The Plasmodium falciparum malaria parasite has continued to evolve resistance to almost all drugs in use. Essentially all other antimalarials that are easy to administer (and sufficiently non-toxic to be used outside the hospital) are too expensive. Even if they were not, resistance to several other new drugs is spreading. Resistance to antimalarials appears to have contributed to an increase in the numbers of infections that develop into severe and complicated disease, such as cerebral malaria, and hence death rates from the disease. This means that across all of sub-Saharan Africa and many of the world's other tropical regions where malaria is endemic, malaria is making a comeback as one of the great killer diseases. The World Bank issued a report in 1993 predicting that mortality from malaria may double in the next decade.
Chloroquine was the "one-cent-a-dose" drug used for over 40 years as the standard antimalarial in the developing world. Plasmodium resistance to the drug apparently evolved in two places, South America and Southeast Asia, in the late 1950s. The resistant parasites arrived in east Africa in 1978, and swept westward to the Atlantic coast in less than 10 years.
Varying degrees of resistance to chloroquine, by far the cheapest and previously most useful anti-malarial, are now reported from almost all countries where the parasite exists. In 1986, none of the Peace Corps volunteers working in villages in the west African country of Benin contracted malaria while taking chloroquine. In 1987, all of them did.
In Kenya, where chloroquine has been useless for a decade, researchers reported in 1194 that more than 25% of malaria cases in a recent study were resistant to the two more modern and expensive antimalarial drugs, mefloquine and doxycycline. Between 1982 and 1986, the death rate from malaria in the paediatric wards of the largest hospital in Zaire rose from 4.8% to 15.3%. The new drug mefloquine has been widely used in Thailand, but in some areas only half the cases now respond to the drug. On the Thailand-Cambodian border, 80% of malaria is mefloquine-resistant.
Resistance to another favoured drug combination, sulfadoxine/pyramethamine is still generally affordable and effective in Africa. Some countries, such as Malawi, have moved to it as the village-level replacement for chloroquine. Resistance to the combination, however, is widespread in Southeast Asia and the Amazon Basin, and is now appearing in parts of Africa.