Today, many different candidates are undergoing testing for safety and immunogenicity in rodents and rabbits, as outlined in review articles 13, 14, 15. in the US alone, providing further incentive for funding bodies, including governments, to support GAS vaccine research.Īs a result of the ASAVI and SAVAC initiatives, new collaborations have been formed, positive advocacy for GAS vaccines has increased, and funding commitments for GAS vaccine development have grown. Therefore, implementing a vaccine programme in the HIC that reduces the GAS infection rate by 20% across all age groups could potentially save approximately $1 billion p.a. Economic assessments in the United States estimated that the annual costs of iGAS and upper respiratory infections exceed $5 billion 12. In 2019 a further positive movement towards the development and implementation of GAS vaccines was achieved through the establishment of two key initiatives: The Strep A Vaccine Global Consortium (SAVAC, ) and the Australian Strep A Vaccine Initiative (ASAVI, Their primary objective is to ensure the development of safe, effective, and affordable GAS vaccines, but they also facilitate connectivity among researchers, analysis of the value of a GAS vaccine, and development of business cases to encourage stakeholder involvement. However, the excessive use of antibiotics for treating GAS pharyngitis and impetigo has played a major role in driving resistance in bystander pathogens 11. Over the past two decades, general antimicrobial resistance has increased, and certain GAS serotypes associated with severe infections have shown increased resistance to clindamycin and macrolides 10. Importantly, GAS laboratory surveillance has revealed no antibiotic resistance in the new clusters responsible for recent outbreaks and no newly-emerged emm types 9. Although no cases of GAS resistance to beta-lactam antibiotics have been reported, there have been reports of reduced susceptibility 7, 8. However, there are stark discrepancies in treatment and diagnosis between high-income countries (HIC) and LMIC, where vaccines would have an even greater impact. In the absence of a GAS vaccine, antibiotics are relied upon for the effective treatment and prevention of transmission. Despite this serotype diversity, different geographical regions experience dissimilar emm-types. More than 250 GAS serotypes have been identified and annotated based on their emm-type genomic sequence that determines the serotype-specific M-protein ( emm). The WHO has taken the lead in this effort by publishing in 2018 a roadmap for the development of the first GAS vaccine 6. Globally, GAS continues to be among the top ten infectious diseases responsible for causing mortality, highlighting the need to develop a GAS vaccine 5. RHD contributes significantly to morbidity and mortality in LMIC, with over 300,000 deaths annually and over 10 million disability-adjusted life years 4. Rheumatic fever is most common in children aged 5 to 15 years, and approximately 460,000 new cases occur each year. The IHME Global Burden of Disease estimates that globally there are more than 40 million cases of RHD 3 with the majority of cases occurring in low- and middle- income countries (LMIC). Untreated or insufficiently treated, GAS infections can also trigger serious immune-related sequelae such as acute rheumatic fever, rheumatic heart disease (RHD), and inflammatory glomerulonephritis 2. Invasive GAS (iGAS) affects more than 600,000 patients globally p.a., with a mortality rate of 25% 1. These include mild conditions such as tonsillitis and impetigo (with over 600 million cases p.a.), to scarlet fever and more severe invasive GAS diseases such as sepsis, toxic shock, and necrotising fasciitis.
Group A Streptococcus (GAS) is a ubiquitous pathogen that causes a wide spectrum of human diseases.
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