 52.07% and the specificity was 96.7%. In
comparison to the results of
culture, the overall sensitivity and
specificity of the IS6110-PCR assay
was 95.59% and 98.12% respectively. While
the corresponding results for
the 16S rRNA gene-PCR were 87.05% and 98.
9%. CONCLUSION: The high
sensitivity and specificity in addition to
the potential for rapid
detection of mycobacteria, makes this test a
useful tool in the clinical
management of mycobacterial infection in
urine. Urine specimens may
contain M. tuberculosis and/or other
mycobacteria; therefore, there are
advantages in using genus-specific primers
in parallel with
species-specific primers in PCR assay.
1926.
Authors
Mulholland K.
Title
Evaluation of vaccines to prevent childhood
pneumonia: lessons relevant to
planning tuberculosis vaccine trials.
[Review] [11 refs]
Source
Clinical Infectious Diseases. 30 Suppl 3:S206-9, 2000 Jun.
Abstract
Bacterial pneumonia in children is usually
caused by one of the two
leading pathogens, Streptococcus pneumoniae
(pneumococcus) and Haemophilus
influenzae, either type b (Hib) or
nonencapsulated types. Hib conjugate
vaccines suitable for use in infants have
been available for about a
decade, and experience with a trial of one
of these vaccines in Africa
showed that the vaccines can prevent Hib
pneumonia, as well as other
manifestations of Hib disease. It also showed
that vaccine trials can
provide useful estimates of the role of Hib
in childhood pneumonia. Trials
of pneumococcal conjugate vaccines that are
currently under way have been
designed to estimate disease burden and
efficacy. A major risk of vaccine
trials that use bacteriologic end points is
that the vaccine may affect
the diagnostic test itself, creating a
misleading impression of efficacy.
Trials of future tuberculosis vaccines are
discussed in light of these
experiences. It is important that the trials
are designed to measure the
effect on all clinical disease, as well as
strict microbiological end
points. The existence of bacille
Calmette-Guerin (BCG) complicates future
trials, and such trials should take into
account possible nonspecific
effects of BCG in addition to its effect on
tuberculosis. [References: 11]
1927.
Authors
Murray J.
Sonnenberg P. Shearer S. Godfrey-Faussett P.
Title
Drug-resistant pulmonary tuberculosis in a
cohort of southern African
goldminers with a high prevalence of HIV
infection.
Source
South African Medical Journal. 90(4):381-6, 2000 Apr.
Abstract
OBJECTIVES: To determine rates of drug
resistance to Mycobacterium
tuberculosis and associated risk factors,
including HIV infection. DESIGN:
Prospective cohort study of patients with
pulmonary tuberculosis. SETTING:
The study population comprised 28,522 men
working on four goldmines in
Westonaria, Gauteng. Health care is provided
at a 240-bed mine hospital,
Gold Fields West Hospital, and its primary
health care facilities.
SUBJECTS: All 425 patients with
culture-positive pulmonary tuberculosis
identified in 1995. OUTCOME MEASURES:
Tuberculosis drug resistance on
enrollment and after 6 months' treatment.
RESULTS: There were 292 cases of
new tuberculosis, 77 of recurrent disease
and 56 prevalent cases in
treatment failure. Two hundred and seven
patients (48.7%) were HIV
infected. Primary resistance to one or more
drugs (9%) was similar to the
11% found in a previous study done on
goldminers in 1989. Primary
multidrug resistance (0.3%) was also similar
(0.8%). Acquired multidrug
resistance was 18.1%: 6.5% for recurrent
disease and 33.9% in treatment
failure cases. Neither HIV infection nor the
degree of immunosuppression
as assessed by CD4+ lymphocyte counts was
associated with drug resistance
at the start or end of treatment. New
patterns of drug resistance were
present in 9 of 52 patients in treatment
failure at 6 months, 1 of whom
was HIV-infected. CONCLUSION: Primary and
acquired drug resistance rates
are stable in this population and are not
affected by the high prevalence
of HIV infection.
1928.
Authors
Olsen AW.
Hansen PR. Holm A. Andersen P.
Title
Efficient protection against Mycobacterium
tuberculosis by vaccination
with a single subdominant epitope from the
ESAT-6 antigen.
Source
European Journal of Immunology. 30(6):1724-32, 2000 Jun.
Abstract
We have investigated the vaccine potential
of two peptides derived from
the 6-kDa early secretory antigenic target
(ESAT)-6 antigen in the mouse
model of tuberculosis. The peptides were
both strongly immunogenic in
B6CBAF1 (H-2b,k) mice and primed recall
responses of the same intensity
after immunization. However, both
tuberculosis infection and immunization
with ESAT-6 resulted in responses focused
towards ESAT-61-20. Multiple
antigen peptide constructs as well as free
peptides were emulsified with
dimethyl dioctadecylammonium
bromide/monophosphoryl lipid A/IL-2 and
tested as experimental vaccines in an i.v.
and aerosol model of
tuberculosis in mice. The peptide were
highly immunogenic and induced
cellular responses of the same magnitude.
However, only vaccines based on
the subdominant ESAT-651-70 epitope promoted
significant levels of
protective immunity and the level of
protection was equivalent to that
achieved with ESAT-6 and BCG. These findings
demonstrate the potential of
peptide-based vaccines against tuberculosis
and indicate that there is not
direct correlation between the hierarchy of
response to naturally
processed peptides and their ability to
induce protective immunity against
Mycobacterium tuberculosis.
1929.
Authors
Paradisi F.
Corti G.
Title
Skeletal tuberculosis and other
granulomatous infections. [Review] [57
refs]
Source
Best Practice & Research in Clinical
Rheumatology. 13(1):163-77, 1999
Mar.
Abstract
After several decades of steadily decreasing
incidence, tuberculosis has
had a resurgence in the past 15 years, not
only in the lungs, but also in
extrapulmonary sites. This is primarily a
result of the AIDS pandemic,
considering that HIV specifically affects
cellular immunity, which is the
first-line defence against tuberculosis. The
generally non-specific
clinical and radiological patterns of
skeletal tuberculosis make it
similar to other bacterial, fungal,
inflammatory and neoplastic diseases
of the bones and joints. Physicians must not
omit tuberculosis in the
differential diagnosis of any
osteo-articular inflammatory process so that
specific treatment may be initiated as soon
as possible. Anti-tuberculous
therapy is beset by important factors that
limit its efficacy, such as the
emergence of drug toxicity and of resistant
or multiresistant
mycobacterial strains. Surgical treatment
may be indicated in selected
cases where medical therapy alone is not
sufficient to eradicate the
problem. Copyright 1999 Harcourt Publishers
Ltd. [References: 57]
1930.
Authors
Pavlou AK.
Turner AP.
Title
Sniffing out the truth: clinical diagnosis
using the electronic nose.
[Review] [118 refs]
Source
Clinical Chemistry & Laboratory
Medicine. 38(2):99-112, 2000 Feb.
Abstract
Recently the use of smell in clinical
diagnosis has been rediscovered due
to major advances in odour sensing
technology and artificial intelligence
(AI). It was well known in the past that a
number of infectious or
metabolic diseases could liberate specific
odours characteristic of the
disease stage. Later chromatographic
techniques identified an enormous
number of volatiles in human clinical
specimens that might serve as
potential disease markers. "Artificial
nose" technology has been employed
in several areas of medical diagnosis,
including rapid detection of
tuberculosis (TB), Helicobacter pylori (HP)
and urinary tract infections
(UTI). Preliminary results have demonstrated
the possibility of
identifying and characterising microbial
pathogens in clinical specimens.
A hybrid intelligent model of four
interdependent "tools", odour
generation "kits", rapid volatile
delivery and recovery systems,
consistent low drift sensor performance and
a hybrid intelligent system of
parallel neural networks (NN) and expert
systems, have been applied in
gastric, pulmonary and urine diagnosis. Initial
clinical tests have shown
that it may be possible in the near future
to use electronic nose
technology not only for the rapid detection
of diseases such as peptic
ulceration, UTI, and TB but also for the
continuous dynamic monitoring of
disease stages. Major advances in
information and gas sensor technology
could enhance the diagnostic power of future
bio-electronic noses and
facilitate global surveillance models of
disease control and management.
[References: 118]
1931.
Authors
Prasad S.
Patankar T.
Title
Computed tomography demonstration of a
fat-fluid level in tuberculous
chylous ascites.
Source
Australasian Radiology. 43(4):542-3, 1999 Nov.
Abstract
The occurrence of fat-fluid levels in
ascites, although rare, is
pathognomic of chylous ascites. The
ultrasound and CT scan findings of a
fat-fluid level in the ascitic fluid of a
patient with abdominal
tuberculosis are described here. Recognition
of this important sign, in
conjunction with other ancillary findings of
abdominal tuberculosis,
assist in establishing the correct
diagnosis. Anti-tuberculous
chemotherapy suffices in treating the
condition, thus obviating the need
for surgical intervention.
1932.
Authors
Purkayastha S. Madan T. Shah A. Krishnamurthy HG. Sarma PU.
Title
Multifunctional antigens of A. fumigatus and
specific antibodies.
Source
Applied Biochemistry &
Biotechnology. 83(1-3):271-83;
discussion 283-6,
297-313, 2000 Jan-Mar.
Abstract
The majority of Aspergillus-induced
infections in man are caused by the
pathogenic fungus A. fumigatus, which
secretes biologically and
immunologically active glycosylated and
nonglycosylated proteins. The
complexity in the antigenic structure of A.
fumigatus and the varying host
immune responses lead to a wide spectrum of
clinical conditions such as
allergic bronchopulmonary aspergillosis
(ABPA), aspergilloma, and invasive
aspergillosis. It is reported that 15-20% of
allergic asthmatics suffer
from Aspergillus-induced allergies. The incidence
of opportunistic
infections, including Aspergillus
infections, has risen because of the
increase in the incidence of HIV and
tuberculosis. Allergic
bronchopulmonary aspergillosis is an
immunologically significant clinical
form where type I and type III
hypersensitivity reactions are involved in
pathogenesis. High levels of specific IgE
and IgG antibodies in these
patients are of diagnostic value. Molecular
characterization of certain
immunodominant allergens and antigens of A.
fumigatus revealed the
presence of complex carbohydrate moieties,
heat-shock proteins, enzyme
activities such as elastase, protease,
catalase, dismutase, and cytotoxic
ribonuclease. A Con A binding
allergen/antigen (45 kDa) and Con A
nonbinding allergen/antigen (18 kDa, Asp fI)
have a multifunctional
nature. The multifunctional nature of these
antigens may play an important
role in the pathogenesis of the disease.
Significant amounts of a major
allergen/antigen of molecular weight 18 kDa
is excreted in large amounts
through the urine of patients with invasive
aspergillosis. Studies on the
structure-function relationship of the
18-kDa allergen/antigen revealed
the involvement of tryptophan residues in
binding with monoclonal
antibodies (MAbs). Also, the histidine
residues and cysteine disulfide
bonds of the 18-kDa allergen are involved in
its catalytic activity. The
high load of multifunctional antigens in the
serum of patients for
prolonged periods, the presence of high
levels of specific antibodies, and
the absence of protective antibodies in ABPA
patients have necessitated
studies on the functional properties of the
antibodies. The present study
shows significant immunoreactivity of
antibodies in patients of ABPA to
fibronectin and collagen. Analysis of IgG
antibodies from the patients of
ABPA showed the presence of DNA-cleaving
activity. These observations
offer a new line of thinking in
understanding the mechanism of
pathogenesis of Aspergillus-induced clinical
manifestations, and may lead
to novel approaches to intervention in the
inflammation and infection
caused by fungal pathogens.
1933.
Authors
Quiros E.
Bettinardi A. Quiros A. Piedrola G.
Maroto MC.
Title
Detection of mycobacterial DNA in
papulonecrotic tuberculid lesions by
polymerase chain reaction.
Source
Journal of Clinical Laboratory
Analysis. 14(4):133-5, 2000.
Abstract
Tuberculids are a heterogeneous group of
cutaneous lesions. Recent
discoveries of M. Tuberculosis DNA in these
lesions by PCR suggest that M.
tuberculosis could play a role in their
pathogenesis. The aim of this
study was to demonstrate the presence of M.
tuberculosis DNA by polymerase
chain reaction in papulonecrotic tuberculid
lesions. Skin biopsy specimens
from ten patients with papulonecrotic
tuberculid lesions (histopathologic
features) were studied. All of them tested
solidly positive in a
tuberculin intradermal test. A
gene-amplification PCR, using primers
capable of amplifying DNA in the M.
tuberculosis complex, was performed to
detect M. tuberculosis DNA in the lesions. A
285-bp sequence specific of
M. tuberculosis complex was amplified and
confirmed by Southern-blot
hybridation with a 32 p 5'-labelled internal
probe. No inhibitors were
detected in the negative PCR samples. The
PCR technique makes the
detection of mycobacterial DNA in
tuberculids a possibility, and therefore
provides a rational basis for
antituberculous therapy and for the clinical
management of these disorders. Copyright
2000 Wiley-Liss, Inc.
1934.
Authors
Ramanathan M. Abdullah AD. Sivadas T.
Title
Hypercalcaemic crisis as the presenting
manifestation of abdominal
tuberculosis: a case report.
Source
Medical Journal of Malaysia. 53(4):432-4, 1998 Dec.
Abstract
This report deals with a young man having
prolonged fever presenting with
hypercalcaemic crisis. Subsequent
investigations confirmed tuberculosis
(TB) peritonitis in the absence of pulmonary
involvement as the cause of
his symptoms. His hypercalcaemia and fever
resolved with anti-TB therapy.
Abdominal TB needs to be included in the
differential diagnosis of
otherwise unexplained hypercalcaemia
especially in our region where TB is
an endemic problem and is treatable.
1935.
Authors
Ruiz-Serrano MJ. Alcala L. Martinez
L. Diaz M. Marin M. Gonzalez-Abad
MJ.
Bouza E.
Title
In vitro activities of six fluoroquinolones
against 250 clinical isolates
of Mycobacterium tuberculosis susceptible or
resistant to first-line
antituberculosis drugs.
Source
Antimicrobial Agents &
Chemotherapy. 44(9):2567-8, 2000 Sep.
Abstract
Two hundred fifty isolates of Mycobacterium
tuberculosis were evaluated
for susceptibility to ciprofloxacin,
ofloxacin, levofloxacin,
grepafloxacin, trovafloxacin, and gemifloxacin
(SB-265805). Levofloxacin,
ciprofloxacin, and grepafloxacin showed the
greatest activity (MIC for 90%
of strains tested [MIC(90)] 1 microg/ml),
although ofloxacin also showed
good activity, with an MIC(90) of 2
microg/ml. Trovafloxacin and
gemifloxacin showed lower in vitro activity, with MIC(90)s of 64
and 8
microg/ml, respectively.
1936.
Authors
Schwander SK. Torres M. Carranza C
C. Escobedo D. Tary-Lehmann M.
Anderson P.
Toossi Z. Ellner JJ. Rich EA.
Sada E.
Title
Pulmonary mononuclear cell responses to
antigens of Mycobacterium
tuberculosis in healthy household contacts
of patients with active
tuberculosis and healthy controls from the
community.
Source
Journal of Immunology. 165(3):1479-85, 2000 Aug 1.
Abstract
Protective immunity against Mycobacterium
tuberculosis requires CD4+
lymphocyte-mediated immune responses and
IFN-gamma activity. As the
primary portal of entry of M. tuberculosis
is the lung, pulmonary immune
responses against multiple M. tuberculosis
Ags were compared between both
M. tuberculosis-exposed tuberculin skin
test-positive healthy household
contacts (HHC) of patients with active
sputum smear and culture-positive
tuberculosis and tuberculin skin
test-positive healthy control individuals
from the community (CC). Frequencies of M.
tuberculosis Ag-specific
IFN-gamma-producing cells, IFN-gamma
concentrations in culture
supernatants, and DNA synthesis in
bronchoalveolar cells (BAC) and PBMC
were studied in HHC (n = 10) and CC (n =
15). Using enzyme-linked
immunospot assay we found higher frequencies
of IFN-gamma-producing cells
with specificity to M. tuberculosis-secreted
Ag 85 (Ag 85) in BAC from HHC
than in BAC from CC (p < 0.022) and
relative to autologous PBMC,
indicating compartmentalization of Ag
85-specific cells to the lungs.
Further, IFN-gamma-producing cells with
specificity to components A and B
of Ag 85 were specifically compartmentalized
to the lungs in HHC (p < 0.
05). IFN-gamma concentrations in culture
supernatants of BAC and
Ag-specific DNA synthesis were low and
comparable in the two subject
groups. Increased immune responses to Ag 85
at the site of repeated
exposure to M. tuberculosis (the lung) may
represent an important
component of protective immunity against M.
tuberculosis. Correlates of
protective immunity against M. tuberculosis
are required for assessment of
the efficiency of anti-tuberculous vaccines.
1937.
Authors
Sheikh M.
Moosa I. Hussein FM. Qurttom MA.
Behbehani AI.
Title
Ultrasonographic diagnosis in abdominal
tuberculosis.
Source
Australasian Radiology. 43(2):175-9, 1999 May.
Abstract
Sonographic findings were retrospectively
analysed in 39 patients with
proven abdominal tuberculosis (TB). The
patients were treated over 15
years at a major teaching hospital, Mubarak
Al-Kabber Hospital, in Kuwait.
The findings included clear or complex
ascites with fine strands,
loculations and debris. The other findings
were lymphadenopathy, bowel
wall thickening, omental mass, focal lesions
in the liver and spleen and
psoas abscess. The sonographic findings in
abdominal TB are not specific
but may give valuable information to prevent
unnecessary laparotomy.
1938.
Authors
Shinnick TM.
Title
Diagnostic test needs for evaluating
antituberculosis vaccines. [Review]
[23 refs]
Source
Clinical Infectious Diseases. 30 Suppl 3:S276-8, 2000 Jun.
Abstract
To aid in the evaluation of preexposure and
postinfection vaccines to
prevent tuberculosis, diagnostic tests are
needed that can clearly
distinguish immunologic protection from
vaccine failure in a timely
manner. The currently available tests to
detect infected persons
(tuberculin skin-test) and confirm active
disease (conventional culture
methods) have limitations in specificity,
sensitivity, or timeliness.
Research to identify (1) surrogate markers
of infection, disease, or
protection and (2) stage-specific antigens
or immune responses holds some
promise for the development of new tests
that can distinguish the various
outcomes of an infection or a vaccination.
[References: 23]
1939.
Authors
Sirgel FA.
Donald PR. Odhiambo J. Githui W.
Umapathy KC. Paramasivan
CN.
Tam CM. Kam KM. Lam CW.
Sole KM. Mitchison DA.
Title
A multicentre study of the early
bactericidal activity of
anti-tuberculosis drugs.
Source
Journal of Antimicrobial Chemotherapy. 45(6):859-70, 2000 Jun.
