Antimalarial Drug Resistance: Problems and Prospects

Abstract

The problems

Malaria in Thailand-emergence of drug resistance

Although the prevalence of malaria in Thailand today is greatly

Reduced ·compared to 30 years ago the threat from malaria remains persistent and serious. In 1947 the mortality rate for malaria was 297.1 deaths per 100,000 population making mal aria the leading cause of death in Thailand. By 1980 the malaria death rate had dropped to 8.1 per 100,000. Still there were 395,442 cases of malaria detected in 1980 and 473,210 in 1981 (1). It is not, however, in the number of current cases or deaths due to Malaria that the present threat from malaria is defined. Rather the Malaria threat comes with the persistent emergence of drug resistance in Thailand and most other malarious regions of the world. Resistance to the antimalarial drug chloroquine by p. Falciparum was first reported in Thailand by Harinasuta and colleagues in 1962 (2). By 1967 it was apparent that chloroquine resistance was a widespread and serious problem in Thailand (3, 4). During the period 1965-1971 clinical trials were begun in Thailand on various alternative therapies (both single and combination drug treatment regimens) to deal with the problem of chloroquine resistance (4, 5). These s~udies produced basically 3 alternative treatments: quinine, quinine combined with tetracycline, and pyrimethamines  ulfonamide combinations. The combination of pyrimethamine with sulfadoxine (fansidar) was initially shown to be particularly effective against chloroquine resistant p. Falciparum (6). However, it was apparent by 1975 that the long-use prospect for pyrimethamine-sulfadoxine was doubtful and over the ensuing 5 year period the cure rate fell from 80% in 1976 to 10% in 1980 (7). Other studies in thailand have confirmed the loss in effectiveness of pyrimethamine - sulfadoxine for resistant p. Falciparum Malaria (8, 9, 10, 35). As of 1982 there remained but one conventional antimalarial

Drug for the treatment of multi-drug resistant  p. Falciparum  malaria in Thailand-quinine or a quinine-tetracycline combination. The use of Quinine in combination with tetracycline speaks to the heart of the issue

Of drug-resistance since quinine itself has been decreasing in effectiveness. Studies at the Bangkok hospital for tropical diseases have shown a progressive decrease in the cure rate for quinine : 94% (1963 - 1979), 86% (1979 - 1980) and 80% (1981) (7). In a recent study pinichpongse and colleagues (1982) (35) observed an overall cure rate of 90% for a 7-day course of quinine in patients from five geographically separate areas of Thailand. Thus, what was once an impressive arsenal of antimalarial drugs for use against p. Falciparum malaria has now been reduced to one perhaps faltering survivor, quinine, bolstered somewhat by its combination with tetracycline. As for prophylaxis against p. Falciparum there are no remaining conventional drugs of choice that can be prescribed with confidence. Only the advent of the new antimalarial drug mefloquine makes matters seem less than disastrous. Even the prospects with mefloquine, as we shall discuss, are not without serious concern. It should be noted that the situation with p. Vivax malaria is comparatively good. Chloroquine in combination with primaquine is effective for prophylaxis and treatment of p. Vivax malaria in thailand (7).