Antimalarial drug quality: methods to detect suspect drugs

Malaria continues to be one of the major public health problems in Africa, Asia and Latin America. Plasmodium falciparum malaria is estimated to be the direct cause of 500 million cases and over 1 million deaths per year, mostly in women and children under the age of 5 years [1,2]. In children, progression of disease from mild to severe is particularly rapid [3]. Plasmodium falciparum has become resistant to many commonly used antimalarials such as chloroquine and sulfadoxine–pyrimethamine. In light of this, the WHO has recommended that all antimalarials should consist of a combination of an artemisinin derivative with a co-drug, such as lumefantrine, amodiaquine, piperaquine or mefloquine (artemisinin-based combination therapy [ACT]) for use as first-line treatment against malaria. This class of drugs is now first-line policy in most malaria-endemic countries [4]. Artemisinin derivatives (ARTs; artesunate, dihydroartemisinin, artemether and arteether) derived from the herb, quinghao (sweet wormwood or Artemisia annua L.; Asteraceae), are the most effective antimalarial drugs available, providing rapid cures. The recent emergence of ART-resistant P. falciparum, on the Thailand/Cambodia border [5], is of very great concern, especially as there is evidence that drug-resistant falciparum malaria has spread from Asia into Africa [6]. Poor-quality antimalarials have been a severe under-recognised public health problem, reducing the effectiveness of these drugs and threatening current treatment policies. There are three main types of poor-quality medicines; degraded, substandard and counterfeit. The WHO defines counterfeit drugs as those that are ‘deliberately and fraudulently mislabeled with respect to identity and/or source’, and may include those with the correct ingredients or with the wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging [101]. Substandard drugs are produced with inadequate attention to good manufacturing practices and may have contents and/or dissolution times outside accepted limits, due to poor quality control [102]. In addition, degraded formulations may result from exposure of good-quality medicines to light, heat and humidity. It can be difficult to distinguish degraded medicines from those that left the factory as substandard, but the distinction is important as the causes and remedies are different. Reports from Asia and Africa indicate that there is widespread production and distribution of counterfeit and substandard antimalarial drugs. However, it can be very difficult to differentiate between them, as it is not always clear whether the actions leading to the production of poorquality drugs were deliberate. Ineffectiveness of antimalarial drugs is of major concern globally as poor-quality drugs undermine treatment, resulting in deaths from a curable disease and engendering drug resistance. The problem of drug counterfeiting appears to be growing despite greater awareness with reports in newspapers, cinema and television campaigns, as well as information posted on the internet. The WHO/International Medical Products Anti-Counterfeiting Taskforce (IMPACT) estimates that counterfeit drugs constitute up to 25%of the total medicine Malaria is a major public health problem in the endemic countries of Africa, Asia and Latin America. Poor quality antimalarials are of major, but neglected, concern in the control of Plasmodium falciparum malaria. They cause treatment failure and economic loss, and engender drug resistance and loss of confidence in health systems. The emergence of resistance to the artemisinin derivatives in Asia bodes ill for malaria control in Africa, and strenuous efforts are needed to improve the quality of the world’s supply of antimalarials. This article reviews the problem and discusses methods available to determine the quality of antimalarials.