GroupA streptococci (GAS) cause a wide spectrum of diseases ranging from benign
pharyngitis and skin
infections to severe invasive disease and the immune sequelae
rheumatic fever and
rheumatic heart disease.
Pharyngitis, one of the most frequent diseases caused by GAS, is highly prevalent in school-age children in temperate climates and a major cause of
antibiotic use. An efficacious
vaccine would reduce disease burden associated with
pharyngitis and the need of care for sick children. Importantly, GAS
pharyngitis is recognised as the main precursor for
acute rheumatic fever so a
vaccine that is efficacious against GAS
pharyngitis should also prevent
acute rheumatic fever and
rheumatic heart disease. It may also prevent post-streptococcal
glomerulonephritis and invasive disease since GAS
pharyngitis is one of the precursors for these clinical syndromes. There has been no clearly articulated pathway for clinical trial design leading to GAS
vaccine registration. This review outlines a clinical development strategy detailing the phases of development required for registration of a candidate GAS
vaccine for GAS
pharyngitis initially, followed by
impetigo and associated sequelae. The major advantages of a strategy first focused on GAS
pharyngitis is an early proof of principle, that can be followed by studies for other clinical syndromes. The end goal being the availability of a preventive tool for the most prevalent GAS-associated diseases globally.