Abstract
The early bactericidal activities (EBAs) of
300 mg isoniazid, 18.5 mg
isoniazid, 600 mg rifampicin and 800 mg
ofloxacin given daily to 262
patients with newly diagnosed pulmonary
tuberculosis in Cape Town,
Nairobi, Madras and Hong Kong were measured
by counting cfu and total
acid-fast bacilli in sputum collections
taken pre-treatment (S1), at 2
days (S3) and at 5 days (S6). In Cape Town,
Nairobi and Madras, the cfu
findings suggested that isoniazid produced a
massive kill, perhaps of
actively growing organisms, during the first
2 days (mean S1-S3 EBAs of
0.636-1.006) but was almost inactive thereafter
(mean S3-S6 EBAs of
0.000-0.081), whereas rifampicin maintained
moderate activity against
slowly growing organisms throughout the 5
days (mean S3-S6 EBAs of
0.242-0.305). This finding suggests that
EBAs measured during the 2-5 day
interval might be able to assess the
sterilizing activity of drugs.
Ofloxacin had moderately high mean S1-S3
EBAs of 0.130-0.391. However, in
Hong Kong rifampicin appeared to be the most
bactericidal drug from the
start, possibly because patients had more chronic
disease. A method of
adjusting the cfu EBAs using total counts
was devised which decreased the
variability between patients within a
treatment group without altering the
mean cfu EBA. This resulted in a large gain
in precision in Hong Kong,
suggesting that their estimates were greatly affected by type II
variation, due to dilution of pus by saliva
and bronchial secretions,
whereas small or no gains were obtained in
the other three centres,
suggesting that the main cause of
variability was type I, due to other
factors.
1940.
Authors
Snider DE Jr.
Title
Ethical issues in tuberculosis vaccine
trials. [Review] [31 refs]
Source
Clinical Infectious Diseases. 30 Suppl 3:S271-5, 2000 Jun.
Abstract
Bacille Calmette-Guerin (BCG) vaccines are
widely used, even though
estimates of efficacy have ranged from zero
to 80%. BCG is a relatively
safe vaccine, but it can cause disseminated
infection, especially in
immunocompromised hosts. Thus, the
development of a more reliably
efficacious and safer vaccine is important
to the control of tuberculosis.
The testing of any new vaccine in human
populations presents a number of
ethical challenges that must be addressed.
These include (1) the
appropriateness of conducting such trials in
developing countries; (2) the
use of a BCG-vaccinated population as the
control group; (3) the provision
of tuberculin skin-test screening and
preventive therapy to study
participants; (4) the involvement of various
"communities" in the
trial(s); (5) the structure and process of
ethical review; (6)
establishing an effective method of
obtaining informed consent; and (7)
the roles and responsibilities of
researchers and others in ensuring that
trial results are available to the study
population after the trial ends.
[References: 31]
1941.
Authors
Stobie L.
Gurunathan S. Prussin C. Sacks DL.
Glaichenhaus N. Wu CY.
Seder RA.
Title
The role of antigen and IL-12 in sustaining
Th1 memory cells in vivo:
IL-12 is required to maintain memory/effector
Th1 cells sufficient to
mediate protection to an infectious parasite
challenge.
Source
Proceedings of the National Academy of
Sciences of the United States of
America.
97(15):8427-32, 2000 Jul 18.
Abstract
IL-12 plays a central role in both the
induction and magnitude of a
primary Th1 response. A critical question in
designing vaccines for
diseases requiring Th1 immunity such as
Mycobacterium tuberculosis and
Leishmania major is the requirements to
sustain memory/effector Th1 cells
in vivo. This report examines the role of
IL-12 and antigen in sustaining
Th1 responses sufficient for protective
immunity to L. major after
vaccination with LACK protein (LP) plus
rIL-12 and LACK DNA. It shows
that, after initial vaccination with LP plus
rIL-12, supplemental boosting
with either LP or rIL-12 is necessary but
not sufficient to fully sustain
long-term Th1 immunity. Moreover, endogenous
IL-12 is also shown to be
required for the induction, maintenance, and
effector phase of the Th1
response after LACK DNA vaccination.
Finally, IL-12 is required to sustain
Th1 cells and control parasite growth in
susceptible and resistant strains
of mice during primary and secondary
infection. Taken together, these data
show that IL-12 is essential to sustain a
sufficient number of
memory/effector Th1 cells generated in vivo
to mediate long-term
protection to an intracellular pathogen.
1942.
Authors
Stover CK.
Warrener P. VanDevanter DR. Sherman DR.
Arain TM.
Langhorne MH. Anderson SW. Towell
JA. Yuan Y. McMurray DN. Kreiswirth
BN.
Barry CE. Baker WR.
Title
A small-molecule nitroimidazopyran drug
candidate for the treatment of
tuberculosis.
Source
Nature.
405(6789):962-6, 2000 Jun 22.
Abstract
Mycobacterium tuberculosis, which causes
tuberculosis, is the greatest
single infectious cause of mortality
worldwide, killing roughly two
million people annually. Estimates indicate
that one-third of the world
population is infected with latent M.
tuberculosis. The synergy between
tuberculosis and the AIDS epidemic, and the
surge of multidrug-resistant
clinical isolates of M. tuberculosis have
reaffirmed tuberculosis as a
primary public health threat. However, new
antitubercular drugs with new
mechanisms of action have not been developed
in over thirty years. Here we
report a series of compounds containing a
nitroimidazopyran nucleus that
possess antitubercular activity. After
activation by a mechanism dependent
on M. tuberculosis F420 cofactor, nitroimidazopyrans
inhibited the
synthesis of protein and cell wall lipid. In
contrast to current
antitubercular drugs, nitroimidazopyrans
exhibited bactericidal activity
against both replicating and static M.
tuberculosis. Lead compound PA-824
showed potent bactericidal activity against
multidrugresistant M.
tuberculosis and promising oral activity in
animal infection models. We
conclude that nitroimidazopyrans offer the
practical qualities of a small
molecule with the potential for the treatment
of tuberculosis.
1943.
Authors
Su WJ.
Tsou AP. Yang MH. Huang CY.
Perng RP.
Title
Clinical experience in using polymerase
chain reaction for rapid diagnosis
of pulmonary tuberculosis.
Source
Chung Hua i Hsueh Tsa Chih - Chinese Medical
Journal. 63(7):521-6, 2000
Jul.
Abstract
BACKGROUND: Polymerase chain reaction (PCR)
techniques have revolutionized
the diagnosis of tuberculosis (TB). PCR has
significantly improved the
sensitivity and specificity of existing
diagnostic methods. In this study,
we report our experience using a modified
IS6110-based nested PCR assay
for rapid diagnosis of pulmonary TB.
METHODS: A total of 327 respiratory
specimens from 275 patients suspected of
having pulmonary TB at Taipei
Veterans General Hospital were tested using
the nested PCR assay,
acid-fast smear and culture for the presence
of Mycobacterium tuberculosis
complex (MTB). Nested PCR was performed with
IS6110-based primers specific
for MTB. We reviewed the medical records of
patients and analyzed the
clinical features. The PCR results were
compared with the final clinical
diagnosis. RESULTS: We identified MTB in 167
of 327 samples by the nested
PCR assay. No non-tuberculous Mycobacterium
(NTM) was identified among the
clinical samples. Diagnosis by PCR took
about 6 hours in this study. The
sensitivity and specificity compared with
culture were 94.7% and 100%,
respectively for the smear-positive,
culture-positive samples, and 76.7%
and 98.6% for the smear-negative,
culture-positive samples. The overall
sensitivity, specificity, positive and
negative predictive values,
compared with culture results, were 91.7%,
98.6%, 98.8% and 90.6%,
respectively. Two specimens positive by PCR
and negative by culture were
taken from patients on anti-TB drug therapy.
These specimens were
culture-positive before anti-TB drug
therapy. After resolution of the
discrepancies by studying the patients'
clinical data, both specificity
and positive predictive value reached 100%.
CONCLUSIONS: The results
indicated that this in-house nested PCR
assay is a rapid and sensitive
method for diagnosing pulmonary TB. It is
also good for excluding
infections caused by NTM.
1944.
Authors
Tak S.
Ahluwalia G. Sharma SK. Mukhopadhya S. Guleria R. Pande JN.
Title
Haemoptysis in patients with a normal chest
radiograph: bronchoscopy-CT
correlation.
Source
Australasian Radiology. 43(4):451-5, 1999 Nov.
Abstract
The exact role of fibre-optic bronchoscopy
(FOB) and CT of the chest in
the diagnosis of patients presenting with
haemoptysis and a normal or
non-localizing chest radiograph has not been
clearly defined. A study was
designed to evaluate 50 patients presenting
with haemoptysis and a normal
or non-localizing chest radiograph using FOB
and high-resolution computed
tomography (HRCT). A definitive diagnosis
was established in 17 (34%)
patients. The aetiologies included
bronchiectasis (24%), bronchial adenoma
(6%), tuberculosis (2%) and bronchitis (2%).
The diagnosis was made by
HRCT in 15 (30%) patients, while FOB was
diagnostic in five (10%)
patients. The diagnosis was made by HRCT and
FOB in all patients with
focal airway abnormalities. Therefore, HRCT
effectively delineated
abnormalities of both the central and peripheral
airways. It is concluded
that CT should be obtained prior to FOB in
all patients presenting with
haemoptysis and a normal or non-localizing
chest radiograph.
1945.
Authors
Triccas JA.
Gicquel B.
Title
Life on the inside: probing mycobacterium
tuberculosis gene expression
during infection. [Review] [60 refs]
Source
Immunology & Cell Biology. 78(4):311-7, 2000 Aug.
Abstract
The identification of Mycobacterium
tuberculosis genes specifically
expressed during infection is a key step in
understanding mycobacterial
pathogenesis. Such genes most likely encode
products required for survival
within the host and for progressive
infection. Recent advances in
mycobacterial genetics have permitted the
development of new techniques
and the adaptation of existing methods to
analyse mycobacterial in vivo
gene expression and virulence. This has
revealed a subset of M.
tuberculosis genes that are differentially
expressed during infection and
has demonstrated that a number of components
contribute to the virulence
of the organism. This information is
expected to provide new strategies to
prevent tuberculosis infection, new targets
for antimicrobial therapy and
new insights into the infectious process.
[References: 60]
1946.
Authors
Van Rie A.
Warren R. Richardson M. Gie RP.
Enarson DA. Beyers N. Van
Helden PD.
Title
Classification of drug-resistant
tuberculosis in an epidemic area.
Source
Lancet.
356(9223):22-5, 2000 Jul 1.
Abstract
BACKGROUND: Traditionally, patients with
drug-resistant tuberculosis are
classified as having acquired drug-resistant
or primary drug-resistant
disease on the basis of a history of
previous tuberculosis treatment. Only
cases of primary drug resistance are assumed
to be due to transmission of
drug-resistant strains. METHODS: This
descriptive study of 63 patients
with drug-resistant tuberculosis assessed
the relative contribution of
transmission of drug-resistant strains in a
high-incidence community of
Cape Town, South Africa, by
restriction-fragment length polymorphism
(RFLP). The RFLP results were compared with
the results obtained by
traditional classification methods.
FINDINGS: According to RFLP
definitions, 52% (33 cases) of
drug-resistant tuberculosis was caused by
transmission of a drug-resistant strain. The
proportion of cases due to
transmission was higher for
multidrug-resistant (64%; 29 cases) than for
single-drug-resistant (no cases)
tuberculosis. By the clinical
classification, only 18 (29%) patients were
classified as having primary
drug-resistant tuberculosis (implying
transmission). The clinical
classification was thus misleading in 25
patients. INTERPRETATION: The
term acquired drug resistance includes
patients infected with strains that
truly acquired drug resistance during
treatment and patients who were
initially infected with or reinfected with a
drug-resistant strain. This
definition could lead to misinterpretation
of surveillance studies,
incorrect evaluation of tuberculosis programmes,
and delayed diagnosis and
treatment of patients with
multidrug-resistant disease. The clinical term
acquired drug resistance should be replaced
with the term "drug resistance
in previously treated cases", which
includes cases with drug resistance
due to true acquisition as well as that due
to transmitted drug-resistant
strains.
1947.
Authors
Viinanen AH. Soini H. Marjamaki
M. Liippo K. Viljanen MK.
Title
Ligase chain reaction assay is clinically
useful in the discrimination of
smear-positive pulmonary tuberculosis from
atypical mycobacterioses.
Source
Annals of Medicine. 32(4):279-83, 2000 May.
Abstract
We evaluated the usefulness of the ligase
chain reaction (LCR) (Abbott LCx
Mycobacterium tuberculosis assay) during the
initial diagnosis of
tuberculosis. LCx was carried out in
parallel with conventional methods
for the analysis of clinical samples. Out of
86 patients who were examined
clinically, 53 were suspected of having
pulmonary tuberculosis, eight had
residual X-ray scars from previous
tuberculosis and 25 served as
asymptomatic controls. Ten bronchoscopy
samples and 237 sputum samples
were analysed by direct microscopy, culture
and LCx. All 11 smear-positive
and two of three smear-negative tuberculosis
patients had at least one
LCx-positive specimen. All samples that were
both LCx- and smear-positive
were culture-positive for M. tuberculosis.
The smear-positive samples from
the five patients with atypical
mycobacteriosis were LCx-negative. There
were three false-positive results: one in a
smear-negative sample from a
patient with M. malmoense infection and two
from two pneumonia patients.
All samples from controls and patients with
previous tuberculosis were
LCx-negative. The sensitivity, specificity
and the positive and negative
predictive values of LCx in patient analysis
were 92.9%, 95.8%, 81.3% and
98.6%, respectively. LCx assay of M.
tuberculosis is useful in rapid
confirmation of tuberculosis or atypical
mycobacteriosis from a
smear-positive sample and may aid in
diagnosing smear-negative
tuberculosis.
1948.
Authors
Vogel FR.
Title
Improving vaccine performance with
adjuvants. [Review] [66 refs]
Source
Clinical Infectious Diseases. 30 Suppl 3:S266-70, 2000 Jun.
Abstract
New
vaccines are presently under development and in testing for the
control of infectious diseases, including
human immunodeficiency virus
(HIV) and tuberculosis. Several of these
vaccines are composed of
synthetic, recombinant, or highly purified subunit
antigens. Subunit
vaccines are designed to include only the
antigens required for protective
immunization and to be safer than
whole-inactivated or live-attenuated
vaccines. However, the purity of the subunit
antigens and the absence of
the self-adjuvanting immunomodulatory
components associated with
attenuated or killed vaccines often result
in weaker immunogenicity.
Immunologic adjuvants are agents that
enhance specific immune responses to
vaccines. Formulation of vaccines with
potent adjuvants is an attractive
approach for improving the performance of
vaccines composed of subunit
antigens. Adjuvants have diverse mechanisms
of action and should be
selected for use on the basis of the route
of administration and the type
of immune response (antibody, cell-mediated,
or mucosal immunity) that is
desired for a particular vaccine.
[References: 66]
1949.
Authors
Wiersma HE.
Van Aalderen WM. Hoekstra MO.
Title
Sputum induction for the diagnosis of
pulmonary tuberculosis [letter;
comment].
Source
Archives of Disease in Childhood. 83(3):276, 2000 Sep.
1950.
Authors
Wilson ME.
Title
Applying experiences from trials of bacille
Calmette-Guerin vaccine.
[Review] [39 refs]
Source
Clinical Infectious Diseases. 30 Suppl 3:S262-5, 2000 Jun.
Abstract
Bacille Calmette-Guerin (BCG) vaccine, a
live vaccine developed to prevent
tuberculosis (TB), has been given to
billions of persons over more than 7
decades. Studies of the efficacy of BCG
vaccine have had widely divergent
results, underscoring the complexity of the
biology and immunology of TB.
The long duration of TB infection, the
heterogeneity of its clinical
expression, and lack of inexpensive,
reliable markers of infection and
disease have made it difficult to study the
impact of a vaccine,
especially in resource-poor areas. A
meta-analysis of data from trials of
BCG vaccine found that studies conducted at
sites that are a greater
distance from the equator are associated
with better vaccine efficacy, a
finding that needs fuller study. BCG vaccine
trials with higher validity
scores showed higher rates of protection.
Ongoing changes, including human
immunodeficiency virus infection and
demographic shifts, should be
considered when developing trials of future
vaccines. Analyses of past
studies of BCG vaccine can identify sources
of variation that may guide
the design of studies of new vaccines.
Rigorous study design and new tools
are needed if studies are to provide clear,
useful answers about new
vaccines. [References: 39]
1951.
Authors
Worku S.
Hoft DF.
Title
In vitro measurement of protective
mycobacterial immunity:
antigen-specific expansion of T cells
capable of inhibiting intracellular
growth of bacille Calmette-Guerin.
Source
Clinical Infectious Diseases. 30 Suppl 3:S257-61, 2000 Jun.
Abstract
We investigated the ability of T cells
expanded with mycobacterial
antigens from healthy purified protein
derivative-reactive donors and
bacille Calmette-Guerin (BCG)-vaccinated volunteers
to inhibit
intracellular growth of BCG. Peripheral
blood mononuclear cells were
incubated for 7 days with mycobacterial
whole lysate, live BCG, tetanus
toxoid as control antigen, or medium alone.
Autologous monocytes were
separated by plastic adherence, allowed to
mature for 6 days, and infected
with BCG before serving as target cells.
Expanded effector cells were
cocultured with target cells for 72 h.
Cocultures were then treated with
0.2% saponin to lyse infected monocytes and
release intracellular BCG.
Quantities of viable BCG present in these
lysates were studied by
colony-forming unit counting and radiometric
labeling. We reproducibly
found that lymphocytes expanded with
mycobacterial whole lysate or live
BCG significantly inhibited the
intracellular growth of BCG, compared with
lymphocytes expanded with tetanus toxoid or
rested in medium. In addition,
BCG vaccination enhanced the ability of T
cells to inhibit intracellular
mycobacterial growth in 3 of 5 volunteers. This
assay may be useful for
estimates of protective immunity induced by
tuberculosis vaccines in human
trials.
1952.
Authors
Young DB.
Title
Current tuberculosis vaccine development.
[Review] [26 refs]
Source
Clinical Infectious Diseases. 30 Suppl 3:S254-6, 2000 Jun.
Abstract
Information derived from the complete genome
sequence of Mycobacterium
tuberculosis makes it possible to develop a
range of new vaccine
candidates. Strategies currently under
investigation include construction
of whole cell live attenuated mycobacterial
vaccines, as well as the use
of individual antigens delivered by a
variety of subunit vaccination
procedures. Fundamental questions associated
with the rational design,
preclinical testing, and future application
of new tuberculosis vaccines
are reviewed. [References: 26]
1953.
Authors
Zahrt TC.
Deretic V.
Title
An essential two-component signal
transduction system in Mycobacterium
tuberculosis.
Source
Journal of Bacteriology. 182(13):3832-8, 2000 Jul.
Abstract
The bacterial two-component signal
transduction systems regulate
adaptation processes and are likely to play
a role in Mycobacterium
tuberculosis physiology and pathogenesis.
The previous initial
characterization of an M. tuberculosis response
regulator from one of
these systems, mtrA-mtrB, suggested its
transcriptional activation during
infection of phagocytic cells. In this work,
we further characterized the
mtrA response regulator from M. tuberculosis
H37Rv. Inactivation of mtrA
on the chromosome of M. tuberculosis H37Rv
was possible only in the
presence of plasmid-borne functional mtrA,
suggesting that this response
regulator is essential for M. tuberculosis
viability. In keeping with
these findings, expression of mtrA in M.
tuberculosis H37Rv was detectable
during in vitro growth, as determined by S1
nuclease protection and primer
extension analyses of mRNA levels and
mapping of transcript 5' ends. The
mtrA gene was expressed differently in
virulent M. tuberculosis and the
vaccine strain M. tuberculosis var. bovis
BCG during infection of
macrophages, as determined by monitoring of
mtrA-gfp fusion activity. In
M. bovis BCG, mtrA was induced upon entry
into macrophages. In M.
tuberculosis H37Rv, its expression was
constitutive and unchanged upon
infection of murine or human
monocyte-derived macrophages. In conclusion,
these results identify mtrA as an essential
response regulator gene in M.
tuberculosis which is differentially
expressed in virulent and avirulent
strains during growth in macrophages.
