MENINGITIS

MENINGITIS

Diagnosis, Diagnostics, Immunodiagnosis & Immunodiagnostics:

January 2003

6172. Akhtar AJ, Alamy ME, Yoshikawa TT. Extrahepatic conditions and hepatic encephalopathy in elderly patients. Am J Med Sci. 2002 Jul;324(1):1-4.

PURPOSE: Extrahepatic conditions can cause, exacerbate, or mimic hepatic encephalopathy in any patient with advanced liver disease, particularly in older persons. The aim of this study was to characterize the clinical features and frequency of extrahepatic conditions and the effect of therapeutic interventions upon the encephalopathy. DESIGN: Survey. SETTING: Inner city community hospital. METHODS: Retrospective chart review of 294 elderly patients (age 65-97) with liver disease and suspected hepatic encephalopathy, during a 15-year period, that included 188 men and 106 women. RESULTS: Extrahepatic conditions were found in 64 patients (22%); 29 (10%) patients had > 1 extrahepatic condition. Category and frequency of the extrahepatic conditions found in these 64 patients were as follows: urinary tract infection, 21 (33%); cellulitis/infected pressure ulcers, 16 (25%); pneumonia, 16 (25%); septicemia (with positive blood cultures), 10 (16%); silent myocardial infarction, 10 (16%); drug toxicity (nonsteroidal anti-inflammatory drugs, sedatives, hypnotics, antidiabetics), 6 (9%); meningitis, 6 (9%); head injury, 5 (8%); stroke, 5 (8%); and subdural hematoma, 5 (8%). CONCLUSION: A significant proportion of elderly patients with liver disease and presumptive diagnosis of hepatic encephalopathy may have extrahepatic condition(s), and the treatment of the latter may improve clinical outcome of such patients. A high index of suspicion, low threshold of diagnostic measures, and prompt treatment of any associated extrahepatic condition are essential to prevent significant morbidity and mortality of these patients.

6173. Baheti R, Laddha P, Gehlot R S. CSF-adenosine deaminase (ADA) activity in various types of meningitis. J. Indian Acad Clin Med 2001; 2(4), 286-7.

Determination of CSF-ADA activity is a reliable to differentiate between and non-tuberculous meningitis. The range of ADA was 6.2 to 21.8 (IU/L) in TBM with a mean of 12.23 (IU/L), while a range between 1.6-5.6 (IU/L) with a mean of 4.37 (IU/L) was noted with pyogenic meningitis. Similarly, ADA levels between 1.11-8.3 (IU/L) with 3.32 (IU/L) mean were observed with aseptic meningitis; whereas a range of 0.33 to 2.8 (IU/L) with a mean of 1.37 observed in control group. CSF-ADA level 6.5 IU/L as a cut –off value of exhibited 95.83% sensitivity and 92.85% specificity in differentiating tuberculosis from non-tuberculous meningitis. CSF – ADA activity is a simple and reliable test in differentiating TBM from other types of meningitis.

6174. Brandt J, Wong C, Mihm S, Roberts J, Smith J, Brewer E, Thiagarajan R, Warady B. Invasive pneumococcal disease and hemolytic uremic syndrome. Pediatrics. 2002 Aug;110(2 Pt 1):371-6.

OBJECTIVE: Severe pneumococcal infections have been associated with hemolytic uremic syndrome (HUS), usually with a poor clinical outcome when compared with Escherichia coli O157 gastroenteritis-associated (D+) HUS. We examined our experience with 12 cases of Streptococcus pneumoniae-associated HUS (SP-HUS) and compare it with a cohort of diarrhea-associated HUS (D+ HUS). METHODS: A retrospective case survey compared 2 unrelated groups of HUS patients. Demographic factors, clinical indices of disease severity, and outcome were used to compare the 2 groups of HUS patients. RESULTS: Twelve children with SP-HUS were studied. Pneumococcal pneumonia with empyema was the most common precipitating illness (67%), pneumococcal meningitis was present in 17% of children, pneumonia with bacteremia in 8%, and both pneumonia and meningitis in 8%. SP-HUS patients were younger than D+ HUS patients (22.1 vs 49 months) and had more severe renal and hematologic disease than D+ HUS patients. Compared with D+ HUS patients, SP-HUS patients were more likely to require dialysis (75% vs 59%) and had a longer duration of hospitalization (33.2 vs 16.1 days) and duration of thrombocytopenia (11.6 vs 6.8 days). SP-HUS patients were also more likely to require platelet transfusions (83% vs 47%) and needed more platelet (4.7 vs 0.5) and packed red blood cell transfusions (7.8 vs 2.0). The 2 groups did not differ significantly in the incidence of extrarenal HUS complications. There were no deaths in either group. Seven patients have been seen for long-term follow-up; 2 developed end-stage renal disease, and 5 have normal renal function. CONCLUSIONS: HUS is a rare but severe complication of invasive pneumococcal infection. Although disseminated intravascular coagulation can also occur in these children, the treatment and follow-up may be different in the 2 conditions. Children with pneumococcal disease and severe hematologic or renal abnormalities should be investigated for evidence of HUS.

6175. Chandramuki A, Lyashchenko K, Kumari HB, Khanna N, Brusasca P, Gourie-Devi M, Satishchandra P, Shankar SK, Ravi V, Alcabes P, Kanaujia GV, Gennaro ML. Detection of antibody to Mycobacterium tuberculosis protein antigens in the cerebrospinal fluid of patients with tuberculous meningitis. J Infect Dis. 2002 Sep 1;186(5):678-83.

Antibodies against Mycobacterium tuberculosis antigens were detected by enzyme-linked immunosorbent assay in cerebrospinal fluid (CSF) samples obtained from 442 patients with tuberculous meningitis (TBM) and 102 control patients. Antibodies were found in the CSF of 87% of patients with clinical (culture-negative) TBM, 72% of patients with culture-positive TBM, and 65% of patients with autopsy-proven TBM. That anti-M. tuberculosis antibodies were detected in the CSF of patients with clinically diagnosed cases more frequently than in patients with culture-positive cases suggests that the detection of antibodies in CSF tends to decrease as bacillary load increases. Of the patients with clinical TBM who were coinfected with human immunodeficiency virus (HIV), 70% exhibited anti-M. tuberculosis antibody in CSF, which suggests that antibody responses in this group were substantially weaker than those in HIV-negative patients with clinical TBM. Some groups showed a stronger response to certain antigens, which suggests that antigen recognition patterns may be specific for the stage of disease.

6176. Davachi F, Bregu H, Lito G. Recurrent Streptococcus pneumoniae meningitis. J Trop Pediatr. 2002 Aug;48(4):249-51. No abstract.

6177. Gilbert B, Menetrey C, Belin V, Brosset P, de Lumley L, Fisher A. Familial isolated congenital asplenia: a rare, frequently hereditary dominant condition, often detected too late as a cause of overwhelming pneumococcal sepsis. Report of a new case and review of 31 others. Eur J Pediatr. 2002 Jul;161(7):368-72. Review.

Congenital isolated asplenia may arise as a minor form of situs abnormalities or result from an unrelated specific defect of spleen development. It is a rare life-threatening condition and pneumococcal sepsis is often the first sign of the disease. We report on the case of a deceased 11-month-old girl and her father who developed recurrent pneumococcal meningitis. The fatal evolution in the girl was due to Streptococcus pneumoniae serotype 23 with intermediate penicillin sensitivity 4 h after amoxicillin (100 mg/kg i.v.) administration. Establishing the diagnosis of congenital isolated asplenia in the case of pneumococcal sepsis can be achieved by performing two easy and non-invasive investigations: searching for Howell-Jolly bodies on blood smears and performing ultrasound examination of the abdomen to look for the spleen. In the case of congenital isolated asplenia, use of appropriate prophylaxis could save the lives of affected children. Our review of the literature yielded 31 cases of congenital isolated asplenia. Thirteen were sporadic and 18 were familial cases involving eight families. CONCLUSION: in the case of Streptococcus pneumoniae sepsis, a systematic search for Howell-Jolly bodies on blood smears and ultrasound examination of the abdomen for the presence of asplenia should be mandatory to detect isolated congenital asplenia. If asplenia is found, potentially life-saving antibiotic prophylaxis and pneumococcal vaccination should be initiated.

6178. Inkelis SH, O'Leary D, Wang VJ, Malley R, Nicholson MK, Kuppermann N. Extremity pain and refusal to walk in children with invasive meningococcal disease. Pediatrics. 2002 Jul;110(1 Pt 1):e3.

OBJECTIVE: Early recognition of invasive meningococcal disease in children may be difficult. Extremity pain and refusal to walk (extremity symptoms) are uncommonly mentioned as clinical findings in children who present with this disease. We sought to determine 1) the frequency of extremity symptoms as part of the clinical presentation in children with invasive meningococcal disease and 2) whether these symptoms help identify children with otherwise unsuspected meningococcal disease. METHODS: We reviewed the medical records of patients who were younger than 20 years and had invasive meningococcal disease from 1985 to 1996 at 3 pediatric referral centers. Children with extremity symptoms were identified and described. We compared clinical and laboratory findings and frequency of adverse outcomes between these children and those with invasive meningococcal disease without extremity symptoms. RESULTS: We identified 274 children with invasive meningococcal disease, 45 (16%) of whom had either history or physical examination evidence of extremity pain (31) or refusal to walk (14) as part of their clinical presentations. Five of the 45 patients had arthritis at the time of presentation. Patients with extremity symptoms at presentation were significantly older (77.9 +/- 62.2 vs 44.0 +/- 56.9 months), had lower temperatures (38.8 +/- 1.2 degrees C vs 39.2 +/- 1.2 degrees C), and had higher band counts (28.2 +/- 15.2% vs 18.1 +/- 12.4%) than did patients without extremity symptoms. There were no significant differences, however, between groups with regard to rash, white blood cell counts, coagulation parameters, prevalence of meningitis, or adverse outcomes. Seventy-three (27%) of the 274 patients had unsuspected disease, and 5 (7%) of these had extremity symptoms at the time of diagnosis. CONCLUSIONS: Sixteen percent of children with invasive meningococcal disease have extremity symptoms at the time of diagnosis. These symptoms may help to identify some patients with otherwise unsuspected invasive meningococcal disease.

6179. John A J P, Lalitha M K, Cherian T, Pai R, Thomas K, Steinhoff M C. Polymerase chain reaction – enzyme immunoassay for diagnosis of pneumococcal meningitis in children and adults. Indian J med Res 2001; 113 (Feb), 48-52. No abstract.

