Mefloquine: the benefits outweigh the risks.

Introduction extensive and mefloquine is not detectable in the CSF. The drug is very slowly eliminated, mainly as a carboxylic acid metabolite, with a half-time of about 1 Falciparum malaria remains one of the world’s biggest killers, accounting for about 2.1 million deaths in 1995— month. It is excreted in breast milk [2]. Mefloquine is effective against many isolates of about 4% of all global mortality. The data are even more appalling than at first glance since most deaths chloroquine-resistant P. falciparum, and has become the drug of first-choice for uncomplicated malaria in many are of children aged under 5 years. The vast majority of malaria deaths are in Africa, where the really big issue parts of SE Asia. Resistance to mefloquine is wellrecognised and worsening in SE Asia, but is not yet is preventing mortality rates from rising in the setting of global warming, worsening drug-resistance, severe universal. In Africa mefloquine is little used, mainly because of its high cost; the parasites, for the most part, poverty, rising population pressure and ‘competing’ disease targets, like acute respiratory infection, TB and retain sensitivity. diarrhoeal illnesses. Inhabitants of developed nations live, for the most part, in non-endemic areas of the world and become exposed only when they choose to travel—for pleasure, Risk5benefit assessment business or war. Most, if not all, antimalarial drugs have been developed with such travellers, mainly All therapeutic drugs have adverse effects: these may be soldiers, in mind [1]. One such drug, mefloquine, has dose/concentration-related or idiosyncratic (much less replaced global malaria mortality as a ‘medical headline’ common, with less relationship to dose and greater risk recently because of the supposedly unacceptable frebecause of their unpredictability). The physician’s job, quency of symptomatic toxicity in travellers. As a result, of course, is to balance anticipated benefit against medical practitioners and patients alike are confused possible risks. about the advisability of prescribing or taking mefloFew would dispute that, faced with established P. quine for malaria prevention. falciparum parasitaemia (especially in non-immune subjects), the risks of the disease massively outweigh risks of drug treatment. It is in the setting of chemoprophylaxis—where the patient is disease-free—that such risk5benefit ‘analysis’ becomes particularly relevant and, Background very often, quite difficult. P. falciparum can be transmitted in most tropical countries, but the intensity of In its search for prophylactic drugs for US servicemen, which was accelerated by the war in Vietnam, the transmission is highest in sub-Saharan Africa, particularly in west Africa. Most British malaria deaths are Walter Reed Army Institute of Research screened over a quarter of a million compounds between 1963 and ‘imported’ from Kenya because of its frequency as a holiday destination. African parasites are usually chloro1976, and mefloquine was one of the more successful products. Its subsequent development to the market quine-resistant but are sensitive to other drugs at the moment. In contrast, the main tourist destinations of was entrusted to Hoffman LaRoche which introduced mefloquine (Lariam) in the mid-1980s for both the SE Asia pose a much lower threat of malaria transmission, but there are exceptions (for detailed advice treatment of uncomplicated malaria and for prophylaxis. The drug’s mode of action against Plasmodium see Bradley & Warhurst [3]): parasites from SE Asia are not only chloroquine-resistant but are often multifalciparum is unknown, but its effects are confined to the pathogenic blood stages of the parasite. Mefloquine drug-resistant. Overall, mefloquine is the drug of choice for travellers is extensively absorbed from the gut, reaching maximum concentrations after about 2 h. It is very lipid-soluble at high risk of acquiring chloroquine-resistant P. falciparum, and gives greater protection than other drugs in and has a large apparent volume of distribution but, even so, partition across the blood5brain barrier is not sub-Saharan Africa. However, because of concerns about