LEPROSY

Diagnosis, Diagnostics, Immunodiagnosis & Immunodiagnostics:

 

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3325.   Banta HD.  Global issues on the agenda at the World Health Assembly: discussion of HIV/AIDS,  leprosy, access to drugs.  JAMA.  286(1):29-30, 2001 Jul 4.

3326.   Danda D.  Cherian AM. Rheumatological manifestations of leprosy and lepra reaction.  Indian Journal of Leprosy.  73(1):58-60, 2001 Jan-Mar.

3327.   Fine PE.  Floyd S.  Stanford JL.  Nkhosa P.  Kasunga A.  Chaguluka S.  Warndorff DK.  Jenkins PA.  Yates M.  Ponnighaus JM. Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy.  Epidemiology & Infection.  126(3):379-87, 2001 Jun.

Abstract

  More than 36000 individuals living in rural Malawi were skin tested with antigens derived from 12 different species of environmental mycobacteria. Most were simultaneously tested with RT23 tuberculin, and all were followed up for both tuberculosis and leprosy incidence. Skin test results indicated widespread sensitivity to the environmental antigens, in particular to Mycobacterium scrofulaceum, M. intracellulare and one strain of M. fortuitum. Individuals with evidence of exposure to 'fast growers' (i.e. with induration to antigens from fast growers which exceeded their sensitivity to tuberculin), but not those exposed to 'slow growers', were at reduced risk of contracting both tuberculosis and leprosy, compared to individuals whose indurations to the environmental antigen were less than that to tuberculin. This evidence for cross protection from natural exposure to certain environmental mycobacteria may explain geographic distributions of mycobacterial disease and has important implications for the mechanisms and measurement of protection by mycobacterial vaccines.

3328.    Hughes RG.  Drake-Lee A.  Nasal manifestations of granulomatous disease. [Review] [13 refs]  Hospital Medicine (London).  62(7):417-21, 2001 Jul.

Abstract

  Granulomatous disease frequently affects the head and neck region, particularly the nose and sinuses. This article describes the most common infectious and non-infectious conditions and their clinical features. [References: 13]

3329.    No Abstract

3330.   Krupnick AI.  Shim H.  Phelps RG.  Cunningham-Rundles C.  Sapadin AN.  Cutaneous granulomas masquerading as tuberculoid leprosy in a patient with congenital combined immunodeficiency. [Review] [30 refs] Mount Sinai Journal of Medicine.  68(4-5):326-30, 2001 Sep-Oct.

Abstract

  Combined immunodeficiency disorders are characterized by abnormalities in cellular and humoral immunity. This classification includes common variable immunodeficiency (CVI), a primary immunodeficiency disorder characterized by hypogammaglobulinemia, recurrent bacterial infections, and significant T-cell abnormalities. Associated autoimmune diseases include rheumatoid arthritis, pernicious anemia, idiopathic thrombocytopenic purpura, and systemic lupus erythematous. Granulomatous lesions in lymphoid tissues, solid organs, and skin have been reported. We describe a patient with CVI who developed cutaneous granulomas with perineural invasion; to our knowledge, this is a previously undescribed feature. [References: 30]

3331.   Kumarasinghe SP.  Some useful clinical clues and techniques in the diagnosis of tuberculoid leprosy.  International Journal of Dermatology.  40(4):301-3, 2001 Apr.

3332.    No Abstract

3333.   Lima CS.  Ribeiro ML.  Souza LA.  Sardella AB.  Wolf VM.  Pessolani MC. Intracellular signals triggered during association of Mycobacterium leprae and Mycobacterium bovis BCG with human monocytes. Microbial Pathogenesis.  31(1):37-45, 2001 Jul.

Abstract

  To gain a better understanding of mycobacteria-host cell interaction, the present study compared the signal transduction events triggered during the interaction of Mycobacterium leprae (the causative agent of leprosy) and of Mycobacterium bovis BCG (an attenuated strain used as a vaccine against leprosy and tuberculosis) with human monocytes. The assays consisted of pre-treating or not THP-1 cells (a human monocytic cell line) with different kinase inhibitors, followed by incubation with fluorescein-labelled bacteria and analysis of bacterial association via fluorescence microscopy. The specific tyrosine kinase (TK) inhibitor tyrphostin AG126 provided the highest rates of association inhibition (>90% for BCG and >65% for M. leprae). The early activation of TKs during mycobacteria-host cell interaction was confirmed by immunoblot analysis, demonstrating that in several host cell proteins mycobacteria stimulated tyrosine phosphorylation. The use of the drugs wortmannin and bisindolylmaleimide I which, respectively, inhibit phosphatidylinositide 3-kinase (PI 3-kinase) and protein kinase C (PKC), produced lower but consistent results within a 35--60% association inhibition range for both bacteria. Dose response curves with these inhibitors were obtained. Similar results were obtained when primary human monocytes were used as host cells, strongly suggesting that TK, PKC and PI 3-kinase signals are activated during the interaction of human monocytes with both pathogenic and attenuated species of mycobacteria. Copyright 2001 Academic Press.

3334.    No Abstract

3335.   Marlowe SN.  Lockwood DN.  Update on leprosy. [Review] [10 refs] Hospital Medicine (London).  62(8):471-6, 2001 Aug.

Abstract

  Leprosy, a result of infection by Mycobacterium leprae, is a leading cause of peripheral neuropathy. The World Health Organization aimed to eliminate leprosy as a public health problem by 2000, but this has not been attained. Patients with leprosy continue to present in the UK. The diagnosis of leprosy is frequently not considered, with resultant pathological and psychological problems for patients. [References: 10]

3336.    

3337.   Mohamed KB. Facial lesions resembling leprosy.  International Journal of Leprosy & Other Mycobacterial Diseases.  69(1):35-7, 2001 Mar.

3338.   Natrajan M.  Katoch K.  Katoch VM.  Patients presenting with defined areas of sensory loss--a preliminary study.  Indian Journal of Leprosy.  73(1):17-26, 2001 Jan-Mar.

