Academic journal article Bulletin of the World Health Organization

Malaria Drug Resistance Gene Identified

Academic journal article Bulletin of the World Health Organization

Malaria Drug Resistance Gene Identified

Article excerpt

A US research group headed by Tom Wellems of the US National Institute for Allergy and Infectious Diseases (NIAID) announced at the end of October that they had identified a gene which mutates to makes the most lethal of the malaria parasites, Plasmodium falciparum, resistant to chloroquine. The gene, dubbed pfcrt, is on chromosome 7, and codes for a protein on the surface of the parasite's stomach. The NIAID group identified the pfcrt gene by crossing chloroquine-sensitive and chloroquine-resistant species of the parasite and by using molecular biology techniques to locate the gene.

Chloroquine is the cheapest of the malaria drugs, and together with DDT spraying to kill mosquitoes, was expected to help eradicate malaria in the 1950s to 1970s. But resistance to chloroquine developed in the mid-1950s in South-East Asia and in South America in 1959, reaching Africa in the 1970s and 1980s, and now extends over most of the tropical world. In Central America, North Africa and China P. falciparum is still sensitive to chloroquine.

David Warhurst, Professor of Protozoal Chemotherapy at the London School of Hygiene and Tropical Medicine, told the Bulletin: "It seems clear that this is a very important result. The level of resistance that the mutations [identified in pfcrt] create is low, but it may open the gate to higher resistance by additional mutations."

Exactly how the gene works and how the mutation creates chloroquine resistance is still a puzzle. A malaria parasite feeds on its host's haemoglobin, producing the waste product hemin, which is toxic to the parasite. Normally the hemin is chemically changed into a form the parasite can eliminate. But chloroquine, as well as several other antimalarial drugs, including amodiaquine, quinine, mefloquine and halofantrine, combine with the hemin and interrupt the transformation process, leaving more toxic hemin that kills the parasite. …

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