By the 1970s, the world’s premier malaria treatment at the time, chloroquine, was failing in Southeast Asia, with resistance to it documented in Africa shortly thereafter. By 2000, chloroquine had become largely ineffective in malaria-endemic countries, while malaria-spreading parasites were also becoming increasingly resistant to available alternatives, such as sulfadoxine/pyrimethamine (SP). Amid dwindling treatment options, clinical research on derivatives of artemisinin, an extract of A. annua, demonstrated the safety and efficacy of artemisinin-based combination therapy (ACT). This promising new class of antimalarial drugs provided an effective alternative to the failing options on the market and has since become the standard of care in most settings.
Although researchers established the efficacy of artemisinin in treating malaria in 1972 and the safety and efficacy of ACTs through clinical trials in the 1980s and 1990s, ACT did not become the first-line antimalarial treatment in most national drug policies until after 2004. In January 2004, a group of malaria researchers, frustrated by the pace of change, published an article in the Viewpoint section of the medical journal The Lancet accusing the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis and Malaria of “medical malpractice” for continuing to support the use of chloroquine in countries where its failure had been documented, despite the availability of ACT. Several months after the article’s publication, the Global Fund’s board reprogrammed already-approved malaria grants and mobilized additional funds for the purpose of enabling malaria-endemic countries to buy the newer, more expensive drugs. This decision spurred explosive demand: 18 African countries adopted ACT as first-line therapy in 2004 alone, while the sale of ACT treatments grew from the tens of thousands in 2001 to 60 to 80 million in 2006.
This case study examines the factors that led to that surge in ACT adoption and the extent to which the 2004 Lancet Viewpoint caused it. The case study analyzes the article’s influence and legacy, the role of drug cost, the decisionmaking processes for drug policy change, the role of supply chain dynamics, and other relevant factors that influenced the decision to adopt ACTs in the 2000s.
The public accusation in The Lancet that the Global Fund had committed medical malpractice by approving grants for ineffective medicines ultimately led to a rapid mobilization of resources, which in turn accelerated the pace of ACT adoption in endemic countries. The Global Fund reprogrammed its malaria portfolio and mobilized additional funds in response to the article. The assurance of available financing for making the switch to ACTs that this decision signaled almost certainly hastened ACT adoption. The WHO, also accused of medical malpractice, did not enshrine ACT as first-line treatment until 2006, when it issued its first edition of malaria treatment guidelines (initiated independently of the article). Although the WHO endorsed ACT in technical consultation reports before then, its lack of “authoritative” guidelines contributed to the view that it moved too slowly on ACTs (though importantly, its role in facilitating data sharing and evidence generation in countries helped provide the evidentiary basis for switching to ACTs).
Several factors influenced the initial slowness to switch to ACTs. First, chloroquine cost about $0.10 per treatment course, whereas a full adult course of the ACT artemether/lumefantrine cost $2.40 in the public sector and several times that in the private and informal sectors, where many people in endemic countries access antimalarial medicines, putting ACTs effectively out of reach. Second, financing options were initially limited by constrained domestic health budgets and meager international aid for malaria budgets. Third, only one manufacturer of a coformulated, fixed-dose ACT existed through the mid-2000s; a quality-assured supply chain capable of meeting demand in all endemic countries did not exist, and it took years to synchronize demand forecasting, country-level procurement, and financing. These financing and supply chain uncertainties, when combined with a dearth of standardized data on resistance prevalence and an initially higher treatment failure threshold, resulted in diverging views on the urgency of the need to change drug policy.
More broadly, contentious politics and resistance to change shaped the trajectory of ACT adoption. Malaria researchers and advocates, on one hand, made the case for switching immediately to ACTs, citing, among other reasons, unacceptably high treatment failure rates from chloroquine and SP and ACT’s comparatively near-miraculous cure rates. On the other hand, factions within some bilateral aid agencies, the WHO, and some endemic-country policymakers and drug manufacturers pushed back on an immediate switch for various technical, financial, and political reasons. Donor pressure to delay switching emerged as a significant impediment on the path to ACT adoption. Critiques of the advocacy strategy used to compel a faster pace of change, meanwhile, include that it may have exerted undue pressure on countries and overlooked regional and national differences in resistance trends.
Today, the breakdown in global cooperation and dismantling of health aid is practically guaranteed to cause a global resurgence in malaria cases and deaths, and to have lasting damaging effects on malaria control efforts. Partial resistance to artemisinin-based drugs, meanwhile, has been documented in Asia and Africa. Advocacy could again have a salient role to play in the future trajectory of malaria control.