Abstract

  Thirty patients presenting with circumscribed areas of clearly demonstrable hypoesthesia were chosen from amongst those attending this Institute. Their history and clinical features were recorded, lepromin test was done for reading at four weeks, and peripheral part of the hypoesthetic area was biopsied for histopathology and immunostaining. The subjects were predominantly adult males with the symptomatic sites limited to the extremities. On routine histopathological examination of the symptomatic sites, the diagnosis of leprosy, using defined criteria, could be made in six cases (20%). Immunostaining of the remaining sections showing either no pathology or a nonspecific pathology revealed the presence of mycobacterial antigen in five of the 24 cases (20.83%). Overall, leprosy could be diagnosed in 11 of the 30 cases studied (36.66%). This study shows that leprosy may be an important cause of circumscribed areas of sensory deficit.

3339.   No Abstract

3340.   No Abstract

 

3341.   Rastogi N.  Legrand E.  Sola C.  The mycobacteria: an introduction to nomenclature and pathogenesis. [Review] [192 refs] Revue Scientifique et Technique.  20(1):21-54, 2001 Apr.

Abstract

  Tuberculosis, caused by Mycobacterium tuberculosis, and leprosy, caused by M. leprae, are diseases known since antiquity. In developing countries, tuberculosis is still the leading cause of mortality due to an infectious disease. Taxonomically, mycobacteria belong to the genus Mycobacterium, which is the single genus within the family of Mycobacteriaceae, in the order Actinomycetales. Actinomycetales include diverse micro-organisms, but mycobacteria and allied taxa are easily distinguished on the basis of the ability to synthesise mycolic acids. Mycobacterial species are traditionally differentiated on the basis of phenotypic characteristics, and the authors provide an updated list of the biochemical tests currently employed and the culture properties that help to discriminate among various species of mycobacteria. However, as the phenotypic characteristics do not allow precise identification of all species, recent molecular taxonomical approaches for mycobacterial classification and phylogeny are also described. Mycobacteria are also a leading cause of infection in various domesticated animals and wildlife. The authors briefly describe the mycobacteria involved in animal infections, the wildlife reservoirs and strategies to control bovine tuberculosis, and the use of molecular tools for diagnostics and epidemiology of mycobacterial infections in animals. The characteristic of intracellular parasitism is discussed, in addition to the fate of pathogenic mycobacteria that have the ability to grow inside phagosomes and phagolysosomes of infected host macrophages. The mycobacterial cell envelope, which is a complex tripartite structure containing a high proportion of lipids (approximately 30% to 40% of the total weight) could play a crucial role in the adaptation of mycobacteria to intracellular growth and survival, immune modulation and drug resistance. [References: 192]

3342.   Shelleh HH.  Al-Shayeb AM.  Khan SA.  Khan LA.  Al-Hateeti HS.  Cold cellulitis: an unusual presentation of leprosy.  Saudi Medical Journal.  22(4):372-3, 2001 Apr.

3343.   Truoc LV.  Ly HM.  Thuy NK.  Trach DD.  Stanford CA.  Stanford JL. Vaccination against leprosy at Ben San Leprosy Centre, Ho Chi Minh City, Vietnam. Vaccine.  19(25-26):3451-8, 2001 May 14.

Abstract

  Three vaccines, BCG alone, BCG + 10(7) killed Mycobacterium vaccae and 10(8) killed M. vaccae alone, were studied in children living in close contact with leprosy. In the year before vaccination, 14/446 (3.1%) children had developed leprosy. Among those who were not vaccinated, 9/74 (12.2%) developed the disease in the first 4 years of the study and 5/65 (7.7%) developed the disease in the second 4 years. In comparison with this, among those vaccinated, 20/343 (5.8%) developed leprosy in the first 4 years and 5/323 (1.5%) developed leprosy in the second 4 years. This represents 52.5% protection in the first 4 years and 80.5% in the second 4 years. There were no significant differences in protection afforded by each of the three vaccines but the success of the killed preparation of M. vaccae is an important finding.

3344.   Vijaikumar M.  D'Souza M.  Kumar S.  Badhe B. Fine needle aspiration cytology (FNAC) of nerves in leprosy.  Leprosy Review.  72(2):171-8, 2001 Jun.

Abstract

  Leprosy is primarily a disease of the peripheral nerves and a technique that is simpler than nerve biopsy is required to evaluate nerve involvement, especially in pure neuritic (PN) leprosy. This study was designed to evaluate the role of FNAC of the nerve in the diagnosis and classification of leprosy. A prospective study was carried out on 25 patients with clinically active leprosy and at least one thickened peripheral sensory nerve. Nerve aspirates were evaluated by May-Grunwald-Giemsa and Fite's staining. Lepromin test, slit skin smears (SSS), skin biopsies (except PN cases) and nerve biopsies were performed and compared with FNAC. FNAC of nerve from 23 cases (92%) yielded diagnostic aspirates. Acid fast bacilli were observed in six cases by FNAC. FNAC and nerve pathology were equally comparable with the other parameters evaluated. Based on the results, cytological criteria were developed for interpreting nerve aspirates and the cases were classified as paucibacillary (18), BB (2), BL (2), LL (1) and non-diagnostic (2). All PN cases showed diagnostic paucibacillary type cytology. FNAC of the nerve yields diagnostic aspirates in leprosy comparable with nerve pathology and the proposed cytological criteria may be useful in classification of nerve aspirates.

3345.   Wakhlu A.  Gaur SP.  Kaushal GP.  Misra A.  Asthana P.  Sircar AR. Response of Mycobacterium habana vaccine in patients with lepromatous leprosy and their household contacts. A pilot clinical study.  Leprosy Review.  72(2):179-91, 2001 Jun.

Abstract

  Single dose vaccination was carried out with Mycobacterium habana vaccine, 31 lepromatous leprosy cases receiving 1.5 mg (1.5 mg = 6.27 x 10(8) bacilli) and 36 household contacts randomly receiving 1.5, 2.0, 2.5 mg vaccine intradermally. Duration of study was 18 weeks. Vaccination induced lepromin conversion in 100% of lepromatous leprosy cases and lepromin negative household contacts and augmentation of lepromin reactivity in 100% of lepromin positive household contacts, which was stable for the 15 weeks duration of follow-up. The maximum augmentation in lepromin reactivity was obtained with 1.5 mg of vaccine, which is probably the supramaximal dose. Overall, post-vaccination, those without prior BCG vaccination scars showed higher mean values of lepromin augmentation. Local vaccination site changes included induration, ulceration, itching, pain and uncomplicated regional lymphadenopathy, all of which remitted spontaneously by 15 weeks. Systemic side-effects noted were pyrexia, ENL and jaundice, and were seen with no greater frequency than that reported in other vaccine trials. Overall, systemic side-effects were easily controlled and were not accompanied by clinically detectable nerve or ocular damage. The safety profile investigations revealed an increase in the mean values of Hb%, RBC count and PCV in household contacts and of PCV in lepromatous patients, post-vaccination. Alterations in the liver function tests were also observed in patients of lepromatous leprosy. Thus, M. habana vaccine appears to be useful in stimulating specific CMI against M. leprae as evidenced by increased lepromin reactivity.

