Streptococcus pyogenes is a major human bacterial pathogen responsible for infection and a broad disease spectrum. Strep A is ubiquitous and can colonize the skin and the throat leading to asymptomatic and symptomatic infections. Asymptomatic infections and carriage, though without any apparent signs and symptoms, can be detected through isolation of bacteria 1,2.
We define disease state transitions as events along the pathway from being well to various Strep A-related conditions to understand the clinical manifestation and prognosis from the time of exposure to infection, direct and indirect complications, and sequelae (Figure-1). The prognosis of symptomatic infections through the Strep A disease spectrum can range from mild, superficial infections of the throat (pharyngitis, tonsillitis) or skin (impetigo, ecthyma) to serious life-threatening invasive infection of deeper tissues and sterile sites (cellulitis, necrotizing fasciitis, osteomyelitis, septic arthritis, bacteremia) 3–7. Both skin and throat infections may also lead to autoimmune complications after a period of latency, including acute rheumatic fever (ARF) and post-streptococcal glomerulonephritis (APSGN), and ARF may progress to rheumatic heart disease (RHD) 4,8.
The most common Strep A disease feature is pharyngitis, which occurs commonly in school-age children. Almost 15–30% of cases of all acute pharyngitis in this age group is caused by Group A Streptococcus, with the global mean rate being 22.1 episodes per 100 child-years 9 and historically during winters and more recently during the spring10. It may be difficult to distinguish Strep A pharyngitis from other causes, but typical presentation and isolation of the bacteria assist in diagnosis. Though serological testing may be done to confirm a diagnosis, it is not useful for timely initiation of treatment as the antibody levels rise only after 2–3 weeks of infection. Tonsillar or peritonsillar abscess may follow pharyngitis 11–14. Skin infections are the second most common Strep A disease sequelae which includes superficial infections like impetigo and pyoderma as well as invasive deep infections such as necrotizing fasciitis and cellulitis with bacteraemia 11. The Incidence of invasive Strep A disease varies across both temporal and spatial scales and has been documented in high-income countries 15–28 but data and evidence are limited in low- and middle-income countries 29,30. The impact of social determinants and primary, secondary, and tertiary prevention on strep A exposure, infection, and disease dynamics are illustrated in Fig. 2. Improved access to healthcare, reduction in poverty, and less crowded living conditions are associated with a lower risk of Strep A exposure and infection, while different prevention strategies are focused on averting the progression of the disease to immune-mediated complications.
The global prevalence of severe strep A disease is estimated to be at least 18.1 million cases and an incidence of 1.78 million new cases annually. The majority of the disease burden are attributed to rheumatic heart disease with at least 15.6 million cases, 282,000 new cases, and 233,000 deaths annually 11. The prevalence (cases per 100,000 population) for rheumatic heart disease and acute post-streptococcal glomerulonephritis are higher in low- and middle-income countries and among indigenous populations 11,12,15. Similarly, a higher incidence of invasive strep A bacteremia (13 cases per 100,000 person-years) in young infants, with a 25% case fatality rate among children aged under 15 years occurs in low- and middle-income countries 21. Milder infections, such as pharyngitis at 616 million cases annually, contribute to the largest number of cases to the global strep A burden 4,11. Although putative virulence factors of Strep A infection contributing to host-pathogen interactions have been identified, the exact mechanism that mediates the switch from localized to non-suppurative lesions like acute rheumatic fever or acute post-streptococcal glomerulonephritis and beyond is unclear 17, 31–33.
There is an evidence gap on transitions across Strep A disease states and sequelae from exposure to serious immune-mediated complications. To address this gap, we conducted an evidence synthesis of state transitions across the Strep A disease spectrum through a scoping review.