Artzy-Randrup Yael, Dobson Andrew P, Pascual Mercedes
Howard Hughes Medical Institute and Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109-1048; Theoretical Ecology Group, Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam 1090 GE, The Netherlands;
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544; and Santa Fe Institute, Santa Fe, NM 87501.
Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):3014-9. doi: 10.1073/pnas.1409467112. Epub 2015 Jan 20.
It is extremely likely that the malaria vaccines currently in development will be used in conjunction with treated bednets and other forms of malaria control. The interaction of different intervention methods is at present poorly understood in a disease such as malaria where immunity is more complex than for other pathogens that have been successfully controlled by vaccination. Here we develop a general mathematical model of malaria transmission to examine the interaction between vaccination and bednets. Counterintuitively, we find that the frailty of malaria immunity will potentially cause both synergistic and antagonistic interactions between vaccination and the use of bednets. We explore the conditions that create these tensions, and outline strategies that minimize their detrimental impact. Our analysis specifically considers the three leading vaccine classes currently in development: preerythrocytic (PEV), blood stage (BSV), and transmission blocking (TBV). We find that the combination of BSV with treated bednets can lead to increased morbidity with no added value in terms of elimination; the interaction is clearly antagonistic. In contrast, there is strong synergy between PEV and treated bednets that may facilitate elimination, although transient stages are likely to increase morbidity. The combination of TBV with treated bednets is synergistic, lowering both morbidity and elimination thresholds. Our results suggest that vaccines will not provide a straightforward solution to malaria control, and that future programs need to consider the synergistic and antagonistic interactions between vaccines and treated bednets.
目前正在研发的疟疾疫苗极有可能与经过处理的蚊帐及其他形式的疟疾防控措施联合使用。在疟疾这类疾病中,免疫情况比其他已通过疫苗接种成功控制的病原体更为复杂,目前对于不同干预方法之间的相互作用了解甚少。在此,我们构建了一个疟疾传播的通用数学模型,以研究疫苗接种与蚊帐之间的相互作用。与直觉相反,我们发现疟疾免疫的脆弱性可能会在疫苗接种和使用蚊帐之间引发协同和拮抗两种相互作用。我们探究了造成这些矛盾关系的条件,并概述了将其不利影响降至最低的策略。我们的分析特别考虑了目前正在研发的三类主要疫苗:红细胞前期疫苗(PEV)、血期疫苗(BSV)和传播阻断疫苗(TBV)。我们发现,BSV与经过处理的蚊帐联合使用可能会导致发病率上升,且在消除疟疾方面没有额外益处;这种相互作用明显是拮抗的。相比之下,PEV与经过处理的蚊帐之间存在很强的协同作用,这可能有助于消除疟疾,尽管过渡阶段可能会使发病率上升。TBV与经过处理的蚊帐联合使用具有协同作用,可降低发病率和消除阈值。我们的结果表明,疫苗并不能为疟疾防控提供简单直接的解决方案,未来的项目需要考虑疫苗与经过处理的蚊帐之间的协同和拮抗相互作用。