Policy ForumPUBLIC HEALTH

Optimizing Investments in Malaria Treatment and Diagnosis

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Science  02 Nov 2012:
Vol. 338, Issue 6107, pp. 612-614
DOI: 10.1126/science.1229045

The Roll Back Malaria (RBM) Partnership has set an ambitious target of achieving near zero deaths from malaria by 2015 (1). Scale-up of insecticide-treated nets, indoor residual spraying of insecticide, and increased access to treatment with artemisinin-based combination therapies (ACTs) over the past decade have led to reductions in malaria incidence of more than 50% in 43 countries, including 8 in Africa (2). However, as an estimated 655,000 malaria deaths still occurred in 2010 (2), with the great majority in sub-Saharan Africa, substantial challenges remain.

Prominent among these challenges is the fact that the private sector is an important source of treatment for suspected malaria in many countries, but drugs available there are primarily composed of affordable, yet often ineffective, monotherapies (3, 4). ACTs, the recommended first-line treatment for malaria (5), are often prohibitively expensive outside of the public sector (6), and drug quality is often poor (7). Beginning in 2009, the Affordable Medicines Facility for Malaria (AMFm), a “factory-gate” subsidy for ACTs, represented one prominent effort to increase access to effective drugs even in the private sector. The first phase of that program ends this year, and initial evaluation suggests that it was largely successful in increasing availability and affordability of ACTs in most, although not all, participating countries, particularly in the private sector (8). Regardless of whether the AMFm initiative continues, the RBM Partnership will confront critical questions about the future of overall diagnosis and treatment strategies, especially regarding how to engage with the private sector.

These decisions will be made in the context of a rapidly evolving epidemiological and financial landscape. Malaria burden varies greatly from country to country, which leads to goals of elimination in Zanzibar (9) and Swaziland (10), even as incidence rates have remained consistently high in parts of West and Central Africa (11). Resistance to artemisinin-based drugs has been detected in Southeast Asia (12, 13). Availability of the artemisinin monotherapies that may promote resistance in Africa has been found to range widely, from virtually absent in Madagascar to nearly half of drug shops sampled in Nigeria (3). Targeting resources properly and maximizing their effectiveness has been rendered even more crucial by the fact that international donations for malaria control declined in 2012 for the first time in a decade (14).

Improved diagnosis has led to steep declines in reported malaria incidence and presumptive treatment in regions of Senegal (15) and Tanzania (16), where malaria makes up only a small fraction of febrile disease (15). However, there are still many places where febrile illness is assumed to be synonymous with malaria (17). Because many private-sector outlets are drug shops that sell medications without confirmatory diagnosis, it is likely that a substantial fraction of antimalarials obtained through the private sector are taken for nonmalarial illnesses, which limits their impact.

Analysis of Private-Sector Antimalarial Demand

Increased focus on private-sector antimalarial markets through the work of groups like ACTwatch (18) and evaluation activities surrounding the AMFm (8) have begun to provide data that we have used to better understand the volume of antimalarials distributed through the private sector, the importance of the private sector in treating febrile disease, and the number of malaria infections reached by these drugs. Full details of data collection and analysis can be found in the supplementary materials (SM). In summary, data on reported febrile illness in children younger than 5 years and the fraction of those receiving antimalarial drugs from the private sector were assembled from all population-representative household surveys conducted since 2000 in malaria-endemic countries in sub-Saharan Africa for which individual survey responses were available (n = 96). The combined data set included records on 680,964 children from 43 countries for whom reports of fever status were recorded; all but two of these surveys did not include fever or treatment-seeking behaviors for ages older than 5. All surveys used multistage cluster randomized sampling from subnational administrative divisions, allowing fever prevalence to be recorded separately at a regional level. Repeated-measures regression models (19) were fitted to adjust survey responses for timing of the survey during the year and to account for variation over surveyed years by extrapolating trends to 2013. Literature reviews were conducted to facilitate extrapolations of fever incidence (fig. S2) and treatment-seeking behavior (fig. S3) to those ≥5 years old, based on surveys recording these measures for both age groups.