 

Apr 02

4101.   AL-Qubati Y, AL-Kubatia A S:Multidrug therapy-the pathway for global leprosy elimination. Indian J Lepr 2000, 72(4), 477-90.(013112) July1, 2001. 

 

Emergence of dapsone-resistant M. leprae and mycobacterial persistance provoked the quest for another solution. More drug were discovered for treatment of leprosy. But the real breakthrough was the recommendation of leprosy control activities was phenomenoal. The impact of MDT has led to the cure of over eight million leprosy sufferers and the saving of one million patients from becoming crippled. Leprosy prevalence has decreased by 80% in ten years. By the end of May 1999 the leprosy burden remained concentrated in only 12 countries of the world. These achivements are mainly attributed to the development and world-wide adoption of the MDT programme.

 

4102.   Brunet RC, Struchiner CJ, Loinaz A. A method for estimating time dependent intervention benefits under arbitrarily varying age and exogenous components of hazard. Lifetime Data Anal  2001 Dec;7(4):377-92

 

A method for estimating the dependence of intrinsic intervention benefits on time elapsed since the intervention took place is proposed. The method is aimed at intervention programs against diseases where one or all of the following components of hazard intensity may undergo important and unknown variations: 1) the intervention benefits to a subject are a function of the time elapsed since the intervention took place, or since inception for a continuing treatment, 2) the subjects vulnerability is an unknown function of their age, 3) the exogenous or environmental baseline intensity, to which all are assumed subjected, fluctuates arbitrarily with calendar time. During the time span of a study, these variables interact in a complex way, possibly masking the real contribution of the intervention. However, with very general assumptions about how hazard components interact, the cumulative hazards of subpopulations treated at different times in the past are shown to be described mathematically by a convolution of the time elapsed dependent intervention benefit function with the age and calendar time dependent baseline intensity. Starting from the cumulative hazards of untreated and treated subpopulations that had the intervention at different times in the past, a method of deconvolution through regularization is proposed to reconstruct the time elapsed dependence of the intervention benefit function. The regularization technique used is of the 'penalized least square smoothing' type, it is applied to the solution of Volterra integral equations of the first kind under noisy inputs. Simulations, to test for the reconstruction of different modes of time elapsed variation of the intervention benefits, are carried out on realistically noisy 'data sets' taken to be available at a limited number of time points. The stability of the estimated reconstructions, to measurement errors, is examined through repeated simulations with random noise added to inputs. The method is applied to a Brazilian data set where BCG vaccination resulted in a small reduction in the cumulated risk of leprosy infection.

 

4103.   Cooke GS, Hill AV. Genetics of  susceptibility to human infectious disease. Nat Rev Genet  2001 Dec;2(12):967-77

 

Before Robert Koch's work in the late nineteenth century, diseases such as tuberculosis and leprosy were widely believed to be inherited disorders. Heritability of susceptibility to several infectious diseases has been confirmed by studies in the twentieth century. Infectious diseases, old and new, continue to be an important cause of mortality worldwide. A greater understanding of disease processes is needed if more effective therapies and more useful vaccines are to be produced. As part of this effort, developments in genetics have allowed a more systematic study of the impact that the human genome and infectious disease have on each other.

4104.   Ghorpade A, Ramanan C: Primary penil tuberculoid leprosy. Indian J Lepr 2000, 72(4),499-500.(013154). July1, 2001. No abstract.

4105.   K, Kashiwabara Y. Multidrug resistant Mycobacterium leprae from patients  with leprosy. Antimicrob Agents Chemother  2001 Dec;45(12):3635-9

 

Sequences of the folP1, rpoB, and gyrA genes were analyzed for 88 isolates of Mycobacterium leprae from leprosy patients in Japan, Haiti, Indonesia, Pakistan, and the Philippines. Thirteen isolates (14.8%) showed representative mutations in more than two genes, suggesting the emergence of multidrug-resistant M. leprae.

4106.   LM, Valdez R, Sordelli DO, Aversa G, Modlin RL, Sieling PA. Signaling lymphocytic activation molecule expression and regulation in human intracellular infection correlate with Th1 cytokine patterns. J Immunol  2001 Nov 15;167(10):5719-24

 

Induction of Th1 cytokines, those associated with cell-mediated immunity, is critical for host defense against infection by intracellular pathogens, including mycobacteria. Signaling lymphocytic activation molecule (SLAM, CD150) is a transmembrane protein expressed on lymphocytes that promotes T cell proliferation and IFN-gamma production. The expression and role of SLAM in human infectious disease were investigated using leprosy as a model. We found that SLAM mRNA and protein were more strongly expressed in skin lesions of tuberculoid patients, those with measurable CMI to the pathogen, Mycobacterium leprae, compared with lepromatous patients, who have weak CMI against M. leprae. Peripheral blood T cells from tuberculoid patients showed a striking increase in the level of SLAM expression after stimulation with M. leprae, whereas the expression of SLAM on T cells from lepromatous patients show little change by M. leprae stimulation. Engagement of SLAM by an agonistic mAb up-regulated IFN-gamma production from tuberculoid patients and slightly increased the levels of IFN-gamma in lepromatous patients. In addition, IFN-gamma augmented SLAM expression on M. leprae-stimulated peripheral blood T cells from leprosy patients. Signaling through SLAM after IFN-gamma treatment of Ag-stimulated cells enhanced IFN-gamma production in lepromatous patients to the levels of tuberculoid patients. Our data suggest that the local release of IFN-gamma by M. leprae-activated T cells in tuberculoid leprosy lesions leads to up-regulation of SLAM expression. Ligation of SLAM augments IFN-gamma production in the local microenvironment, creating a positive feedback loop. Failure of T cells from lepromatous leprosy patients to produce IFN-gamma in response to M. leprae contributes to reduced expression of SLAM. Therefore, the activation of SLAM may promote the cell-mediated immune response to intracellular bacterial pathogens.

