Molecular Epidemiology of Streptococcus Pyogenes Among Children in Bamako, Mali

Data on the epidemiology of group A streptococci (GAS) infection in developing countries is limited. Available publications suggest that not only is disease prevalent, but severe manifestations continue to occur at a high rate. Several promising GAS vaccine candidates are in pre-clinical and clinical development. One approach that has entered clinical trial is the use of a multivalent recombinant fusion peptide vaccine containing amino-terminal M protein fragments. In animal models, these M-protein type-specific epitopes induce protective opsonic antibodies that do not cross-react with human tissues. If type-specific vaccines are to be used in developing countries, then the molecular epidemiology of GAS in these settings must be better characterized. The primary objective of this study is to identify the genotypes (emm type or sub-type) of GAS isolated from 5 to 16 year old schoolchildren with pharyngitis living in a poor urban community in Bamako, Mali. The secondary objectives are: to characterize the molecular epidemiology of GAS pharyngitis among Malian schoolchildren by determining the distribution of genotypes according to age in years, year of study, and season (cold or dry); to estimate the incidence of GAS pharyngitis among 5 to 16 year old schoolchildren living in a poor urban community in Bamako, Mali overall and by age, gender, year of study, and season; and to describe the clinical features of GAS pharyngitis among the Malian schoolchildren. Surveillance for pharyngitis will be conducted at least twice weekly among a cohort of approximately 12,000 children, ages 5-16, attending the four public elementary schools in Djikoroni-para-Sébénikoro, a low-income community in Bamako, Mali. Throat swabs will be obtained when a child enrolled in the cohort complains of a sore throat. GAS isolated from the swabs will be characterized by emm typing. The primary endpoint of the study is the proportion of each emm-type among children with GAS pharyngitis. The secondary endpoints include the following: the proportion of each emm-type among children with GAS pharyngitis overall and according to age in years, year of study, and season (cold or dry); the proportion of children with pharyngitis from whom GAS is isolated; the minimal incidence of GAS pharyngitis per 100,000 children in the catchment area of Djikoroni-para-Sébénikoro overall and according to: age in years, gender, year of study, and season (cold or dry); the incidence density (number of cases per children-weeks of follow up) of GAS pharyngitis among enrolled school children overall and according to: age in years, year of study, and season (cold or dry); and the proportion of children with GAS pharyngitis who experience symptoms such as fever, exudative pharyngitis, tender cervical adenopathy, or scarletiniform rash, overall and by age in years. It is clear that GAS is an important worldwide pathogen and that it has been understudied in much of the developing world. Given the early successes of multivalent M type-specific vaccines, investigations of the molecular epidemiology delineating the distribution of the emm-types of the organism associated with pharyngitis (and therefore presumably acute rheumatic fever) are crucial for designing a vaccine that has utility in preventing rheumatic heart disease and other GAS disease in the developing world. The current protocol is intended to provide data to address these goals.