Private-sector patients receive antimalarials for malaria or fever.

Distribution of sub-Saharan African countries by the fraction of antimalarial recipients estimated to be positive for P. falciparum (x axis), the relative importance of the private sector for febrile treatment (y axis), and the overall size of the private-sector antimalarial market (bubble size). Dotted lines represent median values. Values for each country are given in the SM, table S3.

Rates for both age groups were applied to a high-resolution map of populations across Africa (20) in order to estimate the number of individuals receiving an antimalarial drug for fever annually from the private sector in each administrative unit as the product of the population, the annual fever rate, the fraction receiving antimalarials for fever, and the fraction of antimalarials reportedly received in the private sector.

The expected number of antimalarials received by individuals infected and not infected with malaria was then estimated by multiplying the antimalarial demand in each age group by the prevalence of Plasmodium falciparum malaria (PfPR) in febrile individuals in that age group for each administrative unit. Malaria prevalence in fevers was estimated from a PfPR map in the general population in 2010 (21) adjusted according to an empirical relation between population and febrile prevalence derived from household survey data (22). This multiplication assumed that the decision to seek treatment in the private sector is independent of true malaria infection status, an assumption corroborated by nearly identical positivity rates in those seeking treatment for fever in the public and private sectors in Tanzania (23). The inverse of the malaria prevalence in febrile private-sector treatment seekers represented the fraction of antimalarials taken by individuals with nonmalarial fevers. To capture the uncertainty surrounding these estimates and derive an interquartile range (IQR), values were drawn from distributions for each input variable through 10,000 Monte Carlo repetitions and combined into a distribution of outcomes. Details on assumptions and conversions are provided in SM (tables S1 to S3 and figs. S1 to S3).

The median estimated demand for private-sector antimalarial drugs for fever in 2013 was 153 million (M) for children <5 years old (IQR = 140M to 167M) and 502M for ≥5s (IQR = 426M to 585M) for a total of 655M (IQR = 571M to 746M). More than 90% of the variation in this total was caused by uncertainty in the relative probability of a ≥5-year-old receiving an antimalarial compared with a <5-year-old. Overall, a median of 33.81% of antimalarial drugs (IQR = 29.69 to 37.94%) were estimated to be intended for P. falciparum–positive individuals. Positivity was higher among <5-year-old antimalarial recipients (49.83%, IQR = 43.80 to 55.84%) than ≥5-year-old recipients (28.83%, IQR = 25.34 to 32.36%). An estimated 437M private-sector antimalarials (IQR = 384M to 491M) went to individuals not infected with malaria.

Although considerable uncertainty surrounds these estimates, the magnitude of this market is striking and has important implications for how the malaria community must tackle private-sector case management. It accompanies a substantial public-sector market that saw sales of ACTs alone numbering 181 million in 2011 (2). Given that ACTs are estimated to be about 20% of antimalarials received by febrile children in the public sector in such large markets as Nigeria and the Democratic Republic of the Congo (3), it is plausible that the total annual demand for antimalarials in Africa may be well over one billion treatments. The size of the antimalarial market in the private sector alone dwarfs the number of actual incident malaria cases that occur, estimated to be 174M (range 113M to 239M) in Africa in 2010 (2), which indicated substantial overtreatment of febrile disease as malaria. The analysis conducted here confirms that the majority of private-sector antimalarial drugs are currently received by P. falciparum–negative patients, although this estimate is based on malaria prevalence in 2010 and is likely to change over time as malaria prevalence declines and treatment-seeking behaviors evolve (details of this calculation are provided in SM). This overtreatment means both that most febrile patients are not being treated for the true cause of their illness and that limited global funding and drug supplies could be better targeted to individuals who truly need them.

