Drug resistance

Drug resitance is a major problem in the treatment and prophylaxis of malaria. Malaria parasites have developed resistance against many different types of drug, such as the aminoquinolines as well as the antifolates. In general within a delay of 10 years after the first introduction of the drug resistance tends to appear and then spreads all over the world.

Chloroquine resistance

Several mechanisms have bee put forward to explain the mechanism of chloroquine resistance:

Defects in pigment formation. It is interesting to note that many chloroquine-resistant Plasmodium strains are uncapable of pigment formation. The absence of pigment would protect the parasite against the toxic action of chloroquine.
Amplification of the pfmdr gene. In many chloroquine-resistant isolates multiple copies of a gene homologous to the mammalian mdr gene are found. The mdr gene is often amplified and present in multiple copies in tumour cells that have become resistant to many different anti-cancer drugs. Interestingly an inhibitor of the mdr protein called verapamil is capable of reversing chloroquine resistance in Plasmodium when administered at the same time as the anti-malarial drug.

Since the early 1950s, chloroquine has been widely used, providing effective and safe prophylaxis It is safe in pregnancy, and has relatively few side effects or contraindications. Therefore, chloroquine remains the first line choice of chemoprophylaxis in areas of P. falciparum that are sensitive to the drug. Chloroquine is also effective for the three more benign Plasmodium species, with the exception of P. vivax in Oceana, where high-grade resistance has been reported.

Unfortunately, chloroquine's widespread use has resulted in increased resistance, rendering it ineffective against P. falciparum in many areas of the world. In regions of limited to moderate chloroquine resistance, it may be combined with proguanil, another very safe drug, to enhance protection.

Mefloquine, a drug developed during the Vietnam war, is now generally agreed to be the preferred antimalarial for travellers at high risk for chloroquine-resistant P. falciparum.

Anti-folate resistance

Resistance to Fansidar is now wide spread

Quinine resistance

P. falciparum was originally sensitive to chloroquine, however, strains resistant to this and other antimalarial drugs are now commonplace. Because the parasite is able to multiply very rapidly and sequester within the microvasculature, a life threatening illness may develop in a very short space of time. For malaria treatment quinine is still one of the drugs of choice. Since it is not used in prophylaxis anymore there is littele resistance reported and for this reason nowadays quinine is reserved for treatment only.

Click here to learn more about the mechanisms by which drug resistance may develop.

Click here to read further (WHO text)

Click here to access the WHO Report on Infectious Diseases 2000 publication: "Overcoming Antimicrobial Resistance".

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