Treatment of falciparum malaria in the age of drug resistance.

The growing problem of drug resistance has greatly complicated the treatment for falciparum malaria. Whereas chloroquine and sulfadoxine/pyrimethamine could once cure most infections, this is no longer true and requires examination of alternative regimens. Not all treatment failures are drug resistant and other issues such as expired antimalarials and patient compliance need to be considered. Continuation of a failing treatment policy after drug resistance is established suppresses infections rather than curing them, leading to increased transmission of malaria, promotion of epidemics and loss of public confidence in malaria control programs.Antifolate drug resistance (i.e. pyrimethamine) means that new combinations are urgently needed particularly because addition of a single drug to an already failing regimen is rarely effective for very long. Atovaquone/proguanil and mefloquine have been used against multiple drug resistant falciparum malaria with resistance to each having been documented soon after drug introduction. Drug combinations delay further transmission of resistant parasites by increasing cure rates and inhibiting formation of gametocytes. Most currently recommended drug combinations for falciparum malaria are variants of artemisinin combination therapy where a rapidly acting artemisinin compound is combined with a longer half-life drug of a different class. Artemisinins used include dihydroartemisinin, artesunate, artemether and companion drugs include mefloquine, amodiaquine,sulfadoxine/pyrimethamine, lumefantrine, piperaquine, pyronaridine, chlorproguanil/dapsone. The standard of care must be to cure malaria by killing the last parasite. Combination antimalarial treatment is vital not only to the successful treatment of individual patients but also for public health control of malaria.

Eosinophilic response to falciparum malaria infections.

Eosinophilia was a frequently detected incidental finding during a prospective study of malaria seroepidemiology in Thailand. Blood eosinophil counts were performed every 3 months for a year in 823 Thai soldiers on border guard duty in a malaria endemic area. Soldiers developing malaria were admitted to hospital and more frequent eosinophil counts were done. P. falciparum parasitemia suppressed preexisting eosinophilia but eosinophilia returned following treatment. P. vivax and mixed infections had a similar but less marked effect on the peripheral blood eosinophil count. Eosinophilia in persons from a malaria endemic area may represent a normal late response to malaria infection.

Mefloquine chemoprophylaxis of soldiers on the Thai-Cambodian border.

Chemoprophylaxis of malaria on the Thai-Cambodian border is difficult due to the high level of drug resistance. Thirteen separate companies of Royal Thai Marine Militia were placed on 250 mg weekly mefloquine chemoprophylaxis from August 1989 to January 1990. A mean number of 722 soldiers received two or more doses of mefloquine per month for the five month study. The medication was well tolerated and compliance averaged 91%. Substantial numbers of prophylaxis breakthroughs were seen which resulted in 3.2 cases of malaria/100 man-months. Sixty-eight falciparum malaria cases were documented in men who had taken at least two mefloquine doses in the previous four weeks. No serious neuropsychiatric reactions occurred. Mefloquine chemoprophylaxis failures exist on the Thai-Cambodian border and are one sign of the spread of mefloquine resistance.

Proguanil/sulfamethoxazole malaria chemoprophy-laxis on the Thai-Cambodian border.

383 Thai soldiers on the Thai-Cambodian border were entered into a randomized malaria chemoprophylactic trial. Proguanil (200 mg/day) combined with sulfamethoxazole (1000 or 1500 mg/day) were compared to a standard combination of weekly pyrimethamine/dapsone (Maloprim). Men receiving proguanil/sulfamethoxazole had a significantly lower malaria attack rate than those taking pyrimethamine/dapsone. This was true of both the first five-week phase in which 1000 mg of sulfamethoxazole was used (0.11 vs 0.26; p less than 0.001) and in the second ten weeks in which 1500 mg of sulfamethoxazole was used (0.13 vs 0.30; p less than 0.001). Combined relative efficacy indicated that proguanil/sulfamethoxazole was better than pyrimethamine/dapsone by 64% for Plasmodium vivax and by 38% for P. falciparum. Unenforced compliance as measured by returned pills was greater than 86% in both groups. No serious drug side-effects were observed. Proguanil/sulfamethoxazole may represent a useful chemoprophylactic option in areas of multiple drug-resistant malaria.

Malaria in displaced persons along the Thai-Burmese border.

Malaria epidemiology in displaced Karen ethnic children along the Thai-Burmese (Myanmar) border was observed for 3 years. An active screening process in connection with malaria chemoprophylaxis trials showed a decrease in malaria prevalence over time in children not receiving chemoprophylaxis. The number of malaria cases detected at a primary health care clinic in the same area remained stable.