Immunogenicity and safety of live attenuated hepatitis A vaccine: a multicentric study.

OBJECTIVE: To evaluate immunogenicity and tolerability of single dose live attenuated injectable hepatitis A vaccine in four metropolitan cities of India. METHODS: Live attenuated hepatitis A vaccine was administered to 505 children aged 18 to 60 months in four centers across India. Immunogenicity of the vaccine was assessed by estimation of anti-HAV antibody titer at 6 weeks and 6 months following administration of the vaccine. Safety evaluation of the vaccine was also done during the visits. RESULTS: At 6 weeks, 480 subjects (95%) came for the follow-up and 411 (81.4%) subjects reported at the end of 6 months. The geometric mean titer (GMT) of anti-HAV antibody of the subjects who did not have the seroprotective titer at the baseline were assessed at 6 weeks and 6 months which was 81.04 mIU/ml and 150.66 mIU/ml respectively. At 6 weeks, 95.1 % seroconverted and at the end of 6 months, 97.9 % had seroconverted. Both solicited and unsolicited vaccine-induced local and systemic adverse events were insignificant at all the centers, except swelling and induration in a few. CONCLUSION: Live attenuated injectable hepatitis A vaccine was immunogenic and tolerable with minimal reactogenecity, in this study of single dose schedule. Safety profile was also satisfactory in the study population.

Incidentally Detected Elevated Liver Enzymes: From Liver to Muscle.

We describe 8 children - with incidentally detected isolated elevation of liver enzymes aspartate aminotansferase and alanine aminotransferase - who were extensively evaluated for hepatic causes before finally being diagnosed to have muscular dystrophy. Serum creatinine phosphokinase levels, if performed early during the work-up, may help in diagnosis of muscle disease and avoid unnecessary investigations for liver disease.

Long term follow-up study to evaluate immunogenicity and safety of a single dose of live attenuated hepatitis a vaccine in children.

Worldwide, viral hepatitis continues to be a cause of considerable morbidity and mortality. Mass immunization with a single dose of live attenuated HAV has been shown to significantly reduce disease burden in the community. This was a phase IV, 5-year follow up study carried out at 4 centers (Kolkata, Delhi, Mumbai and Chennai) across India. The subjects with antibody titer <20 mIU/mL at baseline were evaluated for long term immunogenicity. Of the 503 subjects enrolled, 349 subjects were baseline seronegative with an anti-HAV antibody titer <20 mIU/mL. Overall, 343 subjects could be followed up at some point of time during this 5 y post vaccination period. In the last year (60 months) of follow-up, 108 subjects (97.3%) of 111 subjects (who came for follow-up at the end of 5 y) had a protective antibody titer (anti-HAV antibody titer >20 mIU/mL). The seroconversion rates considering seroprotection levels of anti-HAV antibody titer >20 mIU/mL, following vaccination starting from 6 weeks, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months were 95.1%, 97.9%, 98.3%, 96.2%, 97.8%, 92.6% and 97.3%, respectively. The geometric mean concentration (GMC) over the years increased from 64.9 mIU/mL at 6 weeks to 38.1 mIU/mL and 135.2 mIU/mL at 6 months and 12 months, respectively and was maintained at 127.1 mIU/mL at 60 months. In conclusion, the result of this 5-year follow up study showed that the single dose of live attenuated vaccine is well tolerated and provides long-term immunogenicity in healthy Indian children.

Multiple drug resistant non typhoidal Salmonella spp associated with acute diarrheal disease.

Rectal swabs/stool specimens from 115 children (0-5 years) suffering with acute diarrhea were screened for non typhoidal salmonella species. 7 (6%) patients were found to be positive for non typhoidal salmonella. 4 (3.47%) were positive for S. paratyphi B and 3 (2.6%) were positive for S. typhimurium. Multidrug resistance was seen in 57 percent of the strains. All strains were sensitive to Ciprofloxacin. All strains were resistant to Ampicillin followed by Ciprofloxacin. All strains were resistant to Ampicillin followed by Gentamycin (43%), Kanamycin (43%), Tetracycline (43%), Streptomycin (28.5%) and Chloramphenicol (28.5%).

Risk factors for persistent diarrhea among children under 2 years of age. Case control study.