6180. Lanska DJ. Anthrax meningoencephalitis. Neurology. 2002 Aug 13;59(3):327-34. Review.

OBJECTIVE: To review reported cases of anthrax meningoencephalitis and describe the clinical findings, diagnostic test results, treatment, and outcome over the past 50 years. METHODS: Retrospective review of English language articles published since Haight's (1952) review. RESULTS: Thirty-four core articles were identified, describing 70 patients with cutaneous (29%), gastrointestinal (17%), inhalational (39%), and unknown (16%) sources of infection. Clinical signs on presentation included fever, malaise, meningeal signs, hyperreflexia, and delirium, stupor, or coma. CSF analyses demonstrated hemorrhagic meningitis, with positive Gram's stains and CSF cultures. Many patients presented in extremis following a prodromal period of 1 to 6 days, and 75% died within 24 hours of presentation. Despite aggressive treatment in many cases, only 6% (4 of 70) survived, none of whom had pulmonary anthrax. Surviving patients generally had a cutaneous portal of entry, were younger, and had less severely abnormal initial CSF results than patients who died. Most of the survivors recovered fully. Pathologic findings included hemorrhagic meningitis, multifocal subarachnoid and intraparenchymal hemorrhages, vasculitis, and cerebral edema. CONCLUSIONS: Anthrax meningoencephalitis has a high case-fatality rate, even with aggressive antibiotic treatment and supportive therapy. Hemorrhagic meningitis should raise suspicion of anthrax infection, particularly if gram-positive rods are demonstrated on Gram's stain. Anthrax meningoencephalitis can develop from any primary focus, but survival appears to be most likely if meningoencephalitis develops from cutaneous anthrax. Treatment of surviving patients was generally begun before signs and symptoms of meningoencephalitis were present.

6181. Martinez E, Miro JM, Almirante B, Aguado JM, Fernandez-Viladrich P, Fernandez-Guerrero ML, Villanueva JL, Dronda F, Moreno-Torrico A, Montejo M, Llinares P, Gatell JM. Effect of penicillin resistance of Streptococcus pneumoniae on the presentation, prognosis, and treatment of pneumococcal endocarditis in adults. Clin Infect Dis. 2002 Jul 15;35(2):130-9.

We performed a clinical study of pneumococcal endocarditis (PE) in adults at 15 major Spanish hospitals during a 21-year period (1978-1998). During this time, 63 patients had PE due to Streptococcus pneumoniae diagnosed. Of the 63 isolates recovered from these patients, 24 (38%) and 6 (10%) showed resistance to penicillin (minimum inhibitory concentration [MIC], 0.1-4 microg/mL) and cefotaxime (MIC, 1 microg/mL), respectively. Twenty-two (35%) of the patients died. Left-side heart failure, but not penicillin resistance, was independently associated with a higher risk of death (odds ratio, 1.33; 95% confidence interval, 1.04-1.71; P=.026). Patients without meningitis who had PE due to penicillin-resistant S. pneumoniae could be treated with high-dose penicillin or a third-generation cephalosporin if the MIC for penicillin was < or =1 microg/mL. For patients with concurrent meningitis, high doses of cefotaxime could be used if the MIC for cefotaxime was < or =1 microg/mL. Early recognition of heart failure and surgery may help to decrease mortality.

6182. McCracken GH Jr. Rich nations, poor nations, and bacterial meningitis. Lancet. 2002 Jul 20;360(9328):183. No abstract.

6183. Pantosti A, Gherardi G, Conte M, Faella F, Dicuonzo G, Beall B. A novel, multiple drug-resistant, serotype 24F strain of Streptococcus pneumoniae that caused meningitis in patients in Naples, Italy. Clin Infect Dis. 2002 Jul 15;35(2):205-8.

Three adult patients in Naples, Italy, had meningitis due to multiple drug-resistant serotype 24F Streptococcus pneumoniae isolates. The 3 isolates were genetically indistinguishable and shared pbp2b and pspA sequence types with previously characterized penicillin-resistant clones. This serotype 24F strain was found to be the same clonal type as a previously characterized, penicillin-resistant serotype 14 strain. The novel strain has probably arisen through transformation of a serotype 14 strain with type 24F capsular biosynthetic operon sequences.

6184. Saghari S, Woolery-Lloyd H, Nouri K. Squamous cell carcinoma in a patient with Netherton's syndrome. Int J Dermatol. 2002 Jul;41(7):415-6.

A 29-year-old white woman with a history of Netherton's syndrome presented with two squamous cell carcinomas on the right dorsal hand and the left upper arm. She reported a 2-year history of these lesions, which were originally treated as warts. She denied excessive sun exposure, immunosuppressive therapy, or a previous history of skin cancer. Her past medical history included acute renal failure, multiple urinary tract infections, meningitis, and recurrent otitis media as a child. In addition, she had an ovarian abscess at 4 years of age with resulting salpingo-oophorectomy. She also reported a history of severe myopia, glaucoma, and multiple ocular infections with a resulting corneal scar. In addition to atopic dermatitis, she had a 10-year history of psoriasis. Her medications included topical steroids and emollients for atopic dermatitis and psoriasis, in addition to Timolol ophthalmic drops for glaucoma. Her family history was significant for a 22-year-old sister with Netherton's syndrome (Fig. 1). She denied any history of skin cancer in her sister or other members of her family. On physical examination, she had an exfoliative erythroderma, madarosis, and diffuse patchy alopecia. In the bilateral axilla, she had well-defined pink scaly plaques which were confirmed as psoriasis by biopsy. On the right dorsal hand, she had a 1.5 x 1.0 cm pink verrucous plaque (Fig. 2). On the left upper arm, she had a 1.5 x 0.8 cm pink scaly plaque. Biopsies of both sites confirmed squamous cell carcinomas. Both lesions were completely excised with 4 mm margins.

6185. Thomas KE, Hasbun R, Jekel J, Quagliarello VJ. The diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity in adults with suspected meningitis. Clin Infect Dis. 2002 Jul 1;35(1):46-52.

To determine the diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity for meningitis, 297 adults with suspected meningitis were prospectively evaluated for the presence of these meningeal signs before lumbar puncture was done. Kernig's sign (sensitivity, 5%; likelihood ratio for a positive test result [LR(+)], 0.97), Brudzinski's sign (sensitivity, 5%; LR(+), 0.97), and nuchal rigidity (sensitivity, 30%; LR(+), 0.94) did not accurately discriminate between patients with meningitis (>/=6 white blood cells [WBCs]/mL of cerebrospinal fluid [CSF]) and patients without meningitis. The diagnostic accuracy of these signs was not significantly better in the subsets of patients with moderate meningeal inflammation (>/=100 WBCs/mL of CSF) or microbiological evidence of CSF infection. Only for 4 patients with severe meningeal inflammation (>/=1000 WBCs/mL of CSF) did nuchal rigidity show diagnostic value (sensitivity, 100%; negative predictive value, 100%). In the broad spectrum of adults with suspected meningitis, 3 classic meningeal signs did not have diagnostic value; better bedside diagnostic signs are needed.

6186. Totan M. Recurrent pneumococcal meningitis in homozygous C3 deficiency. Indian J Pediatr. 2002 Jul;69(7):625-6.

Congenital deficiencies of complement system proteins are rare. A 4-year-old girl was admitted for meningitis. She had had repeated attacks of pneumococcal meningitis and otitis media at the age of 3 years. Analysis of cerebrospinal fluid showed that this meningitis was due to pneumococcal infection. Complement 3 and CH50 values of the proband and her brother were low, while her parents were normal. The patient was given polyvalent pneumococcal and anti-haemophilus vaccines plus ceftriaxone. Recovery was complete after 15 days of antibiotic therapy. This is the first description of a case of recurrent meningitis with C3 and CH50 deficiency in a Turkish family.

6187. Webb M, Ziauddin A, Okusa MD. Coccidioidomycosis meningitis and syndrome of inappropriate antidiuretic hormone. Am J Med Sci. 2002 Sep;324(3):155-7.

The syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been well described in patients with meningeal spread from metastatic carcinomatosis and bacterial or mycobacterial infections. We describe a 39-year-old white man who was diagnosed with coccidioidomycosis pneumonia 7 years before presentation. He displayed evidence for meningitis with the onset of SIADH. We reviewed the diagnosis of coccidioidomycosis and radiological findings in the central nervous system. Last, we discussed the findings that led to the diagnosis of SIADH.

6188. Yazawa S, Kawasaki S, Fujimoto C, Ohi T. Case report of meningoencephalitis during a concomitant mumps and parvovirus B19 infection. Clin Neurol Neurosurg. 2002 Sep;104(4):380-2.

A 19-year-old, immunologically healthy man suffered from prolonged and intermittent high fever, left parotitis, systemic lymph node swelling, progressive liver dysfunction and leukocytopenia. 11 days after the fever onset, consciousness disturbance and generalized convulsion occurred. By the administration of gamma-globulin and steroid, the patient recovered completely. Serum titers of IgG and IgM specific for both human parvovirus B19 and mumps were elevated, and parvovirus B19 DNA was identified in the serum. It was speculated that overlap infection of mumps and parvovirus B19 made the disease more severe in this patient.

Pathogenesis:

6189. Blattman JN, Cheng LE, Greenberg PD. CD8(+) T cell responses: it's all downhill after their prime. Nat Immunol. 2002 Jul;3(7):601-2. No abstract.

6190. Chretien F, Lortholary O, Kansau I, Neuville S, Gray F, Dromer F. Pathogenesis of cerebral Cryptococcus neoformans infection after fungemia. J Infect Dis. 2002 Aug 15;186(4):522-30.

The pathogenesis of cerebral infection after Cryptococcus neoformans fungemia in outbred mice was investigated. Confocal microscopy and cultures on ficoll-hypaque gradient-separated blood cells were used to detect yeasts in the cytoplasms of monocytes. In semithin brain sections, poorly capsulated yeasts were seen in macrophages in the leptomeningeal space, in monocytes circulating in leptomeningeal capillaries, or in the endothelial cells themselves, strengthening the hypothesis that monocytes and endothelial cells play key roles in the pathogenesis of cryptococcal meningitis. Similar fungal loads and cellular reactions were seen in mice and in 1 patient with acquired immune deficiency syndrome (AIDS), all with acute cryptococcal meningoencephalitis, and in mice and in 1 patient with AIDS, all with cured cryptococcal infection. Immunostaining revealed both the presence of cryptococcal polysaccharide in various brain cells and antigenic variability both from yeast cell to yeast cell and over time. Thus, our data established the relevance and interest that this experimental model has for investigation of the pathogenesis of human cryptococcal meningitis.

6191. George CN, Letha S, Bai SS. A clinical study of chronic morbidity in children following pyogenic meningitis. Indian Pediatr. 2002 Jul;39(7):663-7. No abstract.

6192. Johnson JR, Russo TA. Uropathogenic Escherichia coli as agents of diverse non-urinary tract extraintestinal infections. J Infect Dis. 2002 Sep 15;186(6):859-64.

Escherichia coli isolates from 3 consecutively encountered patients with serious, invasive, non-urinary tract extraintestinal infections (pneumonia, deep surgical wound infection, and vertebral osteomyelitis with associated epidural/psoas/iliacus abscesses) were characterized, using molecular methods, as to extended virulence genotype and phylogenetic background. All 3 isolates exhibited virulence genotypes and genomic profiles characteristic of specific familiar virulent clones of extraintestinal pathogenic E. coli (ExPEC), which traditionally have been regarded primarily as uropathogenic or as associated with meningitis. These included E. coli O1/O2:K1:H7, E. coli O18:K1:H7, and a recently described E. coli O11/O17/O77:K52:H18 clonal group (clonal group A). These findings demonstrate the extraintestinal pathogenic versatility of ExPEC clones, which supports the use of an inclusive designation for such strains and suggests the possibility of cross-syndrome protective interventions. They also provide novel evidence that multidrug-resistant epidemic clonal group A can cause extraintestinal infections other than uncomplicated urinary tract infections and can cause them in hosts other than young women.