1954.
Authors
Zimhony O.
Cox JS. Welch JT. Vilcheze C.
Jacobs WR Jr.
Title
Pyrazinamide inhibits the eukaryotic-like
fatty acid synthetase I (FASI)
of Mycobacterium tuberculosis [see
comments].
Source
Nature Medicine. 6(9):1043-7, 2000 Sep.
Abstract
Tuberculosis treatment is shortened to six
months by the indispensable
addition of pyrazinamide (PZA) to the drug
regimen that includes isoniazid
and rifampin. PZA is a pro-drug of
pyrazinoic acid (POA) (ref. 3), whose
target of action has never been identified.
Although PZA is active only
against Mycobacterium tuberculosis, the PZA
analog 5-chloro-pyrazinamide
(5-Cl-PZA) displays a broader range of
anti-mycobacterial activity. We
have found that the eukaryotic-like fas1
gene (encoding fatty acid
synthetase I, FASI) from M. avium, M. bovis
BCG or M. tuberculosis confers
resistance to 5-Cl-PZA when present on
multi-copy vectors in M. smegmatis.
5-Cl-PZA and PZA markedly inhibited the activity
of M. tuberculosis FASI,
the biosynthesis of C16 to C24/C26 fatty
acids from acetyl-CoA (ref. 6).
Importantly, PZA inhibited FASI in M.
tuberculosis in correlation with PZA
susceptibility. These results indicate that
FASI is a primary target of
action for PZA in M. tuberculosis. Further
characterization of FASI as a
drug target for PZA may allow the
development of new drugs to shorten the
therapy against M. tuberculosis and may
provide more options for treatment
against M. bovis, M. avium and drug
resistant M. tuberculosis.
2437. Al-Matar MJ. Cabral DA. Petty RE. Isolated tuberculous monoarthritis mimicking oligoarticular juvenile rheumatoid arthritis. Journal of Rheumatology. 28(1):204-6, 2001 Jan.
Abstract
Isolatd monoarthritis caused by Mycobacterium tuberculosis in the absence of clinical pulmonary disease is extremely rare in North America. After decades of consistent declines in incidence, a remarkable resurgence of tuberculosis (TB) is occurring in North America. It must always be considered in the differential diagnosis of chronic monoarthritis if devastating sequelae are to be avoided. We describe 2 cases of tuberculous arthritis in young children presenting with monoarthritis of the knee. The presumptive diagnosis in each case was oligoarticular onset juvenile rheumatoid arthritis (JRA). Each had an atypical course for JRA, with lack of response to intraarticular corticosteroid. The diagnosis of TB arthritis was made only with synovial biopsy.
2439. Blomberg B. Spinaci S. Fourie B. Laing R. The rationale for recommending fixed-dose combination tablets for treatment of tuberculosis. Bulletin of the World Health Organization. 79(1):61-8, 2001.
Abstract
There is considerable exigency to take all necessary steps to cure tuberculosis cases and prevent further emergence of drug-resistant tuberculosis. The most important of these steps is to ensure that the treatment, particularly of sputum smear-positive cases, is adequate and that patients adhere to their treatment by supervised, direct observation of drug-taking according to the standardized regimens. Use of fixed-dose combinations (FDCs) of tablets against tuberculosis is now being recommended by WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD) as an additional step to ensuring proper treatment. FDCs simplify the prescription of drugs and the management of drug supply, and may also limit the risk of drug-resistant tuberculosis arising as a result of inappropriate drug selection and monotherapy. Only FDCs of proven quality and proven rifampicin bioavailability should be purchased and used. In most situations, blood levels of the drugs are inadequate because of poor drug quality rather than poor absorption. This is true irrespective of the human immunodeficiency virus (HIV) infection status of the tuberculosis patients (other than those with overt acquired immunodeficiency syndrome, with CD4 counts < 200 cells/mm3). Currently, WHO, IUATLD and their partners are developing strategies for ensuring that only quality FDCs are used in tuberculosis programmes. A simplified and effective protocol for assessment of rifampicin bioavailability has been developed, and laboratories are being recruited to form a supranational network for quality assurance of FDCs. Standardization of FDC drug formulations has been proposed, which limits rifampicin-containing preparations to nine (including a four-drug FDC and three paediatric FDCs).
2445. Gomez-Pastrana D. Torronteras R. Caro P. Anguita ML. Lopez-Barrio AM. Andres A. Navarro J. Comparison of amplicor, in-house polymerase chain reaction, and conventional culture for the diagnosis of tuberculosis in children. Clinical Infectious Diseases. 32(1):17-22, 2001 Jan.
Abstract
A total of 251 clinical specimens (235 gastric aspirates and 16 bronchoalveolar lavages) from 88 children were prospectively tested in a blinded manner for the presence of Mycobacterium tuberculosis complex, by use of the Amplicor M. tuberculosis test and by means of in-house polymerase chain reaction (PCR). The results were compared with those obtained by conventional culture and by direct microscopy. All of the children underwent extended follow-up to verify or exclude the clinical diagnosis of tuberculosis. The results of the different tests, when compared to the final clinical diagnosis, were a sensitivity of 60% and a specificity of 96.8% for in-house PCR, 44% and 93.7% respectively for the Amplicor test, 44% and 100% for mycobacterial culture and 12% and 100% for microscopy. Amplicor tests presented false-positive findings in children without tuberculous infection. We conclude that both in-house PCR and the Amplicor test are rapid methods that can be helpful for difficult or urgent diagnosis of tuberculosis in children. However, efforts should be aimed toward improvement of the sensitivity and specificity of an easy-to-use PCR kit.
2446. Gupta D. Saiprakash BV. Aggarwal AN. Muralidhar S. Kumar B. Jindal SK. Value of different cut-off points of tuberculin skin test to diagnose tuberculosis among patients with respiratory symptoms in a chest clinic. Journal of the Association of Physicians of India. 49:332-5, 2001 Mar.
Abstract
OBJECTIVE: To assess the utility of various cut-off points of tuberculin skin test in making a diagnosis of tuberculosis in patients with respiratory symptoms. METHODS: Tuberculin skin test was conducted on consecutive new patients attending chest clinic for various respiratory symptoms. All subjects were then investigated to establish diagnosis, and categorized into tuberculous and nontuberculous groups. Receiver operating characteristic (ROC) curve was plotted to evaluate discrimination by tuberculin skin test. Sensitivity, specificity and predictive value were also calculated at various cut-off points. RESULTS: Of 250 patients, 59 (23.6%) had tuberculosis on clinical and microbiological criteria (other than the tuberculin test). Sensitivity and specificity of tuberculin test at readings greater than 5, 10 and 15 mm were 0.8136 and 0.7068, 0.6271 and 0.8901, and 0.2034 and 0.9738 respectively. Area under ROC curve for this test was 0.80. CONCLUSION: A cut-off point of 10 mm is likely to be useful in supporting a diagnosis of tuberculosis in patients with strong clinical suspicion of tuberculosis, in other patients, 15 mm cut-off may be more suitable.
2449. Jha BC. Dass A. Nagarkar NM. Gupta R. Singhal S. Cervical tuberculous lymphadenopathy: changing clinical pattern and concepts in management. Postgraduate Medical Journal. 77(905):185-7, 2001 Mar.
Abstract
Tuberculosis is one of the biggest health challenges the world is facing. In this study the clinical pattern of patients with cervical lymphadenitis, who presented to the ear, nose, and throat outpatient department of the Government Medical College Hospital, Chandigarh, India between June 1997 and May 1998 is recorded. Tuberculosis accounted for 60 out of 94 cases of cervical lymph node enlargement. The commonest age group affected was 11-20 years. Constitutional symptoms were not present in most of the patients. Multiple matted nodes were seen in 23 patients but a single discrete node was seen in 18 patients. Upper deep jugular nodes were the most commonly affected lymph nodes. Discharging sinus and abscess formation were uncommon. Fine needle aspiration cytology yielded a positive diagnosis in 52 out of 56 patients. Chest lesions on radiography were evident in 16% of the patients. Mantoux test was positive and was more than 15 mm in most of the patients. This study shows that the classical picture of "scrofula" is no longer seen nowadays and can probably be explained by the earlier presentation of the disease.All the patients were treated with short course daily chemotherapy for six months. Surgery was not required in the majority of patients except in four cases where excision biopsy was performed. Patients with abscess formation were managed with wide bore needle aspiration only. With a minimum six month period of follow up, no patient was found to have a recurrence of local or systemic disease.This study emphasises the role of fine needle aspiration cytology in diagnosis and confirms the efficacy of six months short course chemotherapy.
2454. Kuyucu N. Kuyucu S. Bakirtas A. Karacan C. BCG revaccination and tuberculin reactivity. Indian Journal of Pediatrics. 68(1):21-5, 2001 Jan.
Abstract
Interpretation of tuberculin reactions in revaccinated children is somewhat controversial among paediatricians. In this study, the effect of the number of BCG vaccines on tuberculin reactivity is evaluated. In 2810 healthy children aged 7 to 14 years with purified protein derivative (PPD) testing. Children were grouped according to the concordance of the number of the reported/documented vaccinations to the number of scars. Group 1 and 2 comprised of children 7 to 10 years of age and 11 to 14 years of age respectively, who had non-concordant scar numbers, and Group 3 and 4 included 7 to 10 and 11 to 14 years old children with concordant scar numbers. Mean tuberculin induration sizes were 8.0 +/- 5.7 mm for Group 1, 10.6 +/- 4.9 mm for Group 2, 9.8 +/- 4.9 mm for Group 3 and 10.9 +/- 4 mm for Group 4. As the time interval after the last dose of vaccination increased, mean induration sizes decreased in Group 1 and Group 3. In contrast, the mean reaction sizes of Group 2 and Group 4 showed a positive correlation with the period after the last dose of vaccine. It seems advisable that an induration size > or = 15 mm should not be attributed to BCG vaccination in countries with a high tuberculosis infection prevalence and routine BCG revaccination policies. A detailed investigation for tuberculosis infection and disease should be performed in those cases.
2455. Lenk S. Schroeder J. Genitourinary tuberculosis. [Review] [17 refs] Current Opinion in Urology. 11(1):93-8, 2001 Jan.
Abstract
The worldwide prevalence of tuberculosis is still high and has remained
almost unchanged over the past century as a result of increasing incidence
in countries of the Third World. Twenty per cent of patients with
tuberculosis will develop an extrapulmonary manifestation over time, the
most common site being the genitourinary tract. The patient's history can
lead to the sometimes difficult diagnosis. Radiological imaging helps in
depicting genitourinary tuberculosis. However, the diagnosis of
genitourinary tuberculosis is made on the basis of culture studies and is
supported by polymerase chain reaction. The latter has impressive
sensitivity and specificity, but lacks the ability to determine biological
activity. The combination of three or four anti-tuberculosis drugs over a
course of 6 to 9 months remains the treatment of choice. Drug resistance
is increasing and necessitates tight therapy control. Tuberculosis of the
male seminal duct may be an important cause of male infertility as a
result of multiple epididymidal scarring. In these cases testicular sperm
extraction is the method of choice for sperm retrieval. The outcome of
sperm retrieval followed by intracytoplasmatic sperm injection is not
affected. [References: 17]
2458. Moore SL. Rafii M. Imaging of musculoskeletal and spinal tuberculosis. [Review] [49 refs] Radiologic Clinics of North America. 39(2):329-42, 2001 Mar.
Abstract
The diagnosis of tuberculosis of the musculoskeletal system is difficult
for many reasons. As Walker states, to diagnose tuberculosis one must
consider the possibility. The uncommonness of osteoarticular MTb results
in clinician inexperience, which leads to overlooking the diagnosis.
Subtle early manifestations may elude detection. Negative skin tests and
normal chest films do not exclude the consideration of tuberculosis. The
most conclusive means of reaching the diagnosis (biopsy and culture)
necessitate invasive procedures that are not always definitive, and may
require repeated attempts. Management and surgical decisions, however,
rely on prompt diagnosis; diagnostic delay has prognostic implications and
results in significant morbidity. Musculoskeletal tuberculosis produces no
pathognomonic imaging signs, and in advanced stages mimics other disease
processes. Despite these difficulties, the diagnostician's goal is to
catch the disease as early as possible, because antibiotic treatment can
lead to resolution and obviate more radical management. The radiologist
must be aware of the groups at greatest risk, and typical and atypical
presentations at imaging. The eventual eradication of MTb is conceivable,
although not presently within our grasp. Maintaining reasonable suspicion
and developing cognizance of the patterns of presentation allow the
radiologist to diagnose efficiently the patient who presents with
osteoarticular tuberculosis. [References: 49]
2459. Munk ME. Arend SM. Brock I. Ottenhoff TH. Andersen P. Use of ESAT-6 and CFP-10 antigens for diagnosis of extrapulmonary tuberculosis. Journal of Infectious Diseases. 183(1):175-6, 2001 Jan 1.
2461. Qureshi RN. Samad S. Hamid R. Lakha SF. Female genital tuberculosis revisted. JPMA - Journal of the Pakistan Medical Association. 51(1):16-8, 2001 Jan.
Abstract
OBJECTIVE: To assess the clinical presentation of genital tuberculosis and
to study various modes of diagnosis and treatment. SETTING: The Aga Khan
University Hospital (AKUH), Karachi. METHOD: A retrospective case review
of all index female cases of genital tuberculosis, admitted to AKUH over
twelve years of period. RESULT: A total of 40 cases of genital
tuberculosis were reported during this time period. Majority of cases were
between 25-45 years. The commonest presenting symptoms were infertility
(42.5%) and abdominal pain (42%). Others included fever, ascites,
irregular vaginal bleeding, oligomenorrhea, chest pain and pain in the
flanks. Main mode of treatment was antituberculous drug therapy for
duration of nine months. Only 3 patients had successful pregnancies.
CONCLUSION: Genital tuberculosis should be excluded when managing
infertility in females.
2462. Raut VS. Mahashur AA. Sheth SS. The Mantoux test in the diagnosis of genital tuberculosis in women. International Journal of Gynaecology & Obstetrics. 72(2):165-9, 2001 Feb.
Abstract
OBJECTIVE: To analyze the usefulness of the Mantoux test in the diagnosis
of genital tuberculosis in women of childbearing age. METHOD: In this
report, the investigators studied the ability of a tuberculosis (TB)
Mantoux test to diagnose pelvic tuberculosis. A positive TB Mantoux test
was clearly defined. The positive control group was of 100 women treated
for TB (study group C). The negative control group was of 100 postpartum
women (study group B). The study group was 100 infertile women undergoing
laparoscopy, in some of whom the diagnosis of TB was made (study group A).
RESULT: The Mantoux test had a sensitivity of only 55% and a specificity
of 80% in women with laparoscopically diagnosed tuberculosis. Pelvic focal
reaction was absent in all groups including infertile women with a
positive Mantoux test. CONCLUSION: Mantoux test has limited utility in
diagnosing active genital tuberculosis during the childbearing age.
However, in infertile women with positive a Mantoux test, laparoscopy may
be advocated early.
2463. Research Committee of the British Thoracic Society. First randomised trial of treatments for pulmonary disease caused by M avium intracellulare, M malmoense, and M xenopi in HIV negative patients: rifampicin, ethambutol and isoniazid versus rifampicin and ethambutol. [see comments]. Thorax. 56(3):167-72, 2001 Mar.
Abstract
BACKGROUND: The treatment of pulmonary disease caused by opportunist
mycobacteria is controversial. It is uncertain whether in vitro
sensitivity testing predicts clinical response in the way it does for
Mycobacterium tuberculosis. The literature suggests that the combination
of rifampicin (R) and ethambutol (E) is important whereas isoniazid (H)
may not be, but to date there have been no published reports of randomised
controlled trials in the treatment of these conditions. The British
Thoracic Society has conducted the first such trial, a randomised study of
two regimens in HIV negative patients with pulmonary disease caused by M
avium intracellulare (MAC), M malmoense, and M xenopi. METHODS: When two
positive cultures were confirmed by the Mycobacterium Reference
Laboratories for England, Wales and Scotland, the coordinating physician
invited the patient's physician to enrol the patient. Patients were also
recruited from Scandinavia. Randomisation to 2 years of treatment with RE
or REH was performed from lists held in the coordinator's office.
Clinical, bacteriological, and radiological progress was monitored at set
intervals up to 5 years. RESULTS: From October 1987 to December 1992, 141
physicians entered 223 patients (106 with M malmoense, 75 with MAC, 42
with M xenopi). At entry the RE and REH groups were comparable over a
range of demographic and clinical features. For each species there was no
significant difference between RE and REH in the number of deaths, but
when the three species were combined there were fewer deaths from the
mycobacterial disease with RE (1% v 8%, p=0.018, odds ratio 0.10, exact
95% CI 0.00 to 0.76). For M malmoense the failure of treatment/relapse
rates did not differ appreciably between the regimens, but for MAC there
were fewer failures of treatment/relapses with REH (16% v 41%, p=0.033)
With M xenopi there was a non-significant trend in the same direction (5%
v 18%, p=0.41) and when all three species were combined there was a
significant difference in favour of REH (11% v 22%, p=0.033). There was no
correlation between failure of treatment/relapse and in vitro resistance.
M xenopi was associated with the greatest mortality (57% at 5 years), MAC
was the most difficult to eradicate, and M malmoense had the most
favourable outlook (42% known to be alive and cured at 5 years).
CONCLUSIONS: The results of susceptibility tests performed by the modal
resistance method do not correlate with the patient's response to
chemotherapy. RE and REH are tolerated better than previous regimens
containing second or third line anti-mycobacterial drugs. Treatment of M
malmoense with RE for 2 years is preferable to REH. The addition of H
reduces the failure of treatment/relapse rates for MAC and has a tendency
to do so also for M xenopi, but there is a suggestion that REH is
associated with higher death rates overall. Better regimens are required.
2464. Richter B. Fradis M. Kohler G. Ridder GJ. Epiglottic tuberculosis: differential diagnosis and treatment. Case report and review of the literature. [Review] [32 refs] Annals of Otology, Rhinology & Laryngology. 110(2):197-201, 2001 Feb.
Abstract
A case of a 40-year-old man with tuberculous involvement of the epiglottis
suffering from unsuspected pulmonary tuberculosis is described. The
laryngeal lesions were primarily considered to be highly suspicious for a
neoplastic process rather than an infectious one. After diagnosis, the
patient was treated according a standard protocol and followed up for a
period of 2 years. He is still free of disease. The clinical presentation,
diagnosis, pathological findings, and therapy of the condition are
described. The differential diagnosis and management of epiglottic
tuberculosis are reviewed and discussed. Even though these cases are rare,
otorhinolaryngologists should keep in mind the possibility of tuberculosis
in the differential diagnosis of laryngeal tumors, as the incidence of
tuberculosis in developed countries is steadily increasing. [References:
32]
2465. Sakai J. Matsuzawa S. Usui M. Yano I. New diagnostic approach for ocular tuberculosis by ELISA using the cord factor as antigen. [see comments]. British Journal of Ophthalmology. 85(2):130-3, 2001 Feb.
