As a result of rising levels of drug resistance to conventional monotherapy, the World Health Organization (WHO) and other international organisations have recommended that malaria endemic countries move to combination therapy, ideally with artemisinin-based combinations (ACTs). Cost is a major barrier to deployment. There is little evidence from field trials on the cost-effectiveness of these new combinations.
Methods and Findings
An economic evaluation of drug combinations was designed around a randomised effectiveness trial of combinations recommended by the WHO, used to treat Tanzanian children with non-severe slide-proven malaria. Drug combinations were: amodiaquine (AQ), AQ with sulfadoxine-pyrimethamine (AQ+SP), AQ with artesunate (AQ+AS), and artemether-lumefantrine (AL) in a six-dose regimen. Effectiveness was measured in terms of resource savings and cases of malaria averted (based on parasitological failure rates at days 14 and 28). All costs to providers and to patients and their families were estimated and uncertain variables were subjected to univariate sensitivity analysis. Incremental analysis comparing each combination to monotherapy (AQ) revealed that from a societal perspective AL was most cost-effective at day 14. At day 28 the difference between AL and AQ+AS was negligible; both resulted in a gross savings of approximately US$1.70 or a net saving of US$22.40 per case averted. Varying the accuracy of diagnosis and the subsistence wage rate used to value unpaid work had a significant effect on the number of cases averted and on programme costs, respectively, but this did not change the finding that AL and AQ+AS dominate monotherapy.
In an area of high drug resistance, there is evidence that AL and AQ+AS are the most cost-effective drugs despite being the most expensive, because they are significantly more effective than other options and therefore reduce the need for further treatment. This is not necessarily the case in parts of Africa where recrudescence following SP and AQ treatment (and their combination) is lower so that the relative advantage of ACTs is smaller, or where diagnostic services are not accurate and as a result much of the drug goes to those who do not have malaria.
A randomised effectiveness trial of antimalarial drug combinations used to treat Tanzanian children found artemether-lumefantrine to be the most cost-effective.
For many years, malaria was treated with a course of a single drug. This type of treatment made it easy for malaria parasites to become resistant to antimalarial drugs. This is a major factor contributing to the continuing high death rate from the disease. However, although parasites can easily adapt to resist one drug, adapting to combinations of two or three drugs is much harder. Scientists have therefore developed combinations of antimalarial drugs. One component of these combinations is artemisinin—derived from a Chinese shrub. However, these combination therapies are much more expensive than the older treatments.
The regions worst affected by malaria—Africa and Asia—are also the poorest. And, in these areas, where both individual and government resources are scarce, antimalarial treatments must be cost-effective as well as clinically effective.
Why Was This Study Done?
Most of the estimated 1 million to 3 million people worldwide killed by malaria every year are young children in sub-Saharan Africa. Growing drug resistance, poor prevention programs, and a frequent inability of patients to pay for treatment mean that effective therapy is desperately needed in this part of the world. However, because of differences in drug resistance between regions, a drug combination will not work everywhere. In addition, because of low annual incomes (the average in Tanzania is US$120), heavy subsidies will probably be required to ensure that combination treatments are widely used. With several healthcare problems competing for resources, policymakers are likely to subsidize only the most cost-effective treatments. The researchers wanted to provide policymakers with information on how different combinations of malaria drugs compare in terms of costs, health effects, and cost-effectiveness, so that they can decide which treatment is best for their region.
What Did the Researchers Do and Find?
They compared three combinations that the World Health Organization recommends for countries when making the transition from single-drug therapy. The three combinations—amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP); AQ and artesunate (AS); and artemether-lumefantrine (AL)—were used to treat Tanzanian children. The researchers wanted to find out how many cases of malaria each combination averted (which is also an indication of how much money it saved) and how much the treatment cost. They looked at costs and savings from the perspectives of both healthcare providers and patients.
Compared with no treatment, AL proved to be the most cost-effective; although it cost more for the provider (US$3.01 at day 28 of treatment) than the others, its effectiveness in getting rid of the parasite meant it would save the cost of future treatment. By day 28, AL had averted 382 cases of malaria compared with 279 for AQ+AS, 181 for AQ+SP, and 57 for AQ alone. Also, higher proportions of inaccurate diagnoses of malaria led to lower cost-effectiveness of treatments.
What Do These Findings Mean?
Despite being more expensive, newer drugs can be cost-effective where alternatives fail. Although AL was the most cost-effective in places (such as Tanzania) where the malaria parasites are highly resistant to SP and AQ, the picture is likely to change for other areas. In West Africa, for example, AQ resistance is lower, and AQ+SP and AQ+AS would probably be more cost-effective. And in areas where both these combinations are just as good as AL in preventing recurring disease, they would be more cost-effective than AL. However, since AQ and SP have been used singly for many years, the likelihood is that resistance to these drugs will continue to increase. Accurate diagnosis turns out to be very important for maintaining the cost-effectiveness of combination antimalarial therapies. This will be essential if they are to be incorporated as a sustainable part of local health policies. The researchers also point out that, depending on which perspective is taken (provider or patient), the cost-effectiveness of treatments differs, making it important to compare like with like.
Although investing in costly AL treatments and improving diagnostic capabilities will be a challenge for African governments that currently spend less than US$5 per person per year on healthcare, it will be necessary if they are to seriously tackle the malaria epidemic.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030373
The US enters for Disease Control and Prevention provides malaria information aimed at the general public, physicians, and health workers
The Wellcome Trust; also has malaria information for the general public and covers the science of malaria research, including a downloadable animation of the parasite's life cycle
Medicines for Malaria Venture (MMV) is a charity created to develop new antimalarial drugs through public-private partnerships