Comparison of three malaria chemoprophylactic regimens in residents in east, central and southern Africa. A prospective, randomized multicentre trial in The Netherlands.

There is much confusion about the most effective malaria chemoprophylactic regimen for travellers to chloroquine-resistant areas. For residents, the problem is even more confused. A prospective, multicentre trial was performed between 1987 and 1989 to assess the efficacy of three different malaria chemoprophylactic regimens (chloroquine 300 mg weekly combined with proguanil 100 mg daily, chloroquine 300 mg weekly combined with proguanil 200 mg daily and proguanil 200 mg daily only) in Dutch expatriates, who were departing for a stay of more than one year in East, Central or Southern Africa. Prophylaxis failures (defined as Plasmodium falciparum present in the blood film) were distinguished from failures of compliance by measuring whole-blood drug levels, taken at the same time as the blood slide and sent as filterpaper blood spots. The data of 200 expatriates could be analysed; the overall response rate was 52%. Twenty-six (13%) suffered from a fever; in two of them the blood slide contained P. falciparum. One subject took chloroquine 300 mg weekly with proguanil 200 mg daily, the other 200 mg proguanil daily. Assessment of compliance was possible in 10 of the 26 subjects with a fever; five (50%) were below and five (50%) were above the limit of 0.19 mumol/l. Due to the low incidence of prophylaxis failures, calculation of risks is unreliable. There were strong indications that compliance decreased with time. The ultimate cooperation needed for confirmation of prophylaxis failures and breakthroughs failed. Several factors which could have contributed to this lack of cooperation are discussed.