Abstract
BACKGROUND/AIMS: Diagnosis of ocular tuberculosis is difficult,
particularly the retinal vasculitis type, because most cases occur without
concurrent active pulmonary tuberculosis. Recently, it has been reported
that detection of antibodies against purified cord factor
(trehalose-6,6'-dimycolate, TDM), the best studied, most antigenic, and
most abundant cell wall component of tubercule bacilli, is very useful for
rapid serodiagnosis of pulmonary tuberculosis. In this study, an attempt
was made to evaluate whether the detection of anticord factor antibody is
also useful for diagnosis of ocular tuberculosis and the necessity of
antituberculous therapy for tuberculous retinochoroiditis was discussed.
METHODS: Cases consisted of 15 patients with uveitis and retinal
vasculitis, nine patients with presumed ocular tuberculosis, three
patients with sarcoidosis, and three patients with Behcet's disease. IgG
antibodies against purified cord factor prepared from Mycobacterium
tuberculosis H37Rv were detected by enzyme linked immunosorbent assay.
RESULTS: All cases of clinically presumed ocular tuberculosis were
positive, whereas all of the cases of sarcoidosis or Behcet's disease were
negative for anticord factor antibodies. When the anticord factor antibody
titres were compared on the basis of the presence or absence of previous
antituberculosis chemotherapy, the mean anticord factor antibody titre of
the untreated group showed a tendency to be higher than in the treated
group, but not significantly (p=0.07). CONCLUSIONS: The detection of
anticord factor antibody may be useful to support the diagnosis of ocular
tuberculosis. Additionally, a positive result for anticord factor antibody
may indicate that tubercule bacilli are present in some organ(s) of the
patient even in the absence of active systemic disease.
2466. Soler R. Rodriguez E. Remuinan C. Santos M. MRI of musculoskeletal extraspinal tuberculosis. Journal of Computer Assisted Tomography. 25(2):177-83, 2001 Mar-Apr.
Abstract
PURPOSE: The aim of this study was to describe the MR findings in
extraspinal musculoskeletal tuberculosis (EMT). METHOD: A retrospective
review was conducted of the MR findings of 18 patients with
microbiologically and/or pathologically proven EMT. All MR studies were
performed using T1-and T2-weighted spin echo sequences. T1-weighted spin
echo sequences after Gd-DTPA injection were obtained for 12 patients. The
MR images were evaluated for abnormalities in joints, bones, and soft
tissues, and the results were grouped by anatomic localization, frequency
distribution of structures affected, and morphologic patterns of
involvement. RESULTS: Isolated soft tissue tuberculosis was found in 10
(55.5%) patients and involvement of more than one structure in 8 (44.4%).
Pyomyositis (n = 6) and arthritis with involvement of adjacent soft
tissues (n = 7) were the most common forms of presentation. One patient
presented with isolated fascial superficial tissue involvement in one leg.
Isolated pyomyositis involving one (n = 3) or two (n = 3) muscles was
homogeneous in six cases and showed intermediate (n = 6), low (n = 2), or
high (n = 1) signal intensity on T1-weighted images and a high and very
hyperintense signal on T2-weighted images. The tenosynovitis synovial
fluid was homogeneous (n = 1) or heterogeneous with multiple tiny
hypointense nodules (n = 1) on T2-weighted images. The subdeltoid bursitis
fluid was characterized by homogeneous low signal intensity with a
hyperintense rim (n = 2) on T1-weighted images and homogeneous (n = 1) or
heterogeneous hyperintense signals with areas of low signal intensity (n =
1) on T2-weighted images. In tuberculous arthritis, the synovial joint
fluid (n = 7) showed heterogeneous (n = 4) or homogeneous (n = 3) low
signal intensity on T1-weighted images and high or very high signal
intensity on T2-weighted images. Where involved, the adjacent muscle(s) (n
= 8) were usually hypointense on T1-weighted images and very hyperintense
on T2-weighted images. Associated cellulitis was found in arthritis with
involvement of neighboring soft tissues (n = 5), pyomyositis (n = 2), and
tenosynovitis (n = 1). The images obtained after Gd-DTPA showed peripheral
(n = 10) or heterogeneous (n = 1) enhancement or no enhancement (n = 1).
CONCLUSION: The MR findings for EMT are variable. Although diagnosis is
dependent largely on prior presumption and clinical context, MRI provides
valuable guidelines in defining the extent of the lesions to select the
appropriate treatment and for follow-up of abnormalities.
2467. Souilamas R. Riquet M. Barthes FP. Chehab A. Capuani A. Faure E. Surgical treatment of active and sequelar forms of pulmonary tuberculosis. Annals of Thoracic Surgery. 71(2):443-7, 2001 Feb.
Abstract
BACKGROUND: The incidence of tuberculosis has risen since 1990, and in
some countries, the resistant forms are becoming more and more frequent.
Surgical treatment is once again needed to manage these problems. The
purpose of this study was to analyze the indications and results of
resection, which we performed for pulmonary tuberculosis. METHODS: From
1980 to 1997, 477 patients were operated on for thoracic or intrathoracic
tuberculosis in Laennec Hospital, Paris (259 suffered lung diseases).
There were 165 women and 94 men, aged 25 to 86 years (mean 46 years), from
Europe (n = 148), North Africa (n = 65), Subsaharian Africa (n = 34), Asia
(n = 7), and the West Indies (n = 5). This population was reviewed
concerning the lung tuberculosis (sequelae or active lesions), the
indications of lung resection, the type of resections performed, and the
results at 1, 6, and 12 months. RESULTS: Active lesions were present in 97
cases and sequelae in 162. Surgery was performed for a therapeutic purpose
in 104 patients with sequelae, and in 10 patients with active tuberculosis
(pneumonectomy, n = 19; pleuropneumonectomy, n = 19; lobectomy, n = 54;
and segmentectomy, n = 22). Surgery was performed for a diagnostic purpose
in 54 patients with sequelae, and in 87 patients with active lesions
(lobectomy, n = 32; segmentectomy, n = 19; wedge resection, n = 94, of
which 11 performed by video-assisted thoracoscopy since 1991). One patient
died after pleuropneumonectomy. We observed 25 complications: empyema, n =
7; hemothorax, n = 2; prolonged air leaks, n = 14; and pneumopathy, n = 2.
All patients with active lesions subsequently were given antitubercular
drugs. Follow-up was 100% at 1 month, 57% (n = 92) and 77% (n = 75) at 6
months for patients with sequelae and for patients with active lesions,
respectively. All were asymptomatic with a normal chest roentgenogram. The
number of operations for active lesions is increasing over the years,
while it is decreasing for sequelar lesions. CONCLUSIONS: In our
department, surgery is being performed more frequently to make a diagnosis
in cases of active tuberculosis, and to treat complicated lesions in case
of sequelae. Lung resection for active tuberculosis evolving under
treatment or for drug resistance was rare. However, our study confirms the
good results commonly obtained by surgery and supports the idea that
surgery may help eradicate tuberculosis when social and economic
circumstances render its medical management difficult or hazardous.
2468. Toossi Z. Mayanja-Kizza H. Hirsch CS. Edmonds KL. Spahlinger T. Hom DL. Aung H. Mugyenyi P. Ellner JJ. Whalen CW. Impact of tuberculosis (TB) on HIV-1 activity in dually infected patients. Clinical & Experimental Immunology. 123(2):233-8, 2001 Feb.
Abstract
Active TB in HIV-1-infected subjects is associated with increased
HIV-1-related immunodeficiency and mortality. We assessed plasma viral
load in HIV-1-infected patients with pulmonary TB (HIV/TB) and non-TB
symptomatic HIV-1-infected patients (HIV). HIV-1 load was higher in HIV/TB
compared with HIV at higher CD4 counts (> 500/microl) (P < 0.01), but not
at lower CD4 counts (< 500/microl). We also evaluated the status of HIV-1
gene expression in peripheral blood mononuclear cells (PBMC) and serum
from HIV/TB and CD4-matched healthy HIV-infected patients (HIV/C) by
reverse transcriptase-polymerase chain reaction over a range of CD4 (>
900/microl to < 200/microl). HIV-1 RNA in serum and PBMC correlated to one
another, and both were markedly higher in HIV/TB compared with HIV/C with
higher CD4 counts. Also, during a longitudinal study of anti-tuberculous
chemoprophylaxis in HIV-1-infected patients, 10 subjects who developed TB
had serologies before, at the time, and after the diagnosis of TB. These
HIV/TB patients had an increase in viral load (average 2.5-fold) at the
time of diagnosis of TB (P < 0.05). Overall, these data indicate that the
transcriptional activity of HIV-1 is enhanced in HIV-1-infected patients
with active TB, especially during early HIV-1 disease. As TB often is an
early HIV-1 opportunistic infection, it may particularly favour early
viral replication and dissemination, and therefore contribute to
progression of HIV-1 disease.
2469. Toyoshima M. Chida K. Suda T. Imokawa S. Nakamura H. Wegener's granulomatosis responding to antituberculous drugs. Chest. 119(2):643-5, 2001 Feb.
Abstract
We present a case of Wegener's granulomatosis (WG) that responded to
antituberculous drugs. A 44-year-old woman with multiple nodules on chest
radiograph received a diagnosis of pulmonary tuberculosis because
open-lung biopsy specimens showed caseous granulomas. Her chest shadows
underwent repeated resolution after the start of antituberculous
treatment, and relapse after the cessation of the drugs. Antineutrophil
cytoplasmic antibody was positive (14 enzyme-linked immunosorbent assay
units), and the second lung biopsy specimens showed necrotizing granulomas
and vasculitis without pathogenic organisms. Thus, the patient received a
diagnosis of WG and was successfully treated with
trimethoprim/sulfamethoxazole 10 years after her initial evaluation.
Antituberculous drugs were effective in this case of WG.
2471. van den Berge M. Tinga CJ. Bieger R. A 73-year-old man with chronic lymphocytic leukaemia and a haemorrhagic pleural effusion. Annals of Hematology. 80(3):183-6, 2001 Mar.
Abstract
A 73-year-old man presented with haemorrhagic pleural effusion, having been diagnosed with chronic lymphocytic leukaemia (CLL). The differential diagnosis of haemorrhagic pleural effusion is considered. Tuberculosis and pleural infiltration of CLL are considered most likely. Pleural biopsy confirms the diagnosis of pleural involvement of CLL in this case. Although pleural involvement of CLL has been reported several times the presentation of pleural effusion as the first symptom of CLL has not previously been described.
2472. Van Soolingen D. Molecular epidemiology of tuberculosis and other mycobacterial infections: main methodologies and achievements. [Review] [314 refs] Journal of Internal Medicine. 249(1):1-26, 2001 Jan.
Abstract
In the last decade, DNA fingerprint techniques have become available to
study the interperson transmission of tuberculosis and other mycobacterial
infections. These methods have facilitated epidemiological studies at a
population level. In addition, the species identification of rarely
encountered mycobacteria has improved significantly. This article
describes the state of the art of the main molecular typing methods for
Mycobacterium tuberculosis complex and non-M. tuberculosis complex
(atypical) mycobacteria. Important new insights that have been gained
through molecular techniques into epidemiological aspects and diagnosis of
mycobacterial diseases are highlighted. [References: 314]
2473. Walley JD. Khan MA. Newell JN. Khan MH. Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan. Lancet. 357(9257):664-9, 2001 Mar 3.
Abstract
BACKGROUND: DOTS is the control strategy for tuberculosis promoted by WHO.
Pakistan is currently developing its National Tuberculosis Programme, and
requires guidance on types of direct observation of treatment appropriate
for the local conditions. We did a randomised trial to assess the
effectiveness of different packages for tuberculosis treatment under
operational conditions in Pakistan. METHODS: We enrolled 497 adults with
new sputum-positive tuberculosis. 170 were assigned DOTS with direct
observation of treatment by health workers; 165 were assigned DOTS with
direct observation of treatment by family members; and 162 were assigned
self-administered treatment. The trial was done at three sites that
provide tuberculosis services strengthened according to WHO guidelines for
the purposes of the research, with a standard daily short-course drugs
regimen (2 months of isoniazid, rifampicin, pyrazinamide, and ethambutol,
followed by 6 months of isoniazid and ethambutol). The main outcome
measures were cure, and cure or treatment completion. Analysis was by
intention to treat. FINDINGS: Within the strengthened tuberculosis
services, the health-worker DOTS, family-member DOTS, and
self-administered treatment strategies gave very similar outcomes, with
cure rates of 64%, 55%, and 62%, respectively, and cure or
treatment-completed rates of 67%, 62%, and 65%, respectively.
INTERPRETATION: None of the three strategies tested was shown to be
superior to the others, and direct observation of treatment did not give
any additional improvement in cure rates. The effectiveness of direct
observation of treatment remains unclear, and further operational research
is needed.
2474. Woods GL. Bergmann JS. Williams-Bouyer N. Clinical Evaluation of the Gen-Probe amplified mycobacterium tuberculosis direct test for rapid detection of Mycobacterium tuberculosis in select nonrespiratory specimens. Journal of Clinical Microbiology. 39(2):747-9, 2001 Feb.
Abstract
The performance of the Amplified Mycobacterium Tuberculosis Direct Test
(MTD; Gen-Probe, Inc., San Diego, Calif.) for rapid diagnosis of
extrapulmonary tuberculosis was evaluated by testing 178 nonrespiratory
specimens from 158 patients. Criteria for specimen inclusion were (i) a
positive smear for acid-fast bacilli (n = 54) and (ii) the source if the
smear was negative (tissue biopsies and aspirates and abscess material
were tested; n = 124). Results were compared to those of mycobacterial
culture; clinical history was reviewed when MTD and culture results
disagreed. Forty-eight specimens (27.0%) were positive for mycobacteria,
including 23 Mycobacterium tuberculosis complex specimens; of which 21
were smear positive. Twenty-five specimens were MTD positive; 20 of these
grew M. tuberculosis complex. All of the five MTD-positive, M.
tuberculosis complex culture-negative specimens were considered truly
positive, based on review of the medical record. Of the three
MTD-negative, M. tuberculosis complex culture-positive specimens, two
contained inhibitory substances; one of the two was smear positive.
Excluding the latter specimen from analysis, after chart review, the
sensitivity, specificity, and positive and negative predictive values of
the MTD were 92.6, 100, 100, and 98.7%, respectively, by specimen and
89.5, 100, 100, and 98.6% by patient. Given the few smear-negative samples
from patients with extrapulmonary tuberculosis in our study, additional
similar studies that include more smear-negative, M. tuberculosis complex
culture-positive specimens to confirm our data are desirable.
2475. Woods GL. Molecular techniques in mycobacterial detection. [Review] [35 refs] Archives of Pathology & Laboratory Medicine. 125(1):122-6, 2001 Jan.
Abstract
OBJECTIVE: To assess the clinical utility of the commercial nucleic acid
amplification (NAA) tests (ie, Amplified Mycobacterium Tuberculosis Direct
Test, Gen-Probe, Inc and AMPLICOR Mycobacterium tuberculosis Test, Roche
Molecular Systems, Inc) for direct detection of Mycobacterium tuberculosis
complex. DATA SOURCES: Review of the English-language literature.
CONCLUSIONS: The performance of both NAA tests is excellent (sensitivity,
> or = 95%; specificity, 100%) when testing respiratory specimens that are
smear-positive for acid-fast bacilli (AFB). Only the Gen-Probe assay is
approved for testing respiratory specimens regardless of the AFB smear
result. Data from 3 studies showed that the sensitivity of the
Mycobacterium Tuberculosis Direct Test in smear-negative patients ranged
from 83% to 85%, and that the specificity was 99%. Both NAA tests have
been used to test nonrespiratory specimens; in some studies, the
performance was comparable to the performance obtained for respiratory
specimens, whereas in others, it was lower. The NAA tests also appear to
be reliable tools for rapid detection of M tuberculosis complex in
positive broth cultures of all specimen types (except blood). The impact
of the NAA tests on patient outcome varies based on the result of the AFB
smear. In smear-positive patients, public health and hospital
infection-control resources are predominantly affected. The potential for
influencing patient outcome is much greater when the AFB smear is
negative. In smear-negative patients, the NAA test could provide more
rapid diagnosis of tuberculosis and subsequent initiation of therapy;
eliminate the need for invasive diagnostic procedures, which are both
costly and pose an added risk to the patient; and allow earlier discharge
of hospitalized patients. Prospective studies concerning the
cost-effectiveness of the NAA tests are needed. [References: 35]
2924. Ameixa
C. Friedland JS. Down-regulation of interleukin-8 secretion
from Mycobacterium tuberculosis-infected monocytes by interleukin-4 and -10 but
not by interleukin-13. Infection &
Immunity. 69(4):2470-6, 2001 Apr.
Abstract
Interleukin-8
(IL-8), a CXC chemokine, has a central role in leukocyte recruitment to areas
of granuloma formation in tuberculosis. In the present studies, we investigated
the effect of the T(H)2-derived cytokines IL-4, IL-10, and IL-13 on
Mycobacterium tuberculosis-induced IL-8 secretion from purified human
monocytes. Our results demonstrate that IL-4 and IL-10 have a down-regulatory
effect on IL-8 secretion and that this effect is dose dependent. IL-10 has a
greater effect than IL-4 on secretion, and autologous IL-10 secreted from M.
tuberculosis-infected monocytes also down-regulates IL-8 secretion. The
down-regulatory effect is partly a result of reduced IL-8 mRNA accumulation
analyzed by reverse transcription-PCR. When combined, 1 microM IL-4 and IL-10
had an additive effect in decreasing IL-8 secretion and transcription; there
was no synergy of action. IL-13 did not have any significant effect on IL-8
gene expression or secretion. The inhibitory effect of IL-10 but not of IL-4 is
associated with decreased nuclear binding of the key activating transcription
factor NF-kappaB. We show for the first time that M. tuberculosis causes
up-regulation of nuclear binding of Oct-1 detected by electromobility gel shift
assay. However, neither AP-1 nor Oct-1 nuclear binding was altered by IL-4 or
IL-10. In summary, this study demonstrates that type 2 responses have an
important role in the regulation of M. tuberculosis-induced IL-8 expression but
that the mechanisms by which the different cytokines act are distinct.
2925. Andersen
P. TB vaccines: progress and problems.
[Review] [77 refs] Trends in
Immunology. 22(3):160-8, 2001 Mar.
Abstract
Tuberculosis
(TB) is the biggest killer worldwide of any infectious disease, a situation
worsened by the advent of the HIV epidemic and the emergence of multi-drug
resistant strains of Mycobacterium tuberculosis. The existing vaccine,
Mycobacterium bovis bacille Calmette-Guerin (BCG), has proven inefficient in
several recent field trials. There is currently intense research using
cutting-edge vaccine technology to combat this ancient disease. However, it is
necessary to understand why BCG has failed before we can rationally develop the
next generation of vaccines. Several hypotheses that might explain the failure
of BCG and the strategies designed to address these shortcomings are discussed.
