MALARIA CONTROL IN VIETNAM: IMMUNE DYNAMICS AND ARTEMISININ RESISTANCE

Abstract

Objective: The purpose of this study was to investigate the association between artemisinin-based case management and the incidence of malaria in Vietnam between 1991 and 2010. Moreover, the study aimed to evaluate how this relationship was modulated by host immune dynamics and transmission intensity. Understanding these interactions is critical to mitigating the threat of artemisinin resistance and working towards malaria elimination in the Greater Mekong Subregion.

Methods: In the first part of this thesis, data on reported malaria cases, antimalarial treatment requests, vector control measures, and urbanization metrics from all provinces in Vietnam between 1991-2010 were collected from annual reports of the National Malaria Control Program. Generalized estimating equations were used to investigate the factors associated with malaria incidence. A mathematical model was then developed to evaluate the effects of ACT case management and artemisinin resistance on malaria transmission in hypothetical populations. A subsequent model was fit to malaria case data from Vietnam and used to predict malaria incidence following increased rates of treatment failure as a result of artemisinin resistance.

Results: Statistical analysis revealed a significant (P <0.001) inverse and spatially consistent association between the incidence of malaria in Vietnam and the proportion of antimalarial treatments that contained artemisinin. The dynamic models revealed that decreasing the treatment failure rate reduced the number of asymptomatic cases in both high and low transmission settings, while the number of symptomatic cases increased in the high transmission setting and decreased in the low transmission setting. Increasing the rate of treatment failure increased the number of asymptomatic cases in both transmission settings, while symptomatic cases decreased in the high transmission setting and increased in the low transmission setting. Moreover, the fitted model provided a reasonable picture of the decline of malaria in Vietnam by varying the rate of treatment failure. The model predicted that increased rates of treatment failure in subsequent years would lead to an epidemic.

Conclusions: Artemisinin-based case management was significantly associated with the decline of malaria in Vietnam between 1991 and 2010. However, the population-level effects of ACT case management on incidence may be greater in low transmission settings in populations with low levels of acquired immunity. In particular, reduced immune protection in Vietnam heightens the threat posed by artemisinin-resistant P. falciparum.