Department of Mathematics and Statistics, La Trobe University, Melbourne, Victoria, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
PLoS Comput Biol. 2020 Jun 5;16(6):e1007182. doi: 10.1371/journal.pcbi.1007182. eCollection 2020 Jun.
Group A Streptococcus (GAS) skin infections are caused by a diverse array of strain types and are highly prevalent in disadvantaged populations. The role of strain-specific immunity in preventing GAS infections is poorly understood, representing a critical knowledge gap in vaccine development. A recent GAS murine challenge study showed evidence that sterilising strain-specific and enduring immunity required two skin infections by the same GAS strain within three weeks. This mechanism of developing enduring immunity may be a significant impediment to the accumulation of immunity in populations. We used an agent-based mathematical model of GAS transmission to investigate the epidemiological consequences of enduring strain-specific immunity developing only after two infections with the same strain within a specified interval. Accounting for uncertainty when correlating murine timeframes to humans, we varied this maximum inter-infection interval from 3 to 420 weeks to assess its impact on prevalence and strain diversity, and considered additional scenarios where no maximum inter-infection interval was specified. Model outputs were compared with longitudinal GAS surveillance observations from northern Australia, a region with endemic infection. We also assessed the likely impact of a targeted strain-specific multivalent vaccine in this context. Our model produced patterns of transmission consistent with observations when the maximum inter-infection interval for developing enduring immunity was 19 weeks. Our vaccine analysis suggests that the leading multivalent GAS vaccine may have limited impact on the prevalence of GAS in populations in northern Australia if strain-specific immunity requires repeated episodes of infection. Our results suggest that observed GAS epidemiology from disease endemic settings is consistent with enduring strain-specific immunity being dependent on repeated infections with the same strain, and provide additional motivation for relevant human studies to confirm the human immune response to GAS skin infection.
A 组链球菌（GAS）皮肤感染由多种菌株类型引起，在弱势群体中高度流行。菌株特异性免疫在预防 GAS 感染中的作用尚未得到充分理解，这是疫苗开发中的一个关键知识空白。最近的 GAS 小鼠挑战研究表明，证据表明，需要通过同一 GAS 菌株在三周内进行两次皮肤感染，才能产生杀菌的菌株特异性和持久免疫力。这种产生持久免疫力的机制可能是人群中免疫积累的重大障碍。我们使用 GAS 传播的基于代理的数学模型，研究了仅在特定间隔内两次感染同一菌株后才产生持久菌株特异性免疫的流行病学后果。当将小鼠时间框架与人类相关联时考虑到不确定性，我们将最大感染间隔从 3 周到 420 周进行了变化，以评估其对流行率和菌株多样性的影响，并考虑了在没有最大感染间隔指定的情况下的其他情况。将模型输出与澳大利亚北部的纵向 GAS 监测观察结果进行了比较，该地区存在地方性感染。我们还评估了在这种情况下针对特定菌株的多价疫苗的可能影响。当开发持久免疫力的最大感染间隔为 19 周时，我们的模型产生的传播模式与观察结果一致。我们的疫苗分析表明，如果菌株特异性免疫需要反复感染，则针对特定菌株的多价 GAS 疫苗可能对澳大利亚北部人群中 GAS 的流行率影响有限。我们的研究结果表明，从疾病流行地区观察到的 GAS 流行病学与持久的菌株特异性免疫依赖于同一菌株的重复感染是一致的，并为相关的人类研究提供了额外的动力，以确认人类对 GAS 皮肤感染的免疫反应。