[References: 77]
2926. Arend
SM. van Soolingen D. Ottenhoff TH. van Dissel JT. Repeatedly
negative tuberculin skin tests followed by active tuberculosis in an
immunocompetent individual. Netherlands Journal of Medicine. 58(2):76-81, 2001 Feb.
Abstract
We describe a
woman who was repeatedly tuberculin (PPD) skin test negative after exposure to
smear-positive tuberculosis (TB), but developed active TB with a positive skin
test 7 years later. Molecular epidemiologic evidence is presented that the
infection was contracted 7 years previously from the original source case. PPD
skin testing is subject to many technical and biological variables and this report
underscores that this tool can fail to detect latent TB infection in some
cases. The causes of false-negative and false-positive PPD skin test results
are reviewed.
2927. Barnes PF. Diagnosing latent tuberculosis infection:
the 100-year upgrade. [letter; comment].
American Journal of Respiratory & Critical Care Medicine. 163(4):807-8, 2001 Mar.
2928.
Burton BJ. Assi
A. Pavesio C. Vogt-Koyanagi-Harada syndrome presenting as a severe systemic
illness. Eye. 15(Pt 2):228-9, 2001 Apr.
2929.
Caksen H. Uzum
K. Tutus A. Pott's disease. Clinical
Nuclear Medicine. 26(1):57, 2001 Jan.
Abstract
A 15-year-old boy was hospitalized with a 1-month history lumbago and fever. His family history was noncontributory for tuberculosis, and the findings of the physical examination were normal. The sedimentation rate and C-reactive protein level were 55 mm/hour and 48 mg/l, respectively. The result of a purified protein derivative test was 11 x 10 mm. Results of other tests, including rheumatologic studies, serum agglutination for brucellosis, chest radiography, abdominal ultrasonography, and myelography, were normal. The bone biopsy revealed chronic active inflammation. Mycobacterium tuberculosis was not cultured from clinical specimens. However, the patient's symptoms improved after antituberculosis drugs were begun.
2930. Chen
JS. Chang YL. Cheng HL. Chang YC. Lee YC. Video-assisted thoracoscopic surgery
for the diagnosis of patients with hilar and mediastinal lymphadenopathy. Journal of the Formosan Medical
Association. 100(3):213-6, 2001 Mar.
Abstract
In areas where
tuberculosis (TB) is rare, cases of hilar and mediastinal lymphadenopathy are
often attributed to the diagnosis of sarcoidosis or a malignant process.
However, these manifestations have been only sparsely reported in countries
with high rates of TB. The role of simultaneous lung biopsy in the differential
diagnosis of these patients using a thoracoscopic approach is also
undetermined. In this prospective study, 15 adult patients with hilar and
mediastinal lymphadenopathy were evaluated using video-assisted thoracoscopy
during the period from May 1995 through September 1999. Biopsy of the hilar and
mediastinal lymph nodes was undertaken in all 15 patients, and a wedge biopsy
of the lungs was performed whenever frozen section of the nodes disclosed
granulomatous inflammation. The final diagnoses included sarcoidosis (10
patients), TB (2), metastatic small cell carcinoma (2), and reactive lymphoid
hyperplasia (1). No morbidity or mortality was associated with the operation.
In patients with sarcoidosis and TB, most of the lymph node biopsy specimens
disclosed extensive hyaline fibrosis. Lung biopsy specimens presented small
non-necrotizing granulomas with multinucleated giant cells even in the absence
of demonstrable parenchymal lesions. In the two patients with TB,
identification of acid-fast bacilli and growth of Mycobacterium tuberculosis
occurred only in lung specimens and not in specimens from lymph nodes.
Video-assisted thoracoscopic surgery is a safe, simple, and effective procedure
for the diagnosis of patients with hilar and mediastinal lymphadenopathy. Our
results suggest that for a better differentiation between TB and sarcoidosis,
an additional lung biopsy could be undertaken to provide specimens for microscopic
examination and culture.
2931. Chitale
S. Ehrt S. Kawamura I. Fujimura
T. Shimono N. Anand N. Lu S. Cohen-Gould L. Riley LW. Recombinant Mycobacterium tuberculosis protein
associated with mammalian cell entry.
Cellular Microbiology.
3(4):247-54, 2001 Apr.
Abstract
The ability to
gain entry and resist the antimicrobial intracellular environment of mammalian
cells is an essential virulence property of Mycobacterium tuberculosis. A
purified recombinant protein expressed by a 1362 bp locus (mce1) in the M.
tuberculosis genome promoted uptake into HeLa cells of polystyrene latex
microspheres coated with the protein. N-terminus deletion constructs of Mce1
identified a domain located between amino acid positions 106 and 163 that was
needed for this cell uptake activity. Mce1 contained hydrophobic stretches at
the N-terminus predictive of a signal sequence, and colloidal gold
immunoelectron microscopy indicated that the corresponding native protein is
expressed on the surface of the M. tuberculosis organism. The complete M.
tuberculosis genome sequence revealed that it contained four homologues of mce
(mce1, mce2, mce3, mce4) and that they were all located within operons composed
of genes arranged similarly at different locations in the chromosome. Recombinant
Mce2, which had the highest level of identity (67%) to Mce1, was unable to
promote the association of microspheres with HeLa cells. Although the exact
function of Mce1 is still unknown, it appears to serve as an effector molecule
expressed on the surface of M. tuberculosis that is capable of eliciting plasma
membrane perturbations in non-phagocytic mammalian cells.
2932. D'Agata
EM. Wise S. Stewart A. Lefkowitz LB
Jr. Nosocomial transmission of Mycobacterium tuberculosis from an
extrapulmonary site. Infection Control & Hospital Epidemiology. 22(1):10-2, 2001 Jan.
Abstract
OBJECTIVE: To
assess the extent of nosocomial transmission and risk factors associated with
tuberculin skin test (TST) conversions among healthcare workers (HCWs) exposed
to a patient with genitourinary Mycobacterium tuberculosis. DESIGN:
Retrospective cohort study of exposed HCWs. SETTING: A 275-bed community
hospital in Middle Tennessee. PARTICIPANTS: A total of 128 exposed HCWs and the
index patient, who required drainage of a prostatic abscess and bilateral
orchiectomy and expired after a 27-day hospitalization. Disseminated
tuberculosis was diagnosed at autopsy. METHODS: Contact tracing was performed
on exposed HCWs. Logistic regression was used to identify independent risk
factors associated with TST conversion. RESULTS: A total of 128 HCWs were
exposed to the index patient. There was no evidence of active pulmonary
tuberculosis throughout the patient's hospitalization; TST conversions occurred
only among HCWs who were exposed to the patient during or after his surgical
procedures. A total of 12 (13%) of 95 exposed HCWs who were previously
nonreactive had newly positive TST: 6 of 28 nurses, 3 of 3 autopsy personnel, 2
of 17 respiratory therapists, and 1 of 12 surgical staff. By logistic
regression, irrigation or packing of the surgical site was the only independent
risk factor associated with TST conversion among nurses (odds ratio, 9; 95%
confidence interval, 1.2-67; P=.03). CONCLUSION: Manipulation of infected
tissues of the genitourinary tract can result in nosocomial transmission of
tuberculosis.
2933.
Das K. Madan
K. Sukija P. Gondyal R. Pradhan
G. Kumar S. Kar P. Tubercular abscess
of the liver. Journal of the
Association of Physicians of India. 49:588,
2001 May.
2934. Dick T. Dormant
tubercle bacilli: the key to more effective TB chemotherapy?. Journal of
Antimicrobial Chemotherapy.
47(1):117-8, 2001 Jan.
2935. Ellner JJ. The human immune response to Mycobacterium
Tuberculosis infection and disease. [Review] [18 refs] Kekkaku.
76(2):83-91, 2001 Feb.
2936. Equi
A. Redington A. Rosenthal M. Taylor GM. Jaswon M. Bush A. Pulmonary artery occlusion from
tuberculous lymphadenopathy in a child. Pediatric Pulmonology. 31(4):311-3, 2001 Apr.
Abstract
Occlusion of
the pulmonary artery is a rare complication of mediastinal tuberculosis. We
report on a 10-year-old girl who presented with a tuberculous pericardial
effusion in whom subsequent imaging showed a totally occluded right pulmonary
artery from tuberculous lymphadenopathy. Diagnosis was confirmed by polymerase
chain reaction from a lymph node biopsy. Failure of medical therapy
necessitated surgical reconstruction of her right pulmonary artery.
Postoperatively she has normal perfusion of the right lung and normal lung
function. Copyright 2001 Wiley-Liss, Inc.
2937. Frenz MB. A transient
pleural effusion. Postgraduate Medical Journal. 77(906):273; discussion 283-4, 2001 Apr.
2938. Ghobrial
MW. Albornoz MA. Immune
thrombocytopenia: a rare presenting manifestation of tuberculosis. [Review] [16
refs] American Journal of Hematology.
67(2):139-43, 2001 Jun.
Abstract
We report the case of a 49 year-old male who presented with immune thrombocytopenia (ITP)-induced epistaxis and generalized purpura. During the same hospitalization the patient was also found to have clinical, microbiological, histological, and roentgenographic evidence of disseminated mycobacterial tuberculosis (TB). The hematological and infectious abnormalities, which did not respond to high-dose intravenous corticosteroids and immune globulin (IVIg), resolved after anti-tuberculous treatment. Herein we review the characteristics of this rarely documented association. Copyright 2001 Wiley-Liss, Inc. [References: 16]
2939. Gillespie
SH. Antibiotic resistance in the
absence of selective pressure. [Review] [50 refs] International Journal of Antimicrobial Agents. 17(3):171-6, 2001 Mar.
Abstract
Antibiotic
resistance poses a serious threat to modern medical practice making treatment
more difficult and is associated with increased mortality among patients
infected with resistant organisms. There is clear evidence that acquisition of
resistance is associated with a decrease in the fitness of the organisms at
least in the short term. Evidence from in vitro experiments indicates that
bacteria have the ability to adapt to this deficit and recover fitness on
serial passage. More recent results show that identical organisms isolated from
patients in outbreaks have an initial deficit but that adaptation occurs in
vivo. Strategies directed towards controlling resistance must move beyond
wishful thinking that supposes that these organisms will disappear merely with
control of prescribing. In some cases, resistance will not disappear because
there is no evolutionary disadvantage in being resistant once adaptation has
taken place. It is important, therefore, that we direct our efforts towards
preventing primary resistance emerging and in limiting the spread of resistant
strains. Ultimately, we must look again to new drug discovery to improve our
therapeutic armoury. [References: 50]
2940. Grosser
M. Dittert DD. Luther T.
Re: Molecular detection of M. tuberculosis DNA in tuberculosis and
sarcoidosis. Diagnostic Molecular
Pathology. 10(1):66-8, 2001 Mar.
2941. Hanscheid T. Salgado MJ.
Lito LM. Valadas E.
Löwenstein-Jensen media no longer necessary: too strong a
statement?. American Journal of Clinical Pathology. 115(4):615-7, 2001 Apr.
2942. Harboe M. 25th
Kellersberger memorial lecture, 2000. The contribution of immunology to
tuberculosis control. Ethiopian Medical Journal. 39(1):75-82, 2001 Jan.
2943. Harries
AD. Kwanjana JH. Hargreaves NJ. Van Gorkom J. Salaniponi
FM. Resources for controlling tuberculosis in Malawi. Bulletin of the World
Health Organization. 79(4):329-36,
2001.
Abstract
OBJECTIVE: To
document resources for controlling tuberculosis (TB) in Malawi. METHODS: We
performed a countrywide study of all 43 hospitals (3 central, 22 district and
18 mission) which register and treat patients with TB. To collect data for 1998
on the TB-related workload, diagnostic facilities, programme staff and
treatment facilities, we used laboratory, radiographic and TB registers,
conducted interviews and visited hospital facilities. FINDINGS: The data show
that in 1998, 88,257 TB suspects/patients contributed approximately 230,000
sputum specimens for smear microscopy, 55,667 chest X-rays were performed and
23,285 patients were registered for TB treatment. There were 86 trained
laboratory personnel, 44 radiographers and 83 TB programme staff. Of these,
about 40% had periods of illness during 1998. Approximately 20% of the
microscopes and X-ray machines were broken. Some 16% of the hospital beds were
designated for TB patients in special wards, but even so, the occupancy of beds
in TB wards exceeded 100%. Although stocks of anti-TB drugs were good, there
was a shortage of full-time TB ward nurses and 50% of district hospitals
conducted no TB ward rounds. In general, there was a shortage of facilities for
managing associated HIV-related disease; central hospitals, in particular, were
underresourced. CONCLUSION: Malawi needs better planning to utilize its
manpower and should consider cross-training hospital personnel. The equipment
needs regular maintenance, and more attention should be paid to HIV-related
illness. The policies of decentralizing resources to the periphery and
increasing diagnostic and case-holding resources for central hospitals should
be continued.
2944. Hawkes ND. Thomas GA. Unexplained weight loss and a
palpable abdominal mass in a middle aged woman. Abdominal tuberculosis.
Postgraduate Medical Journal.
77(907):341, 348-9, 2001 May.
2945. Herr H. Kim JU.
Kang GH. Moon KC. Koh JK. Kaposi's sarcoma occurring during
short-term dialysis: report of two cases.
Journal of Korean Medical Science.
16(1):130-4, 2001 Feb.
Abstract
Kaposi's
sarcoma (KS) appears to develop in association with kidney transplantation, but
unlikely with dialysis. We report two cases of classic KS that occurred in
patients receiving short-term (less than 3 yr) dialysis. They have been suffering
from chronic renal failure due to tuberculosis and diabetes mellitus,
respectively. Several to multiple, reddened-violaceous patches, plaques and
nodules were found on the hand and the lower extremities. Laboratory studies
showed no evidence suggesting immunosuppressed state and there was no history
of taking immunosuppressive agents. The biopsies of the two cases revealed
proliferation of spindle-shaped cells focally arranged in bundles and multiple
dilated vascular spaces outlined by an attenuated endothelium with
intravascular and extravasated erythrocytes. The specimens expressed positivity
with CD34 antigen. Human herpesvirus 8 (Kaposi's sarcoma-associated
herpesvirus) was detected in one case by polymerase chain reaction method.
2946. Hertz
C. Kiertscher S. Godowski P.
Bouis D. Norgard M. Roth M.
Modlin R. Microbial lipopeptides stimulate dendritic cell maturation via
Toll-like receptor 2. Journal of Immunology.
166(4):2444-50, 2001 Feb 15.
Abstract
The ability of
dendritic cells (DC) to initiate immune responses in naive T cells is dependent
upon a maturation process that allows the cells to develop their potent
Ag-presenting capacity. Although immature DC can be derived in vitro by
treatment of peripheral blood monocytes with GM-CSF and IL-4, additional
signals such as those provided by TNF-alpha, CD40 ligand, or LPS are required
for complete maturation and maximum APC function. Because we recently found
that microbial lipoproteins can activate monocytes and DC through Toll-like
receptor (TLR) 2, we also investigated whether lipoproteins can drive DC
maturation. Immature DC were cultured with or without lipoproteins and were
monitored for expression of cell surface markers indicative of maturation.
Stimulation with lipopeptides increased expression of CD83, MHC class II, CD80,
CD86, CD54, and CD58, and decreased CD32 expression and endocytic activity;
these lipopeptide-matured DC also displayed enhanced T cell stimulatory
capacity in MLR, as measured by T cell proliferation and IFN-gamma secretion.
The lipid moiety of the lipopeptide was found to be essential for induction of
maturation. Preincubation of maturing DC with an anti-TLR2 blocking Ab before
addition of lipopeptide blocked the phenotypic and functional changes
associated with DC maturation. These results demonstrate that lipopeptides can
stimulate DC maturation via TLR2, providing a mechanism by which products of
bacteria can participate in the initiation of an immune response.
2947. Hoal-van Helden
EG. Hon D. Lewis LA. Beyers N. van Helden PD. Mycobacterial growth in human
macrophages: variation according to donor, inoculum and bacterial strain. Cell
Biology International. 25(1):71-81,
2001.
Abstract
The
microbicidal capacity of the macrophage is frequently evaded by mycobacteria,
leading to tuberculosis (TB). We investigated a number of parameters affecting
the rate of growth of mycobacteria in human monocyte-derived macrophages (MDM).
The results show a great deal of variation in the growth of both Mycobacterium
bovis BCG and M. tuberculosis H37Rv, using a large number of human macrophage
donors, (132 and 40, respectively), but no correlation was seen with the TB
status of the MDM donor. Clumping of the mycobacteria resulted in more vigorous
growth in MDM, suggesting that inoculum size could affect disease progression.
The growth rates of 17 clinical isolates of M. tuberculosis were measured in
macrophages derived from three donors and no consistent or marked differences
between isolates were observed over the 5-day period of growth measurement.
However, all 17 clinical strains grew consistently faster than H37Rv in the
same experiments. Copyright 2001 Academic Press.
2948. Hsu
KF. Hung CF. Cheng WF. He L. Slater LA.
Ling M. Wu TC. Enhancement of
suicidal DNA vaccine potency by linking Mycobacterium tuberculosis heat shock
protein 70 to an antigen. Gene Therapy.
8(5):376-83, 2001 Mar.
Abstract
Naked DNA vaccines represent an attractive approach for generating antigen-specific immunity because of their stability and simplicity of delivery. There are particular concerns with DNA vaccines however, such as potential integration into the host genome, cell transformation, and limited potency. The usage of DNA-based alphaviral RNA replicons (suicidal DNA vectors) may alleviate the concerns of integration or transformation since suicidal DNA vectors eventually cause lysis of transfected cells. To improve further the potency of suicidal DNA vaccines, we evaluated the effect of linking Mycobacterium tuberculosis heat shock protein 70 (Hsp70) to human papillomavirus type 16 (HPV-16) E7 as a model antigen on antigen-specific immunity generated by a DNA-based Semliki Forest virus (SFV) RNA vector, pSCA1. Our results indicated that this suicidal DNA vaccine containing E7/Hsp70 fusion genes generated significantly higher E7-specific T cell-mediated immune responses than vaccines containing the wild-type E7 gene in vaccinated mice. More importantly, this fusion converted a less effective vaccine into one with significant potency against established E7-expressing metastatic tumors. The antitumor effect was predominantly CD8-dependent. These results indicate that linkage of Hsp70 to the antigen may greatly enhance the potency of suicidal DNA vaccines.
2949. Jaramillo E. The impact of media-based health education
on tuberculosis diagnosis in Cali, Colombia.
Health Policy & Planning.
16(1):68-73, 2001 Mar.
Abstract
Tuberculosis (TB) is one of the most
worrying infectious diseases facing less developed countries. Diagnosis and
treatment of those who are transmitting Mycobacterium tuberculosis is
considered a very effective control strategy. Within this strategy the priority
is to achieve high cure rates before attempting to increase case finding.
However, there is a dearth of research on how to increase case finding and
diagnostic coverage in those settings where high cure rates are being achieved.
This paper presents an evaluation of the impact on case finding of a mass media
health education campaign for TB control in Cali, Colombia. The campaign aimed
at increasing case finding and reducing levels of prejudice against people with
TB. The impact assessment shows that the campaign produced an increase of 64%
in the number of direct smears processed by the laboratories and an increase of
52% in the number of new cases of positive pulmonary TB, with respect to the
previous period. Unfortunately, the effects of the campaign were short-lived.
