Incidence of side effects from prophylactic drugs

The number of cases of malaria imported into the United Kingdom is rising (figure), and over half of them are potentially fatal (falciparum malaria). The risks from the disease must be compared sensibly with the risks associated with the drugs recommended for prophylaxis. Obtaining true figures for the incidence of side effects is difficult and in some cases controversial. This is partly because as doctors become more aware of potential side effects, more side effects are looked for and then reported. Also, it is virtually impossible to perform anything other than observational studies on side effects because sending people to malarious areas with placebo drugs only would be unethical.

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Number of cases of malaria, number of cases of falciparum malaria, and number of deaths from malaria in the United Kingdom, 1977-97. Data supplied by the Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine (E Walker, personal communication)

Two other factors make it difficult to determine the incidence of side effects. Firstly, of the huge number of people taking antimalaria drugs some will get concurrent symptoms and diseases while abroad, and deciding whether to attribute these to the antimalaria drugs is difficult. Secondly, attributing subjective side effects to drugs is a common phenomenon, even for placebo drugs.

With short acting drugs (for example, proguanil, which is taken daily) side effects usually occur after just one dose. With longer acting drugs (for example, mefloquine, which is taken weekly), side effects may not become apparent until after the third dose.

Two large studies have reported the incidence of side effects of mefloquine compared with chloroquine and proguanil. Barrett et al found that both regimens had similar rates of any side effect occurring (40%), although most side effects were trivial.1 About 0.7% of travellers taking mefloquine reported severe, disabling neuropsychiatric symptoms compared with 0.09% of people taking chloroquine and proguanil. Also a significantly higher number of moderate neuropsychiatric symptoms occurred in mefloquine users compared with travellers who took chloroquine and proguanil. Steffen et al found that 18.8% of travellers taking mefloquine had experienced side effects while 30.1% of the chloroquine and proguanil group reported problems.