Widespread Artemisinin Resistance Could Wipe Out a Decade of Malaria Investment

Global malaria deaths have been halved in the past decade. Despite such progress, 584,000 people still lost their lives to the disease in 2013. Nine out of ten of those deaths were in Africa, and over three quarters occurred among children under 5 years of age (1). Over 2 billion people are thought to be vulnerable to malaria infection in the Asia Pacific region.

Across the endemic world the recommended first-line treatment for uncomplicated falciparum malaria is artemisinin-based combination therapy (ACT). Large recent investments have extended its coverage substantially, helping to drive down malaria deaths.

However, artemisinin-resistant Plasmodium falciparum malaria has emerged on the Cambodia/Thailand border and has recently been detected as far west as the Myanmar/India border (2). The situation is worryingly reminiscent of previous emergence of resistance to chloroquine, sulfadoxine–pyrimethamine and mefloquine. Artemisinin resistance is a major threat to health security, with the most severe potential effects in sub-Saharan Africa, where the disease burden is highest and systems for monitoring and containment of resistance are inadequate (3).

According to a global model (4) comparing two contrasting future ACT-related scenarios, the economic impact of widespread artemisinin resistance would be more than US$ 0.5 billion each year, seriously undermining years of malaria investment and creating a new economic drain on endemic countries.

Developed by leading malaria experts from Thailand and the United Kingdom, the model compares a global scenario where ACT maintains high levels of efficacy (i.e. cure rates of 95% and artesunate is used to treat severe malaria) with one in which artemisinins face widespread resistance, leading to ACT clinical failure rates of 30% [*] and where policy has reverted to quinine to manage severe malaria. Estimated economic costs were calculated according to additional diagnostic tests and ACT for treatment failures, the cost of treating a higher number of severe malaria cases, and the cost of switching policy to alternative ACT or other first-line therapies once these are available. Estimates of productivity losses associated with the excess morbidity and mortality are also included.

Malaria clinic in Mae Ngao District, Mae Hong Son province, in northern Thailand. Located right next to the Thai/Myanmar border, the province sees a large number of people crossing the border in both directions throughout the year (Credit: Alex Boyesen/DigitalMixes)

The model predicts an annual economic impact of US$ 661 million as a result of artemisinin resistance: Equivalent to approximately one third of estimated total international development assistance for malaria (5).

Artemisinin resistance is also likely to threaten malaria elimination strategies, allowing malaria to continue its demonstrated drain on economic growth. Furthermore, re-introduction of malaria to areas where it has been recently eliminated is also more likely, making costly surveillance systems essential. Inclusion of these factors would imply greater health and economic costs than those described. Estimates of household costs associated with artemisinin resistance have also not been included in this analysis.

Continued support to two urgent and parallel strategies is vital to forestalling the occurrence of widespread artemisinin resistance:

1.       Eliminating artemisinin-resistant parasites in the Greater Mekong sub-region before they spread more widely.

2.       Detecting and containing artemisinin resistance when it does appear (or emerges) in Africa, and other regions. Public health authorities need to conduct active surveillance for resistant parasites in areas where they have not been previously found.

This dual approach would also build preparedness against new emergence of artemisinin resistance, particularly in Africa.

In the past, drug-use patterns in Africa fostered only partly resistant parasites, with high-grade resistance originating from Asia. Use of antimalarial medicines in Africa has intensified significantly in the past decade and some areas are undergoing rapid decreases in malaria transmission, increasing the likelihood of new emergence of high-grade resistance. Nevertheless, since artemisinin-resistant parasites are already circulating in South East Asia, the greatest danger to the efficacy of ACT in Africa is from South–South importation (4).

One paper suggests drug-resistant malaria may be present in Angola, perhaps brought there by an annual flow of some 40,000 Vietnamese migrant workers. It seems plausible that artemisinin-resistant parasites were carried to Angola from Viet Nam and then locally transmitted among migrant workers (6). This kind of spread of artemisinin resistance may also be more likely today because travel between African and Asian capitals is much more frequent than it was even five or ten years ago (7, 8).

Experts concur that the only assured way to stop artemisinin-resistant malaria in the coming decades will be to eliminate the disease completely. In the meantime, the option of preventing the spread of artemisinin resistance across Asia and then to Africa may be very short-lived. To avoid squandering that opportunity, proportionate malaria investments in the Greater Mekong sub-region, its neighbouring countries, and in sub-Saharan Africa, must be sustained.

External financing has largely underpinned 15 years of malaria achievements in all affected regions. Reallocating that support to a consolidated set of countries and regions may have a dramatic effect on the pace and direction that artemisinin resistance spreads.

References:

1.        World malaria report 2014. Geneva, World Health Organization; 2014. (http://www.who.int/malaria/publications/world_malaria_report_2014/en/).

2.        Tun KM et al. Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker. Lancet Infectious Diseases, 2015; 15(4): 415 (http://dx.doi.org/10.1016/S1473-3099(15)70032-0)

3.        Talisuna AO et al. Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems. Lancet Infectious Diseases, 2012; 12(11): 888 (http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(12)70241-4/abstract). 

4.        Lubell Y et al. Artemisinin resistance – modelling the potential human and economic costs.  Malaria Journal, 2014; 13:452 (http://www.malariajournal.com/content/13/1/452).

5.        Financing global health 2013: Transition in an age of austerity. Seattle, Institute for Health Metrics and Evaluation, 2014 (http://www.healthdata.org/policy-report/financing-global-health-2013-transition-age-austerity).

6.        Fortner R. Drug resistant malaria in Africa: A suspected case from Angola (blog post) (http://robertfortner.posthaven.com/drug-resistant-malaria-in-africa-a-suspected-case-from-angola).

7.        Djimdé A. Poised and waiting for malaria’s next move. Cambridge, Wellcome Trust Sanger Institute, 2014 (https://sangerinstitute.wordpress.com/2014/09/12/poised-and-waiting-for-malarias-next-move/).

8.        Ghansah A et al. Monitoring parasite diversity for malaria elimination in sub-Saharan Africa. Science, 2014; 345:1297 (http://www.sciencemag.org/content/345/6202/1297.full).