These findings have at least two important implications. First, passive case
finding is likely to be an insufficient strategy to reach the operational
targets of diagnostic coverage. Secondly, providing basic information about the
earliest symptoms of TB and the procedures for diagnosis can increase
diagnostic coverage, and thus strengthen the effect on infection risk of control
programmes with high cure rates. Further research is required to identify other
strategies that could, first, increase diagnostic coverage and, secondly, make
the intervention effects sustainable.
2950. Julian
E. Cama M. Martinez P. Luquin M. An
ELISA for five glycolipids from the cell wall of Mycobacterium tuberculosis:
Tween 20 interference in the assay.
Journal of Immunological Methods.
251(1-2):21-30, 2001 May 1.
Abstract
Mycobacterium
tuberculosis cell wall contains antigenic glycolipids: phenol-glycolipid (PGL),
diacyltrehalose (DAT), triacyltrehalose (TAT), cord-factor (CF), and
sulpholipid-I (SL-I). In the last decade, the usefulness of these antigens for
the serodiagnosis of tuberculosis has been evaluated mainly using enzyme-linked
immunosorbent assays (ELISA). Currently, there are no conclusive results about
the utility of these glycolipidic antigens, because the results obtained by
different groups are discrepant. In order to explain these discrepancies, we
have investigated the methodological variations in the ELISAs used previously.
Specifically, we have studied the following: the coating solvent, the optimum
amount of glycolipid coated per well, the blocking agent, and the use of
detergent (Tween 20) in the washing buffer. The most significant finding was
that Tween 20 detaches PGL, DAT, TAT and SL-I from microtitre wells. However,
Tween 20 does not remove CF from the wells. In addition, we have found that the
best solvent for coating is n-hexane, that the optimum antigen coating
concentration is 1000 ng/well, and that BSA and gelatin are equally effective
blocking agents. We can therefore conclude that the use of Tween 20 as a
detergent, and the lower antigen coating concentrations (100-200 ng/well), may
well explain some of the discrepancies in previous studies.
2951. Kato-Maeda
M. Bifani PJ. Kreiswirth BN. Small PM.
The nature and consequence of genetic variability within Mycobacterium
tuberculosis. [Review] [37 refs]
Journal of Clinical Investigation.
107(5):533-7, 2001 Mar.
2952.
Kato-Maeda M. Rhee JT. Gingeras TR. Salamon H. Drenkow
J. Smittipat N. Small PM. Comparing genomes within the
species Mycobacterium tuberculosis. Genome Research. 11(4):547-54, 2001 Apr.
Abstract
The study of
genetic variability within natural populations of pathogens may provide insight
into their evolution and pathogenesis. We used a Mycobacterium tuberculosis
high-density oligonucleotide microarray to detect small-scale genomic deletions
among 19 clinically and epidemiologically well-characterized isolates of M.
tuberculosis. The pattern of deletions detected was identical within
mycobacterial clones but differed between different clones, suggesting that
this is a suitable genotyping system for epidemiologic studies. An analysis of
genomic deletions among an extant population of pathogenic bacteria provided a
novel perspective on genomic organization and evolution. Deletions are likely
to contain ancestral genes whose functions are no longer essential for the
organism's survival, whereas genes that are never deleted constitute the
minimal mycobacterial genome. As the amount of genomic deletion increased, the
likelihood that the bacteria will cause pulmonary cavitation decreased,
suggesting that the accumulation of mutations tends to diminish their
pathogenicity. Array-based comparative genomics is a promising approach to
exploring molecular epidemiology, microbial evolution, and pathogenesis.
2953. Khattab T. Fryer C.
Felimban S. Yousef A. Noufal M.
Unusual complication of sickle cell crisis. Journal of Pediatric Hematology/Oncology. 23(1):71-2, 2001 Jan.
2954.
Koss LG. Benign and malignant mesothelial
proliferations. American Journal of
Surgical Pathology. 25(4):548-9, 2001
Apr.
2955. Krishnan A. Patkar D.
Patankar T. Shah J. Prasad S.
Bunting T. Castillo M. Mukherji SK. Craniovertebral junction tuberculosis: a review of 29 cases. Journal of Computer Assisted
Tomography. 25(2):171-6, 2001 Mar-Apr.
Abstract
PURPOSE: The purpose of this work was to
describe the various imaging findings in craniovertebral tuberculosis and the
importance of imaging in treatment in these patients. METHOD: A retrospective
review of MR and CT scans in 29 patients with craniovertebral tuberculosis was
performed. The images were reviewed, paying special attention to both bony
(skull base, atlas, and axis) and soft tissue involvement in addition to
atlantoaxial dislocation, lateral subluxation of the dens, and compression of
the spinal cord. RESULTS: Suboccipital pain with neck stiffness was the most
common presenting symptom in our patients. The skull was involved in 19 of the
29 cases, clivus involvement was seen in 11 patients, and occipital condyle
involvement was present in 14 patients. Detailed analysis of atlas involvement
due to tuberculosis showed the lateral masses to be predominantly affected. The
dens was involved in 18 cases (62%). Soft tissue masses in the prevertebral
area were seen in 22 patients, paravertebral in 27 patients, and epidural
involvement in 25 patients was identified. Atlantoaxial displacement was
present in seven cases, lateral mass-dens subluxation in five, and superior
subluxation of the dens through the foramen magnum compressing the medulla was
seen in two cases. Spinal cord compression with intrinsic cord changes was
noted in 12 cases. All patients received multidrug antituberculous therapy for
1 year. The presence of neurologic deficit and instability of the atlantoaxial
complex was pivotal in further management in these patients. CONCLUSION: A high
degree of clinical suspicion is necessary when confronted with patients with
neck stiffness and tenderness over the upper cervical vertebrae. MRI in these
patients provides a sensitive method for the diagnosis of craniovertebral
tuberculosis.
2956. Lam KY. Lo CY. A critical examination of adrenal
tuberculosis and a 28-year autopsy experience of active tuberculosis. Clinical
Endocrinology. 54(5):633-9, 2001 May.
Abstract
OBJECTIVE: Tuberculosis is potentially fatal
and adrenal gland involvement is uncommonly reported. The aims of the current
study were to define the characteristics of tuberculosis in hospitalized
patients and to analyse the features of adrenal tuberculosis. DESIGN:
Retrospective analysis of autopsies and adrenalectomies. PATIENTS: 13,762
patients (13492 at autopsies and 270 at adrenalectomy). MEASUREMENTS: The
presence of active tuberculosis, the predisposing factors, the pathological
features and organs of involvement were examined. RESULTS: Active tuberculosis
was present in 871 patients (6.5% of all 13492 autopsies). It was first
diagnosed in 70% of these patients during autopsy. Cancers and a history of
recent major operations were the 2 main concomitant factors in the patients
with tuberculosis. Extra-pulmonary tuberculosis was seen in 261 patients (30%).
The five most common extra-pulmonary sites of tuberculosis were the liver,
spleen, kidney, bone and adrenal gland. Adrenal tuberculosis was seen in 52 of
the 871 patients (6%) with active tuberculosis at autopsy and in 3 patients at
adrenalectomy. The adrenal gland was the only organ involved by active
tuberculosis in 14 of these 55 patients (25%; 35 men, 20 women). Tuberculosis
was evident on macroscopic examination of the adrenal glands in 46% of the
patients. On histological examination, caseous necrosis and granulomatous
inflammation with Langhan's giant cells were seen in 71% and 40% of patients,
respectively. Seven patients presented with signs and symptoms of Addison's
disease due to bilateral adrenal involvement. Langhan's giant cells were
frequently seen in histological sections and bilateral enlargement of the
adrenal glands was often noted. Fine needle aspiration cytology was not useful
for diagnosing adrenal tuberculosis. CONCLUSION: Unexpected and extra-pulmonary
tuberculosis such as adrenal tuberculosis has been a common problem. A high
index of suspicion, correct diagnosis and proper treatment are essential for
the management of tuberculosis.
2957. Lan
SH. Chang WN. Lu CH. Lui CC. Chang HW. Cerebral infarction in chronic
meningitis: a comparison of tuberculous meningitis and cryptococcal meningitis.
QJM. 94(5):247-53, 2001 May.
Abstract
Twenty-eight
patients with cerebral infarction secondary to chronic meningitis were
retrospectively identified at our institution over a period of 5 years. They
accounted for 47% (17/36) of tuberculous meningitis (TBM) and 32% (11/34) of
cryptococcal meningitis cases. Single infarctions were found in 15 patients and
multiple infarctions in 13. The distribution of single infarctions was: basal
ganglia 7; internal capsule 3; thalamus 1; cerebellum 1; and cortical infarct
3. Therapeutic outcomes at 3 months were determined using a modified Barthel
INDEX: At follow-up of 3 months or more, 10 had good outcomes while the other
18 had poor outcomes. The 18 with poor outcomes included six who died, and 12
who had severe neurological sequelae. TBM and cryptococcal meningitis shared
similar clinical features, both being frequently associated with other
neurological complications, including hydrocephalus, cranial nerve palsy, and
seizures in our patients. However, extracranial involvement, such as spinal and
pulmonary involvement, was more commonly found in TBM patients. Cerebral
infarction can occur in both the acute stage and later stages of treatment.
Mortality and morbidity are high, and early diagnosis and appropriate
antimicrobial treatment are essential. If hydrocephalus is demonstrated, early
ventricular decompression is needed to prevent further cerebral ischaemia.
2958. Lauzardo
M. Lee P. Duncan H. Hale Y.
Transmission of Mycobacterium tuberculosis to a funeral director during routine
embalming. Chest. 119(2):640-2, 2001
Feb.
Abstract
Several studies
have shown that funeral directors have an increased risk of tuberculosis (TB).
Although there is indirect evidence of transmission of TB from cadavers to
mortuary workers, there is only one recently documented case in the literature.
We report here another case of occupationally acquired TB in a funeral
director, which was confirmed by conventional epidemiology and genotyping. This
case illustrates the risk of TB transmission to mortuary workers from routine
embalming of deceased TB patients with active disease.
2959.
Lee Y. Huang W. Huang J.
Wang J. Yu C. Jiaan B.
Huang J. Efficacy of chemotherapy for prostatic tuberculosis-a clinical
and histologic follow-up study. Urology. 57(5):872-7, 2001 May.
Abstract
OBJECTIVES: To characterize the clinical
features of prostatic tuberculosis and to evaluate the short and long-term
results of antituberculous chemotherapy. METHODS: Eighteen patients (mean age
66.7 +/- 10.2 years) with prostatic tuberculosis were included in this study.
The median pretreatment prostate-specific antigen (PSA) level was 2.7 ng/mL
(range 0.3 to 31). The PSA level was greater than 4.0 ng/mL in 6 patients
(33.3%). Eight patients (44.4%) received a triple-drug regimen of rifampin,
ethambutol, and isoniazid for more than 6 months. The mean duration of
chemotherapy was 7.6 months (range 6 to 12). Of the 8 patients, 3 underwent
chemotherapy longer because of concurrent tuberculosis of other organs. Follow-up
studies included digital rectal examination, total PSA determination, and
transrectal prostate biopsy. RESULTS: Ten patients were eligible for regular
follow-up. All the patients were symptom free during follow-up. The median
length of follow-up was 3.4 years (range 1 to 9). The average number of
follow-up transrectal prostate biopsies was 2.4 (range 2 to 3). The follow-up
histologic findings showed nodular hyperplasia in 7 patients and chronic
inflammatory cell infiltration in 3 patients. No acid-fast bacillus was found
in any follow-up specimen. Similarly, subsequent transrectal biopsy showed no
relapse after a median length of 3.4 years of follow-up. Of the 6 patients with
elevated PSA levels, the post-treatment PSA returned to normal in 3 patients.
CONCLUSIONS: Our results suggest that a triple-drug regimen of 6 months'
duration can successfully control prostatic tuberculosis. Histologic follow-up
is a good method for monitoring the efficacy of treatment. Transrectal prostate
biopsy is an important tool for the diagnosis and follow-up of prostatic
tuberculosis.
2960. Marques
MA. Ant nio VL. Sarno EN.
Brennan PJ. Pessolani MC.
Binding of alpha2-laminins by pathogenic and non-pathogenic mycobacteria and
adherence to Schwann cells. Journal of
Medical Microbiology. 50(1):23-8, 2001
Jan.
Abstract
The ability of
Mycobacterium leprae to specifically bind alpha2-laminins of Schwann cells has
been described recently as being an important property of the leprosy bacillus,
which could explain the neural tropism of M. leprae. Therefore, the extent of
the expression of alpha2-laminin-binding properties among mycobacteria was
investigated. In an ELISA-based assay, all three species of Mycobacterium
tested (M. tuberculosis, M. chelonae and M. smegmatis) expressed
laminin-binding capacity, suggesting that the ability to bind alpha2-laminins
is conserved within the genus Mycobacterium. This report also demonstrated that
not only M. leprae but all the mycobacterial species tested readily interacted
with the ST88-14 cells, a human schwannoma cell line, and that the addition of
soluble alpha2-laminins significantly increased their adherence to these cells.
These results failed to demonstrate the presence in M. leprae of a unique
system based on alpha2-laminins for adherence to Schwann cells.
2961. Marsman WA. Jie C.
van Meyel JJ. Dysphagia caused
by esophageal tuberculosis. Netherlands Journal of Medicine. 58(2):82-5, 2001 Feb.
Abstract
This report
describes two patients with dysphagia who appeared to have esophageal
tuberculosis. One patient had a fistula draining into a mediastinal mass. Both
patients responded promptly to treatment with tuberculostatics. Surgery was not
required. Esophageal tuberculosis is a rare entity.
2962. McMurray DN. Disease model: pulmonary tuberculosis.
[Review] [10 refs] Trends Mol Med.
7(3):135-7, 2001 Mar.
Abstract
In spite of a
massive effort to apply the tools currently available for tuberculosis (TB)
control, both in this country and abroad, it is clear that complicating factors
[for example, HIV co-infection, drug resistance, lack of patient compliance
with chemotherapy, variable efficacy of Bacille Calmette-Guerin (BCG) vaccine]
will prevent disease control unless new drugs, vaccines and diagnostic tests
are developed (1). The publication of the complete genome sequence of
Mycobacterium tuberculosis in 1998 (2) has facilitated a directed search for
virulence genes, new drug targets, and vaccine antigens. This research effort
has been made possible by the availability of highly biologically relevant
animal models of pulmonary TB ((3)). [References: 10]
2963. Meddows-Taylor
S. Pendle S. Tiemessen CT. Altered
expression of CD88 and associated impairment of complement 5a-induced
neutrophil responses in human immunodeficiency virus type 1-infected patients
with and without pulmonary tuberculosis.
Journal of Infectious Diseases.
183(4):662-5, 2001 Feb 15.
Abstract
The effect of
infection with human immunodeficiency virus type 1 (HIV patient group),
infection with Mycobacterium tuberculosis (TB patient group), and coinfection
with both of these organisms (HIV/TB patient group) on the expression of CD88
on polymorphonuclear leukocytes (PMNL) was determined by using a
receptor-specific monoclonal antibody and flow cytometry. A significant reduction
in the fluorescence intensity of CD88 on PMNL was observed in the HIV and
HIV/TB groups, compared with both the healthy donor (HD) and TB groups.
Furthermore, when degranulation of PMNL was induced by ligation of CD88 by
complement 5a (C5a), a large proportion of patients in the HIV and the HIV/TB
groups was found to have reciprocal degranulation responses. Patients in the 2
HIV groups also were found to have significantly reduced C5a-induced
chemotactic responses and significantly elevated peripheral levels of C5a des
Arg, compared with the HD and TB groups. These differences may contribute to
the increased susceptibility of HIV-1-infected individuals to secondary
microbial infections.
2964. Melzer
M. Warley A. Chrystie I. Milburn
H. O'Sullivan D. Anonymous testing for
HIV in tuberculosis cases and contacts.
Lancet. 357(9259):888, 2001 Mar
17.
2965.
O'Brien RJ. Nunn PP.The need for
new drugs against tuberculosis. Obstacles, opportunities, and next steps.
American Journal of Respiratory & Critical Care Medicine. 163(5):1055-8, 2001 Apr.
2966.
Olobo JO. Geletu
M. Demissie A. Eguale T.
Hiwot K. Aderaye G. Britton S. Circulating TNF-alpha, TGF-beta,
and IL-10 in tuberculosis patients and healthy contacts. Scandinavian Journal of Immunology. 53(1):85-91, 2001 Jan.
Abstract
Levels of
tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and
interleukin (IL)-10 in plasma of pulmonary tuberculosis (TB) patients and
healthy contacts and plasma and pleural fluid of patients with tuberculous pleuritis
were examined by enzyme immunoassay. Plasma TNF-alpha and IL-10 were elevated
to significant levels in healthy contacts. High levels of TGF-beta and IL-10
were also detected in plasma from TB patients and healthy contacts. Pleural
fluid contained all three cytokines with the level of IL-10 being highest
followed by TGF-beta and TNF-alpha. Plasma of tuberculous pleuritis patients
also had detectable levels of the three cytokines. Increased levels of
TNF-alpha in plasma of contacts and to some extent pleural fluid of pleuritis
patients, is perhaps to limit the infection, while elevated IL-10 in plasma of
TB patients and contacts and pleural fluid would perhaps modulate excess
proinflammation. Elevated TGF-beta in TB patients suggests its role in the immunopathogenesis.
2967. Orlovic
D. Kularatne R. Ferraz V.
Smego RA Jr. Dual pulmonary
infection with Mycobacterium tuberculosis and Pneumocystis carinii in patients
infected with human immunodeficiency virus. Clinical Infectious Diseases. 32(2):289-94, 2001 Jan 15.
Abstract
During a
22-month period, we identified 39 patients with human immunodeficiency virus
(HIV) infection (mean CD4(+) count, 90 cells/mm(3)) who were hospitalized with
pneumonia and who had sputum and/or other specimens that tested concurrently
positive for both Mycobacterium tuberculosis and Pneumocystis carinii. The most
common chest x-ray abnormality was a reticulonodular pattern or bilateral
infiltrates (n=26). Serum lactate dehydrogenase levels were elevated in 17
(85%) of 20 of patients tested (mean value, 2208 U/L). Mean O(2) saturation and
PO(2) were 89% and 64 mm Hg, respectively. A majority (24 patients [62%])
received both antituberculous and anti-PCP therapy (17 with steroids), and 22
improved. All ten patients who received no treatment for PCP improved and were
discharged from the hospital, whereas 4 (80%) of the 5 persons who received no
antituberculous treatment had a poor outcome (P<.001; OR=43). Patients with
HIV or acquired immune deficiency syndrome may present with both TB and PCP; of
the 2, TB seems to account for the most severe features of disease.
2968. Otieno
MW. Remick SC. Whalen C. Adult Burkitt's lymphoma in
patients with and without human immunodeficiency virus infection in Kenya.
