# Program: Treatment of Malaria

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Published: 2009

# In a nutshell

• The Problem: Malaria is a potentially fatal disease, one of the leading causes of child mortality in Africa.
• The Program: A variety of drug treatments are used to address malaria; artemisinin combination therapy (ACT) is the World Health Organization's recommended approach.
• Track record: Antimalarial drugs have been rigorously shown to cure malaria. There is strong evidence that ACT is more effective than other drug regimens.
• Cost-effectiveness: We have little information about cost-effectiveness. Depending on drug resistance in an area, switching from existing treatment to ACT could cost approximately $5,450 per death (and ~320 less severe malaria episodes) averted. • Bottom line: We believe that ACT is a costly but effective method of improving health in the developing world. ## Basics of the program ### What is the program? What problem does it target? Malaria is one of the leading causes of child deaths in Africa. (For more, see our brief review of the symptoms and causes of malaria.) Antimalarial drugs can treat and cure uncomplicated malaria.1 Broadly, there are two types of treatments: • Artemisin-based combination therapy (ACT). This is the World Health Organization's (WHO's) recommended approach.2 • Other approaches. Either (a) non-artemisinin based combination therapy or (b) monotherapies.3 The WHO does not recommend these methods of treatment for uncomplicated malaria.4 ### What are the components required to implement this program - how does it work? This program requires: • Diagnosis. A system for accurately diagnosing those with malaria so that they can be treated. • Distribution. A method for delivering the drugs to those individuals in need. • Drugs. Access to high quality, recommended drugs. (For more on the issue of drug quality, see our brief review of the problem of low quality drugs in the developing world.) • Patient adherence to the drug regimen. Adherence to ACT's 3-7 day course of treatment is important, and generally achievable.5 ## Program track record ### Micro evidence: Has this program been rigorously evaluated and shown to work? Numerous "high-quality" trials have demonstrated that antimalarial drugs cure malaria, as measured by complete eradication of malaria from the body of the patient.6 (For our definition of "high-quality, see criteria for evaluating programs page.) A meta-analysis of 11 high-quality studies comparing ACTs to monotherapies found that ACTs significantly reduced the portion of cases not cured.7 ### Macro evidence: Has this program played a role in large-scale success stories? We have identified no such success stories. More on the general idea of "macro evidence" here. ## Cost-effectiveness We have not done thorough cost-effectiveness analysis of this program. Because such analysis is highly time-consuming - and because the results can vary significantly depending on details of the context - we generally do not provide cost-effectiveness analysis for an intervention unless we find what we consider to be a strong associated giving opportunity. We provide some preliminary figures based on the Disease Control Priorities in Developing Countries report, which we previously used for cost-effectiveness estimates until we vetted its work in 2011, finding major errors that raised general concerns. Jamison et al. (2006) provides a range of$2.00-$9.12 as the cost of ACT drugs for one course of treatment.8 The report does not directly estimate the cost-effectiveness (in life-change terms) of ACT, but it does give figures for switching from existing treatments to ACT. No average or range is given, but the cost is stated to be under$150 per disability-adjusted life-year (DALY) when drug resistance is high and over $150 per DALY when drug resistance is low.9 (More on the DALY metric here.) A simple conversion calculation10 implies that$150 per DALY is equivalent to about $5450 for every 321 cases of malaria - one of which would be fatal - averted. ## Sources • 1. This report deals with uncomplicated malaria as opposed to severe malaria. "Uncomplicated malaria is defined as symptomatic malaria without signs of severity or evidence (clinical or laboratory) of vital organ dysfunction. The signs and symptoms of uncomplicated malaria are nonspecific. Malaria is, therefore, suspected clinically mostly on the basis of fever or a history of fever." World Health Organization 2010, Pg 13. • 2. "To counter the threat of resistance of P. falciparum to monotherapies, and to improve treatment outcome, WHO recommends that artemisinin-based combination therapies be used for the treatment of uncomplicated P. falciparum malaria (see also Annex 7)." World Health Organization 2010, Pg 13. The WHO provides this information about the specific drugs recommended for use in ACT: "In addition to the four ACT combinations – artemether plus lumefantrine (AL), artesunate plus amodiaquine (AS+AQ), artesunate plus mefloquine (AS+MQ), and artesunate plus sulfadoxine-pyrimethamine (AS+SP) – already recommended for the treatment of uncomplicated P. falciparum malaria there