Antimalarial drug resistance has been defined as the “ability of a parasite strain to survive and/or multiply despite the administration and absorption of a drug given in doses equal to or higher than those usually recommended but within tolerance of the subject”
The above definition been modified to specify that the drug in question must “gain access to the parasite or the infected red blood cell for the duration of the time necessary for its normal action”
A distinction must be made between a failure to clear malarial parasitaemia or resolve clinical disease following a treatment with an antimalarial drug and true antimalarial drug resistance. While drug resistance can cause treatment failure, not all treatment failure is due to drug resistance. Many factors can contribute to treatment failure including;
– Incorrect dosing
– non-compliance with duration of dosing regimen,
– poor drug quality,
– drug interactions,
– poor or erratic absorption,
Probably all of the above factors, while causing treatment failure (or apparent treatment failure) in the individual, may also contribute to the development and intensification of true drug resistance through increasing the likelihood of exposure of parasites to suboptimal drug levels.
In general, resistance appears to occur through spontaneous mutations that confer reduced sensitivity to a given drug or class of drugs.
For some drugs, only a single point mutation is required to confer resistance, while for other drugs, multiple mutations appear to be required. Provided the mutations are not deleterious to the survival or reproduction of the parasite, drug pressure will remove susceptible parasites while resistant parasites survive.
Single malaria isolates have been found to be made up of heterogeneous populations of parasites that can have widely varying drug response characteristics, from highly resistant to completely sensitive. Similarly, within a geographical area, malaria infections demonstrate a range of drug susceptibility. Over time, resistance becomes established in the population and can be very stable, persisting long after specific drug pressure is removed.
The effect of development of resistance to malaria medications, is that there is increasing complications from malaria and prolong hospital stay for patients being managed for malaria. Added to this, is increasing mortality especially for the vulnerable – pregnant women, immune suppressed and children.
Preventing and containing antimalarial drug resistance
The prevention and control of antimalaria drug resistance is clearly stated by WHO as described below.
Several factors influence the emergence and spread of drug resistant malaria parasites, including the number of parasites exposed to a drug, the drug concentration to which the parasites are exposed, and the simultaneous presence of other antimalarials in the blood to which the parasite is not resistant.
In areas where the recommended antimalarial treatments remain fully efficacious, correct medicine use must be promoted, with special attention to expanding diagnostic testing, quality-assured treatment, and good patient adherence to the prescribed treatment. Further extending basic malaria interventions, including vector control, will reduce the number of parasites exposed to a drug and the risk of resistance.
Use of oral artemisinin-based monotherapy (oAMT) is considered a contributing factor to the development and spread of resistance to artemisinins. WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of oAMT, and promote access to quality-assured ACTs for the treatment of falciparum malaria.
Countries where resistance to artemisinins or to ACT partner drugs is reported need to intensify malaria control in order to reduce the burden of the disease, and delay or prevent the spread of resistance. Prevention and containment activities need to build on, expand and accelerate ongoing national efforts to control and eliminate malaria. In areas of low transmission where antimalarial drug resistance is present, countries should target rapid elimination of falciparum malaria to limit the risk of spread and minimize the impact of resistance in the region.