Abstract
BackgroundWith 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 FindingsTo 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/SignificanceThe 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.
Highlights
Recent years have seen an increasing appreciation of the significance of Plasmodium vivax as a threat to global health
Transmission model The human component of our P. vivax transmission model is formulated by dividing the population into classes based on infection status (Fig. 1A): S, for naıve individuals who are susceptible to both infection and disease; E, for exposed or inoculated humans who are not yet infectious; I, for infectious humans that can transmit the pathogen to the vector; Q, for individuals that have acquired some degree of immunity from disease and are more weakly infectious than those in class I; and H1...n, a chain of n dormant classes for humans who carry liver-stage hypnozoites
Cases show significant autocorrelation peaks between the months of August-November and those from January to June, providing an estimated latency period between 5 and 8 months (Fig. 2E), and a mean value of 7 months (Fig. 2F). This relatively long interval is compatible with the ‘‘temperate’’ strains of P. vivax, rather than the ‘‘tropical types’’ with short and frequent relapses found in more endemic parts of Indian Meteorological Department in Pune (India) [14,33]
Summary
Recent years have seen an increasing appreciation of the significance of Plasmodium vivax as a threat to global health. Estimates of the population at risk of the disease have been upgraded to between 2.5 and 2.6 billion, and the number of annual infections to 130–435 million [1]. With the persisting gaps in our understanding of its transmission dynamics (despite rare theoretical studies [6,7]) and mode of action of available treatments, P. vivax malaria is among the world’s most neglected diseases [2,3,4,8]. Central questions remain on the role of relapses in its population dynamics, especially on the importance of treating hypnozoites to interrupt transmission [9]. With over a hundred million annual infections and rising morbidity and mortality, Plasmodium vivax malaria remains largely a neglected disease. The dependence of this malaria species on relapses and the potential significance of the dormant stage as a therapeutic target, are poorly understood
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