Bogus antimalarials: a forgotten tale.

Abstract

While most malaria research nowadays focuses on the development of a vaccine, alternative drug therapy or the implementation of vector-control methods such as insecticide-impregnated bednets, Newton et al.1xFake artesunate in southeast Asia. Newton, P. et al. Lancet. 2001; 357: 1948–1950Abstract | Full Text | Full Text PDF | PubMed | Scopus (166)See all References report some alarming findings on antimalarial drug quality in southeast Asia. These bogus, substandard antimalarials include drugs that are either counterfeit (i.e. produced illegally by rogue manufacturers), or past their shelf-life (e.g. because of inadequate storage conditions). In both cases this can lead to substandard concentrations of the active ingredient in distributed drugs. Substandard antimalarials could potentially be of importance to public health in a number of ways. First, substandard drugs and associated treatment failure will increase the patient's risk of severe malaria and death. Second, widespread use of substandard drugs will lead to the rapid emergence of drug-resistant strains (especially in hyperendemic areas, such as southeast Asia, where Plasmodium populations are known to be very heterogeneous). Third, substandard drug concentrations can be toxic and can have severe side-effects for treated patients (e.g. high chloroquine plasma concentrations can lead to cardiac arrythmia and a quinine overdose can lead to blindness). Finally, the drugs could also have a significant economic impact as patients or the public health services will have to deal with the cost of higher treatment-failure rates. On another note, substandard and counterfeit drugs could also confound the interpretation of past and present clinical and treatment studies.The artemisinin derivative artesunate, in combination with slower acting antimalarials such as mefloquine, has now become the recommended treatment for Plasmodium falciparum malaria in southeast Asia, especially in areas of multidrug resistance 2xEffects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study. Nosten, F. et al. Lancet. 2000; 356: 297–302Abstract | Full Text | Full Text PDF | PubMed | Scopus (388)See all References. Newton et al. investigated the distribution of substandard artesunate in Cambodia, Laos, Myanmar, Thailand and Vietnam. 104 samples of artesunate were bought from shops, pharmacies, non-government organizations and hospitals over a period of one year, and examined for artesunate content using a colorimetric assay (Fast Red TR dye technique). This test is inexpensive (US$0.02 per tablet for a US$ 1.00 adult treatment course according to the authors) and measures the alkali decomposition product of artesunate and a diazonium salt; a yellow color being indicative of artesunate presence. Of the 104 samples, 29% (varying between 11 to 64% depending on country of origin) were found to contain no artesunate. Surprisingly, counterfeit artesunate packages and drugs could be identified readily by looking at package holograms, bar codes, printing or tablet colour, size, weight, consistency or taste. The authors conclude that substandard artesunate is widely distributed in southeast Asia, but suggest that, based on the latter findings, education campaigns highlighting the distribution of bogus drugs could have a significant impact if patients will be able to differentiate between the genuine and fake article. Controlling the distribution of substandard drugs is obviously difficult and becomes a political issue, as for example illegal manufacturing has to be curtailed by regulatory authorities, depending on the political will of local governments.Although there have been isolated reports of substandard antimalarial drugs being distributed in Cambodia (artesunate and mefloquine), Cameroon (chloroquine), Kenya (pyremethamine and sulfadene), Namibia (primaquine), Nigeria (chloroquine, quinine, pyremethamine and sulphadoxine), Sudan (chloroquine), Tanzania (chloroquine) and Uganda (chloroquine) and Venezuela (primaquine), this is the first multi-country survey showing the extent of the distribution of substandard antimalarials – a cause for concern.