6193. Josefson D. Cochlear implants carry risk of meningitis, agencies warn. BMJ. 2002 Aug 10;325(7359):298. No abstract.

Vaccines:

6194. Furesz J. Safety of live mumps virus vaccines. J Med Virol. 2002 Jul;67(3):299-300. No abstract.

6195. Perez-Trallero E, Vicente D, Montes M, Cisterna R. Positive effect of meningococcal C vaccination on serogroup replacement in Neisseria meningitidis. Lancet. 2002 Sep 21;360(9337):953. No abstract.

6196. Wuorimaa T, Kayhty H. Current state of pneumococcal vaccines. Scand J Immunol. 2002 Aug;56(2):111-29. Review.

Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and acute otitis media in children and adults worldwide. According to World Health Organization estimates, at least 1 million children under 5 years of age die each year from pneumococcal pneumonia. The emergence of resistant strains necessitates the development of an effective vaccine with a large serotype coverage. The 11 most common serotypes cause 72-83% of all serious pneumococcal diseases worldwide. Currently marketed 23-valent pneumococcal polysaccharide vaccine provides large serotype coverage and offers a less expensive option. However, it is efficacious only in adults but not in infants. Conjugate vaccines offer a solution by generating immunological memory already at early age. A recently licensed 7-valent conjugate vaccine is immunogenic and efficacious in infants. Its serotype coverage might be sufficient in Europe and North America, but not in Africa, Asia and Oceania. A need exists to develop pneumococcal vaccines with lower cost and larger serotype coverage. Several 11-valent pneumococcal conjugate vaccines are being evaluated in phase I-III trials. This study reviews the current state of pneumococcal problem and pneumococcal vaccines in clinical use.

Therapy:

6197. Krysan DJ, Kemper AR. Claims of equivalence in randomized controlled trials of the treatment of bacterial meningitis in children. Pediatr Infect Dis J. 2002 Aug;21(8):753-8.

OBJECTIVE: To evaluate claims of therapeutic equivalence in studies of the treatment of bacterial meningitis in children. METHODS: We performed a systematic review of randomized controlled trials of antimicrobial therapy for bacterial meningitis in children indexed in MEDLINE and published after 1980 and that claimed equivalency. The sample size of each trial was compared with the minimum sample size needed to rigorously claim equivalence. The primary endpoint was case fatality. RESULTS: Twenty-five studies were identified that met the inclusion criteria. Two of these were specifically designed to test equivalence, and the remaining based claims of equivalence on failed tests of superiority. The majority of these trials (24 of 25) that claimed equivalence had sufficient sample size to exclude a 20% difference in mortality between the tested therapies. Only 3 of the 25 trials could exclude a 10% difference in mortality. CONCLUSION: Few of the trials in this study had sufficient sample size to claim equivalence within 10% of the expected mortality. Proving equivalency is challenging because large sample sizes are often needed to ensure adequate statistical power to rule out clinically important differences between the standard of care and new therapies.

6198. Singh UK, Prasad R, Kumar R, Jaiswal BP. Management of diarrhoea in practice. Indian J Pediatr. 2002 Aug;69(8):687-95.

Diarrhoea, a major cause of morbidity and mortality can be produced by a variety of etiological factors. Management protocol includes assessment of the child, physical examination, lab-evaluation, assessment of severity of dehydration and rehydration therapy using either of the following - WHO - ORS, Home available fluids (HAF), sugar salt solution (SSS), improve WHO-ORS, Amino acid fortified ORS, rice based ORS, low osmolarity ORS. Intravenous fluids are required if patients can't accept orally. Commonly observed electrolyte disturbances are hypernatremia, hyponatremia and hypokalemia. Concussion is a common problem and can result due to electrolyte imbalance, cavernous sinus thrombosis, associated meningitis, shigella encephalopathy and hypoglycemia in undernourished children. Treatment includes i.v. diazepam and i.v. glucose and correction of electrolyte imbalance. Additional treatment interventions include antimicrobial drugs including antibiotics, antimotility drugs, absorbents, nutritional and micro and macro nutrient supplementation.

April 2003

6812. Boyle RJ, Curtis N, Kelly N, Garland SM, Carapetis JR.Clinical implications of inducible beta-lactamase activity in Gram-negative bacteremia in children. Pediatr Infect Dis J. 2002 Oct;21(10):935-40.

BACKGROUND: Organisms of the spp., indole-positive spp., spp. and (ESCaPPM) group are a common cause of hospital-acquired bacteremia and share the potential to develop beta-lactam resistance during therapy. The emergence of such resistance may have adverse consequences, but the frequency with which this occurs has not been studied in children. It has been suggested that such organisms should be treated with combination antimicrobials or carbapenems, but the optimal regimen is uncertain.AIM To determine the frequency with which beta-lactam resistance develops during ESCaPPM sepsis in children and the optimal treatment of such sepsis. METHODS: A review of the case notes and microbiologic records of all cases of ESCaPPM bacteremia and meningitis managed at a tertiary children's hospital during a 6-year period. RESULTS: Fifty-eight cases were identified, and in three (5%) cases beta-lactam resistance emerged during treatment, with adverse clinical consequences in two cases. Clinical and microbiologic outcome was similar in those treated with carbapenems and in those treated with a beta-lactam and aminoglycoside combination. Cefotaxime resistance was found in 57, 30, 24 and 7% of children who had received carbapenems, cephalosporins, penicillins or no/other antimicrobials in the month before ESCaPPM sepsis, respectively.

CONCLUSIONS: The emergence of beta-lactam resistance during treatment of ESCaPPM sepsis is uncommon in our hospital but can have adverse consequences. Where isolates are reported as susceptible to both classes of drugs, an extended spectrum penicillin in combination with an aminoglycoside may be preferable first line treatment of ESCaPPM sepsis to a carbapenem or quinolone.

6813. Bui TT, Delgado CA, Simon HK. Infant seizures not so infantile: first-time seizures in children under six months of age presenting to the ED. Am J Emerg Med. 2002 Oct;20(6):518-20.

Data regarding first-time seizures in children <or=6 months of age is limited. This retrospective study, therefore, reviews the presentation, management, and outcome of children <or=6 months of age presenting to a pediatric tertiary care facility with a first-time seizure. Charts for 31 patients were identified and reviewed. Nineteen patients (61%) received sepsis work-ups. Two of the 31 (7%) had infectious etiologies. One of these infants, a 3-month-old who presented with only a history of fever and eyes rolling back but otherwise appeared well on initial presentation, had pneumococcal meningitis. Neuroimaging studies were performed in 22 (71%) patients with 12 of 22 (54%) having abnormal findings. Electroencephalogram (EEGs) were performed on 22 patients (71%) with 11 (50%) showing seizure activity. Electrolytes were checked on 19 patients (61%) with 5 being clinically significant. Etiologies included idiopathic (32%), congenital anomalies (26%), inborn errors of metabolism (16%), electrolyte abnormalities (16%), infection (7%), and trauma (3%). In conclusion, unlike children >6 months of age in whom febrile seizures and idiopathic seizure disorders are most common, a large percentage of children <or=6 months of age presenting with first-time seizures have significant underlying pathology. This pathology often includes immediately life-threatening conditions in these children who may look deceptively well on initial evaluation. Copyright 2002, Elsevier Science (USA).

6814. Chadwick DR, Lever AM. The impact of new diagnostic methodologies in the management of meningitis in adults at a teaching hospital. QJM. 2002 Oct;95(10):663-70.

BACKGROUND:Suspected meningitis is a frequent reason for admission to hospital in the UK. While bacterial meningitis requires prompt antibiotic therapy to reduce mortality and morbidity, enteroviral meningitis, the most frequent viral cause, is almost invariably a benign disease. Aim: To determine the clinical presentation, laboratory findings and outcome of meningitis by microbiological aetiology and patient age, and to assess the clinical management of adults presenting with meningitis, with reference to national guidelines. DESIGN:Retrospective case-note review. METHODS:Adult (>14 years) admissions to Addenbrooke's Hospital with meningitis or meningococcal septicaemia March 1996-September 2001 were audited retrospectively. The case definition was: symptoms compatible with meningitis, and either abnormal CSF (leukocytes >5x10(9)/ml) or meningococcal disease. The only exclusion criterion was the presence of a ventricular shunt. RESULTS:Only 30% of patients seen by a General Practitioner were given pre-admission antibiotics. In a substantial number of cases, including those with bacterial meningitis, antibiotic administration was delayed either because patients were sent for CT head scans (delaying a lumbar puncture) or because the diagnosis was not considered, especially in elderly patients with reduced conscious levels. There were no confirmed cases of H. influenzae meningitis. Overall outcomes in terms of mortality and disability were similar to UK national data. A surprising number of patients (40%) were afebrile on admission.

DISCUSSION:The proportion of patients with meningitis given pre-hospital antibiotics by GPs is still worryingly low, although early hospital management has improved. Improved diagnostic facilities, particularly viral PCR assays, reduce antibiotic usage and hospital stay, with considerable financial savings.

6815. Chinchankar N, Mane M, Bhave S, Bapat S, Bavdekar A, Pandit A, Niphadkar KB, Dutta A, Leboulleux D.Diagnosis and outcome of acute bacterial meningitis in early childhood. Indian Pediatr. 2002 Oct;39(10):914-21.

OBJECTIVE: To estimate frequency of acute bacterial meningitis (ABM) in early childhood in hospital admissions, to describe clinical and diagnostic features, and to analyze mortality, complications and long term sequelae. DESIGN: Prospective study. SETTING: Pediatric wards and Rehabilitation Center of KEM Hospital, Pune. METHOD: Study subjects between the ages of 1 months to 5 years with ABM were recruited. Clinical details were recorded. CSF was analysed by routine biochemical methods, antigen detection tests (Latex agglutination LAT) and microbiological studies on special media. Management was as per standard rotocols. Survivors were followed up long term with neurodevelopmental studies and rehabilitation programmes. RESULTS: In a study period of 2 years, 54 children (1.5% of all admissions) satisfied the criteria of ABM in early childhood; 78% were below one year and 52% were under the age of six months. Chief presentation was high fever, refusal of feeds, altered sensorium and seizures. Meningeal signs were present in only 26%. CSF C-reactive protein was positive in 41%, gram stain was positive in 67% LAT in 78% and cultures grew causative organisms in 50% of the cases. The final etiological diagnosis (as per LAT and/or cultures) were Streptococcus pneumoniae 39% Hemophilus influenzae type b 26% and others in 35% The others included one case of Neisseria meningitidis and 10 who were LAT negative and culture sterile. 39% patients developed acute neurological complications during the hospital course. 31% children with ABM died in hospital or at home soon after discharge. Six were lost to follow up. Of the 31 children, available for long term follow up (1-3 years), 14 (45%) had no sequelae. The remaining had significant neurodevelopmental handicaps ranging from isolated hearing loss to severe mental retardation with multiple disabilities.

CONCLUSION: ABM in early childhood has a considerable mortality, morbidity and serious long term sequelae. Neurodevelopmental follow up and therapy should begin early. Etiological diagnosis can be enhanced by LAT and good culture media. H. influenzae b and S. pneumoniae account for more than 60% of ABM in early childhood.