International Journal of Cancer. 92(5):687-91,
2001 Jun 1.
Abstract
Prior to the acquired immunodeficiency syndrome (AIDS) epidemic, one or two cases of adult Burkitt's lymphoma (BL) were seen annually at the Kenyatta National Hospital, the national referral medical center in Nairobi, Kenya. To investigate the influence of human immunodeficiency virus (HIV) infection in adult BL in Kenya, we conducted a national prevalence survey of all patients 16 years of age and older with BL. A systematic review of medical records of all patients diagnosed with BL between 1992 and 1996 was performed. The diagnosis of BL was based and confirmed on review of pathological material from time of original diagnosis. HIV serology was confirmed by enzyme-linked immunosorbent assay (ELISA). Twenty-nine adult patients with BL were identified during the 5-year study period. Of these patients, 17 (59%) were males, 12 (41%) were females, and the median age was 26 years. Nineteen patients (66%) with BL were HIV-seropositive. The proportion of men was similar in HIV-seropositive and -seronegative patients (58% vs 60%). HIV-seropositive BL patients were significantly older than seronegatives (median 35 vs 19.5 years, p < 0.001). HIV-seropositive patients uniformly presented with constitutional or B symptoms and advanced BL accompanied by diffuse lymph node involvement, whereas the clinical presentation of HIV-seronegative patients during this time period was reminiscent of the "typical" endemic pattern of disease with complete sparing of peripheral lymph nodes. The overall survival of HIV-seropositive cases was significantly worse than that of the HIV-seronegative cases; median survival in the HIV-seropositive patients was 15 weeks. There is an approximate 3-fold increase in the incidence of adult BL during the time period of this study, which is attributable to the AIDS epidemic. In this setting, patients often present with disseminated disease, diffuse peripheral lymphadenopathy and fever, the latter two of which heretofore have been commonly associated with non-lymphoproliferative disorders such as Mycobacterium tuberculosis and sexually transmitted diseases in Kenya. These observations warrant inclusion of AIDS-related BL in the differential diagnosis of the adult patient with unexplained fever and lymphadenopathy in Kenya. The corollary is that HIV infection is virtually excluded in an adult patient without peripheral lymphadenopathy and biopsy-proven BL. Copyright 2001 Wiley-Liss, Inc.
2969. Patnaik
M. Liegmann K. Peter JB.
Rapid detection of smear-negative Mycobacterium tuberculosis by PCR and
sequencing for rifampin resistance with DNA extracted directly from
slides. Journal of Clinical
Microbiology. 39(1):51-2, 2001 Jan.
Abstract
Conventional
methods for identification of Mycobacterium tuberculosis from culture can take
6 weeks. To facilitate the rapid detection of M. tuberculosis and to assess the
risks of drug resistance, we developed a technique of eluting DNA directly from
sputum slides and performing PCR for the detection of M. tuberculosis DNA,
followed by sequencing the rpoB gene to detect rifampin resistance. This entire
process requires only 48 h. Forty-seven sputum specimens submitted for
microscopy for detection of acid-fast bacilli (AFB) and for mycobacterial
culture and susceptibility testing were assessed after elution from the slides
and extraction. M. tuberculosis-specific DNA was amplified in a nested PCR with
previously described primers (primers rpo95-rpo293 and rpo105-rpo273), followed
by analysis on a 4% agarose gel for a 168-bp product. Automated sequencing was
performed, and the sequences were aligned against a database for detection of
anomalies in the rpoB gene (codons 511 to 533) which indicate rifampin
resistance. Of the 47 sputum specimens tested, 51% (24 of 47) were culture
positive (time to positive culture, 2 to 6 weeks). Smears for AFB were positive
for 58% (14 of 24) of the specimens and were negative for 42% (10 of 24) of the
specimens. All 24 culture-positive sputum specimens (14 microscopy-positive and
10 microscopy-negative sputum specimens) were positive by PCR with eluates from
the smears. Forty-nine percent (23 of 47) of the sputum specimens were negative
for M. tuberculosis by smear, culture, and PCR. Of the isolates from the
culture-positive samples, five were rifampin resistant by sequencing; all five
were also rifampin resistant by in vitro susceptibility testing. Of these
rifampin-resistant M. tuberculosis isolates, two were microscopy negative for
AFB. Patients who are negative for AFB and culture positive for M. tuberculosis
can now be identified within a day, allowing institution of therapy and
reducing isolation time and medical costs.
2970. Pene
F. Papo T. Brudy-Gulphe L. Cariou
A. Piette JC. Vinsonneau C. Septic shock and thrombotic microangiopathy due to
Mycobacterium tuberculosis in a nonimmunocompromised patient. Archives of
Internal Medicine. 161(10):1347-8, 2001
May 28.
2971. Price
NM. Farrar J. Tran TT. Nguyen TH. Tran TH.
Friedland JS. Identification of
a matrix-degrading phenotype in human tuberculosis in vitro and in vivo. Journal of Immunology. 166(6):4223-30, 2001 Mar 15.
Abstract
Tuberculous
meningitis is characterized by cerebral tissue destruction. Monocytes, pivotal
in immune responses to Mycobacterium tuberculosis, secrete matrix
metalloproteinase-9 (MMP-9), which facilitates leukocyte migration across the
blood-brain barrier, but may cause cerebral injury. In vitro, human monocytic
(THP-1) cells infected by live, virulent M. tuberculosis secreted MMP-9 in a
dose-dependent manner. At 24 h, MMP-9 concentrations increased 10-fold to 239
+/- 75 ng/ml (p = 0.001 vs controls). MMP-9 mRNA became detectable at 24--48 h.
In contrast, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) gene
expression and secretion were similar to constitutive levels from controls at
24 h and increased just 5-fold by 48 h. In vivo investigation revealed MMP-9
concentration per leukocyte in cerebrospinal fluid (CSF) from tuberculous
meningitis patients (n = 23; median (range), 3.19 (0.19--31.00) ng/ml/cell) to
be higher than that in bacterial (n = 12; 0.23 (0.01--18.37) ng/ml/cell) or
viral meningitis (n = 20; 0.20 (0.04--31.00) ng/ml/cell; p < 0.01). TIMP-1,
which was constitutively secreted into CSF, was not elevated in tuberculous
compared with bacterial meningitis or controls. Thus, a phenotype in which
MMP-9 activity is relatively unrestricted by TIMP-1 developed both in vitro and
in vivo. This is functionally significant, since MMP-9 concentrations per CSF
leukocyte (but not TIMP-1 concentrations) were elevated in fatal tuberculous
meningitis and in patients with signs of cerebral tissue damage
(unconsciousness, confusion, or neurological deficit; p < 0.05). However,
MMP-9 activity was unrelated to the severity of systemic illness. In summary,
M. tuberculosis-infected monocytic cells develop a matrix-degrading phenotype,
which was observed in vivo and relates to clinical signs reflecting cerebral
injury in tuberculous meningitis.
2972. Ray M. Goraya JS.
Basu S. Parmar V. Perinatal
tuberculosis. Indian Journal of Pediatrics.
68(4):343-5, 2001 Apr.
Abstract
Perinatal tuberculosis is insufficiently
understood. Its early diagnosis is essential but often difficult as the initial
manifestations may be delayed. Improved screening of women at risk and
sensitivity of the medical community are necessary. A coherent system of
cooperation between the hospital and community services and between
pediatricians and adult physicians is indispensable to find the index adult
case to break the chain of contagion as well as to offer prophylactic therapy
to the children at risk. We hereby report a baby with perinatal tuberculosis
who was not offered any prophylactic therapy inspite of the mother being
diagnosed to have pulmonary tuberculosis.
2973. Rodriguez
JC. Ruiz M. Climent A. Royo G. In
vitro activity of four fluoroquinolones against Mycobacterium tuberculosis.
International Journal of Antimicrobial Agents.
17(3):229-31, 2001 Mar.
Abstract
The in vitro
activity of ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin against
strains of Mycobacterium tuberculosis was studied. Moxifloxacin and
levofloxacin showed the greatest activity having an MIC(90) of 1 mg/l. The
MIC(90) for ofloxacin was 2 mg/l and for ciprofloxacin 4 mg/l. Further studies
should be made to determine the role played by these compounds in the treatment
of tuberculosis.
2974. Ruhul
A. Suzuki Y. Takatorige T. Tatara
K. Shirakura R. [Usefulness of self ligation mediated
polymerase chain reaction: a rapid method for fingerprinting in molecular
epidemiology of tuberculosis]. Kekkaku. 76(1):9-18, 2001 Jan.
Abstract
Restriction
fragment length polymorphism (RFLP) analysis based on the insertion sequence IS
6110 has been used as one of the powerful tools for epidemiological study of
tuberculosis. However this technique requires more than 1 micro-gram of DNA and
two days for completion. To overcome these inconvenience, we have modified a
PCR-based method, self ligation mediated PCR (SL-PCR) on the molecular
epidemiological study. This method uses a pair of primers whose orientations
are from inside to outside of IS 6110. The DNA fragments flanking IS 6110 are
amplified by the PCR by using the Sau 3A I digested and ligated chromosomal DNA
of Mycobacterium tuberculosis strains. By using this method, M. tuberculosis
strains can be differentiated within 8 hours.
2975. Sahly
HM. Adams GJ. Soini H. Teeter L. Musser JM. Epidemiologic differences between
United States- and foreign-born tuberculosis patients in Houston, Texas.
Journal of Infectious Diseases.
183(3):461-468, 2001 Feb 1.
Abstract
The proportion
of foreign-born tuberculosis patients in the United States is increasing. To
analyze the epidemiology of tuberculosis in foreign-born people,
culture-positive patients with tuberculosis in Houston, Texas, were interviewed
from October 1995 through September 1998, and their isolates were molecularly
characterized. Of the 1131 patients included in the study, 795 (70.3%) were US
born and 336 (29.7%) were foreign born. The decrease in tuberculosis case rate
among US-born people was 3.5 times that of foreign-born people. Significantly
more US-born than foreign-born patients belonged to strain clusters (71.3% vs.
29.5%; P<.001). Risk factors associated with strain clustering were as
follows: black ethnicity, low income, and homelessness in US-born patients and
homelessness in foreign-born patients. Isolates from foreign-born patients were
more likely to be resistant to >/=1 drug (15.4% vs. 8.4%; P=.001) and to be
multidrug resistant (2.4% vs. 0.7%; P=.027) than isolates from US-born patients.
These observations warrant increased emphasis on this distinct subpopulation of
tuberculosis patients.
2976. Sarlak AY. Gundes H.
Gundes S. Alp M. Primary sternal
tuberculosis: a rare unhealed case treated by resection and local rotational
flap. Thoracic & Cardiovascular
Surgeon. 49(1):58-9, 2001 Feb.
Abstract
Primary sternal tuberculosis is very rare.
Only few cases have been reported in the English-language literature. We
present a case of primary sternal tuberculosis that had intractable drainage
for 18 months. Diagnosis was confirmed with biopsy, and there were no other
tuberculous foci. No improvement was achieved in the status of the wound
despite 4 months of chemotherapy. We applied the principles as in bacterial
osteomyelitis of sternum, resected the wound and covered it with a pectoralis
major musculocutaneous rotational flap. The wound healed, and there was no
recurrence 24 months after surgery.
2977. Schwebach
JR. Jacobs WR Jr. Casadevall A. Sterilization of Mycobacterium tuberculosis Erdman samples by
antimicrobial fixation in a biosafety level 3 laboratory. Journal of Clinical Microbiology. 39(2):769-71, 2001 Feb.
Abstract
Incomplete
sterilization of Mycobacterium tuberculosis Erdman cultures followed 1 h of
incubation in low concentrations of glutaraldehyde (0.5 and 1.0%) or azide. In
contrast, 2.5% glutaraldehyde, paraformaldehyde (2 or 4%), Vesphine IIse or 5%
formalin sterilized these samples after 1 h. These results suggest caution in
removing fixed M. tuberculosis samples from biosafety level 3.
2978. Sessler R. Konyar H.
Hasche G. Olbricht CJ. The
haemodialysis patient with night sweats, ascites, and increased CA 125.
Nephrology, Dialysis, Transplantation.
16(1):175-7, 2001 Jan.
2979. Sigurdarson ST. Field FJ.
Schlesinger LS. Esophageal tuberculosis:
a rare but not to be forgotten entity.
American Journal of Medicine.
110(5):415-6, 2001 Apr 1.
2980. Sirgel F. Venter A.
Mitchison D. Sources of variation in studies of the early bactericidal
activity of antituberculosis drugs.
Journal of Antimicrobial Chemotherapy.
47(2):177-82, 2001 Feb.
Abstract
The early bactericidal activity (EBA) of
antituberculosis drugs can be measured as the daily fall in cfu counts of
Mycobacterium tuberculosis in sputum, usually during the first 2 days of
treatment. In studies of low potency drugs, it is necessary to compare the
treated group of patients with a group who receives no chemotherapy (Nil
group). Over the past 10 years, five Nil groups of between five and 13 patients
have been studied in Cape Town and two Nil groups in Hong Kong. There was a
suggestion of an increase in variation within the Cape Town groups, as shown by
a regression of variance size against study date (P = 0.06), which could not be
attributed to technical causes. It might indicate increasing host resistance in
the Western Cape epidemic of tuberculosis. Since the weighted mean of all Nil
groups at Cape Town was 0.00036, very close to zero, it would seem safe to test
means of treated groups against zero thus increasing precision and avoiding ethical
problems in delaying treatment. In contrast to Nil groups, the variation found
in five groups who received 300 mg isoniazid daily (INH 300) was uniform and
homoscedastic, possibly because the additional variation was caused mainly by
individual differences in plasma isoniazid concentrations and patient body
weights. The mean EBA in the INH 300 series was 0.575 with 95% confidence
limits of 0.515 and 0.636.
2981.
Soini H. Musser JM. Molecular
diagnosis of mycobacteria. [Review] [37 refs] Clinical Chemistry. 47(5):809-14, 2001 May.
Abstract
Tuberculosis is
one of the leading infectious diseases in the world and is responsible for more
than 2 million deaths and 8 million new cases annually. Because of the slow
growth rate of the causative agent Mycobacterium tuberculosis, isolation,
identification, and drug susceptibility testing of this organism and other
clinically important mycobacteria can take several weeks or longer. During the
past several years, many molecular methods have been developed for direct
detection, species identification, and drug susceptibility testing of
mycobacteria. These methods can potentially reduce the diagnostic time from
weeks to days. Currently, two nucleic acid amplification methods, the Enhanced
Mycobacterium tuberculosis Direct Test (Gen-Probe) and the Amplicor
Mycobacterium tuberculosis Test (Roche Diagnostic Systems), have been approved
by the Food and Drug Administration for direct detection of M. tuberculosis
from clinical specimens. PCR-based sequencing has become commonly used to
identify many mycobacterial species. DNA probes have been widely used for
species determination of the most commonly encountered mycobacteria.
High-density oligonucleotide arrays (DNA microarrays) also have been applied to
simultaneous species identification and detection of mutations that confer
rifampin resistance in mycobacteria. [References: 37]
2982. Soini H. Pan X.
Teeter L. Musser JM. Graviss EA. Transmission dynamics and
molecular characterization of Mycobacterium tuberculosis isolates with low copy
numbers of IS6110. Journal of Clinical
Microbiology. 39(1):217-21, 2001 Jan.
Abstract
Population-based analysis of Mycobacterium tuberculosis transmission in
Houston, Tex., over 5 years identified 377 patients infected with an isolate
containing one to four copies of IS6110. The isolates were analyzed by
spoligotyping and assigned to one of three major genetic groups based on
nucleotide polymorphisms in codons katG 463 and gyrA 95. Prospectively obtained
patient interviews were reviewed to assess epidemiologic links between
apparently clustered patients. A total of 13 groups of isolates with the same
IS6110 profile were identified, representing 326 of the 377 patients (86.5%;
range 2 to 113 patients). In contrast, 28 groups of isolates containing 334
patients (88.6%) had the same spoligotype (range, 2 to 143 patients).
Combination of IS6110 profile and spoligotype data identified 31 clusters with
300 patients (79.6%; range, 2 to 82 patients). All 377 isolates belonged to
major genetic group 1 (77 patients) or genetic group 2 (300 patients); no major
genetic group 3 isolates were identified. Among the 228 patients interviewed,
33 patients (14.5%) were directly linked to another patient in the same
cluster. Possible epidemiologic links were also found among 11 patients.
Moreover, many clusters consisted of individuals with the same ethnicity. In
conclusion, we confirmed that IS6110 profiling and spoligotyping together
provide enhanced molecular discrimination of M. tuberculosis isolates with low
copy numbers of IS6110. Identification of epidemiologic links among some of the
patients verified that the combination of these two methods reliably indexes
tuberculosis transmission.
2983. Solomon A. Silicosis
and tuberculosis: Part 2--a radiographic presentation of nodular tuberculosis
and silicosis. International Journal of Occupational & Environmental
Health. 7(1):54-7, 2001 Jan-Mar.
Abstract
Indolent
nodular pulmonary tuberculosis (TB) in workers exposed to silica dust may go
undetected clinically and radiographically, especially in the absence of
identification of tubercle bacilli in sputum. Illustrative cases demonstrating
the radiographic manifestations of coexistent pulmonary silicosis and the
indolent form of nodular TB are presented. Alterations in the usual chronologic
progress, a rapid advance in nodular profusion or size outside the expected
time frame, and distinct pattern alterations are features indicating the
presence of TB associated with silicosis.
2984. Southwick KL. Hoffmann K.
Ferree K. Matthews J. Salfinger M. Cluster of tuberculosis cases in North Carolina: possible
association with atomizer reuse. American Journal of Infection Control. 29(1):1-6, 2001 Feb.
Abstract
BACKGROUND:
Three patients with identical strains of M tuberculosis (TB) underwent
bronchoscopy on the same day at hospital A. METHODS: We reviewed each patient's
clinical history, hospital A's infection control practices for bronchoscopies,
and specimen and isolate handling at each of 3 laboratories involved. We
searched for possible community links between patients. Restriction fragment
length polymorphism was performed on TB isolates. RESULTS: The first patient
who underwent bronchoscopy had biopsy-confirmed granulomatous pulmonary TB. A
sputum sample collected from the third patient 6 weeks after the bronchoscopy
produced an isolate with an identical restriction fragment length polymorphism
pattern to isolates collected during the bronchoscopies. No evidence existed
for community transmission or laboratory contamination; the only common link
was the bronchoscopy. Different bronchoscopes were used for each patient.
Hospital ventilation and wall-suctioning were functioning well. Respiratory
technicians reported sometimes reusing the nozzles of atomizers on more than
one patient. A possible mechanism for transmission was contamination from the
first patient of the atomizer if it was used to apply lidocaine to the pharynx
and nasal passages of other patients. CONCLUSIONS: A contaminated atomizer may
have caused TB transmission during bronchoscopy. Hospital A changed to
single-use atomizers after this investigation.
2985. Spindola
de Miranda S. Kritski A. Filliol I.
Mabilat C. Panteix G. Drouet E. Mutations in the rpoB gene of
rifampicin-resistant Mycobacterium tuberculosis strains isolated in Brazil and
France. Memorias do Instituto Oswaldo Cruz.
96(2):247-50, 2001 Feb.
Abstract
We evaluated
the mutations in a 193bp of the rpoB gene by automated sequencing of rifampicin
(RMP)-resistant and susceptible Mycobacterium tuberculosis strains isolated
from Brazil (25 strains) and France (37 strains). In RMP-resistant strains,
mutations were identified in 100% (16/16) from France and 89% (16/18) from
Brazil. No mutation was detected in the 28 RMP-susceptible strains. Among
RMP-resistant or RMP-susceptible strains deletion was observed. A double point
mutation which had not been reported before was detected in one strain from
France. Among French resistant strains mutations were found in codons 531
(31.2%), 526, 513 and 533 (18.7% each). In Brazilian strains the most common
mutations were in codons 531 (72.2%), 526 (11.1%) and 513 (5.5%). The
heterogeneity found in French strains may be related to the fact that most of
those strains were from African or Asian patients.
