Acute Rheumatic Fever Biomarker Project
The Leducq Foundation announces a call for applications in October 2021.
Acute rheumatic fever initiates a slow but progressive process of heart valve damage termed rheumatic heart disease. While the incidence of acute rheumatic fever declined sharply in high income countries throughout the second half of the 20th century, rheumatic heart disease remains a significant cause of cardiovascular morbidity and mortality in in low- and middle-income countries. There is currently no sensitive and specific diagnostic test for acute rheumatic fever. Instead, a constellation of clinical and laboratory findings is used to make the diagnosis. Initially proposed in 1944, the Jones criteria have been used since to guide the diagnosis of acute rheumatic fever. These criteria have been revised in 1992 and again in 2015, but they remain imperfect.
Comparison of the number of individuals living with rheumatic heart disease to the incidence of acute rheumatic fever suggests that acute rheumatic fever is frequently undiagnosed. Better accuracy in the diagnosis of acute rheumatic fever would lead to greater and more appropriate antibiotic therapy for prevention of recurrent rheumatic fever, which is a major determinant of prognosis. Beyond the direct patient benefit, greater diagnostic certainty could reduce inappropriate antibiotic use. Additionally, a definitive diagnostic test for ARF would facilitate surveillance, accurate assessments of disease burden, better informed policy-making, and group A streptococcal vaccine development efforts.
One key barrier to the development of a diagnostic test for acute rheumatic fever is our incomplete understanding of the disease pathogenesis. While group A strep infection is well substantiated as the initiating event, the contributions of bacterial factors and host responses, which ultimately determine whether a given patient develops acute rheumatic fever, are still poorly understood. The role of pathogen and host genetic determinants remains an area of ongoing investigation, as does the immune response, both humoral and cellular, in disease development. The quest for a sensitive and specific diagnostic test for acute rheumatic fever will therefore almost certainly begin with new insights into the molecular pathogenesis of the disease.
The challenge for the applicants is to identify a biomarker(s) for acute rheumatic fever that can serve as a basis for a test or panel of tests to accurately distinguish patients with acute rheumatic fever from individuals who do not have acute rheumatic fever.
The total award is $8,000,000 over five years for the Acute Rheumatic Fever Biomarker Project.
Leducq Foundation applications are submitted via an online application service hosted by Altum ProposalCENTRAL. Click here to go directly to the application website.