Committee on Genetics, Genomics and Systems Biology, The University of Chicago, Chicago, IL, 60637, USA.
Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.
Nat Commun. 2024 Aug 26;15(1):7343. doi: 10.1038/s41467-024-51468-6.
Intervention efforts against falciparum malaria in high-transmission regions remain challenging, with rapid resurgence typically following their relaxation. Such resilience co-occurs with incomplete immunity and a large transmission reservoir from high asymptomatic prevalence. Incomplete immunity relates to the large antigenic variation of the parasite, with the major surface antigen of the blood stage of infection encoded by the multigene and recombinant family known as var. With a stochastic agent-based model, we investigate the existence of a sharp transition in resurgence ability with intervention intensity and identify molecular indicators informative of its proximity. Their application to survey data with deep sampling of var sequences from individual isolates in northern Ghana suggests that the transmission system was brought close to transition by intervention with indoor residual spraying. These results indicate that sustaining and intensifying intervention would have pushed malaria dynamics to a slow-rebound regime with an increased probability of local parasite extinction.
在高传播地区针对恶性疟原虫的干预措施仍然具有挑战性，通常在放松干预措施后疟疾会迅速反弹。这种弹性与不完全免疫和高无症状流行率导致的大量传播储备并存。不完全免疫与寄生虫的大量抗原变异有关，感染的血阶段主要表面抗原由多基因和重组家族编码，称为 var。我们使用基于随机主体的模型研究了干预强度与复苏能力之间存在的急剧转变，并确定了与其接近程度相关的分子指标。将其应用于来自加纳北部个体分离株的 var 序列深度采样的调查数据表明，室内滞留喷洒干预使传播系统接近转变。这些结果表明，维持和加强干预将使疟疾动态进入缓慢反弹阶段，寄生虫局部灭绝的可能性增加。