 

4107.   PN. Detection of Mycobacterium leprae DNA by polymerase chain reaction in the blood of individuals, eight years after completion of anti-leprosy therapy. Mem Inst Oswaldo Cruz  2001 Nov;96(8):1129-33

 

Thirty eight patients with indeterminate leprosy (HI), at least 4 to 6 years after discharge from multibacillary (MB) or paucibacillary (PB) schemes of anti leprosy multidrug therapy (MDT), were submitted to traditional diagnostic procedures for leprosy and to polymerase chain reaction (PCR) analysis of different clinical samples for detection of Mycobacterium leprae DNA. No significant difference was observed for any of the parameters analyzed between PB or MB schemes of treatment and no indications were found for more efficient outcome of HI using the MB scheme. Remarkably, 18 (54.5%) of the individuals were PCR positive in at least one of the samples: positivity of PCR was highest in blood samples and four individuals were PCR positive in blood and some other sample. Upon comparison of PCR results with clinical and histopathological parameters, no correlation was found between PCR-positivity and eventual relapse. This is the first report on detection of M. leprae DNA in PB patients, more than half a decade after completion of MDT, suggesting that live bacilli are present and circulating much longer than expected, although reinfection of the individuals can not be excluded. Overall, we feel that because of the high sensitivity of the assay, extreme care should be taken about association of PCR results, efficacy of treatment and disease status.

 

4108.   Vekatesan K, Nirmal Deo, Girdhar A, Girdhar B K: Multiple dose pharmacokinetics of clofazimine in leprosy. Indian J Pharmac 2001,33(2), 136-7. (016536) Aug 16, 2023

 

Study was conducted to evaluate multiple dose pharmacokinetics of clofazimine. It suggests that a steady state might be reached with 36-60 daily doses of the drug. The observation that AUC values/basal plasma levels are not so much proportionate to the length of the drug administration is indicative of extensive deposition and retention of the drug in the tissues and slow release from there.

 

July 02

 

4696.   Cambau E, Bonnafous P, Perani E, Sougakoff W, Ji B, Jarlier V. Molecular detection of rifampin and ofloxacin resistance for patients who experience relapse of multibacillary leprosy. Clin Infect Dis. 2002 Jan 1;34(1):39-45.

 

Molecular detection of rifampin resistance (rpoB analysis) in Mycobacterium leprae was determined for 49 patients who experienced relapse of multibacillary leprosy and for 34 untreated patients. Molecular detection of ofloxacin resistance (gyrA analysis) was determined for the 12 patients who experienced relapse and who had received ofloxacin. Results of molecular tests were compared with the reference susceptibility test in the mouse footpad. Overall, the efficiency of molecular detection--that is, positive DNA amplification--was 95%, whereas that of the in vivo test was 55% (P<.001). Results of molecular detection and in vivo test were fully concordant when both were available—that is, for 35 rifampin--sensitive cases of leprosy (no rpoB mutation), 4 ofloxacin-sensitive cases (no gyrA mutation), 11 rifampin-resistant cases (rpoB missense mutations), and 1 ofloxacin-resistant case (gyrA mutation). rpoB and gyrA analysis appears to be an effective method for detection of rifampin and ofloxacin resistance in patients with leprosy.

 

4697.   Habib AA, Mozaffar T.  The neuropathology of leprosy. Arch Neurol. 2002 Jan;59(1):138-40. No abstract.

4698.   Massa R, Morello M, Sancesario G, Bernardi G.  Sural nerve without nerve fibers in leprous neuropathy. Arch Neurol. 2002 Feb;59(2):306. No abstract.

4699.   Modlin RL.  Learning from leprosy: insights into contemporary immunology from an ancient disease. Skin Pharmacol Appl Skin Physiol. 2002 Jan-Feb;15(1):1-6. Review.

 

Leprosy provides an ideal model to study immune responses in humans and in skin. Learning from leprosy, we have gained insight into mechanisms of host resistance and susceptibility to infection. New paradigms include the role of Th1/Th2 cytokines, the ability of CD1 to present nonpeptide antigens to T cells, the ability of microbial lipoproteins to stimulate antimicrobial activity in monocytes and the demonstration that T cells can mediate a direct antimicrobial activity through release of granulysin. Together, these findings provide a rationale for developing new strategies to treat and prevent infectious disease. Copyright 2002 S. Karger AG, Basel

 

4700.   Newton SM, Lau C, Gurcha SS, Besra GS, Wright CW.  The evaluation of forty-three plant species for in vitro antimycobacterial activities; isolation of active constituents from Psoralea corylifolia and Sanguinaria canadensis.J Ethnopharmacol. 2002 Jan;79(1):57-67. Review.

 

Extracts from forty-three plant species were selected on account of reported traditional uses for the treatment of TB and/or leprosy. These were assayed for antimycobacterial activities. A simple in vitro screening assay was employed using two model species of mycobacteria, M. aurum and M. smegmatis. Crude methanolic extracts from three of the plants, C. mukul, P. corylifolia and S. canadensis, were found to have significant antimycobacterial activity against M. aurum only (MIC=62.5 microg/ml). Bioassay guided fractionation led to the isolation of two known benzophenanthridine alkaloids, sanguinarine (1) and chelerythrine (2), from the roots S. canadensis and the known phenolic meroterpene, bakuchiol (3) from the seeds of P. corylifolia. The fractionation of the resin of C. mukul lead to a decrease in antimycobacterial activity and hence further work was not pursued. Compound (2) was the most active against M. aurum and M. smegmatis (IC(50)=7.30 microg/ml [19.02 microM] and 29.0 microg/ml [75.56 microM], respectively). M. aurum was the most susceptible organism to all three compounds. No significant difference in antimycobacterial activity was observed when the two alkaloids were tested for activity in media of differing pH values. The activities of the pure compounds against M. aurum were comparable with those against M. bovis BCG with compound (2) being the most active (M. bovis BCG, IC(50)=14.3 microg/ml [37.3 microM]). These results support the use of these plants in traditional medicine.

