The Potential Elimination of Plasmodium vivax Malaria by Relapse Treatment: Insights from a Transmission Model and Surveillance Data from NW India

Background: With over a hundred million annual infections and rising morbidity and mortality, Plasmodium vivax malaria remains largely a neglected disease. In particular, the dependence of this malaria species on relapses and the potential significance of the dormant stage as a therapeutic target, are poorly understood. Methodology/Principal Findings: To quantify relapse parameters and assess the population-wide consequences of anti-relapse treatment, we formulated a transmission model for P. vivax suitable for parameter inference with a recently developed statistical method based on routine surveillance data. A low-endemic region in NW India, whose strong seasonality demarcates the transmission season, provides an opportunity to apply this modeling approach. Our model gives maximum likelihood estimates of 7.1 months for the mean latency and 31% for the relapse rate, in close agreement with regression estimates and clinical evaluation studies in the area. With a baseline of prevailing treatment practices, the model predicts that an effective anti-relapse treatment of 65% of those infected would result in elimination within a decade, and that periodic mass treatment would dramatically reduce the burden of the disease in a few years. Conclusion/Significance: The striking dependence of P. vivax on relapses for survival reinforces the urgency to develop more effective anti-relapse treatments to replace Primaquine (PQ), the only available drug for the last fifty years. Our methods can provide alternative and simple means to estimate latency times and relapse frequency using routine epidemiological data, and to evaluate the population-wide impact of relapse treatment in areas similar to our study area. Author Summary: Plasmodium vivax, one of the four species responsible for malaria in humans, represents today a much larger global public health problem than previously recognized. The neglect of P. vivax is still apparent in the limited efforts made so far to understand the regional dynamics of the disease, and in the non-existence of practical models to guide and evaluate control measures. One main impediment is the overall uncertainty in the dynamic role of the hidden reservoir, resulting from the liver stage known as hypnozoites and responsible for relapses, a characteristic feature of this species. Current control efforts and elimination plans are therefore hampered in their ability to quantify the impact of effective anti-relapse treatments. This paper applies a P. vivax transmission model to surveillance data from a semi-arid region (in NW India), whose clear demarcation of the transmission and relapse seasons makes it especially suited for estimating relapse parameters such as frequency and rate. The model results quantify the striking dependence of P. vivax on relapses for its survival, supporting the feasibility of regional elimination and lending support to the expressed urgency of replacing Primaquine, the anti- relapse drug now in use for over fifty years with unsatisfactory efficacy, resistance and side-effects.