Session 3: Preventative Measures-Balancing Risks Efficacy of drug prophylaxis

With the spread of chloroquine resistance Plasmodium falciparum the control of malaria has become increasingly complex¹. In recent years, particular concern has arisen over how best to prevent malaria in non-immune international travellers². Prior to the recognition of the potential toxicity of some antimalarial drugs, malaria preventive guidelines switched from chloroquine to the newer compound antimalarial drugs and to amodiaquine; this adjustment was made when sentinel cases alerted clinicians that breakthrough infections occurred in travellers to East Africa taking chloroquine prophylaxis^3-5. Changes were also supported by data derived from field studies illustrating the effectiveness of these drugs for therapy in indigenous populations^6-9. However, international studies have now documented serious adverse reactions to pyrimethamine/dapsone¹⁰ ,pyrimethamine/sulphadoxine¹¹, and amodiaquine¹², and caution is required with their use¹³. Rates in British users concur with international estimates¹⁴. Specialists preparing malaria preventive guidelines have, therefore, preferred to recommend the use of relatively safe antimalarial drugs, like chloroquine and proguanil, provide they offer non-immune travellers adequate protection against. P.falciparum infections². Substantial difficulty has arisen, however, in the definition of 'adequate protection'. Field studies in indigenous communities with partial immunity can provide concise biological measures of parasite resistance to drugs¹⁵. Unfortunately, these data cannot be used directly to determine the expected efficacy of chemoprophylactic drugs in non-immune populations². The transmission of malaria and the degree and intensity of resistance vary even within small geographical areas. Comprehensive patterns of resistance cannot be mapped out on a countrywide or regional basis for logistic reasons, and are restricted focally to discrete study locations. Furthermore, it is not clear how closely we can correlate the therapeutic potency of antimalarial drugs for semi-immune populations with the prophylactic potency of drugs used by non-immune subjects. An exhaustive review of the efficacy of antimalarial drugs, using both therapeutic and prophylactic data, is clearly unfeasible. A summary of most therapeutic studies has been documented elsewhere¹⁵. This paper focuses instead on the efficacy of chemoprophylaxis in the reduction of morbidity. It draws together efficacy data generated from studies conducted in both partially immune and non-immune populations. Modifications to current malaria preventive guidelines are discussed.