A Race to Save Lives
August 19, 2014
While the world has been preoccupied by the recent Ebola outbreak in West Africa, news emanating from Southeast Asia may portend even more severe consequences for the continent. A study published in the July 31 issue of the New England Journal of Medicine (NEJM) has made it increasingly clear that the world faces the threat of losing one of its most important tools in the global fight against malaria.
Artemisinin is considered the world’s most effective treatment against the deadliest form of malaria, caused by the parasite Plasmodium falciparum and transmitted by Anopheles mosquitos. This ancient drug is a major reason why over 3 million lives have been saved since the year 2000. Unfortunately, resistance to this first line drug appeared almost a decade ago in Western Cambodia. By definition, parasites are considered resistant when at least 10% of malarial patients in a given area still have the parasites in their blood after three days of exposure to artemisinin therapy. Parasite resistance is driven by a number of factors, including misdiagnosis, underdosing, delays in access to care, and substandard and counterfeit drugs.
The recent study, led by Elizabeth Ashley of the Mahidol Oxford Tropical Medicine Research Unit in Bangkok, analyzed blood samples of over 1,200 malaria patients in seven Asian and three African countries through a two year open-label, randomized trial. The researchers concluded that resistance is now widespread across northern and western Cambodia, Thailand, Vietnam and eastern Myanmar. As mosquitoes – and the parasites they carry – know no borders, the increased prevalence of resistant malaria poses a clear and significant threat to the substantial recent gains against this deadly disease. While there is no definitive evidence of resistance to artemisinin outside of Southeast Asia, it has been suspected in Suriname, where an investigative study is now underway, and in Guyana and French Guyana, where other studies are expected to start soon. Should resistant malaria reach Africa – home to 90% of global malarial deaths – it would not be long until the gains of the past decade are reversed.
The high prevalence of parasite resistance in the Mekong amplifies concerns we have raised in our work. CSIS published a paper and video in November of 2013, and hosted discussions with global malaria experts as part of a day-long conference on health in the Greater Mekong Subregion, assessing major challenges and potential solutions in the global fight to stop artemisinin resistance. It is a problem that requires concerted efforts to eliminate the parasites from the region, which can only be accomplished with extensive cooperation, across both borders and sectors.
There are some strategies to counter resistance in the near term. For several years - even before resistance to artemisinin was suspected - public health officials have recommended that it be used in combination with another class of antimalarial drug. This “ACT” (artemisinin combination therapy) strategy has generally been successful, although in its January 2014 status report, the World Health Organization (WHO) noted that ACT treatment failures are not uncommon. Indeed, Cambodia and Thailand have seen a fivefold increase in such treatment failures in recent years, due to resistance to both artemisinin and its partner drugs.
Another option to counter resistance may be to extend the duration of treatment. In that regard, there was a glimmer of encouraging news in the NEJM study: the effectiveness of a 6-day course of ACT to treat malaria (vs. the standard of 3 days) was almost 98%.
Despite the NEJM study’s alarming findings, there have been other positive developments in the fight against ARM over the last year. The Global Fund to Fight AIDS, Tuberculosis and Malaria has launched a 100 million dollar initiative, joining a large international coalition that is now working with the World Health Organization (WHO) and the countries of the Mekong to combat this menace. Just this month, the non-profit Malaria No More announced a new public-private partnership with the Asia-Pacific Leaders Malaria Alliance and the Asian Development Bank, in an effort to further mobilize resources and rally regional leadership on this issue. A molecular marker of artemisinin resistance has been identified, which should greatly facilitate tracking the spread of resistance. And with the Medicines for Malaria Venture helping to coordinate the efforts of over 300 partners from both the public and private sectors in over 50 countries, there is now a robust portfolio of drugs in the research and development pipeline. Indeed, promising results from an early phase two trial of KAE609, a drug in a brand new class of antimalarials, appeared in the same July 31 issue of NEJM. Unfortunately, it will likely be several years before any of these drugs are ready for distribution, making the need to prolong the life of artemisinin even more critical.
Even so, most researchers in the field believe that without bold and urgent measures to eliminate the parasites, it is only a matter of time before artemisinin-resistant malaria spreads and we lose the current mainstay of antimalarial treatment. Echoing comments he shared at CSIS last November, Nick White, a senior author on the Ashley study (and lead author on the KAE609 study), noted that “It may still be possible to prevent the spread of artemisinin-resistant malaria parasites across Asia and then to Africa by eliminating them, but that window of opportunity is closing fast…conventional malaria control approaches won't be enough – we will need to take more radical action and make this a global public health priority, without delay."
