Does the burden of Group A Streptococcus in Auckland justify a Vaccine? A study of the burden of Group A Streptococcal diseases in Auckland, and the potential to prevent them through vaccination

Abstract

Aims: New Zealand has a high burden of Group A Streptococcal (GAS) related disease, especially Acute Rheumatic Fever (ARF), which can develop following GAS pharyngitis. Rates of ARF are especially high in Maori and Pacifika children and children in low socioeconomic status households. ARF is highly preventable through timely intervention with antibiotics during GAS pharyngitis, but can lead to serious damage to the heart (Rheumatic Heart Disease (RHD)), leading to lifelong disability. There has been significant progress towards developing a vaccine against GAS that might prevent these diseases, leading to several vaccine candidates, all yet to reach licensure status. The aims of this study were to determine which vaccine candidate is the more applicable to the Auckland Paediatric (0-19 year old) population, estimate the burden of serious GAS diseases and if possible, determine the predictive potential protection afforded by this vaccine. Method: This thesis consists of three separate investigations. The burden of serious GAS diseases (ARF, Acute Post-streptococcal Glomerulonephritis and Invasive GAS infections) was determined for the Auckland 0-19 year old population. Data was collected from the Rheumatic Fever Register, hospital discharge records and clinical laboratory results. Using molecular laboratory techniques, the epidemiology of the strains of GAS causing disease were determined. A literature review was conducted to determine the most clinically advanced GAS vaccine in development. The burden of disease and molecular epidemiology of the causative strains was compared to the strains protected against by the most advanced vaccine candidate, and the burden of disease potential prevented by this vaccine was predicted. Results: ARF - 1054 individuals were recruited over 20 years. The greatest rates of ARF occurred in Maori and Pacifika children between 5-15 years old. Invasive GAS diseases - 232 individuals were recruited over 10 years. The greatest rates of invasive disease occurred in Maori and Pacifika children under 5 years old, especially those under 24 months old. Molecular epidemiology - 77 unique strains were identified over 428 clinical isolates. 68% of the clinical isolates belonged to a strain which was protected against the 30-valent vaccine. Forty-three potential vaccine candidates were identified in the literature review. Four of these vaccine candidates had at the time of the literature review, passed phase I clinical trials, with one having passed phase II clinical trials. The 26-valent NH2 vaccine was determined to be the most clinically advanced and applicable vaccine for the study population, of which an expanded 30-valent version is in development. This 30-valent NH2 vaccine candidate was chosen as the vaccine for this thesis. Up to 55% of cases over the timeframe of this study were predicted to be prevented by this vaccine. Conclusion: GAS is a common cause of bacterial pharyngitis; in Auckland it is of concern due to the high rates of invasive disease and ARF which develop. There is a 30-valent vaccine in development with the potential to prevent up to 55% of cases occurring in the 0-19 year old population in Auckland.