6816. Chitkara MB, Ryan LM, Stockwell D, Wiedermann BL. Can a clinical decision rule decrease antibiotic use in viral meningitis? Arch Pediatr Adolesc Med. 2002 Dec;156(12):1195-8. No abstract.

6817. Nashkevich NN, Akalovich S, Louneva N, Heavner GA, Voitenok NN. A monoclonal antibody and an enzyme immunoassay for human Ala-IL-8(77).J Immunol Methods 2002 Dec 1;270(1):37-51

Interleukin-8 (IL-8) plays a central role in neutrophil chemotaxis and exerts a wide range of effects on various cells, ranging from tumor angiogenesis to impairment of neuronal signaling. Two main forms of IL-8 exist, one containing 77 amino acids (Ala-IL-8(77)) and a second containing 72 amino acids (Ser-IL-8(72)), which comprise more than 90% of IL-8 protein in cell cultures. IL-8(77) was reported to be produced predominantly by endothelial cells and is known as "endothelial" IL-8. IL-8(72) predominates in monocyte cultures and is known as "leukocyte" IL-8. While both forms have equal chemotactic activity in vivo, recent data suggest that their biological activities might be different. Here we describe the generation of a mouse monoclonal antibody (mAb) specific for IL-8(77) and the development of a corresponding immunoassay. Various immunization protocols were investigated. Immunization with conjugates of a peptide from the N-terminus of IL-8(77) (NTP(77)) resulted in the production of an IgG1 mAb (N11) that recognizes human IL-8(77) and neutralizes its chemotactic activity. A sensitive ELISA specific for IL-8(77) was developed using N11 for capture and a biotinylated mAb to IL-8(72) for detection. Using this immunoassay it was shown that the only form of IL-8 secreted in cell culture was IL-8(77) and that the IL-8(72) present was the result of proteolysis of IL-8(77). IL-8(77) was detected in plasma and cerebrospinal fluid (CSF) from patients with sepsis and meningitis.

6818. Patel VB, Bhigjee AI, Bill PL, Connolly CA.Cytokine profiles in HIV seropositive patients with tuberculous meningitis.J Neurol Neurosurg Psychiatry 2002 Nov;73(5):598-9 No abstract.

Pathogensis:

6819. Bulgan T, Gilbert CE. Prevalence and causes of severe visual impairment and blindness in children in Mongolia. Ophthalmic Epidemiol. 2002 Oct;9(4):271-81.

BACKGROUND: Reliable epidemiological data on the prevalence and causes of visual loss in children are difficult to obtain, but are essential for planning. No such data are available from Mongolia. AIM: To determine the prevalence and causes of severe visual impairment and blindness (SVI/BL) in children from a defined area of Mongolia, using several methods of identification. METHODS: Children with presenting visual acuities of <6/60 in the better eye who lived in 10 of the 18 provinces (Aimaks) were identified 1) by family doctors 2) in the school for the blind 3) by visiting eye departments in the capital. All eligible children were examined (or data extracted from hospital records) and the cause of visual loss determined using the WHO classification system. RESULTS: Sixty-four children with SVI/BL before refraction were identified who lived in the 10 study Aimaks. They were recruited by family doctors (52); by home visits (3); from hospital records (4); or from the school for the blind (5). The prevalence of SVI/BL before refraction was 0.19/1,000 children (95% CI 0.16-0.22), decreasing to 0.16/1,000 after refraction (95% CI 0.13-0.19) but there was considerable variation from Aimak to Aimak. The major causes of SVI/BL were lesions of the lens (34%), central nervous system disorders (19%), lesions of the whole globe (e.g. microphthalmos) (14%), and retinal conditions (12.5%). Hereditary factors were responsible for 27% of causes, and 17% of children were blind following acquired conditions of childhood. The underlying cause could not be determined in 48%. The causes of SVI/BL was analysed in a further 16 children who lived outside the study Aimaks to compare the causes in children in special education with those not in schooling, and by age. CONCLUSION: The prevalence estimate obtained was lower than anticipated, and possible reasons are discussed. The pattern of causes of SVI/BL is similar to that in children in schools for the blind in China, but is very different from other Asian countries. Meningococcal meningitis was the most common preventable cause of SVI/BL, and immunisation is being considered. Other preventable causes were rare, and the majority of children needing surgical intervention had already been identified and referred for treatment. The control of blindness in children could possibly be improved by better management of conditions requiring surgery, and by the provision of low vision devices.

6820. Geyik MF, Kokoglu OF, Hosoglu S, Ayaz C.Acute bacterial meningitis as a complication of otitis media and related mortality factors. Yonsei Med J. 2002 Oct;43(5):573-8.

The aim of this study was to evaluate the characteristics of patients with acute bacterial meningitis (ABM) developed secondary to acute and chronic otitis media (OM). Between 1991 and 2001, among 269 adult patients with ABM, 56 who were secondary to OM were included in the study. We reviewed the charts of patients who were diagnosed as ABM following acute or chronic OM. Risk factors associated with mortality were determined by using a logistic regression model. The mean age of the patients, 38 male and 18 female, was 25.8 +/- 10.8 years (range 14 - 65). Forty-four of these cases (79%) have had chronic OM, of whom 19 (43% of the 44) have also had chronic mastoiditis and 12 (27% of the 44) acute OM. Twenty-three patients (41%) died, during either hospitalization or the follow-up period. Univariate analysis revealed comatose mental status on admission, inappropriate antibiotic treatment before admission, and elevated erythrocyte sedimentation rate (ESR) as significant risk factors for mortality. In multifactorial analysis, comatose mental status (OR=42.5, CI=6.4-280.1, p=0.001) and elevated ESR (OR=1.0, CI=1.01-1.07; p=0.005) remained as significant predictors for mortality. In conclusion, the primary sources of infection leading to the development of ABM should be investigated carefully to reduce the morbidity and mortality rates. It is hoped that this study will raise awareness among general practitioners and otolaryngologists concerning the role of ABM as one of the most important complications of OM.

6821. Kubo S, Takimoto H, Hosoi K, Toyota S, Karasawa J, Yoshimine T.Osteomyelitis of the odontoid process associated with meningitis and retropharyngeal abscess--case report. Neurol Med Chir (Tokyo). 2002 Oct;42(10):447-51.

A 52-year-old man complaining of headache and nuchal pain was treated initially under a diagnosis of bacterial meningitis. The meningitis resisted antibiotic therapy, and one week later was complicated by a ruptured retropharyngeal abscess, which led to the correct diagnosis of osteomyelitis of the odontoid process of the axis. His neck was immobilized in a high neck collar and the retropharyngeal abscess was treated by repeated drainage and irrigation. A long course of antibiotic administration finally resolved the infection. Osteomyelitis of the odontoid process is rare and presents with peculiar signs and symptoms. Careful consideration of the differential diagnosis is needed for the early detection of this potentially serious condition.

6822. Leask SJ, Done DJ, Crow TJ.Adult psychosis, common childhood infections and neurological soft signs in a national birth cohort. Br J Psychiatry. 2002 Nov;181:387-92.

BACKGROUND: Neurological soft signs preceding adult-onset schizophrenia suggest a neurodevelopmental origin and could reflect physical illness in childhood. AIMS: To investigate possible associations of adult-onset psychosis with neurological soft signs and common infectious illnesses in childhood. METHOD: Using data from the UK National Child Development Study, a longitudinal general population sample, odds ratios were calculated for clinical diagnoses of common childhood viral illnesses and later adult psychotic illness, childhood epilepsy and a range of neurological soft signs. RESULTS: The number of illnesses per individual did not relate either to the number of soft signs, or to any particular adult outcome. Schizophrenia, affective psychosis and epilepsy were not associated with common childhood illness but were associated with neurological soft signs and an increased, but small, frequency of previous meningitis and tuberculosis. CONCLUSIONS: Overall the data support the notion of neurological soft signs as markers of disordered neurodevelopment in schizophrenia (but the early neurological abnormalities are not caused by infectious illness) and an association between meningitis or tuberculosis in childhood and a small proportion of cases of epilepsy, affective psychosis and schizophrenia.

Vaccines:

6823. Zhou F, Bisgard KM, Yusuf HR, Deuson RR, Bath SK, Murphy TV.Impact of universal Haemophilus influenzae type b vaccination starting at 2 months of age in the United States: an economic analysis. Pediatrics. 2002 Oct;110(4):653-61.

OBJECTIVE: To evaluate the economic impact of universal Haemophilus influenzae type b (Hib) vaccination starting at 2 months of age. METHODS: Decision-tree-based analysis was conducted of a hypothetical US birth cohort of 3 815 469 infants using population-based vaccination coverage and disease incidence data. All costs were estimated from both the direct cost (medical and nonmedical) and societal perspectives. Net present value, cost-effectiveness ratios, and benefit-cost ratios of the US Hib vaccination program were evaluated. RESULTS: The results of these analyses showed that the universal vaccination program using the Hib conjugate vaccines in the United States in 2000 was cost-saving from both the direct and societal perspectives, with the benefit of the Hib vaccination program (net present value) from the direct cost and societal perspectives of $0.95 billion and $2.09 billion, respectively. Without a Hib vaccination program, the direct and societal costs of Hib invasive cases would be $1.35 billion and $2.58 billion, respectively. The direct and societal costs of the Hib vaccination program were estimated at $0.39 billion and $0.48 billion, respectively. The direct and societal benefit-cost ratios for the Hib vaccination program were 3.4 and 5.4, respectively. Varying the proportion of vaccines purchased and administered in the public versus the private sector and the proportion of combination vaccine versus monovalent vaccine administered did not have much effect on the results.

CONCLUSIONS: Regardless of the perspective (direct cost or societal) and the assumptions used, the benefit-cost ratios of the US vaccination program are >1.0. Potential changes in the program, including use of more or less Hib combination vaccines, would not significantly alter the benefit-cost ratio. The national Hib vaccination program is highly cost beneficial and results in substantial cost savings.

Therapy:

6824. Irazuzta JE, Pretzlaff RK, Zingarelli B, Xue V, Zemlan F. Modulation of nuclear factor-kappaB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis. Crit Care Med. 2002 Nov;30(11):2553-9.

OBJECTIVE: This study was designed to evaluate the use of moderate hypothermia in a model of meningitis-induced brain injury and its effect on the activation of nuclear factor-kappaB, biological markers of neuronal injury, and neurobehavioral performance. DESIGN: Randomized, prospective animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Animals underwent a basilar cistern tap receiving either sterile saline as a placebo or an equivalent volume of a group B streptococcal suspension. Sixteen hours after inoculation, animals were stratified by their clinical severity score, were randomized to either hypothermic (32-34 degrees C) or normothermic (37-39 degrees C) conditions, and received antibiotics. Hypothermic animals were kept under these temperature conditions for 6 hrs before rewarming. Two protocols were used. For the first protocol, changes in nuclear factor-kappaB activation and heat shock protein induction at 24 hrs and 48 hrs after inoculation were evaluated. In the second protocol, serum C-tau concentrations at 5 days and neurobehavioral performances at 3 wks were assessed. MEASUREMENTS AND MAIN RESULTS: Meningitis triggered a >50% increase in cerebral nuclear factor-kappaB activation. The addition of a 6-hr period of hypothermia reduced nuclear factor-kappaB activation by 32% when measured at the end of the hypothermic period. At 48 hrs, this decrease in nuclear factor-kappaB activation was no longer apparent, but there was a significant decrease in the heat shock response. Serum C-tau concentrations at 5 days postinjury, a biomarker of brain injury, were reduced by 69% in hypothermic treated animals. Furthermore, hypothermia reduced the brain water content of infected animals. However, hypothermia did not improve the animals' neurobehavioral performance.

