Diagnosis and outcome of acute bacterial meningitis in early childhood.

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 protocols. 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.

Safety and immunogenicity of Haemophilus influenzae type B vaccine given in combination with DTwP at 6, 10 and 14 weeks of age.

OBJECTIVE: To assess the immunogenicity and reactogenicity of a tetanus conjugate Haemophilus influenzae type b vaccine (Act-Hib) when extemporaneously mixed and administered as a DTwP-Hib combination using an Indian DTwP vaccine (BE DTwP) in comparison with a licensed DTwP-Hib combination vaccine. METHODS: 378 healthy infants were enrolled and randomly allocated to receive either three doses, at 6, 10 and 14 weeks of age, of Act-Hib in combination with BE DTwP (Group A, n = 160), TetrAct-Hib (Group B, n = 160), or BE DTwP and Act-Hib as separate injections (Group C, n = 58). Sera collected before the first dose and one month after the third dose were tested for antibodies to vaccine antigens. Safety was determined using parental diary cards. RESULTS: Anti-Hib antibody concentrations indicative of short-term protection (> 0.15 g/ml) were elicited in all but one subject in Group A (99.3%), and all subjects in Groups B and C. The concentration of 1 g/ml, considered to provide long-term protection, was achieved in 96.7%, 100% and 98.2% of the infants in Groups A, B and C, respectively. All children displayed satisfactory responses to the three DTwP component antigens, TetrAct-Hib eliciting higher titers against diphtheria and tetanus than BE DTwP. No vaccine-associated serious adverse events occurred. The BE DTwP vaccine was associated with more reports of fever than TetrAct-Hib, but most symptoms were regarded as mild and all resolved without sequelae. CONCLUSIONS: Combining Act-Hib and a local DTwP vaccine did not affect the anti-Hib response. In countries where DTwP vaccine available for use in the EPI program is manufactured by a local or other developing country manufacturer, mixing it with lyophilised Act-Hib is a reasonable option though the immunogenicity may have to be documented before routine use. However, use of TetrAct-Hib combination vaccine would be preferable in view of its lower reactogenicity and superior immunogenicity with respect to diphtheria and tetanus.