Epidemiological data over the past two decades attest to the resurgence of yellow fever outbreaks in sub-Saharan Africa (1), with more than 1 million cases between 1986 and 1990 (2). In Africa, children under the age of 15 years now account for 70-90%, of the cases (3-7). As a result, WHO recommended that yellow fever vaccination be included in national EPI (Expanded Programme on Immunization) activities in endemic countries and that it be given to infants at the same time as measles immunization at 9 months of age (8). Although this schedule of immunization will not prevent some infants from contracting yellow fever infection during epidemics, immunization of infants younger than 4 months old with yellow fever (17D strain) vaccine can produce serious side-effects, such as encephalitis (9, 10), and WHO recommends that infants younger than 6 months should not be vaccinated (11).
As part of a study to assess the immunogenicity of AIK-C measles vaccine (Kitasato strain) in infants aged 6 months (12), yellow fever (17D strain) vaccine was administered in parallel. The goals were to evaluate immune responses in infants at 6 and 9 months of age, and to assess adverse effects of the yellow fever vaccine in infants, particularly at 6 months of age. The yellow fever study also served as a randomization control in the AIK-C study.
Study area and population
The study was conducted in Asamankese, the capital of East Akim District in Southern Ghana. Yellow fever is not endemic in the district (population approximately 100 000) and no yellow fever has been reported in the last 10 years. Routine immunization is carried out as recommended by the Ghana Ministry of Health and infants receive yellow fever immunization at 9 months of age. Yellow fever immunization coverage was 28% in Asamankese during the study, slightly higher than the national average of 24% (13). There were no confirmed or suspected cases of yellow fever in the area during the study.
Infants aged 6 months (24-27 weeks) who had been attending the Asamankese mother and child health clinic regularly and had received all the required immunizations (BCG at birth, three doses of oral poliovirus vaccine, and three of diphtheria-pertussis-tetanus) were identified during routine clinic visits. The study was explained to the parents and their verbal consent obtained for participation. Children were randomly allocated to one of two groups that received yellow fever immunization at 6 months or at 9 months. To blind the study, infants receiving the yellow fever vaccine at 9 months received the AIK-C measles vaccine at 6 months (group A), and those receiving the yellow fever vaccine at 6 months received the Schwartz measles vaccine at 9 months (group B). A total of 420 infants were enrolled in the study, with 200 infants in group A and 220 in group B. A child was excluded from the study if he/she was malnourished (<80% of expected weight for age), or febrile (temperature [greater than equal to) 38 [degrees] C), or had a previous history of measles (according to mother's report).
Immunization and blood sampling
A single 0.5 ml dose of reconstituted 17D yellow fever vaccine was administered to each infant by subcutaneous injection. Approximately 1 ml of whole blood was taken prior to immunization and 3 months post-immunization. Infants who received yellow fever immunization at 9 months had two pre-immunization blood samples taken (at 6 and 9 months) to exclude possible seroconversion due to contact with the wild virus. Blood samples were collected in labelled polystyrene tubes, transported chilled to the Noguchi Institute on the same day, centrifuged, separated and the sera stored at -20 [degrees] C until used.
The vaccine for the study was manufactured by the Institute Pasteur, Dakar (Lot number E 5263) and obtained from EPI of the Ghanaian Ministry of Health. …