CONCLUSION: The findings from this study suggest that hypothermia produces a transitory attenuation of nuclear factor-kappaB activation in meningitic brain injury and improvement in some biomarkers of neuronal injury. The consequence of intermittent suppression of nuclear factor-kappaB activation by inducing specific periods of hypothermia requires further study.

6825. Kanner AA, Vogelbaum MA, Mayberg MR, Weisenberger JP, Barnett GH. Intracranial navigation by using low-field intraoperative magnetic resonance imaging: preliminary experience. J Neurosurg. 2002 Nov;97(5):1115-24.

OBJECT: Intracranial navigation by using intraoperative magnetic resonance (iMR) imaging allows the surgeon to reassess anatomical relationships in near-real time during brain tumor surgery. The authors report their initial experience with a novel neuronavigation system coupled to a low-field iMR imaging system. METHODS: Between October 2000 and December 2001, 70 neurosurgical procedures were performed using the mobile 0.12-tesla PoleStar N-10 iMR imaging system. The cases included 38 craniotomies, 15 brain biopsies, nine transsphenoidal approaches, and one drainage of a subdural hematoma. Tumor resection was performed using the awake method in seven of 38 cases. Of the craniotomies,image-confirmed complete or radical tumor resection was achieved in 28 cases, subtotal resection in eight cases, and open biopsies in two cases. Tumor resection was controlled with the use of image guidance until the final intraoperative images demonstrated that there was no residual tumor or that no critical brain tissue was at risk of compromise. In each stereotactic biopsy the location of the biopsy needle could be verified by intraoperative imaging and diagnostic tissue was obtained. Complications included a case of aseptic meningitis after a biopsy and one case of temporary intraoperative failure of the anesthesia machine. Awake craniotomies were performed successfully with no permanent neurological complications.

CONCLUSIONS: Intraoperative MR image-based neuronavigation is feasible when using the Odin PoleStar N-10 system for tumor resections that require multiple other surgical adjuncts including awake procedures, cortical mapping, monitoring of somatosensory evoked potentials, or electrocorticography. Use of the system for brain biopsies offers the opportunity of immediate verification of the needle tip location. Standard neurosurgical drills, microscopes, and other equipment can be used safely in conjunction with this iMR imaging system.

6826. Ouma JR. Recurrent meningitis due to unrecognised skull fracture.S Afr Med J. 2002 Oct;92(10):778-9. 36: No abstract.

July 2003

7380. Antinori S. Signs of meningeal irritation: what is their diagnostic accuracy? Clin Infect Dis. 2003 Jan 1;36(1):125-6 No abstract available.

7381. Behzad-Behbahani A, Klapper PE, Vallely PJ, Cleator GM. BK virus DNA in CSF of immunocompetent and immunocompromised patients. Arch Dis Child. 2003 Feb;88(2):174-5.

AIM: To investigate the possible aetiological role of BK and JC viruses in immunocompetent and immunocompromised children with suspected encephalitis and meningoencephalitis. METHODS: The polymerase chain reaction and microplate hybridisation method was employed for the detection of polyomavirus DNA in 266 CSF specimens collected from immunocompetent and immunocompromised patients. RESULTS: BK virus DNA was detected in three (2.1%) CSF samples taken from patients aged 2-5 years; two were patients with acute lymphocytic leukaemia without overt neurological symptoms, the other was a patient with suspected encephalitis. BK virus DNA was also detected in two (1.6%) CSF samples taken from older children in the age range 10-16 years; both children had suspected encephalitis. JC virus DNA was not found in any CSF sample from either age group. CONCLUSIONS: Detection of BK virus in the CSF of immunocompromised and immunocompetent patients with suspected neurological disease suggests that this virus may have had a pathogenic role in the aetiology of this condition.

7382. Bonsu BK, Harper MB. Utility of the peripheral blood white blood cell count for identifying sick young infants who need lumbar puncture. Ann Emerg Med. 2003 Feb;41(2):206-14.

STUDY OBJECTIVE: We assess the utility of the peripheral blood WBC count as a screen for lumbar puncture among young infants evaluated for serious bacterial infections. METHODS: We performed logistic regression modeling and receiver operating characteristic curve analysis of peripheral blood WBC count and cerebrospinal fluid WBC count for results obtained from 3- to 89-day-old infants undergoing a full sepsis evaluation. RESULTS: Twenty-two of 5,353 (4.1 per 1,000) infants had acute bacterial meningitis. For diagnosing acute bacterial meningitis, the peripheral blood WBC count was poorly discriminating and significantly inferior to the cerebrospinal fluid WBC count. This was true both when the odds of meningitis were modeled to vary linearly and as a U-shaped function of the peripheral blood WBC count. When relying on single and interval-based high-risk thresholds of peripheral blood WBC counts alone, the majority of infants with acute bacterial meningitis would have been missed. CONCLUSION: Decisions to perform or withhold lumbar puncture should not be based on prevailing interpretations of the total peripheral blood WBC counts to maximize detection of bacterial meningitis in young infants.

7383. Finn A. More lumbar punctures, please! Arch Dis Child. 2003 Feb;88(2):177. No abstract available

7384. George C N, Letha S, Sushama Bai S. Clinical study of chronic morbidity in chldre following prygenic meningitis. Indian Pedit 2002, 39(7), 663-7. (21866) Vol 38, No. 21, 1 Nov 2002.

7385. Green DA, Ansari BM, Davis S, Cameron D. Reagent strip testing of cerebrospinal fluid.Trop Doct. 2003 Jan;33(1):31-2. No abstract available

7386. Hertzig T, Weber M, Greiffenberg L, Holthausen BS, Goebel W, Kim KS, Kuhn M. Antibodies present in normal human serum inhibit invasion of human brain microvascular endothelial cells by Listeria monocytogenes. Infect Immun. 2003 Jan;71(1):95-100.

Listeria monocytogenes causes meningitis and encephalitis in humans and crosses the blood-brain barrier by yet unknown mechanisms. The interaction of the bacteria with different types of endothelial cells was recently analyzed, and it was shown that invasion into, but not adhesion to, human brain microvascular endothelial cells (HBMEC) depends on the product of the inlB gene, the surface molecule InlB, which is a member of the internalin multigene family. In the present study we analyzed the role of the medium composition in the interaction of L. monocytogenes with HBMEC, and we show that invasion of HBMEC is strongly inhibited in the presence of adult human serum. The strong inhibitory activity, which is not present in fetal calf serum, does not inhibit uptake by macrophage-like J774 cells but does also inhibit invasion of Caco-2 epithelial cells. The inhibitory component of human serum was identified as being associated with L. monocytogenes-specific antibodies present in the human serum. Human newborn serum (cord serum) shows only a weak inhibitory activity on the invasion of HBMEC by L. monocytogenes.

7387. Koedel U, Angele B, Rupprecht T, Wagner H, Roggenkamp A, Pfister HW, Kirschning CJ. Toll-like receptor 2 participates in mediation of immune response in experimental pneumococcal meningitis. J Immunol. 2003 Jan 1;170(1):438-44.

Heterologous expression of Toll-like receptor (TLR)2 and CD14 in Chinese hamster ovary fibroblasts was reported to confer responsiveness to pneumococcal peptidoglycan. The present study characterized the role of TLR2 in the host immune response and clinical course of pneumococcal meningitis. Pneumococcal infection of mice caused a significant increase in brain TLR2 mRNA expression at both 4 and 24 h postchallenge. Mice with a targeted disruption of the TLR2 gene (TLR2-/-) showed a moderate increase in disease severity, as evidenced by an aggravation of meningitis-induced intracranial complications, a more pronounced reduction in body weight and temperature, and a deterioration of motor impairment. These symptoms were associated with significantly higher cerebellar and blood bacterial titers. Brain expression of the complement inhibitor complement receptor-related protein y was significantly higher in infected TLR2-/- than in wild-type mice, while the expression of the meningitis-relevant inflammatory mediators IL-1beta, TNF-alpha, IL-6, macrophage-inflammatory protein (MIP)-2, inducible NO synthase, and C3 was similar in both genotypes. We first ectopically expressed single candidate receptors in HEK293 cells and then applied peritoneal macrophages from mice lacking TLR2 and/or functional TLR4 for further analysis. Overexpression of TLR2 and TLR4/MD-2 conferred activation of NF-kappaB in response to pneumococcal exposure. However, pneumococci-induced TNF-alpha release from peritoneal macrophages of wild-type and TLR2/functional TLR4/double-deficient mice did not differ. Thus, while TLR2 plays a significant role in vivo, yet undefined pattern recognition receptors contribute to the recognition of and initiation of the host immune defense toward Streptococcus pneumoniae infection.

7388. Mishra OP, Batra P, Ali Z, Anupurba S, Das BK. Cerebrospinal fluid lysozyme level for the diagnosis of tuberculous meningitis in children. J Trop Pediatr. 2003 Feb;49(1):13-6.

Lysozyme activity was assayed in the cerebrospinal fluid (CSF) of 32 tuberculous meningitis (TBM), 17 bacterial meningitis, 10 partially treated bacterial meningitis, 18 encephalitis and 18 control subjects. The mean CSF lysozyme activity was significantly raised (p < 0.001) in TBM patients compared with other study groups. A cut-off CSF lysozyme level of > or = 26 U/l had a sensitivity and specificity of 93.7 and 84.1 per cent, respectively for the diagnosis of TBM. Overall, it was found to be a better test than any other single test and thus can be used for rapid and early diagnosis of TBM in children.

7389. Sadler F, Fox A, Neal K, Dawson M, Cartwright K, Borrow R. Genetic analysis of capsular status of meningococcal carrier isolates. Epidemiol Infect. 2003 Feb;130(1):59-70.

The meningococcal capsule is the primary virulence factor with systemic isolates requiring full expression of the capsule but with capability to down-regulate the capsule in order to invade. The meningococcal capsular operon is composed of a number of genes that are involved in capsular synthesis and transport. Differences in capsular synthesis genes may allow discrimination between meningococcal serogroups whereas absence of genes for either synthesis or transport imply that the meningococcus is unencapsulated. Although mechanisms such as slipped-strand mispairing and acquisition of insertion sequences have been demonstrated to be involved in regulation of capsular expression, few studies have addressed the mechanisms of capsular expression in carrier isolates. Following a community-based intervention programme for an outbreak of meningococcal disease, we collected meningococcal carrier isolates from the intervention area and control areas. We undertook genetic analysis of the capsular operon and the mechanisms of capsular regulation, together with an investigation of the potential of capsular genes to identify the genogroup of non-serogroupable isolates. Use of the siaD gene allowed the discrimination of 30/89 (34%) non-serogroupable isolates into B, C, W135 and Y with a siaA gene PCR permitting the characterization of a further 6 isolates whose capsules contained sialic acid. Slipped-strand mispairing was evident in only 4 of 13 genogroupable B isolates and the insertion sequence IS1301 was found in 2 of 36 siaA-positive isolates. Of 51 non-genogroupable isolates 25 (49%) were shown to be ctrA negative. There was a higher percentage of ctrA-positive isolates (P<0.001) amongst meningococcal strains obtained from those sampled in non-intervention schools than those sampled at intervention schools. The ctrA-negative isolates warrant further investigation of their genotypic organization since such avirulent strains may be important in conferring natural protection against invasive disease. We found that after mass antibiotic prophylaxis, recolonization occurs preferentially with non-pathogenic meningococcal strains. This as implications for assessment of the benefits of mass antibiotic and vaccination programmes for outbreak control. Previously expressed concerns of increased risk due to removal of protective ora may have been overstated.

