ViewpointAverting a malaria disaster
Section snippets
Will artemisinin resistance be encouraged?
Some have argued that artemisinin derivatives are so effective in the management of severe malaria that they should be withheld from use in uncomplicated malaria in those areas where they are not needed, so as to protect them from the development of resistance. However, combination chemotherapy does protect the artemisinin derivatives from the development of resistance. If the drug is always used in combination with another unrelated antimalarial drug, then, provided they are at least partially
Toxic effects
In animals, intramuscular injections of the oil-based compounds arteether and artemether have induced an unusual and selective pattern of damage to certain brainstem nuclei.12 This damage seems to result from sustained exposure of the central nervous system, which is a consequence of the very slow absorption of these drugs from the intramuscular site. By contrast, in animals, the therapeutic ratio is substantially larger after oral administration of these same drugs, and, for the water-soluble
Cost
Cost is usually the major factor that determines the use of antimalarial drugs. Combinations with artemisinin derivatives would, in general, be expected to double the treatment cost for individual patients. But increased short-term costs should result in overall savings in the longer term. If combination treatment translates into a 3–5 year extension in the useful lifespan of chloroquine, amodiaquine, or PSD (as it has done for mefloquine on the western border of Thailand), the overall cost
Regulatory requirements
To ensure compliance with drug combinations, the individual components should ideally be formulated together in a single tablet or liquid preparation. However, such formulations would need the expensive pharmacokinetic, pharmaceutic, and toxicological studies required for regulatory approval—and who will pay for these? A less satisfactory but simpler alternative initially would be to combine separate components in blister packs, as is done for the multiple-drug treatment of tuberculosis and
What is to be done?
Normally, the answer is more research, and more research is certainly required. However, with a concerted effort, this research could be completed within 2 years. Critical decisions often need to be taken with incomplete knowledge. Time is running out in Africa; four countries—Malawi, Kenya, Botswana, and South Africa—have already been forced to use PSD as their first-line antimalarial. When this happened in southeast Asia, high-level resistance developed within a few years and mefloquine had
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