 

 

4701.   Singh D; Thakur K; Kalpana; Goel A. Micro bacterium scrofulaceum: an isolate from pericardial effusion Indian Journal of Tuberculosis 2002 Jan; 49(1): 49-51.

ABSTRACT: Non-tuberculous mycobacteria (NTM) cause pulmonary disease indistinguishable form tuberculosis (TB). In the present case. Mycobacterium scrofulaceum was isolated from pericardial fluid in a five year old child and was confirmed by molecular deoxyribonucleic acid (DNA) probe specifically designed and biochemical test at the Central JALMA Institute of Leprosy, Agra. The previous tuberculous pleural effusion was probably a predisposing factor in this case. No similar case has been found in literature inspite of our best efforts.

 

Oct 2002

5448.   Alto WA.  Treatment of Hansen's disease. Am Fam Physician. 2002 Apr 1;65(7):1280, 1282; discussion 1282. No abstract.

5449.   Bastos RR.  Experience of leprosy. Lancet. 2002 Jun 1;359(9321):1949.  No abstract.

5450.   Brophy PJ. Microbiology. Subversion of Schwann cells and the leper's bell. Science. 2002 May 3;296(5569):862-3. No abstract.

5451.   Campos WR, Rodrigurs CA, Orefice F, Monteiro LG. Identification of M. leprae in conjunctiva of  leprosy patients using the superior tarsal conjunctiva scrape technique. Indian J. Lepr 1998; 74(4): 397-403. Abstract: Technique of superior tarsal conjunctive scrape was used for identifying M. leprae in the conjunctiva in 56 leprosy patients (all of them multibacillary), some untreated and others treated with multidrug therapy). The technique of tarsal conjunctiva scrape was shown to be more suitable than conjunctival biopsy for identifying lepra bacilli. This technique is also easier to perfom and has shown a statistical relation between baciloscopical index of skin (BIsk) and bacilloscopical index of tarsal conjunctiva (BIconj) values. Thus, if the bacilli can be identified at tarsal conjunctiva can assume greater systemic bacillary load in patients.

 

5452.   Cemerski S, Cantagrel A, Van Meerwijk JP, Romagnoli P. Reactive oxygen species differentially affect T cell receptor-signaling pathways. J Biol Chem. 2002 May 31;277(22):19585-93.

 

Oxidative stress plays an important role in the induction of T lymphocyte hyporesponsiveness observed in several human pathologies including cancer, rheumatoid arthritis, leprosy, and AIDS. To investigate the molecular basis of oxidative stress-induced T cell hyporesponsiveness, we have developed an in vitro system in which T lymphocytes are rendered hyporesponsive by co-culture with oxygen radical-producing activated neutrophils. We have observed a direct correlation between the level of T cell hyporesponsiveness induced and the concentration of reactive oxygen species produced. Moreover, induction of T cell hyporesponsiveness is blocked by addition of N-acetyl cysteine, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, and catalase, confirming the critical role of oxidative stress in this system. The pattern of tyrosine-phosphorylated proteins was profoundly altered in hyporesponsive as compared with normal T cells. In hyporesponsive T cells, T cell receptor (TCR) ligation no longer induced phospholipase C-gamma1 activation and caused reduced Ca(2+) flux. In contrast, despite increased levels of ERK1/2 phosphorylation, TCR-dependent activation of mitogen-activated protein kinase ERK1/2 was unaltered in hyporesponsive T lymphocytes. A late TCR-signaling event such as caspase 3 activation was as well unaffected in hyporesponsive T lymphocytes. Our data indicate that TCR-signaling pathways are differentially affected by physiological levels of oxidative stress and would suggest that although "hyporesponsive" T cells have lost certain effector functions, they may have maintained or gained others.

5453.   Chae GT, Kim MJ, Kang TJ, Lee SB, Shin HK, Kim JP, Ko YH, Kim SH, Kim NH. DNA-PCR and RT-PCR for the 18-kDa gene of Mycobacterium leprae to assess the efficacy of multi-drug therapy for leprosy. J Med Microbiol. 2002 May;51(5):417-22.

 

DNA-PCR and reverse transcription (RT)-PCR for the 18-kDa protein of Mycobacterium leprae were used to examine the efficacy of multi-drug therapy (MDT) in leprosy. MDT was administered for 0-24 months. Fourteen (63.6%) of 22 patients showed positive PCR results after treatment for 12 months and the positive results decreased to 30% after 24 months of MDT. These results did not correlate with the bacterial index (BI) or the IgM antibody titre for the phenolic glycolipid (PGL)-1. One-dimensional densitometric analysis of agarose gels from PCR from the longitudinal study showed a gradual reduction of the 360-bp band after 12-24 months of MDT. RT-PCR for mRNA of the 18-kDa protein successfully tracked bacterial RNA changes in the biopsies and confirmed a decrease in the RNA of M. leprae in patients after MDT for 12 months. Thus, DNA-and RT-PCR for the 18-kDa protein of M. leprae are effective in assessing the efficacy of MDT for leprosy.

5454.   Chakrabarty AN, Dastidar SG, Sen A, Banerjee P, Roy R. Leprosy bacillus – possibly the first chemoautomatic human pathogen cultivated in vitro and characterised. Indian J expl Biol. 2001; 39(10), 962-83. No abstract.

5455.   Geluk A, van Meijgaarden KE, Franken KL, Subronto YW, Wieles B, Arend SM, Sampaio EP, de Boer T, Faber WR, Naafs B, Ottenhoff TH. Identification and characterization of the ESAT-6 homologue of Mycobacterium leprae and T-cell cross-reactivity with Mycobacterium tuberculosis. Infect Immun. 2002 May;70(5):2544-8.