These averages mask substantial heterogeneities ( Fig. 1). Of the consumers estimated to have bought an antimalarial medicine in the private sector, the fraction who were likely infected with malaria varied widely, from <1% in Djibouti and Swaziland to 56% in Burkina Faso. In eight countries, more than half of all antimalarials were estimated to be received in the private sector. Considerable heterogeneity existed within countries as well as across countries (SM and fig. S4).

Conclusions

Ultimately, all individuals with fever should receive appropriate treatment following accurate diagnosis according to World Health Organization (WHO) guidelines. Achieving this aim in the African private sector, however, will require a diagnostic test for the estimated 655M febrile individuals who purchase treatment there; only about 50 million rapid diagnostic tests were delivered globally in 2010 (2). Resources available for rolling out diagnostic tests and distributing ACTs in the private sector are likely to remain insufficient to reach the significant demand estimated here in the short term (24). Until resources are sufficient to properly diagnose and effectively treat all patients, it will be necessary to prioritize attempts to improve the availability of diagnostic tests and effective malaria drugs so that they will have the greatest impact on morbidity and mortality.

Interventions like private-sector ACT subsidies that can improve access to effective drugs will have the greatest probability of each treatment curing a malaria infection even in the absence of strong diagnosis if implemented in those countries on the right of the figure ( Fig. 1), where estimated malaria prevalence in fevers is highest. Given the relatively lesser importance of the private sector for febrile treatment in countries in the bottom quadrants, private-sector interventions may be considered a lower priority in these areas. ACT subsidies are likely to be most cost-effective if implemented in countries in the upper-right quadrant. Although this quadrant includes only 13 out of 39 countries, they tend to have some of the highest demand for antimalarials in the private sector, together accounting for 70% of all estimated volumes (461 million annually). Improved accessibility of diagnostic tests in these countries has the greatest potential to prevent the unnecessary antimalarial treatments, but prioritizing deployment to the private sector of countries in the upper-left quadrant, where the highest proportions of antimalarials are currently taken unnecessarily, has the potential to be the most cost-effective use of resources available for diagnosis. Intranational heterogeneity indicates that some countries may benefit from prioritization at a subnational level.

These metrics are dynamic. Investment and policy decisions will need to be updated accordingly. The private-sector axis may be adjusted over time as new population-representative surveys reveal changes in treatment-seeking behavior and fever incidence, and the increasing frequency of population prevalence surveys (21) should permit regular updating of malaria maps. In addition, our consideration of the private sector in general could not detect variations in how interventions might affect more informal outlets versus private health-care facilities. Patterns of ACT overtreatment may differ from those estimated here for antimalarials in general if taken more frequently by certain age groups or in certain sectors.

Our analysis shows that, across sub-Saharan Africa, about one-quarter of private-sector antimalarials are obtained for children under the age of 5 years, but these children are much more likely to be infected with malaria than the general population. Malaria deaths in children under 5 also account for ∼90% of all deaths from the disease (2). These numbers suggest that substantial opportunities exist to improve the value for money of malaria case-management interventions by prioritizing resources not only by geography but also age.

As long as resources remain insufficient to fully implement universal diagnosis and treatment, the short-term goal should be to target investments in privatesector diagnosis to places where overtreatment is high, while ensuring that affordable ACTs are used instead of the current, suboptimal treatments, even in the absence of diagnosis, in places where overtreatment is low. In the longer term, three transformations are needed across most countries. First, diagnosis rather than presumptive treatment should be the first response for fever management. Second, only effective combination treatments should be widely available in both the public and private sectors. Third, everyone should have access to quality and affordable care and treatment. Until those transformations occur, country-tailored interventions supported by optimally distributed global funding could have a tremendous impact in further accelerating progress against malaria.

References and Notes

  1. Acknowledgments: J.M.C. and B.M. received support from the Bill & Melinda Gates Foundation (BMGF) and the UK Department for International Development; J.M.C. and A.M.W. were also supported by UNITAID. A.J.T. received support from BMGF and National Institute for Allergy and Infectious Diseases, NIH. P.W.G. was funded by the Wellcome Trust.
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