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Chloroquine is an antimalarial drug. Doctors can usually cure people who are infected with the malaria parasite with various drugs, including this one, but sometimes the parasite is immune to a certain drug. In the case of chloroquine resistance, the parasite appears to have evolved in a way that prevents the drug from getting into the parasite cell. Chloroquine resistance is important for malaria control in areas of the world where the disease exists.
Four different species of parasite cause malaria. These are Plasmodium falciparum, P. vivax, P. malariae and P. ovale. Three of these species cause non-life-threatening disease, but P.falciparum can potentially kill infected people. In the 1930's, a scientist with the Bayer company in Germany named Hans Andersag identified chloroquine as a potentially useful chemical. It became a treatment for malaria in 1946. Chloroquine, therefore, has been in use for decades.
These types of drugs are always designed to target one or more specific features of a parasite. In the case of chloroquine, the targets appear to be the genetic material of the parasite and the storage and detoxification of certain products. With all these actions together, the drug manages to kill the parasite.
To work on the parasite, though, chloroquine has to get inside the Plasmodium cell. Each individual cell of the parasite has a cell structure, and one of the features of the cell is a food vacuole, enclosed areas where the food that the cell ingests break down. It is these food vacuoles that chloroquine molecules congregate in, and the effects of the drug occur. Scientists believe that the drug prevents the cell from collecting toxic waste products of the food and rendering them harmless. The cell then dies from the toxic molecules inside.
Malaria patients over the years have received chloroquine and other antimalarials. The parasite that was originally susceptible to the drug developed chloroquine resistance in response to its effects. Resistance appears to be genetic in origin, and is due to certain parasites that had a variation in genetic material surviving chloroquine treatment. These new versions of parasites then became the predominant type in areas where chloroquine treatment killed off all the susceptible Plasmodia. The dangerous form of malaria, Plasmodium falciparum is resistant to the drug in many areas, and P. vivax may also be resistant.
One explanation for chloroquine resistance is that the parasite's genes produced new versions of transporter molecules. These transporter molecules help move substances, such as drugs, across membranes. One theory about chloroquine resistance is that new versions of transporters manage to send chloroquine molecules back out of the vacuole to reduce potential damage to the parasite. The exact manner in which Plasmodium resists the effects of the drug is not, however, well known.