7390. Saravolatz LD, Manzor O, VanderVelde N, Pawlak J, Belian B. Broad-range bacterial polymerase chain reaction for early detection of bacterial meningitis. Clin Infect Dis. 2003 Jan 1;36(1):40-5.

The diagnosis of bacterial meningitis often depends on isolation of bacteria on culture, which may take 24-48 h. DNA amplification techniques could provide rapid diagnosis, which would guide the clinician in antimicrobial therapy decisions. This study determined the clinical utility of polymerase chain reaction (PCR) for the diagnosis of meningitis with use of a broad range of bacterial primers. Seventy-four cerebrospinal fluid specimens obtained from 70 patients were subjected to PCR with use of primers derived from conserved regions of the bacterial 16S RNA gene. The test characteristics for the broad-range bacterial PCR were as follows: sensitivity, 100%; specificity, 98.2%; positive predictive value, 94.4%; and negative predictive value, 100%. Broad-range bacterial PCR may be useful for excluding the diagnosis of meningitis, and the results may influence the decision to initiate or discontinue antimicrobial therapy.

7391. Sehgal A, Jyothi MC, Dubey NK. Comparison of tympanic and rectal temperatures in febrile children. Indian Pediatr. 2003 Feb;40(2):135-40.

The present study was designed to assess the accuracy of tympanic membrane temperature (TMT) in predicting "core" body temperature and to compare rectal temperature (RT) and TMT in febrile pediatric patients with and without meningitis. Sixty children diagnosed as having meningitis by cerebro-spinal fluid (CDF) analysis formed the cases and 60 non-meningitic febrile patients, chosen as continuous enrollment, formed the controls. Rectal and ear temperatures were assessed in both groups. Ear temperature was significantly higher in cases as compared to controls. The difference between reading of ear temperature and rectal temperature was also significantly higher in cases as compared to controls. Significant correlations were seen between ear temperature and various parameters of CSF profile.

7392. Seth R, Sharma U, Diagnostic criterion for tuberculose meningitis. Indian J Pediat 2002, 69(4), 299-303.(20842)Vol 38, No. 20, 16 oct 2002.

7393. Shah Z A, Rasool R, Salahuddin M. Clinical utility of routine diagnostic methods and electrophoresis for estimation of acute phase proteins in cerebrospinal fluid of neonates with bacterial meningitis. J med Sci 2002, 5(1), 56-8. (22038)Vol 38, No. 21, 1 Nov 2002.

Pathogenesis:

7394. Ki M, Park T, Yi SG, Oh JK, Choi B. Risk analysis of aseptic meningitis after measles-mumps-rubella vaccination in Korean children by using a case-crossover design. Am J Epidemiol. 2003 Jan 15;157(2):158-65.

Epidemiologic study of a vaccine's adverse events is not easy; so many countries have no reliable data. Vaccines containing the Urabe or Hoshino strain have been withdrawn from use in several countries. However, the data are not strong enough to form the basis of a recommendation not to use specific strains. The authors used a case-crossover design to estimate the relative risk of aseptic meningitis in children after receiving the measles-mumps-rubella vaccine in Korea. Study subjects were hospitalized children aged 8-36 months who had aseptic meningitis in 1998. Cases were confirmed by hospital chart reviews using previously defined criteria. Through a telephone survey, the authors obtained vaccination date and place information from parents' vaccination records. Study results showed that no significant risk was associated with the Jeryl Lynn or Rubini strain of the vaccine (relative risk = 0.6, 95% confidence interval (CI): 0.18, 1.97). For the Urabe or Hoshino strain, the relative risk was 5.5 (95% CI: 2.6, 11.8); the risk increased in the third week after vaccination (relative risk = 15.6, 95% CI: 5.9, 41.2) and was elevated until the sixth week. The case-crossover design was useful in confirming the risk of acute adverse events after receiving vaccines.

7395. Overturf GD. Indications for the immunological evaluation of patients with meningitis. Clin Infect Dis. 2003 Jan 15;36(2):189-94.

Although people with bacterial meningitis lack adequate protective antibody against the invading pathogen, most do not have an underlying immunodeficiency. Certain comorbid conditions increase the risk for development of bacterial sepsis and meningitis. In addition, certain congenital complement deficiencies, defects of antibody production, or asplenia may be first recognized by the occurrence of bacterial meningitis, particularly when it occurs in infants or young children. Deficiencies of the terminal components of complement (C5-C9) or properdin have been associated with recurrent or invasive neisserial infections, and asplenia, agammaglobulinemia, and deficiencies of the early components of complement (e.g., C1-C3) are associated with risks of infections caused by Streptococcus pneumoniae, Haemophilus influenzae, and meningococci. The presence of congenital or acquired immunodeficiencies should be considered in persons who present with bacterial meningitis on the basis of the etiology, clinical epidemiology, and presence of other risk factors.

7396. Posteraro B, Sanguinetti M, Sanglard D, La Sorda M, Boccia S, Romano L, Morace G, Fadda G. Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Mol Microbiol. 2003 Jan;47(2):357-71.

Resistance to fluconazole is a possible event during prolonged suppressive drug therapy for cryptococ-cal meningitis, the most frequently encountered life-threatening manifestation of cryptococcosis. The knowledge of this resistance at the molecular level is important for management of cryptococcosis. In order to identify genes involved in azole resistance in Cryptococcus neoformans, a cDNA subtraction library technique was chosen as a strategy. First, a fluconazole-resistant mutant BPY22.17 was obtained from a susceptible clinical isolate BPY22 by in vitro exposure to the drug. Then, a subtractive hybridization procedure was used to compare gene expression between the obtained strains. We identified a cDNA overexpressed in the fluconazole-resistant strain BPY22.17 that was used as a probe to isolate the entire gene in a C. neoformans genomic library. Sequence analysis of this gene identified an ATP Binding Cassette (ABC) transporter-encoding gene called C. neoformans AntiFungal Resistance 1 (CnAFR1). Disruption of CnAFR1 gene in the resistant isolate (BPY22.17) resulted in an enhanced susceptibility of the knock-out mutant cnafr1 against fluconazole, whereas reintroduction of the gene in cnafr1 resulted in restoration of the resistance phenotype, thus confirming that CnAFR1 is involved in fluconazole resistance of C. neoformans. Our findings therefore reveal that an active drug efflux mechanism can be involved in the development of azole resistance in this important human pathogen.

7397. Shapiro S, Miller A, Lahat N, Sobel E, Lerner A. Expression of matrix metalloproteinases, sICAM-1 and IL-8 in CSF from children with meningitis. J Neurol Sci. 2003 Jan 15;206(1):43-8.

The combined expression of the inflammatory mediators, matrix metalloproteinases (MMPs), soluble form of intracellular adhesion molecule ICAM-1 (sICAM-1) and interleukin (IL)-8, was evaluated in children infected with bacterial or viral meningitis. MMP-2 and IL-8 were detected in all CSF samples and were enhanced in both bacterial and viral infected samples, compared to those from control children. The expression of MMP-9 as well as sICAM-1 was not detected in control CSF while observed in viral infected and further elevated in bacterial infected samples. This pilot study supports a role for MMPs, IL-8 and sICAM in infectious meningitis and suggests further research to determine their possible use as biomarkers for various forms of meningeal infection as well as the use of their specific antagonists as potential therapeutic agents for central nervous system (CNS) inflammatory processes.

7398. Xu J, Millar BC, Moore JE, Murphy K, Webb H, Fox AJ, Cafferkey M, Crowe MJ. Employment of broad-range 16S rRNA PCR to detect aetiological agents of infection from clinical specimens in patients with acute meningitis—rapid separation of 16S rRNA PCR amplicons without the need for cloning. J Appl Microbiol. 2003;94(2):197-206.

AIMS: The aim of this study was to develop a polyacrylamide gel electrophoresis (PAGE) method for the rapid separation of 16S rRNA PCR amplicons from aetiological agents of acute meningitis. METHODS AND RESULTS: Blood samples from 40 patients with suspected acute meningococcal meningitis were examined for the presence of causal agents, including Neisseria meningitidis employing two methods: (i) broad-range 16S rRNA PCR in conjunction with PAGE and automated sequencing and (ii) species-specific PCR employing ABI TaqMan technology for N. meningitidis. Analysis of clinical specimens employing 16S rRNA PCR yielded 33/40 (82.5%) positive for the presence of bacterial DNA. Species-specific PCR yielded 30/40 (75%) clinical specimens positive for N. meningitidis. Prior to separation by PAGE, only 6/33 (18.2%) amplicons were able to be identified by sequence analysis, the remaining amplicons (n=27) did not yield an identification due to the presence of mixed 16S rRNA PCR amplicons. Following separation, amplicons were re-amplified and sequenced, yielding 24/27 (88.9%) positive for N. meningitidis and three specimens positive for Acinetobacter sp., Staphylococcus aureus and Streptococcus pneumoniae. One specimen was positive for both N. meningitidis and Streptococcus spp. and another specimen was positive for N. meningitidis and Pseudomonas sp., by broad-range PCR. Seven clinical specimens were negative for N. meningitidis and other eubacteria using both detection techniques. CONCLUSIONS: Clinical specimens including blood and cerebrospinal fluid from patients with suspected acute bacterial meningitis, may become contaminated with commensal skin flora, resulting in difficulties in downstream sequencing of pathogen plus contaminant DNA. This study allows for the rapid separation of amplified pathogen from contaminant DNA. SIGNIFICANCE AND IMPACT OF STUDY: This study demonstrated the usefulness of the rapid separation of multiple 16S rRNA PCR amplicons using a combination of PAGE and automated sequencing, without the need of cloning. Adoption of this technique is therefore proposed when trying to rapidly identify pathogens in clinical specimens employing broad-range 16S rRNA PCR.

Vaccines:

7399. Lebel MH, Kellner JD, Ford-Jones EL, Hvidsten K, Wang EC, Ciuryla V, Arikian S, Casciano R. A pharmacoeconomic evaluation of 7-valent pneumococcal conjugate vaccine in Canada. Clin Infect Dis 2003 Feb 1;36(3):259-68

The objective of this study was to evaluate the projected health benefits, costs, and cost-effectiveness of pneumococcal conjugate vaccination for infants and children aged <5 years in Canada. A health state model incorporating incidence, vaccine efficacy, costs, and transitional probabilities for the health states (well, meningitis, bacteremia, otitis media, pneumonia, and death) was constructed for a 10-year time horizon. Implementation of a pneumococcal conjugate vaccine program in Canada for each annual birth cohort of 340,000 persons observed over 10 years would be expected to save approximately 12 lives and 100,000 cases of pneumococcal disease over 10 years, resulting in total savings of $67 million (Canadian dollars [Can$]). Vaccination of healthy infants would result in net savings for society if the vaccine costs less than Can$50 per dose. Moreover, for a vaccine purchase price of Can$67.50, infant vaccination would cost society Can$79,000 per life-year gained. Pneumococcal conjugate vaccination is a potentially cost-effective means of pneumococcal disease prevention.

