Dynamics of the Immune Response in Children to the 23-valent Pneumococcal Capsular Polysaccharide Vaccine (Pneumovax)

The details are as described below:

1. Study site Kilifi District Hospital.
2. Study population and sampling Cases and controls from the Kilifi Birth Cohort who are alive at the end of the cohort observation (at the age of 24 months) and remain resident in Kilifi District will be vaccinated with a single 0.5 ml sub-cutaneous dose of 23 valent pneumococcal polysaccharide vaccine (Pneumovax 23) to compare the dynamics of the anti-capsular antibody response to 5 capsular antigens chosen to represent different immunological profiles of the pneumococcal capsular polysaccharides (1, 6B, 14, 19F, 23F).
3. Recruitment Potential study subjects will be identified and their mothers will be approached, informed about the study, including the necessity to undergo HIV testing, and invited to take part. A fieldworker will explain the rationale and procedures for the study and will give the mother an information sheet/consent form to take away. The mother will also be given an appointment slip and a fare to return to the hospital on the appointment date. Appointments will be at ward 1. When the mother returns the fieldworker will go through the consent form again and will ask the mother to sign. The mother will be counselled and her child will be HIV tested. If the participant is positive the child will be referred to the Kilifi Family Clinic. If the participant is negative, the child will receive the single dose of Pneumovax (23 valent polysaccharide vaccine). The mother will be given a schedule of 2 further appointments for blood tests and at each visit the fare to and from the hospital will be provided by KEMRI. Study subjects who have been vaccinated and subsequently do not attend will be visited by FW on a motorcycle to invite them to keep their appointments the very next day. Information will be collected concerning age, sex and environmental exposures such as: number of elder and younger sibling in the house, cooking smoke exposure, passive cigarette smoking, recent admission to hospital.

Definition of cases:

Cases of IPD, ARI or radiographic pneumonia and meningitis will be defined as episodes of illness, requiring admission to hospital, that occur to cohort members between birth and the age of 23 months that also meet at least one of the following syndrome definitions: INVASIVE PNEUMOCOCCAL DISEASE is defined by a positive result on EITHER of the following criteria: (i) culture of S. pneumoniae from any normally sterile site including blood, CSF, lung, synovial fluid but excluding middle ear fluid and external eye swabs. OR (ii) Two-fold rise in anti-PsaA antibody concentration measured by ELISA in two serum samples obtained at least 5 days apart 21 AND presence in urine of pneumococcal capsular polysaccharide detected by latex agglutination assay 46. ARI is defined by an acute (<2 weeks) history of cough or difficulty in breathing accompanied by a raised respiratory rate (≥50/min in a child <12 months, ≥40/min in a child 12-23 months). ARI is severe if there is, in addition, chest indrawing, and very severe if there is, in addition, central cyanosis and prostration or inability to drink 47.

RADIOGRAPHIC PNEUMONIA is defined as ARI accompanied by radiographic consolidation. All radiographs will be rated both by study physicians and by a consultant radiologist. "Radiographic consolidation" will only be considered to be present if documented by both observers.