Abstract
Artemisinin combination therapies (ACTs) are the WHO-recommended first-line therapies for uncomplicated Plasmodium falciparum malaria. The emergence and spread of artemisinin-resistant genotypes is a major global public health concern due to the increased rate of treatment failures that result. This is particularly germane for WHO designated 'high burden to high impact' (HBHI) countries, such as Burkina Faso, where there is increased emphasis on improving guidance, strategy, and coordination of local malaria response in an effort to reduce the prevalence of P. falciparum malaria. To explore how the increased adoption of ACTs may affect the HBHI malaria setting of Burkina Faso, we added spatial structure to a validated individual-based stochastic model of P. falciparum transmission and evaluated the long-term effects of increased ACT use. We explored how de novo emergence of artemisinin-resistant genotypes, such as pfkelch13 580Y, may occur under scenarios in which private-market drugs are eliminated or multiple first-line therapies (MFT) are deployed. We found that elimination of private market drugs would result in lower treatment failures rates (between 11.98% and 12.90%) when compared to the status quo (13.11%). However, scenarios incorporating MFT with equal deployment of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) may accelerate near-term drug resistance (580Y frequency ranging between 0.62 to 0.84 in model year 2038) and treatment failure rates (26.69% to 34.00% in 2038), due to early failure and substantially reduced treatment efficacy resulting from piperaquine-resistant genotypes. A rebalanced MFT approach (90% AL, 10% DHA-PPQ) results in approximately equal long-term outcomes to using AL alone but may be difficult to implement in practice.
Highlights
Despite the United Nations’ Millennium Development Goals leading to substantial reductions in the global burden of infectious disease, malaria remains a serious public health risk in many parts of Africa, Asia, and South America
The spatial distribution of 580Y in the model simulations confirms that (i) emergence is stochastic but with relatively low variance, (ii) “hot spots” of elevated drug resistance are likely during establishment of drug restraint genotypes, and (iii) under high prevalence conditions, high treatment coverage contributes to the acceleration of local selection for the 580Y mutation
While the evolution of drug resistance by the P. falciparum parasite is a pressing concern, in high burden to high impact (HBHI) countries drug resistance evolution is secondary to the need to increase access to and usage of Artemisinin combination therapies (ACTs)
Summary
Despite the United Nations’ Millennium Development Goals leading to substantial reductions in the global burden of infectious disease, malaria remains a serious public health risk in many parts of Africa, Asia, and South America. Plasmodium falciparum malaria remains holoendemic in at least eleven countries, mainly in western and central Africa, and these countries have recently come under a WHO grouping called high burden to high impact (HBHI) which recognizes that the most severely affected malaria-endemic countries will require additional resources and greater policy imagination [1]. Artemisinin-resistant parasites can either be imported from other regions (e.g., spread across Southeast Asia), or they may emerge independently as in Guyana, PapuaNew Guinea, and Rwanda [3, 4, 7]. This raises the possibility that HBHI countries may be at risk for artemisinin resistance appearing due to de novo emergence or the importation of a resistant parasite
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