is now sufficient evidence on safety and efficacy of dihydroartemsinin plus piperaquine (DHA+PPQ) for its addition to the list of ACTs options recommended for the treatment of uncomplicated falciparum malaria." World Health Organization 2010, Pg 16. • 3. • Non-artemisinin based combination therapy: "Non-artemisinin based combination treatments include sulfadoxine-pyrimethamine plus chloroquine (SP+CQ) or amodiaquine (SP+AQ). The prevailing high levels of resistance to these medicines as monotherapy have compromised their efficacy even in combinations. There is no convincing evidence that chloroquine plus sulfadoxine- pyrimethamine provides any additional benefit over SP, so this combination is not recommended; amodiaquine plus sulfadoxine-pyrimethamine can be more effective than either drug alone; but it is usually inferior to ACTs, and it is no longer recommended for the treatment of malaria." World Health Organization 2010, Pg 14. • Monotherapy: Antimalarial treatment with a single medicine (either a single active compound or a synergistic combination of two compounds with related mechanism of action). • 4. • Non-artemisinin based combination therapy: "It is usually inferior to ACTs, and it is no longer recommended for the treatment of malaria." World Health Organization 2010, Pg 14. • Monotherapy: "Artemisinins should not be used as monotherapy, as this will promote resistance to this critically important class of antimalarials." World Health Organization 2010, Pg 21. In addition, the WHO finds little evidence to support recommending non-artemisinin based combination therapies before monotherapies, implying that ACT is recommended before non-artemisinin based combination therapies. The WHO writes, " Non-artemisinin based combination treatments include sulfadoxine-pyrimethamine plus chloroquine (SP+CQ) or amodiaquine (SP+AQ). The prevailing high levels of resistance to these medicines as monotherapy have compromised their efficacy even in combinations. There is no convincing evidence that chloroquine plus sulfadoxine-pyrimethamine provides any additional benefit over SP, so this combination is not recommended; amodiaquine plus sulfadoxine-pyrimethamine can be more effective than either drug alone; but it is usually inferior to ACTs, and it is no longer recommended for the treatment of malaria." World Health Organization 2010, Pg 14. • 5. Regarding adherence: "Patient adherence is a major determinant of the response to antimalarials, as most treatments are taken at home without medical supervision. To achieve the desired therapeutic effectiveness, a medicine must be efficacious and it must be taken in the correct doses at the proper intervals. Studies on adherence suggest that 3-day regimens of medicines such as ACTs are adhered to reasonably well, provided that patients or caregivers are given an adequate explanation at the time of prescribing and/or dispensing." World Health Organization 2010, Pg 24. Treatment course is 3-7 days: "When given alone or in combination with rapidly eliminated compounds (tetracyclines, clindamycin), a 7-day course of treatment with an artemisinin compound is required (see Annex 3 for details). This long duration of treatment with the artemisinins can be reduced to 3 days when given in combination with slowly eliminated antimalarials. " World Health Organization 2010, Pgs 14-15. • 6. • Definition of cure: "The objective of treating uncomplicated malaria is to cure the infection as rapidly as possible. Cure is defined as the elimination from the body of the parasites that caused the illness." World Health Organization 2010, Pg 6. • Evidence of effectiveness: "A total of 47 trials met the inclusion criteria. All five ACT combinations were shown to have failure rates of Reviews of RCTs completed comes from World Health Organization 2010, Pgs 135-151. See there for more detail. • 7. World Health Organization 2006, Pg 17. • 8. "Baird (2005) reports that ACT costs range from US$2.00 (artesunate-amodiaquine, three doses in 48 hours) to US$9.12 (artemether-lumefantrine, six doses in 48 hours) per adult treatment; WHO has obtained the latter drug for US$2.40 per adult treatment for qualified purchasers, meaning those from low-income malarious countries."

Jamison et al. 2006, Pg 419

• 9.

"Figure 21.3 shows that a switch from chloroquine to SP is cost-effective (less than $150 per DALY averted) when chloro- quine resistance is above 35 percent. Switching from chloro- quine to ACT becomes cost-effective as chloroquine resistance reaches around 37 percent. Switching from SP to ACT becomes cost-effective as SP resistance reaches 12 percent. This low threshold is due to the high growth rate of resistance to SP when it is used as a first-line therapy." Jamison et al. 2006, Pg 424 • 10. Mathers, Ezzati, and Lopez (2007, Pg 8, Table 3) implies that each episode of malaria averted counts for 0.1 DALYs, and that 1 in approximately 320 cases (the ratio between deaths and episodes) results in a death and thus an additional 33 DALYs. This in turn implies that$150 per DALY is equivalent to ~$17 per episode averted, and so ~$5450 would avert the ~321 episodes necessary to avert a single death.