Abstract
BackgroundArtemisinin combination therapy is recommended as first-line treatment for falciparum malaria across the endemic world and is increasingly relied upon for treating vivax malaria where chloroquine is failing. Artemisinin resistance was first detected in western Cambodia in 2007, and is now confirmed in the Greater Mekong region, raising the spectre of a malaria resurgence that could undo a decade of progress in control, and threaten the feasibility of elimination. The magnitude of this threat has not been quantified.MethodsThis analysis compares the health and economic consequences of two future scenarios occurring once artemisinin-based treatments are available with high coverage. In the first scenario, artemisinin combination therapy (ACT) is largely effective in the management of uncomplicated malaria and severe malaria is treated with artesunate, while in the second scenario ACT are failing at a rate of 30%, and treatment of severe malaria reverts to quinine. The model is applied to all malaria-endemic countries using their specific estimates for malaria incidence, transmission intensity and GDP. The model describes the direct medical costs for repeated diagnosis and retreatment of clinical failures as well as admission costs for severe malaria. For productivity losses, the conservative friction costing method is used, which assumes a limited economic impact for individuals that are no longer economically active until they are replaced from the unemployment pool.ResultsUsing conservative assumptions and parameter estimates, the model projects an excess of 116,000 deaths annually in the scenario of widespread artemisinin resistance. The predicted medical costs for retreatment of clinical failures and for management of severe malaria exceed US$32 million per year. Productivity losses resulting from excess morbidity and mortality were estimated at US$385 million for each year during which failing ACT remained in use as first-line treatment.ConclusionsThese ‘ballpark’ figures for the magnitude of the health and economic threat posed by artemisinin resistance add weight to the call for urgent action to detect the emergence of resistance as early as possible and contain its spread from known locations in the Mekong region to elsewhere in the endemic world.
Highlights
Artemisinin combination therapy is recommended as first-line treatment for falciparum malaria across the endemic world and is increasingly relied upon for treating vivax malaria where chloroquine is failing
The excess mortality associated with artemisinin resistance is a product of: i) an increased proportion of artemisinin combination therapy (ACT) failures in uncomplicated malaria, a proportion of which become severe; and, ii) patients with severe malaria who are treated with quinine instead of artesunate [4]
Baseline and resistance scenarios This analysis compares a baseline scenario characterized by an ACT failure rate of 5% against a scenario of 30% ACT failure rate, a conservative estimate compared with the fate of previous first-line treatments [14] and with a recent study from the northwestern border of Thailand, an area where artemisinin resistance is established, where the failure rate for artesunate-mefloquine in the treatment of Plasmodium falciparum was 58% [10]
Summary
Artemisinin combination therapy is recommended as first-line treatment for falciparum malaria across the endemic world and is increasingly relied upon for treating vivax malaria where chloroquine is failing. Artemisinin resistance was first detected in western Cambodia in 2007, and is confirmed in the Greater Mekong region, raising the spectre of a malaria resurgence that could undo a decade of progress in control, and threaten the feasibility of elimination. The magnitude of this threat has not been quantified. The past decade has seen substantial progress in malaria control, with local elimination a feasible objective in parts of the Asia-Pacific, Middle East, Latin America and even in some areas of sub-Saharan Africa (SSA) Much of this progress has been ascribed to the increasing availability of artemisinin compounds, with their rapid clearance. The recent identification of Kelch mutations associated with artemisinin resistance on chromosome 13 is likely to better specify just how far it has already spread [13]
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