Date Published: June 03, 2015
Publisher: The American Society of Tropical Medicine and Hygiene
Author(s): John P. Renschler, Kelsey M. Walters, Paul N. Newton, Ramanan Laxminarayan.
Many antimalarials sold in sub-Saharan Africa are poor-quality (falsified, substandard, or degraded), and the burden of disease caused by this problem is inadequately quantified. In this article, we estimate the number of under-five deaths caused by ineffective treatment of malaria associated with consumption of poor-quality antimalarials in 39 sub-Saharan countries. Using Latin hypercube sampling our estimates were calculated as the product of the number of private sector antimalarials consumed by malaria-positive children in 2013; the proportion of private sector antimalarials consumed that were of poor-quality; and the case fatality rate (CFR) of under-five malaria-positive children who did not receive appropriate treatment. An estimated 122,350 (interquartile range [IQR]: 91,577–154,736) under-five malaria deaths were associated with consumption of poor-quality antimalarials, representing 3.75% (IQR: 2.81–4.75%) of all under-five deaths in our sample of 39 countries. There is considerable uncertainty surrounding our results because of gaps in data on case fatality rates and prevalence of poor-quality antimalarials. Our analysis highlights the need for further investigation into the distribution of poor-quality antimalarials and the need for stronger surveillance and regulatory efforts to prevent the sale of poor-quality antimalarials.
Each year malaria causes an estimated 207 million (M) clinical cases worldwide resulting in an estimated 627,000–1,238,000 deaths (0.3–0.6% of clinical cases), the majority in sub-Saharan Africa.1,2 Children under 5 years of age in this region have the highest risk of contracting and dying from malaria.3 Artemisinin-based combination therapies (ACTs) are the first-line treatment recommended by the World Health Organization (WHO) and are vital to reduce the burden of childhood malaria.1,4,5 In Africa, the widespread availability of ACTs through both public and private sectors has lowered malaria morbidity and mortality rates1 and reduced the selection pressure for emergence of drug-resistant parasite strains caused by monotherapies.4 Despite the clinical advantage of ACTs, many non-artemisinin-based monotherapies (including chloroquine, quinine, halofantrine, and amodiaquine) are still widely available throughout the private sector.6,7
We calculated the number of under-five deaths caused by Plasmodium falciparum (referred to as malaria) infections that persist because children consume poor-quality antimalarials instead of efficacious antimalarials across 39 countries in sub-Saharan Africa. We performed an uncertainty analyses using Latin hypercube sampling (LHS) (10,000 simulations) described by Blower and others.19 We performed all analyses using the R programming language and created an interactive, publicly available R package that can be used to perform and visualize our calculations using alternative input values (S1).
Our uncertainty analysis results provide estimates of under-five malaria mortality associated with consumption of poor-quality antimalarials. Table 1 presents the results from 10,000 calculations performed following the LHS scheme with the probability distributions described in Supplemental Tables 1–3. The estimated median number of under-five malaria deaths associated with consumption of poor-quality antimalarials across the 39 countries was 122,350 (IQR: 91,577–154,736). Nigeria, which had the largest estimated number of antimalarial sales to under-five malaria-positive children (30,225,237 courses), as well as the highest prevalence of poor-quality antimalarials (64%), accounted for a majority of the estimated deaths, with a median of 74,188 (IQR: 54,931–96,132) (Figures 1 and 2).13,21Table 1 and Figure 3 present the number of deaths caused by poor-quality antimalarials as a percentage of 2010 under-five malaria death estimates. Figure 4 presents the number of deaths caused by poor-quality antimalarials as a proportion of 2012 all-cause under-five death estimates (Supplemental Table 5). Supplemental Table 4 presents the median number of deaths caused by poor-quality antimalarials alongside 2010 under-five deaths due to other causes.
There are several reasons it is difficult to estimate the health burden associated with widespread use of poor-quality antimalarials in sub-Saharan Africa. These reasons contribute to the uncertainty of our numerical results.