Counterfeit and substandard antimalaria drugs threaten crisis in Africa, experts warn

In a study published in the journal, an international team of researchers report that some cases of medicines on sale in Africa have been deliberately counterfeited by criminals or are of poor quality because of factory errors. Both types are not only potentially harmful to the patient but also risk promoting the emergence of drug resistance among the parasites that cause malaria.

According to the World Malaria Report 2010, malaria killed an estimated 781,000 people in 2009, mainly young children and pregnant women. It is caused by parasites that are injected into the bloodstream by infected mosquitoes.

The most effective antimalarial drugs are the artemisinin derivatives, which have the advantages over other antimalarial drugs (such as chloroquine and mefloquine) of having few side-effects but the fastest action. Although the drugs have been used on their own as monotherapy, fears over the development of resistance mean that they are recommended for use in conjunction with one or more other drugs as artemisinin-based combination therapies, now recommended by the WHO as the first-line treatment for uncomplicated falciparum malaria globally.

There has been a dramatic rise in reports of poor-quality and counterfeit antimalarials in Africa. To find out more about the different types of medicines circulating and what they contain, and to look for evidence of where they might have come from, the researchers examined antimalarials - collected in 11 African countries between 2002 and 2010 - that they believed to be either counterfeit or substandard.

Analysis of the medicines showed that some counterfeits contained a mixture of wrong active pharmaceutical ingredients, some of which might initially alleviate malaria symptoms but would not cure malaria. Worse still, these unexpected ingredients could cause potentially serious side-effects, particularly if they were to interact with other medication that a patient was currently taking, such as antiretroviral therapies for HIV.

Some of the counterfeits also contained small amounts of artemisinin derivatives, perhaps to try to ensure that the drug would pass simple authenticity tests. Taken at such low levels, the drug is unlikely to rid the body of malaria parasites, leading to the emergence of strains of the parasite resistant to artemisinin.

The researchers identified pollen found in some of the tablets, which indicated that the counterfeit medicines originated in eastern Asia. Indeed, in 2001, police in Guangzhou, China, arrested Nigerian and Chinese men for production of counterfeits of the antimalarial halofantrine. No evidence of counterfeit pharmaceutical production in Africa was found in the pollen analysis; however, production facilities for packaging materials for counterfeit antimalarials have been seized in Nigeria.

Dr Paul Newton from the Wellcome Trust-Mahosot Hospital-Oxford University Tropical Medicine Research Collaboration in Laos, who led the research, says: "Public health organisations must take urgent, coordinated action to prevent the circulation of counterfeit and substandard medicines and improve the quality of the medicines that patients receive. We must move finally away from the use of single drugs and towards the exclusive use of combination therapies.

"The enormous investment in the development, evaluation and deployment of antimalarials is wasted if the medicines that patients actually take are, due to criminality or carelessness, of poor quality and do not cure. Malaria can be readily treated with the right drugs of good quality, but poor-quality medicines - as well as increasing mortality and morbidity - risk exacerbating the economic and social impact of malaria on societies that are already poor.

"Worse still, they encourage drug resistance, potentially resulting in the failure of artemisinin treatments, with profound consequences for public health in Africa. Failure to take action will put at risk the lives of millions of people, particularly children and pregnant women."

Dr Newton and colleagues argue that multiple parallel strategies are needed to tackle this problem. Among their recommendations is increased investment in national medicine regulatory authorities in Africa to regulate the quality of the medications and to improve access to good-quality, affordable artemisinin combination therapies.

Commenting on the research, Dr Jimmy Whitworth, Head of International Activities at the Wellcome Trust, said: "This research is very worrying and should act as an early warning. We have already begun to see the emergence of drug-resistant malaria parasites in South-east Asia; substandard and counterfeit antimalarials and the availability of artemisinin monotherapies threaten to lead to the spread of drug resistance in Africa. If this happens, the effect could be devastating on efforts to control malaria in Africa."

Combating infectious diseases is one the strategic priorities of the Wellcome Trust. Much of this work is carried out at a local level in regions where disease is endemic. This includes several major overseas programmes, including the Wellcome Trust Major Overseas Programme unit in Laos, headed by Dr Newton.