Academic journal article Bulletin of the World Health Organization

Interventions to Improve the Use of Antimalarials in South-East Asia: An Overview

Academic journal article Bulletin of the World Health Organization

Interventions to Improve the Use of Antimalarials in South-East Asia: An Overview

Article excerpt


The benefits of the few drugs available for the treatment of malaria are often reduced owing to poor use. Except for the artemisinin derivatives which have recently been widely deployed in the South-East Asia region (1), resistance has emerged to all antimalarials (2-5). While chloroquine and quinine have been effective for the longest periods, in many malaria-endemic areas chloroquine can no longer be used against Plasmodium falciparum and quinine is under threat (6).

The UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) has for many years supported the development of antimalarials and provided funds for the discovery of new drugs with novel mechanisms of action against malaria parasites, which is a costly and time-consuming undertaking. International and government agencies and pharmaceutical companies spend hundreds of millions of dollars for an average of 10-15 years to develop and test each new regimen. Because the market for antimalarials consists mostly of poor people there is little chance of profit from this vast investment and research effort. In addition, there are technical difficulties to find safe, effective and structurally novel compounds. Efforts to develop "new" structural analogues have met with problems, e.g. rapid development of cross-resistance (quinine, mefloquine, halofantrine, enpiroline), and TDR continues to screen a wide range of herbal, anticancer and antibiotic compounds for antimalarial activity -- too often with little success. The past 20 years have shown that drug resistance develops faster than our ability to develop new drugs. Owing to problems of drug resistance and the limited ability of those who need the new drugs to pay for them, there has been reduced investment by the private pharmaceutical sector to support research and development of drugs for malaria and other tropical diseases.

Development of drug resistance

Field reports suggest that drug resistance has two phases: the emergence of resistant strains over a period of several years, and the dissemination of these strains which may occur over several months, depending on whether vectors or humans are the agents of spread. Often populations with a high incidence of malaria, who are also highly mobile such as miners, loggers, and other temporary workers, are implicated in the rapid spread of resistant strains across large geographical areas and country borders. Selection under drug pressure is probably an important factor during the emergent phase of resistance, its role during the dissemination phase being much more complex. Suboptimal regimens could hasten the emergence of resistance through selection when relapses occur after treatment. Another mechanism for resistance is through reinfections following drug administration when the levels are no longer parasitocidal. While both mechanisms (relapse or reinfection) can occur following full regimens, it is highly probable that incomplete, sub-lethal regimens will lead to more rapid development of resistance.

In general, antimalarial drugs can be used in three situations: against severe malaria, or uncomplicated malaria, or for prophylaxis. Since clinically severe malaria is of the greatest public health importance and its treatment is least likely to foster the development of resistance, some regimens which can be used in all three situations should be reserved for severe malaria only. However, as drugs for uncomplicated malaria become expensive, or difficult to take, or ineffective, the health authorities in South-East Asia have recently considered permitting these types of drugs (e.g. artemisinins) for treating uncomplicated malaria and even for prophylaxis.

Improving the use of antimalarials. Based on these considerations, a Phase-IV research arm -- the Task Force for Improved Use of Antimalarials -- was created within TDR in 1993. The Task Force concentrated on the South-East Asian region with the objective of establishing, through research, the measures that should be taken to protect the few existing antimalarials in this region, which had the highest level of multidrug resistance against malaria in the world. …

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