Modeling the potential health effects of future Strep A vaccines

We used the Strep A vaccine impact model to estimate the potential health impacts of future Strep A vaccination at global, regional and national levels and by country income category. Based on WHO recommended Strep A vaccine product attributes¹⁵, we estimate lifetime health benefits among vaccinated cohorts, focusing on the burden of avoided streptococcal A disease for pharyngitis, impetigo, invasive disease, cellulitis, and RHD We developed this static cohort model to We analyze strategic scenarios for vaccination at birth and at age 5 years and predict that approximately one-third of the annual global RHD burden could be avoided with future Strep A vaccination. Did. By region, the impact of vaccination in terms of averted burden per fully vaccinated person was highest in North America for cellulitis and in sub-Saharan Africa for RHD, the highest underlying disease per 100,000 population. This is because the burden is relatively high for cellulitis and RHD in North America and linen. Saharan Africa, respectively. By income level, the total vaccine-avoidable burden against pharyngitis, impetigo, invasive disease, cellulitis, and RHD is primarily due to the demographic effect of increasing population size at the target age for vaccination. , was highest in low- and middle-income countries.

Our health impact estimates are used in clinical development, interpretation of existing data, assessment of data collection needs to fill critical evidence gaps, prioritization and implementation across the end-to-end continuum of discovery, development and research. provide useful decision support in policy making for Providing safe, effective and affordable (future) streptococcal A vaccines. While the vaccine-avoidable burden of disease is an important public health priority, the impact of high morbidity and mortality on the young adult population represents substantial productivity losses from an economic perspective. It also leads to^7,17. This requires a broader global public health value proposition analysis to infer an end-to-end perspective of vaccine development to capture continued vaccine development.^{14,twenty four,twenty five,26}and the global benefits of future Strep A vaccines are estimated to be very positive²⁷.

Our research has limitations. We estimated only the direct effect of Strep A vaccination and excluded the indirect effect on pathogen transmission prevention. Evidence on the mode of transmission of Strep A is valuable for developing transmission kinetic models for estimating the overall (direct and indirect) effects of vaccination. Such estimates likely enhance the impact of Strep A vaccines, especially vaccines administered in the first few years of life, given the peak incidence of severe invasive disease occurring in infants and the elderly. It is considered. As an alternative to endogenous modeling of propagation dynamics, the influence of indirect herd effects can be extrapolated by specifying a base multiplier of the direct effects in the static cohort model. Haemophilus influenzae Type B vaccine, pneumococcal vaccine, rotavirus vaccine²⁸. However, if the Strep A vaccine significantly alters infectivity, a transmission kinetics model may be required to assess the non-linearity of Strep A infection kinetics.²⁹.Beyond the period of protection provided by vaccination, the median age of infection and the burden of streptococcal A infection may change, and herd immunity in the unvaccinated population may increase the burden of streptococcal A infection. may be mitigated³⁰.

Evidence on the natural history of disease dynamics may be useful in simulating disease progression, such as progression from acute rheumatic fever to RHD. We estimated the impact of vaccination on averted streptococcal A load for pharyngitis, impetigo, invasive disease, cellulitis, and RHD, but not for acute rheumatic fever and acute post-streptococcal glomerulonephritis. Pathogenic pathways between immune-mediated sequelae and streptococcal A infection and these diseases were excluded. Excluding ARF and APSGN underestimates the impact of vaccines to prevent these diseases, whereas excluding pathogenic pathways between infection and immune-mediated sequelae, including RHD, impact of vaccination at age 5. may be overestimated and the effect on infants may be underestimated. vaccination. In our model, we hypothesized that vaccination of a 5-year-old child would prevent her RHD complication occurring at 5 years of age. However, some of these cases may be avoided by infant vaccination schedules that prevent infection prior to ARF and RHD. Further epidemiological or immunological studies are needed to model this scenario.

The vaccine impact model can be extended to include other streptococcal A pathologies and sequelae to estimate additional health benefits of vaccination that avoid morbidity and mortality attributed to these pathologies. . The health benefits of vaccination in reducing streptococcal A infections may reduce the use of corresponding antibiotics (for the treatment of streptococcal A infections), and the model is to reduce streptococcal A infections. Infections that may be characterized by the availability of high-quality observational data on prescribing patterns and levels of antibiotic use in the treatment of type 3 infections. WHO believes vaccination has additional value in reducing antibiotic consumption³¹. Reducing antibiotic consumption may actually reduce the risk and rate of antibiotic resistance in off-target or bystander pathogens such as Strep A and pneumococci. It may also reduce the risk of microbiome disruption hypothesized to cause chronic health conditions.³².

Vaccine impact predictions are based on hypothetical vaccines that meet WHO-recommended product characteristics.¹⁵, and licensed streptococcal A vaccines may have different characteristics. The vaccination coverage assumptions are based on historical trends in vaccination coverage. Haemophilus influenzae Coverage values ​​for Hib3 are not available for the type B vaccine (Hib3) or for the third dose of diphtheria, tetanus, and pertussis vaccines, and the coverage and magnitude of future streptococcal A vaccines may differ. In addition, assumptions regarding the kinetics of protection duration and attenuation of vaccine-derived immunity may differ from future evidence from clinical trials and efficacy studies.

To our knowledge, our model is the first to predict the impact of vaccines against multiple streptococcal infections in over 200 countries. Two of his other studies have developed similar models, but they have been adjusted for Australian and New Zealand data.^17,18. Both countries have RHD endemic among marginalized indigenous peoples and have advanced disease surveillance systems. Models developed for these countries included the risk of developing ARF and her subsequent progression to RHD. However, data on the risk of ARF and progression to RHD are limited in other countries, so only the incidence of RHD was modeled in this study. Better epidemiological data will improve predictions of future disease burden and vaccine impact.

In conclusion, based on the WHO-recommended product attributes of the Strep A vaccine, we conclude that the health benefits of vaccination in avoiding disease burden such as pharyngitis, impetigo, invasive disease, cellulitis, RHD, etc. developed a Strep A vaccine impact model to estimate . Global, regional, national and national income levels. Health impact estimates for Streptococcal type A vaccination are useful inputs for generating economic impact estimates based on cost-effectiveness analyses.³³ And for societal impact estimates based on benefit-cost analyses, we collate useful evidence towards the full value of vaccine evaluation.^{twenty four,34} For Streptococcus A vaccine.