Abstract
BACKGROUND: Pharyngitis due to group A Streptococcus (GAS) represents a major cause of outpatient visits and antibiotic use in the United States. A leading vaccine candidate targets 30 of the > 200 emm types of GAS. We aimed to assess natural protection conferred by GAS against respiratory symptoms. METHODS: In a 5-year study among school-aged children in Pittsburgh, Pennsylvania, pharyngeal cultures were obtained from children at 2-week intervals, and active surveillance was conducted for respiratory illnesses. We assessed protection via the relative odds of previous detection of homologous strains (defined by field-inversion gel electrophoresis banding pattern), emm types, and emm clusters at visits where GAS was detected with symptoms, vs visits where GAS was detected without symptoms. We used a cluster bootstrap of children to adjust estimates for repeated sampling. RESULTS: At visits where previously detected GAS emm types were identified, we estimated 81.8% (95% confidence interval [CI], 67.1%-91.7%) protection against typical pharyngitis symptoms among children reacquiring the same strain, and 94.5% (95% CI, 83.5%-98.6%) protection among children acquiring a distinct strain. We estimated 77.1% (95% CI, 33.7%-96.3%) protection against typical symptoms among children acquiring partially heterologous emm types belonging to a previously detected emm cluster. Protection was evident after both symptomatic and asymptomatic detections of GAS. We did not identify strong evidence of protection against atypical respiratory symptoms. CONCLUSIONS: Within a 5-year longitudinal study, previous detection of GAS emm types was associated with protection against typical symptoms when homologous strains were subsequently detected. Naturally acquired protection against partially heterologous types suggests that emm type-based vaccines may have broader strain coverage than what has been previously assumed.