 

In this paper we describe identification and characterization of Mycobacterium leprae ESAT-6 (L-ESAT-6), the homologue of M. tuberculosis ESAT-6 (T-ESAT-6). T-ESAT-6 is expressed by all pathogenic strains belonging to the M. tuberculosis complex but is absent from virtually all other mycobacterial species, and it is a promising antigen for immunodiagnosis of tuberculosis (TB). Therefore, we analyzed whether L-ESAT-6 is a similarly powerful tool for the study of leprosy by examining T-cell responses against L-ESAT-6 in leprosy patients, TB patients, and exposed or nonexposed healthy controls from areas where leprosy and TB are endemic and areas where they are not endemic. L-ESAT-6 was recognized by T cells from leprosy patients, TB patients, individuals who had contact with TB patients, and healthy individuals from an area where TB and leprosy are endemic but not by T cells from individuals who were not exposed to M. tuberculosis and M. leprae. Moreover, leprosy patients who were not responsive to M. leprae failed to respond to L-ESAT-6. A very similar pattern was obtained with T-ESAT-6. These results show that L-ESAT-6 is a potent M. leprae antigen that stimulates T-cell-dependent gamma interferon production in a large proportion of individuals exposed to M. leprae. Moreover, our results suggest that there is significant cross-reactivity between T-ESAT-6 and L-ESAT-6, which has implications for the use of ESAT-6 as tool for diagnosis of leprosy and TB in areas where both diseases are endemic.

 

5456.   Manandhar R, Shrestha N, Butlin CR, Roche PW. High levels of inflammatory cytokines are associated with poor clinical response to steroid treatment and recurrent episodes of type 1 reactions in leprosy. Clin Exp Immunol. 2002 May;128(2):333-8. Abstract: Levels of leprosy antigen-induced interferon-gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in 96 leprosy patients with type 1 reactions (T1R) before, during and after a standard 12-week course of steroids. Peripheral blood mononuclear cells (PBMC) from leprosy patients with untreated T1R produced significantly more TNF-alpha than leprosy patients without T1R. Median levels of IFN-gamma and TNF-alpha in T1R patients fell during treatment with steroids; however, TNF-alpha levels increased as the steroid dose was reduced. Median IL-10 levels increased throughout the steroid treatment period and were associated strongly with TNF-alpha levels. Patients with high cytokine levels had a poorer recovery of sensory or voluntary muscle nerve function, a higher risk of reactivation of symptoms during steroid treatment, and a higher risk of another episode of T1R within 2 months of completing the steroid regimen. Rapid and effective reversal of the inflammatory process in T1R is critical to prevent permanent nerve damage from T1R and monitoring cytokine levels during treatment may be useful.

5457.   Mukherjee J, Majumdar AK, Bandopadhyay A, Acharya B, Reddy MU, Nayak A. Telemedicine for leprosy. IETE Tech Rev. 2001; 18(4), 243-52.  Indian Institute of Technology, Kharagpur developed a prototype telemedicine system for the treatment of tropical disease. Keeping in view the available infrasturcture in the country, designed the system in such a way, so that it can function even at a very low bit rate data communication channel (telephone line). The domain of discourse is chronic tropical diseases which are endemic in the eastern India. To start with , it selected leprosy and dermatological disorfers. In the proposed system, it adopted a store and forward approach. The bulk of the patient  information such as patient’s history, signs and symptoms, old prescription’s diagnostic test reports and images etc are transferred before doctors at two ends start discussion about the patient. The physicians at the referral end could browse through the patient-data and advise accordingly. During online conferencing, the physicians at the two ends could converse with each other  and discuss with respect to  a test report and image by annotations, diagram, texts etc. the system has also the back-end database support for storage and retrieval of patients data. Presently a prototype a system has been developed and installed at the School of Tropical Medicine (STM), Calcutta for in-house testing and training of the doctors. Briefly presents different features of this system with respect to the treatment and diagnosis of leprosy. A few experimental sessions were carried out between Calcutta and Kharagpur.

5458.   Sirmour SK, Verma PK, Singh JN, Okhandiar P. LDH isozymes with anamalous bands in semen of leprosy patients. Indian J Lepr. 1998; 74(4), 405-9.  Activity of LDH isozymes was evaluated electrophoretically on 7% acrylamide gel in semen of 37 leprosy patients (15 with borderline, 12 with borderline tuberculoid and ten with lepromatous leprosy) and ten fertile men of 30-45 years of age. Significantly lower activities were recorded of LDH1 in all categories of leprosy patients. Similarly, lowering of LDH2 activity was noticed in borderline and lepromatous cases only, lowering of LDH4 activity in lepromatous cases only and LDH5 activity was lowered in borderline leprosy patients. Lowest activity was lowered in borderline leprosy patients. Lowest activity of LDH3 and absence if LDHx were significantly higher. This exceptional increase in activity was found to be due to presence of additional (anomalous) isozymes bands of LDH3, LDHx and LDH4 in 25% of borderline tuberculoid patients. Additional bands of LDH3 have also been located in 40% of the borderline leprosy patients.

5459.   Sreevatsa, Hari M, Gupte MD. Quality control tests for vaccines in leprosy vaccine trial, Avadi. Indian J Lepr. 1998; 74(4), 389-95.  Anopheles virus is found in deep- forested areas where manual surveys are very difficult because of inaccessibility. Geographic Information System (GIS) and a Boolean operator have been used to map areas where the species is likely to be found. Being a forest-based species, thematic maps of forest cover, altitude, rainfall and temperature were prepared. Overlaying and integration of thematic maps were done using Arc/Info NT and analysis by Arc/view 3.1 (GIS ESRI) software. The results were validated through reported distribution and were found correct. The technique can cover vast and inaccessible areas, fast and easily duplicable in other parts of the world. Once the vector distribution is known, species-specific control measures can be formulated.

 

Pathogenesis:

5460.   Brahmbhatt S, Hussain R, Zafar S, Dawood G, Ottenhoff TH, Drijfhout JW, Bothamley G, Smith S, Lopez FV, Dockrell HM. Human T cell responses to peptides of the Mycobacterium leprae 45-kD serine-rich antigen. Clin Exp Immunol. 2002 Apr;128(1):140-8.

 

In order to identify T cell epitopes within the Mycobacterium leprae 45-kD serine-rich antigen, we analysed responses to overlapping 17-mer peptides encompassing the whole antigen in non-exposed UK controls, Pakistani leprosy patients and tuberculosis patients in both the United Kingdom and Pakistan. This antigen has been described as M. leprae-specific, although it has a hypothetical homologue in M. tuberculosis. Human peripheral blood mononuclear cells were stimulated with peptide for 5 days and IFN-gamma measured in supernatants by ELISA. Some peptides were recognized more frequently by T cells from tuberculoid leprosy patients than those from UK controls, suggesting that such T cell epitopes might have diagnostic potential, while other peptides induced greater responses among UK control subjects. Short-term cell lines confirmed that these assays detected specific T cell recognition of these peptides. However, many tuberculosis patients also recognized these potentially specific peptides suggesting that there could be a true homologue present in M. tuberculosis.