A case control study was done at the Institute of Child Health, Madras, among prospectively recruited children aged 1-23 months to identify the risk factors for persistent diarrhea. Cases were children with diarrhea persisting for > 14 days. Controls were children with acute diarrhea who had recovered within 7 days. Two controls for each case, matched for age were recruited. The total number of cases and controls recruited were 170 and 340. Fifteen risk factors for association with persistent diarrhea were studied. When the factors were adjusted for covariables by logistic regression, only 6 factors were found to be significant, namely, malnutrition (OR 2.9; 95% CI 1.9-4.5), dysenteric stools (OR 2.4; 95% CI 1.3-4.3), indiscriminate use of antimicrobials (OR 2.4; 95% CI 1.6-3.9), associated illnesses (OR 2.1; 95% CI 1.5-3.1), stools > 10/day (OR 1.8; 95% CI 1.2-2.8) and persistence of dehydration (OR 1.4; 95% CI 1.2-1.7). However, when invasive diarrhea was excluded, weight loss during study period became a significant factor. It is concluded that all children with acute diarrhea should be investigated for associated illnesses and treated adequately, indiscriminate use of antimicrobials should be avoided and nutritional support should be provided.

Comparative evaluation of the antipyretic efficacy of ibuprofen and paracetamol.

An open multicentric trial was conducted on 175 patients to compare the antipyretic efficacy of ibuprofen (7 mg/kg) and paracetamol (8 mg/kg). Children between the age of 4 months and 12 years with fever were admitted to the study, 85 in the ibuprofen group and 90 in the paracetamol group. The axillary temperatures were recorded at half hourly intervals for 2 hours. The mean fall in temperature at 1, 1.5 and 2 hours was similar in both groups and the differences were not statistically significant (p greater than 0.05). At half hour, the fall in temperature (mean +/- SEM) for ibuprofen was 0.1975 +/- 0.0409 and for paracetamol was 0.3843 +/- 0.0490. This absolute difference of 0.19 degrees C was statistically significant (p less than 0.05). We conclude that ibuprofen has antipyretic activity comparable to that of paracetamol and that it could be a valuable alternative antipyretic in clinical practice. There is a need to repeat this trial with higher doses of ibuprofen, to establish a dose response of the drug, if any, and to find an optimally effective dose.

Management of acute diarrhoea in children.

Acute diarrhoeal disease is one of the major killers in children in the developing countries. A management protocol consisting of "Triple A" (assessment, analysis of clinical presentation and action plan protocol) approach has been found to be rewarding in our set-up. The matter has been dealt with by the authors in this article in its proper perspective.

Role of Candida in indirect pathogenesis of antibiotic associated diarrhoea in infants.

One hundred and thirty seven isolates of Candida species were isolated from antibiotic associated diarrhoea cases and were examined to study the role of Candida in the pathogenesis of diarrhoea in infants. The quantitative estimation of yeast population by simple gram stain smear revealed more than 70% of the cases had 3+ score. The isolates further screened for detection of beta-lactamases. Among the isolated Candida sp, beta-lactamases was secreted by C. albicans, C. tropicalis, C. krusei and C. parapsilosis. Further, 46% of the Candida isolates were found to be produced 741-1110 mU/ml of beta-lactamases, suggesting that these enzyme would inactivate penicillin group of drugs and cause failure in the therapy directed against other diarrhoegenic bacteria.

Clinical and viral marker pattern of acute sporadic hepatitis in children in Madras, South India.

One hundred and twenty-seven children who presented with features of acute hepatitis during the period February 1995 to January 1996 were studied. Specific aetiologic agents were identified in 89 per cent. Of these, 67.7 per cent were due to a single virus, whereas 21.3 per cent were due to two or more hepatitis viruses. Hepatitis A virus (HAV) was the sole infecting agent in 38.6 per cent of cases, hepatitis B virus (HBV) in 13.4 per cent of cases, and hepatitis E virus (HEV) in 15.7 per cent of cases. Mixed infections were due to HAV and HBV co-infection (7.1 per cent), HAV and HEV (13.4 per cent), and the combination of HAV, HBV, and HEV (0.8 per cent). In 11 per cent, none of the markers (HAV to HEV) were identified. Acute sporadic hepatitis in children can occur due to a single hepatitis virus type or, at times, due to co-infection with a combination of two enterally transmitted viruses or enteral and parenterally transmitted viruses. Improving personal hygiene and active immunization are essential in the prevention of these viral illnesses. This study was done in a referral centre and hence we report a higher morbidity (13.4 per cent) and mortality (12.6 per cent) rate in all groups of infection. Hence, apart from the viruses, factors such as the age of the child, nutritional status, and treatment taken prior to hospitalization should be taken into consideration to predict the prognosis in a given child.