Rheumatic heart disease: A review of the current status of global research activity

Rheumatic heart disease (RHD) is a serious and long-term consequence of acute rheumatic fever (ARF), an autoimmune sequela of a mucosal infection by Streptococcus pyogenes (Group A Streptococcus, Strep A). The pathogenesis of ARF and RHD is complex and not fully understood but involves host and bacterial factors, molecular mimicry, and aberrant host innate and adaptive immune responses that result in loss of self-tolerance and subsequent cross-reactivity with host tissues. RHD is entirely preventable yet claims an estimated 320 000 lives annually. The major burden of disease is carried by developing nations and Indigenous populations within developed nations, including Australia. This review will focus on the epidemiology, pathogenesis and treatment of ARF and RHD in Australia, where: streptococcal pyoderma, rather than streptococcal pharyngitis, and Group C and Group G Streptococcus, have been implicated as antecedents to ARF; the rates of RHD in remote Indigenous communities are persistently among the highest in the world; government register-based programs coordinate disease screening and delivery of prophylaxis with variable success; and researchers are making significant progress in the development of a broad-spectrum vaccine against Strep A.