5461.   Brophy PJ. Microbiology. Subversion of Schwann cells and the leper's bell. Science. 2002 May 3;296(5569):862-3.  No abstract.

5462.   Chae GT, Kim MJ, Kang TJ, Lee SB, Shin HK, Kim JP, Ko YH, Kim SH, Kim NH. DNA-PCR and RT-PCR for the 18-kDa gene of Mycobacterium leprae to assess the efficacy of multi-drug therapy for leprosy. J Med Microbiol. 2002 May;51(5):417-22.

 

DNA-PCR and reverse transcription (RT)-PCR for the 18-kDa protein of Mycobacterium leprae were used to examine the efficacy of multi-drug therapy (MDT) in leprosy. MDT was administered for 0-24 months. Fourteen (63.6%) of 22 patients showed positive PCR results after treatment for 12 months and the positive results decreased to 30% after 24 months of MDT. These results did not correlate with the bacterial index (BI) or the IgM antibody titre for the phenolic glycolipid (PGL)-1. One-dimensional densitometric analysis of agarose gels from PCR from the longitudinal study showed a gradual reduction of the 360-bp band after 12-24 months of MDT. RT-PCR for mRNA of the 18-kDa protein successfully tracked bacterial RNA changes in the biopsies and confirmed a decrease in the RNA of M. leprae in patients after MDT for 12 months. Thus, DNA- and RT-PCR for the 18-kDa protein of M. leprae are effective in assessing the efficacy of MDT for leprosy.

5463.   Geluk A, van Meijgaarden KE, Franken KL, Subronto YW, Wieles B, Arend SM, Sampaio EP, de Boer T, Faber WR, Naafs B, Ottenhoff TH. Identification and characterization of the ESAT-6 homologue of Mycobacterium leprae and T-cell cross-reactivity with Mycobacterium tuberculosis. Infect Immun. 2002 May;70(5):2544-8.

 

In this paper we describe identification and characterization of Mycobacterium leprae ESAT-6 (L-ESAT-6), the homologue of M. tuberculosis ESAT-6 (T-ESAT-6). T-ESAT-6 is expressed by all pathogenic strains belonging to the M. tuberculosis complex but is absent from virtually all other mycobacterial species, and it is a promising antigen for immunodiagnosis of tuberculosis (TB). Therefore, we analyzed whether L-ESAT-6 is a similarly powerful tool for the study of leprosy by examining T-cell responses against L-ESAT-6 in leprosy patients, TB patients, and exposed or nonexposed healthy controls from areas where leprosy and TB are endemic and areas where they are not endemic. L-ESAT-6 was recognized by T cells from leprosy patients, TB patients, individuals who had contact with TB patients, and healthy individuals from an area where TB and leprosy are endemic but not by T cells from individuals who were not exposed to M. tuberculosis and M. leprae. Moreover, leprosy patients who were not responsive to M. leprae failed to respond to L-ESAT-6. A very similar pattern was obtained with T-ESAT-6. These results show that L-ESAT-6 is a potent M. leprae antigen that stimulates T-cell-dependent gamma interferon production in a large proportion of individuals exposed to M. leprae. Moreover, our results suggest that there is significant cross-reactivity between T-ESAT-6 and L-ESAT-6, which has implications for the use of ESAT-6 as tool for diagnosis of leprosy and TB in areas where both diseases are endemic.

 

5464.   Hailu A. The use of direct agglutination test (DAT) in serological diagnosis of Ethiopian cutaneous leishmaniasis. Diagn Microbiol Infect Dis. 2002 Apr;42(4):251-6.

 

Leishmania aethiopica (L.a.) is the main species of Leishmania that causes Ethiopian cutaneous leishmaniasis (ECL). The routine diagnosis of ECL depends on parasitological examination of smear, culture or biopsy. In this study, DAT was set-up and evaluated for its diagnostic performance using defined sera of 45 ECL patients, 18 visceral leishmaniasis (VL) patients, 12 patients with other diseases, and 37 normal controls. The test was also evaluated in 64 patients clinically diagnosed as ECL, leprosy, or other skin diseases. Using L.a. derived antigen, the sensitivity and specificity of the test was determined to be 90.5% and 91.8% respectively. However, using antigen derived from a non-homologous strain, only 4 sera of 21 active ECL patients were positive. Eighteen sera of VL patients were positive irrespective of the different antigen sources. The data show that DAT can be a useful addition to the diagnosis of ECL.

5465.   Lockwood DN. Leprosy elimination-a virtual phenomenon or a reality? BMJ. 2002 Jun 22;324(7352):1516-8. Review.  No abstract.

5466.   Manandhar R, Shrestha N, Butlin CR, Roche PW. High levels of inflammatory cytokines are associated with poor clinical response to steroid treatment and recurrent episodes of type 1 reactions in leprosy. Clin Exp Immunol. 2002 May;128(2):333-8.

 

Levels of leprosy antigen-induced interferon-gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in 96 leprosy patients with type 1 reactions (T1R) before, during and after a standard 12-week course of steroids. Peripheral blood mononuclear cells (PBMC) from leprosy patients with untreated T1R produced significantly more TNF-alpha than leprosy patients without T1R. Median levels of IFN-gamma and TNF-alpha in T1R patients fell during treatment with steroids; however, TNF-alpha levels increased as the steroid dose was reduced. Median IL-10 levels increased throughout the steroid treatment period and were associated strongly with TNF-alpha levels. Patientswith high cytokine levels had a poorer recovery of sensory or voluntary muscle nerve function, a higher risk of reactivation of symptoms during steroid treatment, and a higher risk of another episode of T1R within 2 months of completing the steroid regimen. Rapid and effective reversal of the inflammatory process in T1R is critical to prevent permanent nerve damage from T1R and monitoring cytokine levels during treatment may be useful.