Therapy:

7400. Atwood CS, Perry G, Smith MA. Cerebral hemorrhage and amyloid-beta. Science. 2003 Feb 14;299(5609):1014 No abstract available

7401. Baker PM, Keeling DM, Murphy M. Plasma exchange as a source of protein C for acute-onset protein C pathway failure. Br J Haematol. 2003 Jan;120(1):167-8. No abstract available.

7402. Posteraro B, Sanguinetti M, Sanglard D, La Sorda M, Boccia S, Romano L, Morace G, Fadda G. Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Mol Microbiol. 2003 Jan;47(2):357-71.

October 2003

8078. Abdulkader I, Cameselle-Teijeiro J, Forteza J. Signet-ring cells associated with pseudomembranous colitis. Virchows Arch. 2003 Apr;442(4):412-4. Epub 2003 Apr 03. No abstract.

8079. Bauters TG, Swinne D, Stove V, Nelis HJ. Detection of single cells of Cryptococcus neoformans in clinical samples by solid-phase cytometry. J Clin Microbiol. 2003 Apr;41(4):1736-7.

A method based on solid-phase cytometry for the detection and enumeration of single cells of Cryptococcus neoformans in serum and cerebrospinal fluid is described. Both viable and nonviable cells are detected by using fluorescence viability labeling and immunofluorescence. This 30-min procedure has a detection limit of 3 to 6 cells per ml.

8080. Bonora S, Zanusso G, Raiteri R, Monaco S, Rossati A, Ferrari S, Boffito M, Audagnotto S, Sinicco A, Rizzuto N, Concia E, Di Perri G. Clearance of 14-3-3 protein from cerebrospinal fluid heralds the resolution of bacterial meningitis. Clin Infect Dis. 2003 Jun 1;36(11):1492-5. Epub 2003 May 16.

The 14-3-3 protein, a cerebrospinal fluid (CSF) marker of neuronal damage that was recently adopted for the diagnosis of Creutzfeldt-Jakob disease, is also found in the CSF of patients with a variety of neurological disorders. We prospectively studied 12 consecutive patients with purulent bacterial meningitis and found that 14-3-3 protein was detected in all patients at admission to the hospital. All patients who recovered cleared 14-3-3 protein from the CSF before discharge from the hospital (this was the first CSF marker to clear), whereas those who died never cleared the protein.

8081. Cepok S, Zhou D, Vogel F, Rosche B, Grummel V, Sommer N, Hemmer B. The immune response at onset and during recovery from Borrelia burgdorferi meningoradiculitis. Arch Neurol. 2003 Jun;60(6):849-55.

BACKGROUND: Borrelia burgdorferi causes a wide range of neurologic syndromes. In Europe, acute meningoradiculitis is the most common manifestation. OBJECTIVE: To address the nature of the immune response during the course of B burgdorferi meningoradiculitis, with special respect to the early and late changes in cerebrospinal fluid (CSF). METHODS: Serial immunophenotyping was performed and cytokine measurements were obtained in the peripheral blood and CSF of 12 European patients with definite B burgdorferi meningoradiculitis. RESULTS: Early during infection and before initiation of treatment, we observed high levels of interleukin (IL) 10, IL-6, and IL-8, and large numbers of B cells and plasma cells in the CSF of most patients. At the same time, we found a mainly unspecific intrathecal antibody synthesis. During resolution of the infection, cytokine levels normalized rapidly and plasma cells disappeared from the CSF. In parallel, the percentage of B cells in the CSF increased over several months, accompanied by rising levels of intrathecally produced B burgdorferi-specific antibodies. CONCLUSIONS: Our findings demonstrate that the early phase of B burgdorferi meningoradiculitis is characterized by a well-coordinated immune response involving specific cytokine release and plasma cell recruitment, followed by a long-lasting, antigen-specific B-cell response in the central nervous system.

8082. Chan KH, Ho PL, Cheung RT, Tsang KL, Fong GC, Cheng PW, Ho SL. Tuberculous meningitis with tuberculomata presenting as postpartum pyrexia of unknown origin. Hosp Med. 2003 May;64(5):306-7. No abstract.

8083. Foudrinier F, Villena I, Jaussaud R, Aubert D, Chemla C, Martinot F, Pinon JM. Clinical value of specific immunoglobulin E detection by enzyme-linked immunosorbent assay in cases of acquired and congenital toxoplasmosis. J Clin Microbiol. 2003 Apr;41(4):1681-6.

The clinical value of immunoenzymatic (enzyme-linked immunosorbent assay) detection of anti-Toxoplasma immunoglobulin E (IgE) was assessed by studying 2,036 sera from 792 subjects, comprising seronegative controls and subjects with acute, active, reactivated, or congenital toxoplasmosis. Included were nonimmunized adults; pregnant women with recently acquired infection (acute toxoplasmosis); immunocompetent subjects with recently acquired severe infection (active toxoplasmosis) expressed as fever, adenopathies, splenomegaly, pneumonia, meningitis, or disseminated infection; subjects-some of them immunocompromised-whose previously moderate IgG antibody levels rose, suggesting a reactivation of quiescent toxoplasmosis; and infants born to seroconverted mothers and evaluated for diagnosis of congenital infection and therapeutic management. Specific IgE antibodies were never detected in seronegative subjects. They were present in 85.7% of asymptomatic seroconverters and in 100% of seroconverters with overt toxoplasmosis, following two different kinetics: in the former, the specific IgE titer generally presented a brief peak 2 to 3 months postinfection and then fell rapidly, whereas specific IgE persisted at a very high titer for several months in the latter. IgE emerged concomitantly with the increase in IgG during toxoplasmic reactivation. For neonatal diagnosis of congenital toxoplasmosis, IgE was less informative than IgM and IgA (sensitivities, 59.5, 64.3, and 76.2%, respectively) and had a specificity of 91.9%. Nevertheless, simultaneous measurement of the three isotypes at birth improved the diagnostic yield to 81% relative to the combination of IgA and IgM. Emergence of specific IgE during postnatal treatment for congenital toxoplasmosis is a sign of poor adherence or inadequate dosing.

8084. Gonzales N, Tyler KL, Gilden DH. Recurrent dermatomal vesicular skin lesions: a clue to diagnosis of herpes simplex virus 2 meningitis. Arch Neurol. 2003 Jun;60(6):868-9. No abstract.

8085. Intapan PM, Maleewong W, Sawanyawisuth K, Chotmongkol V. Evaluation of human IgG subclass antibodies in the serodiagnosis of angiostrongyliasis. Parasitol Res. 2003 Apr;89(6):425-9. Epub 2002 Nov 26.

Immunoglobulin G subclass antibody (IgG1, IgG2, IgG3, and IgG4) responses to the rat lungworm, Angiostrongylus cantonensis, were analyzed using the immunoblotting technique in an attempt to further improve the sensitivity and specificity for the serodiagnosis of human angiostrongyliasis. Serum samples from patients with proven angiostrongyliasis and from clinically suspected cases of angiostrongyliasis with eosinophilic meningitis were tested. Sera from patients with other parasitic illnesses and from healthy volunteers were also analyzed. The results indicate that the immunoblotting used to detect IgG4 antibodies to the antigenic band of an approximate molecular mass of 29 kDa from young adult somatic extract of A. cantonensis is the most reliable test. It gives accuracy, sensitivity, specificity, and positive and negative predictive values of 89.2%, 75%, 95%, 85.7% and 90.4%, respectively. More importantly, the test can discriminate between human angiostrongyliasis, gnathostomiasis and cysticercosis, three diseases that produce eosinophilic meningitis.

8086. Jorgensen GE, Hammarin AL, Bratt G, Grandien M, Flaegstad T, Johnsen JI. Identification of a unique BK virus variant in the CNS of a patient with AIDS. J Med Virol. 2003 May;70(1):14-9.

Human polyomavirus BK (BKV; GenBank or EMBL or DDBJ accession no. NC001538) is often reactivated in immunosuppressed patients. Reactivation has been associated primarily with excretion of the virus in the urine, and there have been few reports of renal and/or neurological disease caused by BKV in patients with acquired immunodeficiency syndrome (AIDS). Polymerase chain reaction, Southern blotting, and sequencing were used to detect and identify the noncoding control region (NCCR) of BKV in different tissues in an AIDS patient with meningoencephalitis, retinitis, and nephritis. An undescribed reorganized NCCR variant of the virus, completely different from the variants detected in peripheral blood leukocytes (PBLs) and urine, was identified in the cerebrospinal fluid (CSF) and CNS tissues. These results suggest that rearrangements in the NCCR of the virus have resulted in a BKV variant, which is better adapted to the host cell machinery of the cells in CNS tissue. The rearranged variant (BKV CNS) might have been involved in the initiation and/or development of the pathological lesions observed in the CNS-related tissues of this patient. Copyright 2003 Wiley-Liss, Inc.

8087. Kelley TW, Prayson RA, Ruiz AI, Isada CM, Gordon SM. The neuropathology of West Nile virus meningoencephalitis. A report of two cases and review of the literature. Am J Clin Pathol. 2003 May;119(5):749-53. Review.

West Nile virus (WNV) is an emerging mosquito-transmitted encephalitis virus first recognized in North America in 1999. The pathologic manifestations of WNV infection have not been well defined. This study documents the clinicopathologic features, including autopsy findings, of 2 cases: an 81-year-old man who contracted WNV infection with meningoencephalitis and a polio-like paralysis and a hospitalized 74-year-old woman with meningoencephalitis who acquired WNV through transfusion. The pathologic findings in both cases were marked by perivascular and leptomeningeal chronic inflammation, microglial nodules, and neuronophagia, predominantly involving the temporal lobes and brainstem. These findings also were present in the spinal cord, especially the lumbar region, of the patient with polio-like paralysis. In both cases, most of the inflammatory infiltrate was composed of CD3+ T lymphocytes (a predominance of CD8+ over CD4+ T cells), CD68+ macrophages, and rare CD20+ B lymphocytes. These cases further define the clinical and pathologic spectrum of central nervous system disease in WNV infection.

8088. Lledo L, Gegundez MI, Saz JV, Bahamontes N, Beltran M. Lymphocytic choriomeningitis virus infection in a province of Spain: analysis of sera from the general population and wild rodents. J Med Virol. 2003 Jun;70(2):273-5.

Lymphocytic choriomeningitis virus (LCMV) is a rodent-borne virus belonging to the family Arenaviridae, genus Arenavirus, which causes a wide spectrum of human disease. However, data on LCMV infection in Spain is scant. To investigate whether this virus causes infection in Spain, 400 serum samples from the general population (191 males, 209 females) and 100 from wild rodents were studied by immunofluorescence assay (IFA) using L-929 cells infected with LCMV. The study was performed in the "Community of Madrid," a region with both rural and urban areas in different ecological settings. Of the 400 human serum samples tested, antibodies against LCMV were detected in 7 (1.7%). No statistical differences in prevalence were found with respect to either age or rural or urban residence, but differences were seen with respect to sex. Nine (9%) of the rodent serum samples were positive. These results confirm the occurrence of LCMV infections in Man and rodents in Spain. Copyright 2003 Wiley-Liss, Inc.

