Modeling the development of acquired clinical immunity to Plasmodium falciparum malaria

被引:29
作者
Gatton, ML [1 ]
Cheng, Q
机构
[1] PO Royal Brisbane Hosp, Queensland Inst Med Res, Malaria & Scabies Grp, Div Infect Dis & Immunol, Brisbane, Qld 4029, Australia
[2] Univ Queensland, Australian Ctr Int & Trop Hlth & Nutr, Herston, Qld, Australia
[3] Australian Army, Malaria Inst, Dept Drug Resistance & Diagnost, Enoggera, Qld, Australia
关键词
D O I
10.1128/IAI.72.11.6538-6545.2004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Individuals living in regions where malaria is endemic develop an acquired immunity to malaria which enables them to remain asymptomatic while still carrying parasites. Field studies indicate that cumulative exposure to a variety of diverse Plasmodium parasites is required for the transition from symptomatic to asymptomatic malaria. This study used a simulation model of the within-host dynamics of P. falciparum to investigate the development of acquired clinical immunity under different transmission conditions and levels of parasite diversity. Antibodies developed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), a clonally variant molecule, were assumed to be a key human immunological response to P. falciparum infection, along with responses to clonally conserved but polymorphic antigens. The time to the development of clinical immunity was found to be proportional to parasite diversity and inversely proportional to transmission intensity. The effect of early termination of symptomatic infections by chemotherapy was investigated and found not to inhibit the host's ability to develop acquired immunity. However, the time required to achieve this state was approximately double that compared to when no treatment was administered. This study demonstrates that an immune response primarily targeted against PfEMP1 has the ability to reduce clinical symptoms of infections irrespective of whether treatment is administered, supporting its role in the development of acquired clinical immunity. The results also illustrate a novel use for simulation models of P. falciparum infections, investigation of the influence of intervention strategies on the development of naturally acquired clinical immunity.
引用
收藏
页码:6538 / 6545
页数:8
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