2986. Stratta
P. Messuerotti A. Canavese C.
Coen M. Luccoli L. Bussolati B. Giorda L. Malavenda
P. Cacciabue M. Bugiani M.
Bo M. Ventura M. Camussi G.
Fubini B. The role of metals in autoimmune vasculitis: epidemiological
and pathogenic study. Science of the Total Environment. 270(1-3):179-90, 2001 Apr 10.
Abstract
BACKGROUND: A
possible relationship between Silica (Si) exposure and antineutrophil cytoplasm
antibodies (ANCA)-associated vasculitis has been reported. Furthermore,
tuberculosis (TBC) has been frequently described in patients with silicosis,
and TBC infection shares with ANCA-associated vasculitis the formation of
granulomas. Therefore, an intriguing network including Silica, Vasculitis, TBC
and ANCA might be hypothesized. The aim of this work was to further investigate
these correlations using both epidemiological and pathogenic approaches.
METHODS: Study I--epidemiological study. A case-control study to compare the
occupational histories of 31 cases of biopsy proven vasculitis (18 pauci-immune
crescentic glomerulonephritis, 9 microscopic polyangitis, 4 Wegener's
granulomatosis) with those of 58 age, sex and residence-matched controls
(affected by other kidney diseases), was performed. Occupational Health
physicians designed an appropriate questionnaire in order to evaluate a wide
spread of exposures and calculate their entity by the product of Intensity x
Frequency x Duration. Study II--tuberculosis association. A case-control study
to evaluate the frequency of a previous history of tuberculosis (TBC) in 45
patients with vasculitis and 45 controls were performed. Study III--ANCA
positivity. A case-control study to evaluate the presence of ANCA was performed
by testing blood samples of 64 people with previous professional exposure and
65 sex/age matched patients hospitalized in a General Medicine Unit.
Furthermore, the same evaluation was made in a pilot study in 16 patients with
ongoing or previous TBC. Study IV--experimental study. The oxygen free radicals
(OFR) and IL-12 production (both involved in the pathogenesis of vasculitis)
from human phagocytic cells stimulated with an amorphous (diatomaceous earth)
and a crystalline (quartz) form of Si at the doses of 10 and 100 microg ml(-1)
was evaluated. RESULTS: Study I--a positive history of exposure to Si resulted
in significantly more present in cases (14/31 = 45%) than in controls (14/58 =
24%, P = 0.04, OR = 2.4) and no other significant exposure association was
found (including asbestos, mineral oil, formaldehyde, diesel and welding fumes,
grain and wood dust, leather, solvents, fungicides, bitumen, lead and paint).
Study II--past TBC infection was significantly more present in patients with
vasculitis (12/45 = 26%) than in controls (4/45 = 8%, P < 0.05). Study
III--ANCA was present in 2/64 exposed people (vs. 0/65 controls, P = NS) and
0/16 patients with TBC. Study IV--both amorphous and crystalline Si forms
represented a stimulus for OFR and IL-12 production, but quartz resulted as a
greater inductor. CONCLUSIONS: We conclude that Si exposure might be a risk
factor for ANCA-associated vasculitis, possibly enhancing endothelial damage by
phagocyte generation of oxygen free radicals and Th1 differentiation by an
excessive IL-12 phagocyte production. Frequency of TBC was significantly higher
in vasculitis patients. ANCA was not frequent in the preliminary examination of
people with previous professional exposure or patients with TBC, but the number
of samples evaluated is too small to allow conclusions.
2987. Suzuki
N. Kudo K. Sano Y. Ito K. Can Mycobacterium tuberculosis infection
prevent asthma and other allergic disorders?.
International Archives of Allergy & Immunology. 124(1-3):113-6, 2001 Jan-Mar.
Abstract
It is generally
considered that tuberculosis (TB) is a disease which upregulates Th1 cell
function. There is a hypothesis that infection of Mycobacterium tuberculosis
may prevent allergic disorders such as bronchial asthma. However, our clinical
experience of patients with TB somewhat conflicts this hypothesis. Hence, we
investigated Th1/Th2 balance in the peripheral blood of patients with active TB
by measuring serum levels of IgE antibody and by intracellular cytokine assay.
We found that serum levels of IgE in the patients with active TB were
significantly higher than in those with lung cancer or with COPD. In the TB
patients, titers of IgE tended to correlate with disease severity.
Intracellular cytokine assay demonstrated that IFN-gamma-positive cells were
significantly decreased in the patients with active TB compared to normal
controls. The ratio of IFN-gamma-positive (Th1-like)/IL-4-positive (Th2-like)
cells was remarkably reduced in the TB patients (p < 0.0001). This ratio
showed a significant negative correlation with erythrocyte sedimentation rate
and with C-reactive protein. Therapy against TB for 2-3 months did not result
in significant changes of the Th1/Th2 ratio. These findings suggest that
infection of M. tuberculosis does not systematically upregulate Th1 cells in
some patients, and is unlikely to prevent allergic disorders like asthma. Copyright
2001 S. Karger AG, Basel
2988. Syriopoulou V. Brooks JB.
Daikos GL. Electron-capture gas chromatographic-chemical ionization mass
spectrometric study of sera from people vaccinated with bacille Calmette-Guerin
for characteristic metabolites. Journal
of Chromatography. B, Biomedical Sciences & Applications. 751(1):143-51, 2001 Feb 10.
Abstract
Serum samples from 26 individuals vaccinated
with bacille Calmette-Guerin (BCG) and from 26 controls (10 patients with
pulmonary tuberculosis and 16 non BCG-vaccinated healthy individuals) were
analyzed by frequency-pulsed electron-capture gas chromatography (FPEC-GC) and
chemical ionization gas chromatography-mass spectrometry (CIGC-MS) for the
presence of characteristic metabolites. A distinct pattern consisted of
tuberculostearic acid (TSA) and a peak, labeled peak 1, was observed in all
BCG-vaccinated individuals, whereas only three of 26 controls generated this
chromatography profile. TSA was detected in all patients with pulmonary
tuberculosis but peak 1 was absent. Sera drawn from 12 individuals 11 to 14
days after BCG vaccination yielded three transitional FPEC-GC profiles. A
permanent FPEC-GC profile consisting of TSA and of a full scale peak 1 appeared
28 days to a few months after BCG vaccination. Peak 1 was tentatively
identified by CIGC-MS as 9-methyl-hexacosanol. The findings suggest that peak 1
may serve as a marker to detect Mycobacterium bovis BCG and to distinguish
individuals infected with M. tuberculosis from individuals vaccinated with BCG.
2989. Tan SH. Tan HH.
Sun YJ. Goh CL. Clinical utility
of polymerase chain reaction in the detection of Mycobacterium tuberculosis in
different types of cutaneous tuberculosis and tuberculids. Annals of the
Academy of Medicine, Singapore.
30(1):3-10, 2001 Jan.
Abstract
INTRODUCTION:
The role of polymerase chain reaction (PCR) in the diagnosis of cutaneous
tuberculosis in clinical practice has not been defined as no PCR assay has been
tested in a large-scale clinical study. The objective of this study was to test
the clinical utility of a PCR assay in the diagnosis of different types of
cutaneous tuberculosis and tuberculids. MATERIALS AND METHODS: Analysis of
archival biopsy specimens by a nested PCR assay targeting IS6110 of
Mycobacterium tuberculosis (M. tb) DNA was performed in a tertiary-care skin
hospital in Singapore. PCR results were compared with cultures and concordance
with final diagnosis. PATIENTS AND SPECIMENS: One hundred and nineteen skin
biopsies from 105 patients comprising 58 cases of confirmed or highly probable
cutaneous tuberculosis, ranging from multibacillary infections to
paucibacillary forms and 47 cases of possible tuberculids were analysed.
Twenty-four subjects with non-tuberculous granulomas and normal skin controls
were included. RESULTS: In 14 immunocompromised patients with multibacillary
mycobacterial infections (AFB+ on biopsy), PCR was positive in 9 patients.
Correlating PCR results with the final diagnosis, the PCR technique was 100%
sensitive and specific in this group. In paucibacillary tuberculosis, PCR
positivity rates were 55% for tuberculosis verrucosa cutis (38 cases) and 60%
for lupus vulgaris (5 cases). When confirmed cases of tuberculosis were
considered, the overall sensitivity was 73%. In 26 cases of erythema induratum,
PCR was positive in 54% and correlated with a documented response to
anti-tuberculous treatment in 80%. CONCLUSIONS: The use of PCR in the routine
diagnostic panel for cutaneous tuberculosis should take into consideration the
differential sensitivities for different clinical types. In the setting of an
immunocompromised patient with AFB+ lesions, PCR has a definite role in rapid
diagnosis and in differentiating atypical mycobacterial infection from
tuberculosis. Where paucibacillary tuberculosis is suspected, clinical decision
should not be based on PCR results alone. In erythema induratum, we found some
correlation between PCR results and response to anti-tuberculous therapy.
2990. Tovar-Rivera
T. Sanchez-Colon S. Padierna-Olivos L. Masso-Rojas F. Estrada-Parra
S. Mondragon-Gonzalez R. Jimenez-Martinez MC. Sanchez-Garcia FJ. Connectivity patterns in
tuberculosis and leprosy patients are indistinguishable from that of healthy
donors. Scandinavian Journal of
Immunology. 53(5):520-7, 2001 May.
Abstract
Connectivity,
the self-defined interactions between antigen-recognising molecules in a
network system can in part be assessed by measuring the reactivity of a given
serum against an ordered set of immunoglobulin (Ig)G F(ab')2 fractions,
separated by means of isoelectric focusing so that, the serum reactivity
against the whole set of fractions defines a characteristic pattern of
connectivity. Deviations from the normal condition (healthy donors) have so far
been documented for two autoimmune diseases: systemic lupus erythematosus (SLE)
and pemphigus vulgaris, as well as for human immunodeficiency virus (HIV)-1
infection. We tested here if bacterial infections lead to alterations in
connectivity. In addition, we wanted to test if two antigenically related bacteria
would produce similar or otherwise distinctive connectivity patterns.
Connectivity analysis was applied on the sera from tuberculosis and leprosy
patients and the sera from healthy donors were used as control. No
statistically significant differences between the three groups studied were
found. These results have implications for theories that set the origin of
autoimmune diseases in microbial infections. To the best of our knowledge, this
is the first attempt to analyze the connectivity status in bacterial
infections.
2991. Turgut M. Multifocal extensive spinal tuberculosis
(Pott's disease) involving cervical, thoracic and lumbar vertebrae. British Journal of Neurosurgery. 15(2):142-6, 2001 Apr.
Abstract
An unusual case is reported of a 53-year-old
woman presenting with spinal tuberculosis involving cervical, thoracic and
lumbar vertebrae. The patient originally presented with progressive
quadriparesis, fever, night sweats and weight loss. Imaging studies
demonstrated vertebral body destruction with and without paraspinal and/or
intraspinal abscess in cervical, thoracic and lumbar regions. The laboratory
studies confirmed the diagnosis of Pott's disease and the patient was placed on
anti-tuberculosis chemotherapy. The anterior approach was used for removal of
the infected necrotic material, bone grafting and instrumentation, in both
cervical and thoracic vertebrae. The postoperative course was uneventful and
the patient made an excellent neurological recovery. The present report is of
the first published case of an extensive spinal tuberculosis involving
cervical, thoracic and lumbar spine.
2992.
Vasishta RK.
Kakkar N. Singhi P. Banjerjee AK. Pathological case of the month. Cystic desmoplastic
medulloblastoma of infancy. Archives of Pediatrics & Adolescent
Medicine. 155(4):517-8, 2001 Apr.
2993. Viveiros M. Amaral L. Enhancement of antibiotic activity
against poly-drug resistant Mycobacterium tuberculosis by phenothiazines.
International Journal of Antimicrobial Agents.
17(3):225-8, 2001 Mar.
Abstract
Phenothiazines
have been shown to inhibit the in vitro growth of multi-drug resistant
(resistant to rifampicin and isoniazid) Mycobacterium tuberculosis (MDRTB).
They have been considered as potential adjuvants to regimens employing four or
more antibiotics for the management of freshly diagnosed infections of M.
tuberculosis in patients from areas known to have a high prevalence of MDRTB.
Chlorpromazine has been shown to enhance the activity of antibiotics (except
ethambutol) to which M. tuberculosis is susceptible. This might result in a
reduction in the dose of some or all of the antibiotics employed without
sacrificing the integrity of treatment. Chlorpromazine, thioridazine and
promethazine were shown to enhance the activity of rifampicin and streptomycin when
used in combinations at concentrations that are minimally effective when
employed separately against clinical strains of M. tuberculosis resistant to
two or more antibiotics (poly-drug resistant MTB). The phenothiazines had no
effect on the activity of isoniazid against poly-drug resistant MTB.
2994. Wallis
RS. Palaci M. Vinhas S. Hise AG. Ribeiro FC.
Landen K. Cheon SH. Song HY.
Phillips M. Dietze R. Ellner JJ.
A whole blood bactericidal assay for tuberculosis. Journal of Infectious Diseases. 183(8):1300-3, 2001 Apr 15.
Abstract
The
bactericidal activity of orally administered antituberculosis (anti-TB) drugs
was determined in a whole blood culture model of intracellular infection in
which microbial killing reflects the combined effects of drug and immune
mechanisms. Rifampin (Rif) was the most active compound studied and reduced the
number of viable bacilli by >4 logs. Isoniazid (INH), 2 quinolones, and
pyrazinamide (PZA) showed intermediate levels of activity. Ethambutol exerted
only a bacteristatic effect; amoxicillin/clavulanate was inactive. The
combination of INH-Rif-PZA showed strong activity against 11 drug-sensitive
isolates (mean, -3.8 log) but no activity against 12 multidrug-resistant (MDR)
strains. The combination of levofloxacin-PZA-ethambutol had intermediate
bactericidal activity against MDR isolates (mean, -1.2 log) but failed to equal
that of INH-Rif-PZA against sensitive isolates (P<.001). The whole blood
BACTEC method (Becton Dickinson) may be useful for the early clinical evaluation
of new anti-TB drugs and in the management of individual patients.
2995. Wang PD. Lin RS. Drug-resistant tuberculosis in
Taipei, 1996-1999. American Journal of
Infection Control. 29(1):41-7, 2001
Feb.
Abstract
OBJECTIVES: To
determine the trends, patterns, and risk factors associated with drug-resistant
tuberculosis, we conducted a hospital-based retrospective study in Taipei.
METHODS: Clinical and bacteriologic data were routinely collected from 453
patients with a diagnosis of tuberculosis who were treated at Taipei Municipal
Chronic Disease Hospital from January 1996 through December 1999 for whom
drug-susceptibility testing was done. RESULTS: Resistance to at least one drug
was identified in 154 (34%) out of the 453 patients, and 34 (7.5%) patients
were resistant to at least isoniazid and rifampin. Among the 199 patients with
recurrent tuberculosis, 98 (49.2%) had isolates that showed resistance to at
least one drug. Among the 254 new patients, 56 (22.0%) had isolates that were
drug resistant. For all 453 patients, resistance to rifampin was most common
(17.4%), followed by resistance to isoniazid (13.9%), streptomycin (13.7%),
ethambutol (8.2%), and kanamycin (3.5%). A history of previous tuberculosis
therapy (odds ratio = 9.4; 95% CI, 2.9-28) and being born outside of Taiwan
(odds ratio 3.3; 95% CI, 1.1-34) were significant risk factors for multidrug
resistance. CONCLUSIONS: Our data suggest that the Taipei tuberculosis control
program should be rapidly strengthened by expanded use of directly observed
therapy and more careful bacteriologic and clinical follow-up, particularly in
cases of recurrence and in persons born outside of Taiwan in tuberculosis
endemic areas. Our results also indicate that the regular measuring of rates of
drug resistance and the monitoring and guiding of tuberculosis treatment
programs could increase the therapeutic response rate and prevent the
appearance of newly acquired resistance in patients with tuberculosis. In
addition, with high rifampin resistance (17.4%), the regulated market for
rifampin is essential in Taiwan.
2996. Wigginton JE. Kirschner D. A model to predict
cell-mediated immune regulatory mechanisms during human infection with
Mycobacterium tuberculosis. Journal of
Immunology. 166(3):1951-67, 2001 Feb 1.
Abstract
A key issue for
the study of tuberculosis infection (TB) is to understand why individuals
infected with Mycobacterium tuberculosis experience different clinical
outcomes. Elaborating the immune mechanisms that determine whether an infected
individual will suffer active TB or latent infection can aid in developing
treatment and prevention strategies. To better understand the dynamics of M.
tuberculosis infection and immunity, we have developed a virtual human model
that qualitatively and quantitatively characterizes the cellular and cytokine
control network operational during TB infection. Using this model, we identify
key regulatory elements in the host response. In particular, factors affecting
cell functions, such as macrophage activation and bactericidal capabilities,
and effector T cell functions such as cytotoxicity and cytokine production can
each be determinative. The model indicates, however, that even if latency is
achieved, it may come at the expense of tissue damage if the response is not properly
regulated. A balance in Th1 and Th2 immune responses governed by IFN-gamma,
IL-10, and IL-4 facilitate this down-regulation. These results are further
explored through virtual deletion and depletion experiments.
2997. Zink
A. Haas CJ. Reischl U. Szeimies
U. Nerlich AG. Molecular analysis of skeletal tuberculosis
in an ancient Egyptian population.
Journal of Medical Microbiology.
50(4):355-66, 2001 Apr.
Abstract
A
paleomicrobiological study was performed on 37 skeletal tissue specimens from
cadavers in the necropolis of Thebes-West, Upper Egypt, (2120-500 BC) and four
from the necropolis of Abydos (3000 BC). The subjects had typical
macromorphological evidence of osseous tuberculosis (n = 3), morphological
alterations that were not specific, but probably resulted from tuberculosis (n
= 17), or were without morphological osseous changes (n = 21). DNA was
extracted from these bone samples and amplified by PCR with a primer pair that
recognised the Mycobacterium tuberculosis complex insertion sequence IS6110. To
confirm specificity of the analysis, the amplification products of several
samples were subjected to restriction enzyme digestion, or direct sequencing,
or both. In 30 of the 41 cases analysed, ancient DNA was demonstrated by
amplification by the presence of the human beta-actin or the amelogenin gene
and nine of these cases were positive for M. tuberculosis DNA. The results were
confirmed by restriction endonuclease digestion and sequencing. A positive
result for M. tuberculosis DNA was seen in two of the three cases with typical
morphological signs of tuberculosis and amplifiable DNA, in five of 13
non-specific, but probable cases (including two cases from c. 3000 BC), but
also in two of 14 cases without pathological bone changes. These observations
confirm that tuberculosis may be diagnosed unequivocally in skeletal material
from ancient Egypt, even dating back to c. 3000 BC. As a positive molecular
reaction was observed in most of the typical cases of skeletal tuberculosis, in
about one-third of non-specific, but probable tuberculous osseous changes and,
surprisingly, in about one-seventh of unremarkable samples, this suggests that
infection with M. tuberculosis was relatively frequent in ancient Egypt.