On achieving consensus on the prevention of malaria

The giving of drugs to healthy people to prevent a disease of low probability demands an almost impossible level of safety from the compound used. Chloroquine’s 50 year safety record must be unique amongst antimicrobials and it is only the emergence of drug resistance which has forced prescribers to look elsewhere. Not surprisingly, some promising alternative contenders have failed to measure up: sulphadoxine/pyrimethamine (Fansidar) and amodiaquine were both summarily abandoned as prophylactics after they were implicated in clear-cut serious adverse advents. The latest compound to be officially endorsed as a chemoprophylactic, mefloquine (Lariam), has come under intense pressure from the media in the UK for over a year because of adverse effects that are often subjective and far from clear-cut. In considering the risk/benefit ratio for mefloquine it is clear that, at present, it provides the best protection against Plasmodium falciparum malaria in visitors to subSaharan Africa. Observations on American Peace Corps volunteers in West Africa from 1989 to 1992 demonstrated that weekly mefloquine was 86% more effective than prophylaxis with chloroquine plus proguanil. When breakthrough infections in over 145,000 Swiss travellers who had stayed in East Africa for less than 1 year were analysed it was found that in people who used no chemoprophylaxis the incidence of P. falciparum malaria was 1.2% per month; mefloquine gave 91% protection, compared with 72% for chloroquine and proguanil. More recently a three-fold reduction in P. falciparum malaria imported into the UK from Kenya against a background of apparently stable malaria transmission led to the conclusion that the best explanation appeared to be the widespread use of mefloquine and a reduction in the use of chloroquine and proguanil by travellers. The only dissenting data came from The Netherlands with the report of P. falciparum infections in several travellers who had been taking mefloquine during October and November 1994. The authors proposed that, when the compound was started only 1 week before departure for a malarious area, protection might be sub-optimal for those infected early in the course of their visit since steady-state serum concentrations of mefloquine are reached only after 6–8 weeks. Adverse effects of drugs taken to prevent malaria are remarkably common. A postal and telephone survey conducted among British travellers between November 1993 and February 1995 found that 41% had experienced some adverse effect irrespective of whether they were taking mefloquine or the combination of chloroquine plus proguanil. There was no significant difference between the two regimens in the much smaller proportion of travellers who had either changed or stopped their prophylactic as a result. These authors concluded that about 0.7% of travellers taking mefloquine can expect to have a neuropsychiatric adverse event unpleasant enough to prevent them temporarily from carrying out their dayto-day activities, compared with 0.09% of those taking