Multi-center surveillance for pneumonia & meningitis among children (<2 yr) for Hib vaccine probe trial preparation in India.

Background & objectives: Severe clinical pneumonia and meningitis caused by Haemophilus influenzae type b in children less than 5 yr old is preventable by use of Hib vaccine. However, data on Hib burden in India are limited. To support an evidence-based decision for Hib vaccine introduction in India, a vaccine probe study was planned. This paper presents the results of the preparatory phase for such a study, which aimed to determine the feasibility of conducting a randomized vaccine probe study and to estimate the incidence of all causes of pneumonia and meningitis. The preparatory study included population-based, hospital-based and carriage surveillance. Methods: Children aged 18-24 months and were enrolled at PGIMER, Chandigarh, CMC, Vellore and NICED, Kolkata, from July 2005 to December 2006. At the time of enrollment, parents were informed about the signs and symptoms of pneumonia and meningitis, and were encouraged to take the child to study hospitals for treatment. Hospitalized children less than two years of age suspected of having pneumonia and/or meningitis were enrolled in study hospitals, whether or not they were from the cohort population. Patients were examined clinically and received chest radiograph for suspected cases of pneumonia or lumbar puncture for suspected cases of meningitis. Blood culture was done for both pneumonia and meningitis patients. Cerebrospinal fluid (CSF) was tested for biochemistry, culture, latex agglutination test and polymerase chain reaction. Nasopharyngeal swabs were collected from healthy children less than 2 yr of age at immunization clinics to estimate Hib carriage. Results: A cohort of 17,951 children were recruited for the population-based arm. The incidence of severe clinical pneumonia ranged from 2717 to 7890 per 100,000 child-years of observation; suspected meningitis ranged from 1971 to 2433 per 100,000 child-years of observation. In the hospital-based study 7/90 (7.8%), 29/98 (29.6%) and 38/181 (21.0%) of CSF samples with cell count ≥100 WBCs/mm3 were purulent at Chandigarh, Kolkata and Vellore respectively. Of these purulent CSF samples, Hib was detected in 2, 6 and 11 cases, respectively. The Hib nasopharyngeal carriage prevalence ranged from 6.0 - 7.6 per cent. Interpretation & conclusions: Incidence of severe clinical pneumonia is comparable with other studies from India but that of suspected meningitis is higher. Although rates of Hib meningitis cannot be calculated from a hospital-based study, there is evidence of Hib meningitis in these study settings. Hib carriage prevalence indicates that Hib is present and circulating in these study areas. There is a significant burden of pneumonia and meningitis among children in India. Continued strengthening of laboratory capacity and bacterial surveillance systems are necessary.