While Plasmodium falciparum malaria commands much attention because of high human fatality in sub-Saharan Africa, the comparatively “benign” Plasmodium vivax malaria continues to exact a significant toll on 40% of the world population, and is increasingly becoming a major public health concern primarily in south-east Asia. Unlike falciparum malaria, clinical interventions by the interruption of blood-stage transmission is ineffective in P. vivax because of the liver-stage hypnozoites, a dormant phase of the parasite's life cycle that can trigger relapses months after the original infection has subsided. The current “radical cure” for vivax malaria combines blood-stage treatment with primaquine (PQ), a hypnozoitecide in use for over 50 years despite impaired efficacy from drug resistance, poor patient compliance and safety concerns.
Considering the importance of relapses as a hidden reservoir for vivax malaria, especially in epidemic areas with intermittent transmission, the public health implications of using an improved anti-relapse drug are poorly understood due to insufficient tools for quantifying its population-wide benefits. To address this problem we adopt a population dynamics approach as follows. We formulate a dynamical model of P. vivax transmission, and use recently developed likelihood-based inference methods to parametrize it from time series surveillance data from an epidemic region in NW India. We then use the maximum-likelihood model to quantify the fraction of relapses that require effective treatment in order to suppress, and even eliminate, vivax malaria in the study area.
Results/Conclusions
Our model gives maximum likelihood estimates for mean latency and relapse rate of 7.1 months and 31% respectively, which correspond closely to values from clinical evaluation studies in the area. Given the prevailing treatment practices in India as a baseline, the model predicts that a successful treatment of 30-40% of relapses alone would drastically reduce disease burden within a decade, and result in extinction of the parasite species in 25 years. Furthermore, the impact of relapse treatment is inversely related with preceding transmission intensity, which suggests a cost-effective policy of selectively applying treatment following years of low transmission if resources are limited and the development of resistance becomes a concern.
The sensitive dependence of P. vivax on relapses can inform the debate on how to more effectively control the disease. Our approach can provide effective means of evaluating population-wide impacts of relapse treatment in some regions, and should encourage the development of better alternatives to PQ in the light of renewed enthusiasm for global malaria eradication.