We reviewed published literature and unpublished data from 1999 to Feb 20, 2012, for the chemical analysis and packaging of antimalarial drugs in southeast Asia and sub-Saharan Africa. We searched PubMed, WHO documents, US Pharmacopeia databases, anticounterfeiting networks, and unpublished documents obtained via experts in the specialty for English-language articles using the following search terms in combination: “malaria”, “antimalarials”, “survey”, “counterfeit drugs”, “substandard drugs”,
ReviewPoor-quality antimalarial drugs in southeast Asia and sub-Saharan Africa
Introduction
3·3 billion people are at risk of malaria, which is endemic in 106 countries. Between 655 000 and 1·2 million people die every year from Plasmodium falciparum infection.1, 2 Much of this morbidity and mortality could be avoided if drugs available to patients were efficacious, high quality, and used correctly. Children in sub-Saharan Africa and southeast Asia have the highest risk of contracting and dying from malaria. The global burden of malaria has reduced in the past decade,3 and endemic countries are reliant on the long-term availability of effective antimalarial drugs to maintain this progress.4
In endemic regions, antimalarial drugs are widely distributed and self-prescribed (incorrectly and correctly) for the many febrile episodes attributed to malaria. Insufficient facilities to check the quality of antimalarial drugs, poor consumer and health-worker knowledge about these drugs, their cost, and the paucity of appropriate regulatory and punitive action makes these drugs attractive targets for counterfeiters.5, 6 Reports of poor-quality antimalarial drugs have increased in the past decade, partly because of growing awareness and concern;6, 7, 8 however, the issue may be much greater than it seems because most cases are probably unreported, reported to the wrong agencies, or kept confidential by pharmaceutical companies.6, 9, 10 Of the many public health consequences of poor-quality antimalarial drugs, drug resistance is a particular concern. Low concentrations of active pharmaceutical ingredient in poor-quality antimalarial drugs can result in subtherapeutic concentrations of drug in vivo, which contributes to the selection of resistant parasites.11, 12 Artemisinin derivatives are the most effective drugs against malaria, and artemisinin-based combination treatments are the recommended first-line treatments for P falciparum malaria.12, 13 Resistance or tolerance to artemisinin derivatives has been described in western Cambodia, and is characterised by slow rates of parasite clearance after treatment.14 Although a causal relation between poor-quality artemisinin derivatives and artemisinin resistance has not been confirmed, modelling analyses suggest that underdosing of patients can play an important part in the spread of resistance.15
Poor-quality antimalarial drugs are very likely to jeopardise the unprecedented progress and investments in control and elimination of malaria made in the past decade. In this Review we assess the issue of poor-quality antimalarial drugs, particularly the artemisinins, emphasise the mechanisms that determine their existence and effect in sub-Saharan Africa and southeast Asia, and describe potential interventions to combat this problem.
Section snippets
Definitions of drug quality
We obtained data for samples in two categories: drugs failing chemical assay analysis and drugs failing package testing; these categories were not mutually exclusive. No universally accepted definitions exist for the different types of poor-quality drugs and national terminologies are diverse. Some nations, and some of those involved in intellectual property law, are concerned that the word counterfeit could wrongly lead to the classification of some legitimate generic drugs as such, thus
Southeast Asia
From 1999 to 2010, seven multicountry surveys with data from seven countries in southeast Asia included chemical assays or packaging analysis for 1437 samples of seven antimalarial drugs, including artemether, artesunate, chloroquine, mefloquine, quinine, sulfadoxine–pyrimethamine, and tetracycline. 1173 samples (82%) were obtained with convenience sampling with no randomisation of outlet selection. All studies used some form of chemical analysis with one or more of the following techniques:
Sub-saharan Africa
21 surveys from 21 countries in sub-Saharan Africa involved chemical assay or packaging analysis for 2634 antimalarial samples, including amodiaquine, artemotil, artemether, artemesinin-combination treatments, artesunate, chloroquine, mefloquine, quinine, proguanil, and pyrimethamine (table8, 10, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49). 796 (35%) of 2297 samples failed chemical analysis with one or more of the techniques described above for southeast Asia (
Discussion
Poor-quality antimalarial drugs are an immediate and urgent threat in health facilities, pharmacies, grocery stores, and homes, and are exposing patients, health-care workers, and governments to increases in morbidity, mortality, economic losses, and drug resistance. Antimalarial drugs comprise 25% of the drugs consumed in malarious countries, and when these drugs are of poor quality, they afflict the most vulnerable populations.6 Issues of poor quality are not limited to antimalarial drugs,
Search strategy and selection criteria
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