 

5467.   Mempel M, Musette P, Flageul B, Schnopp C, Remling R, Gachelin G, Kourilsky P, Ring J, Abeck D.  T-cell receptor repertoire and cytokine pattern in granuloma annulare: defining a particular type of cutaneous granulomatous inflammation. J Invest Dermatol. 2002 Jun;118(6):957-66.

Granuloma annulare is a common granulomatous infiltration of the skin of unknown etiopathogenesis. We analyzed granuloma annulare biopsies in 11 patients and could find in all patients significant numbers of CD4-T cells. These cells showed a broad usage of the different T cell receptor Vbeta families and a rather unbiased repertoire when the complementary determining region 3 spectra were analyzed by the Immunoscope technique. Comparison with the peripheral blood mononuclear cell repertoire, however, identified in all patients few skin-specific expansions, which were for one patient also present in two distinct skin sites. Extensive sequence analysis of the complementary determining region 3 region confirmed the presence of a limited number of skin-specific expansions together with various nonspecific T cell infiltrations. Analysis of the intralesional cytokine expression revealed abundant production of interleukin-2, which was not dominant in granulomas from leprosy patients and was not reflected by the cytokine profile in peripheral blood mononuclear cells. These results demonstrate the capacity of the granulomatous response to recruit T cells in high numbers with only few clones expanding specifically. The high local production of interleukin-2 might thereby play an important role in the nonspecific attraction of T cells to the granulomatous site.

5468.   Meyer TN, Thoma A, Fawcett S, Ginty M, Veltry K. Decompression of the common peroneal nerve: experience with 20 consecutive cases. Plast Reconstr Surg. 2002 Apr 15;109(5):1755-6; discussion 1756. No abstract.

5469.   Rambukkana A, Zanazzi G, Tapinos N, Salzer JL. Contact-dependent demyelination by Mycobacterium leprae in the absence of immune cells. Science. 2002 May 3;296(5569):927-31.

 

Demyelination results in severe disability in many neurodegenerative diseases and nervous system infections, and it is typically mediated by inflammatory responses. Mycobacterium leprae, the causative organism of leprosy, induced rapid demyelination by a contact-dependent mechanism in the absence of immune cells in an in vitro nerve tissue culture model and in Rag1-knockout (Rag1-/-) mice, which lack mature B and T lymphocytes. Myelinated Schwann cells were resistant to M. leprae invasion but undergo demyelination upon bacterial attachment, whereas nonmyelinated Schwann cells harbor intracellular M. leprae in large numbers. During M. leprae-induced demyelination, Schwann cells proliferate significantly both in vitro and in vivo and generate a more nonmyelinated phenotype, thereby securing the intracellular niche for M. leprae.

5470.   Rodriguez I, Alvarez EL, Fernandez C, Miranda A. Comparison of a recombinant-antigen enzyme immunoassay with Treponema pallidum hemagglutination test for serological confirmation of syphilis. Mem Inst Oswaldo Cruz. 2002 Apr;97(3):347-9.

 

A recombinant-antigen enzyme immunoassay (EIA), BioSCREEN anti-Treponema pallidum, was compared favorably with the T. pallidum hemagglutination test, in the detection of specific antibodies in different groups of sera from patients with primary (n = 38), secondary (n = 10), early latent (n = 28) and congenital syphilis (n = 2), patients with leptospirosis ( n= 8), infectious mononucleosis (n = 7), hepatitis (n = 9), diabetes mellitus (n = 11), rheumatoid arthritis (n = 13), leprosy (n = 11), tuberculosis (n = 9), HIV/Aids ( n= 12), systemic lupus erythematosus (n = 4), rheumatic fever (n = 3), old-persons (n = 9), pregnant women (n = 29) and blood donors (n = 164). The coincidence between them was 95.1%. The sensitivity and specificity of the EIA were 93.3% and 95.5%, respectively. Fifteen serum specimens belonging to old-persons, pregnant women, blood donors, and patients with human leptospirosis, hepatitis, diabetes mellitus, tuberculosis and rheumatic fever gave false-positive results by Venereal Disease Research Laboratory and/or Rapid Plasma Reagin. The EIA can be used as alternative method for the serological confirmation of syphilis.

5471.   Zumla A, Grange J. Infection and disease caused by environmental mycobacteria. Curr Opin Pulm Med. 2002 May;8(3):166-72. Review.

 

Many species of mycobacteria that normally live as environmental saprophytes, the environmental mycobacteria (EM), are opportunist causes of disease in humans and animals. Many, but not all, cases are associated with some form of immune deficiency. An increasing number of species and clinical presentations are being described, and advances are being made in the understanding of the underlying predisposing factors. In recent years, four aspects of EM disease have become particularly relevant to human health: (1) the high prevalence of EM disease in patients with AIDS; (2) the emergence of Buruli ulcer, an ulcerative skin disease caused by Mycobacterium ulcerans, as the third most prevalent mycobacterial disease; (3) the effect of infection by EM on the immune responses to BCG vaccination and on the course and outcome of tuberculosis and leprosy; (4) the controversy over the involvement of mycobacteria, notably M. avium subspecies paratuberculosis, in human inflammatory bowel disease. These aspects change the status of EM from mere curiosities to important direct, indirect, and putative causes of serious and increasingly common human disease.

 

Vaccines

5472. Gupte MD et al.  Comparative leprosy vaccine trial in South India. Indian J Lepr 1998; 74(4):369-88. Provides results from a controlled, double blind, randomised, prophylactic leprocy vaccine trial conducted in South India. Four vaccines, viz BCG, BCG + killed M. leprae, M. w and ICRC were studied in this trial in comparison with normal saline placebo. From about 300000 people, 216000 were found eligible for vaccination and among them, 171400 volunteered to participate in the study. Intake for the study was completed in two and a half years from January 1991. There was no instance of serious toxicity of side effects subsequent to vaccination for which premature decoding was required. All the vaccine candidate was safe for human use. Decoding was done after the completion  of second survey in December 1998. Results for vaccine efficacy are based on examination of more than 70% of the original “vaccinated” cohort population, in both the first and the second resurveys. It was possible to assess the overall protective efficacy of the candidate vaccines against progressive and serious forms of leprosy. BCG + killed M. leprae provided 64% protection (CI 50.4-73.9), ICMR provided 65.5% protection (CI 1.9-43.8) and BCG gave 34.1% protection (CI 13.5-49.8)…

 

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