A phase II/III double-blind, dose-finding clinical trial of a combination of mefloquine, sulfadoxine, and pyrimethamine (Fansimef) in falciparum malaria.

Fansimef is a combination of 250 mg mefloquine (base), 500 mg sulfadoxine, and 25 mg pyrimethamine per tablet. One hundred and fifty adult male Brazilian patients at Belém (Pará), who had peripheral blood smears positive for Plasmodium falciparum, with or without clinical symptoms of falciparum malaria, were treated in a double-blind randomized fashion with either one, two or three tablets of Fansimef. Of those receiving one tablet (48 patients), 81% were cured and 19% exhibited RI recrudescences. All the patients receiving two or three tablets of Fansimef (49 patients in each group) were cured. The rates of initial clearance of parasitaemia and fever were similar in all treatment groups. Tolerance was good at all dose levels. The main side-effects included nausea, vomiting, dizziness, diarrhoea and abdominal pain, but these were mild and transient and required no specific treatment. The incidence of vomiting and nausea was highest in patients given the three-tablet dose. The results of various haematological, biochemical and urine analyses were not adversely altered by the administration of Fansimef.

Treatment of falciparum malaria with quinne and tetracycline or combined mefloquine/sulfadoxine/pyrimethamine on the Thai-Kampuchean border.

Three different regimens were compared for treatment of falciparum malaria in displaced Kampucheans living in encampments on the Thai-Kampuchean border in 1983: single dose 750 mg mefloquine, 1.5 g sulfadoxine, 75 mg pyrimethamine (MSP); 600 mg quinine 8-hourly for 3 days and 500 mg tetracycline 8-hourly for 7 days (Q3T7); or 600 mg quinine 8-hourly for 7 days and 500 mg tetracycline 8-hourly for 7 days (Q7T7). Radical cure rates were 98% (40/41) for MSP, 76% (32/42) for Q3T7 and 92% (33/36) for Q7T7. The criterion for treatment failure was reappearance of parasites by 35 days after commencement of treatment or no parasite clearance. Treatment failures comprised one case of reduction but no clearance of parasites (RII resistance) for MSP, 10 recrudescences (RI) for Q3T7 and 3 recrudescences (RI) for Q7T7. The radical cure rate for Q3T7 was significantly lower than that for MSP (P less than 0.01), whilst Q7T7 significantly from the other groups. Parasite clearance time was shorter (2.4 days) with MSP than with Q3T7 (3.5 days) and Q7T7 (3.3 days). There was little difference in side effects between the regimens, and tolerance was good. The MSP and Q7T7 regimens are both effective for treatment, but the single dose of MSP is much easier to manage than 7 days of quinine and tetracycline.

In vitro susceptibility of Plasmodium falciparum collected from pyrimethamine-sulfadoxine sensitive and resistant areas in Thailand.

Seventy Plasmodium falciparum isolates, collected from two geographically separate areas of Thailand, were tested for their in vitro responses to pyrimethamine, sulfadoxine, and a combination of these two drugs. The effects of pyrimethamine and pyrimethamine-sulfadoxine combinations against P. falciparum isolates were found to be significantly greater in a northern area where the combined drug was an effective therapeutic agent than in a south-eastern area, near the Thai-Kampuchean border, where the combined drug was no longer effective. However, the actions of sulfadoxine against parasites obtained from the two areas were not significantly different. There was no significant difference between the mean values of plasma 4-aminobenzoic acid (PABA) in falciparum malaria patients and in healthy controls. The test for PABA determinations used in this study gave positive readings with both PABA and sulfadoxine.

An epidemiological early warning system for malaria control in northern Thailand.

Parasitological data for the years 1973-81 were examined to determine the years of "acceptable" or "normal" transmission of malaria, for every district of northern Thailand. The monthly mean number of cases and the mean plus 2 standard deviations (SD) were calculated for the selected years and plotted on log-linear graph paper. The resulting graphs were distributed to the Malaria Sector Offices. Sector Chiefs were then responsible for plotting the monthly observed number of cases of malaria as the data became available; if the observed incidence was more than 2 SD greater than the "normal" mean for that month, the Zone and Regional Malaria Offices were informed. Retrospective analysis of data from districts where malaria outbreaks had occurred indicated that the method provides an effective warning of impending epidemics. It is expected that the resulting earlier implementation of appropriate remedial control measures will lead to a reduction in malaria incidence in the region.

Evaluation of the antimalarial activity of the phenanthrenemethanol halofantrine (WR 171,669).

Halofantrine (WR 171,669) was administered to 27 nonimmune subjects infected with the multi-drug resistant Vietnam Smith strain of Plasmodium falciparum. It was also administered to three other subjects, one infected with the Cambodian Buchanan strain of P. falciparum, and two with blood-induced infection with the Chesson strain of P. vivax. It cured infections with all three parasites. Against the highly chloroquine-resistant Smith strain, it was curative in single day treatment regimens. The drug was well tolerated and produced rapid clearance of parasitemia in every case.

An evaluation of five regimens for the outpatient therapy of falciparum malaria in Thailand 1980-81.

Five regimens for the radical treatment of falciparum malaria were compared in five geographically separate areas of Thailand. The cure rate for sulfadoxine-pyrimethamine was found to be low in the area of the Kampuchean border and in the northeastern and western parts of the country. This distribution may be related to the spread of resistant parasites through the migration of labourers. A 7-day course of quinine was found to be uniformly effective, with an overall cure rate of 90% in these primary infections with comparatively low parasitaemia.