8089. Michael JS, Lalitha MK, Cherian T, Thomas K, Mathai D, Abraham OC, Brahmadathan KN. Evaluation of polymerase chain reaction for rapid diagnosis of tuberculos meningitis. Indian J Tuberc 2002, 49(3), 133-7. ISA 000698, Vol 39, No 1, 1 Jan 2024

8090. Nowak DA, Boehmer R, Fuchs HH. A retrospective clinical, laboratory and outcome analysis in 43 cases of acute aseptic meningitis. Eur J Neurol. 2003 May;10(3):271-80.

Forty-three consecutive cases of acute aseptic meningitis (AAM) presenting within a 24-months period were retrospectively analysed with respect to clinical symptomatology, cerebrospinal fluid (CSF) findings, clinical course, treatment and outcome. Nineteen of the 43 AAM cases (44%) were caused by enterovirus, one by HIV (2%), two by Varicella zoster virus (5%), three due to herpes simplex virus I (7%), two due to herpes simplex virus II (5%), one due to Central European encephalitis virus (2%), and in 15 patients (35%) the aetiology of AAM remained unknown. Headache (100%) and fever (93%) were the presenting symptoms in the majority of cases. Signs of preceding infection were predominantly gastrointestinal in the enterovirus subgroup, but were inconsistently observed in the other subgroups. CSF findings at the first lumbar tap on admission generally revealed lymphomonocytic pleocytosis of less than 500 cells per micro l, mild to moderately elevated protein and normal lactate and glucose levels. Initial therapy consisted of an empirical antiviral and antibiotic regimen until a serological diagnosis was available. Acyclovir, effective only in herpes family viruses, was initially administered to all AAM cases. Effective therapy for other viral pathogens are not broadly available and treating AAM of unknown aetiology imposes a particular problem. The average hospitalization time ranged from 16 to 31 days. Patients were either discharged home (72%) or transferred to a rehabilitation centre (28%). The outcome was good (40%) to fair (51%) in the majority of cases.

8091. Sirisanthana V, Puthanakit T, Sirisanthana T. Epidemiologic, clinical and laboratory features of scrub typhus in thirty Thai children. Pediatr Infect Dis J. 2003 Apr;22(4):341-5.

BACKGROUND: Scrub typhus, a potentially fatal rickettsial infection, is common in Asia. Although serologic surveys suggested that as many as one-fourth of cases of scrub typhus might be in children, very few reports of childhood scrub typhus are available in the medical literature. OBJECTIVES: To document the clinical, laboratory and epidemiologic characteristics of pediatric patients with scrub typhus. METHODS: From January 1, 2024 to December 31, 2001, all pediatric patients at Chiang Mai University Hospital who had obscure fever for >5 days were tested for indirect immunofluorescent antibody (IFA) against Orientia tsutsugamushi, the causative organism of scrub typhus. Scrub typhus was diagnosed on the basis of either a single IFA titer against O. tsutsugamushi > or =1/400 or a 4-fold or greater rise in IFA titer to at least 1/200. RESULTS: Thirty children with scrub typhus were enrolled. Most were diagnosed during the rainy months of June to November. Common physical signs included lymphadenopathy (93%), hepatomegaly (73%), eschar (68%), conjunctival hyperemia (33%), maculopapular rash (30%) and splenomegaly (23%). Eleven patients had interstitial pneumonitis and 1 patient had meningitis. All patients responded well to doxycycline or chloramphenicol. The average interval to defervescence after treatment was 29 h (range, 6 to 72). CONCLUSIONS: Clinical and epidemiologic features of 30 pediatric patients with scrub typhus are reported in a prospective study. The presence of eschar was helpful in making the diagnosis. Complications included pneumonitis and meningitis. All cases responded well to treatment with antibiotic.

8092. Skelly M, Hoffman J, Fabbri M, Holzman RS, Clarkson AB Jr, Merali S. S-adenosylmethionine concentrations in diagnosis of Pneumocystis carinii pneumonia. Lancet. 2003 Apr 12;361(9365):1267-8.

Pneumocystis carinii is unable to synthesise S-adenosylmethionine and thus scavenges this intermediate. We aimed to test whether measurement of concentrations of this metabolic intermediate in plasma could provide a new method for rapid diagnosis of Pneumocystis carinii pneumonia (PCP). We measured S-adenosylmethionine plasma concentrations in 12 healthy controls, 16 patients with confirmed or suspected PCP, and 36 patients with other infections. Median concentration in healthy controls was 106 nmol/L (range 86-128), but the protein was undetectable in eight patients with histologically proven and seven with suspected PCP, and was 8 nmol/L in another confirmed case (p<0.0001). In 36 patients with other infections, S-adenosylmethionine concentrations were much the same as in controls: 18 had bacterial pneumonia, two tuberculosis, five cryptococcal meningitis, three had other infections, and eight had asymptomatic HIV-1 infection. After treatment for PCP, S-adenosylmethionine concentrations rose rapidly in all but one patient who died of the disease. Measurement of plasma S-adenosylmethionine concentrations could prove useful for diagnosis of PCP and assessment of patients' response to treatment.

Pathogenesis:

8093. Cottagnoud P, Gerber CM, Majcherczyk PA, Acosta F, Cottagnoud M, Neftel K, Moreillon P, Tauber MG. The stereochemistry of the amino acid side chain influences the inflammatory potential of muramyl dipeptide in experimental meningitis. Infect Immun. 2003 Jun;71(6):3663-6.

Intrathecal injections of 50 to 100 micro g of (N-acetylmuramyl-L-alanyl-D-isoglutamine) muramyl dipeptide (MDP)/rabbit dose-dependently triggered tumor necrosis factor alpha (TNF-alpha) secretion (12 to 40,000 pg/ml) preceding the influx of leukocytes in the subarachnoid space of rabbits. Intrathecal instillation of heat-killed unencapsulated R6 pneumococci produced a comparable leukocyte influx but only a minimal level of preceding TNF-alpha secretion. The stereochemistry of the first amino acid (L-alanine) of the MDP played a crucial role with regard to its inflammatory potential. Isomers harboring D-alanine in first position did not induce TNF-alpha secretion and influx of leukocytes. This stereospecificity of MDPs was also confirmed by measuring TNF-alpha release from human peripheral mononuclear blood cells stimulated in vitro. These data show that the inflammatory potential of MDPs depends on the stereochemistry of the first amino acid of the peptide side chain and suggest that intact pneumococci and MDPs induce inflammation by different pathways.

8094. Prasadarao NV, Srivastava PK, Rudrabhatla RS, Kim KS, Huang SH, Sukumaran SK. Cloning and expression of the Escherichia coli K1 outer membrane protein A receptor, a gp96 homologue. Infect Immun. 2003 Apr;71(4):1680-8.

Escherichia coli is one of the most common gram-negative bacteria that cause meningitis in neonates. Our previous studies have shown that outer membrane protein A (OmpA) of E. coli interacts with a 95-kDa human brain microvascular endothelial cell (HBMEC) glycoprotein, Ecgp, for invasion. Here, we report the identification of a gene that encodes Ecgp by screening of an HBMEC cDNA expression library as well as by 5' rapid amplification of cDNA ends. The sequence of the Ecgp gene shows that it is highly similar to gp96, a tumor rejection antigen-1, and contains an endoplasmic reticulum retention signal, KDEL. Overexpression of either Ecgp or gp96 in both HBMECs and CHO cells increases E. coli binding and invasion. We further show that Ecgp gene-transfected HBMECs express Ecgp on the cell surface despite the presence of the KDEL motif. Northern blot analysis of total RNA from various eukaryotic cells indicates that Ecgp is significantly expressed in HBMECs. Recombinant His-tagged Ecgp blocked E. coli invasion efficiently by binding directly to the bacteria. These results suggest that OmpA of E. coli K1 interacts with a gp96-like molecule on HBMECs for invasion.

8095. Riggio MP, Lennon A. Specific PCR detection of Peptostreptococcus magnus. J Med Microbiol. 2003 Apr;52(Pt 4):309-13.

Peptostreptococcus magnus is the most pathogenic and one of the most common Gram-positive anaerobic cocci found in human clinical specimens. The organism has been isolated in pure culture from a range of serious infections, including meningitis and endocarditis. However, isolation of Peptostreptococcus magnus from the oral cavity has rarely been attempted. Identification of Peptostreptococcus magnus in clinical specimens is reliant upon microbiological culture and biochemical methods, which often give ambiguous results. The aim of this study was to develop a PCR assay for the specific detection of Peptostreptococcus magnus in oral clinical specimens. PCR primers specific for Peptostreptococcus magnus DNA were derived by comparison of 16S rRNA gene sequences and selection of primers that demonstrated specificity at their 3' ends for Peptostreptococcus magnus. PCR positivity for Peptostreptococcus magnus DNA was indicated by the amplification of a 553 bp product. The PCR assay was then used to attempt detection of Peptostreptococcus magnus DNA in subgingival plaque samples from adult periodontitis patients and pus aspirates from subjects with acute dento-alveolar abscesses. The PCR assay was demonstrated to be highly specific for Peptostreptococcus magnus DNA, since no PCR products were obtained when genomic DNA from a wide range of other oral bacteria, including closely related Peptostreptococcus species, was used in the PCR assay. Confirmation of specific amplification of Peptostreptococcus magnus DNA was obtained by digestion of PCR products with the restriction endonuclease RsaI, which gives a unique restriction profile for Peptostreptococcus magnus. Of the 33 subgingival plaque samples analysed, 2 (6 %) were positive for Peptostreptococcus magnus DNA. None of the 60 pus aspirates analysed was positive for Peptostreptococcus magnus DNA. It is concluded that Peptostreptococcus magnus is not a major pathogen in adult periodontitis or dento-alveolar abscesses. The PCR assay provides a more rapid, specific and sensitive alternative to conventional methods for identification of Peptostreptococcus magnus in clinical specimens.

Vaccines:

8096. Breuer J. Monitoring virus strain variation following infection with VZV: is there a need and what are the implications of introducing the Oka vaccine? Commun Dis Public Health. 2003 Apr;6(1):59-62.

Varicella zoster virus (VZV) is a stable virus showing relatively little variation. Nevertheless, recent data have shown there to be at least four distinct viral strains. For the most part these are geographically segregated, but in areas of the world such as the UK, where mixed populations live, there is evidence for spread of all the genotypes. Little is known about the biological differences, if any, between these strains, yet recent data have shown that even a single nucleic acid change can affect the biological behaviour of the virus. The Oka vaccine has been licensed for mass vaccination in the US and for limited use in the UK, particularly in seronegative healthcare workers. Virological surveillance is needed to support these programmes and study the effect on virus spread. Evidence for VZV superinfection of latently infected individuals with different strains, and the increasing detection of VZV in association with clinical conditions such as viral meningitis, suggest more data are needed on the transmissibility and biological properties of the virus.

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