Current issues in the prevention of rheumatic fever.

Variation in strain virulence helps to account for the wide spectrum of group A streptococcal diseases and for their striking epidemiological variation. Recent studies of the genetic control of the expression of the virulence factors of group A streptococci (GAS) are beginning to illuminate such variation. Although still obscure, the pathogenesis of acute rheumatic fever (RF) requires primary infection of the throat by highly virulent GAS strains. Those that have clearly caused RF contain large hyaluronate capsules and extended M-protein molecules. The M molecule contains some epitopes cross-reactive with host tissues, and also has superantigenic properties like the secreted GAS erythrogenic toxins. In settings where ARF has become rare, GAS pharyngitis continues to be quite common but is most often caused by relatively attenuated strains. These, however, may colonize the throat avidly, and often stubbornly. GAS "skin strains" that cause pyoderma (impetigo) are molecularly distinct from "throat strains". Although they may secondarily colonize and infect the throat, the pyoderma strains are generally less virulent and are not rheumatogenic. Some skin strains, however, may cause acute glomerulonephritis. The diagnosis, treatment and prevention of GAS pharyngitis is reviewed in relation to the varying prevalence of RF in different geographical and social settings.