Malaria treatment and drug resistance

The malaria parasite is capable of becoming resistant to the action of anti-malaria drugs. This is due to small changes in the parasite DNA (point mutations). Over-prescription of anti-malarials (confusion with other febrile diseases) and the uncontrolled selling of poor quality drugs contribute to the increase in drug resistant parasites.

The widespread and increasing occurrence of P. falciparum resistant against affordable anti-malarial drugs, such as chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) is more and more hampering the fight against malaria. CQ and SP are still the most widely used drugs for treatment in most of Africa, because of low cost and availability. However, when more than 30% of treatments fail, as is the case in many parts of Africa, change to another first-line treatment is recommended. At present, the World Health Organisation recommends that all countries experiencing resistance to conventional mono-therapies, such as chloroquine or sulfadoxine-pyrimethamine, should use combination therapies, preferably artemisinin-based combination therapies (ACTs) for P. falciparum malaria. Artemisinin-based combination therapy (ACT) uses a combination of anti-malaria drugs, one of which is an artemisinin derivative (e.g. artesunate, artemether or dihydroartemisinin). Artemisinin can be extracted from a plant, A. annua. Under the name ‘Qinghaosu’, it has been used in traditional Chinese medicine to treat fever for over 2000 years.

 

Approach

KIT Biomedical Research participates in drug studies in which the efficacy of therapeutic options is being assessed. These studies benefit from the fact that KIT Biomedical Research has developed a fast, sensitive, reliable and quantitative method for the detection of parasite survival during and after drug treatment which will help clinicians to monitor and, if necessary, adjust the treatment regimen. This technology, quantitative nucleic acid sequence-based amplification (QT-NASBA) allows for the quantification of P. falciparum over a wide range of levels of parasitaemia, 10 – 108 parasites/ml of blood. Furthermore, our institute has technologies in place that can determine the presence of point mutations in the parasite DNA that may contribute to the development of drug resistant parasites. As drug efficacy studies also require distinguishing between re-infection and appearance of parasites due to treatment failure (recrudescence), KIT Biomedical Research performs genetic analysis of Plasmodium that can separate these two phenomena.

The work is carried out in collaboration with several research groups in disease endemic countries and often KIT scientists participate in the fieldwork.

 

Focal points

  • Design of and participation in drug trials
  • Measuring efficacy of treatment and prediction of treatment outcome with molecular methods.
  • Conducting genetic analysis of the Plasmodium parasite for the presence of DNA point mutations that confer drug resistance
  • Perform genetic analysis to distinguish between recrudescence and re-infection

Example

KIT Biomedical Research and the Blue Nile Research and Training Institute  (Wad Medani, Sudan) studied the efficacy of CQ and SP treatment of uncomplicated malaria in Central-East Sudan. Genetic analysis of the malaria parasite was performed in order to study the presence of point mutations in the P. falciparum DNA that confer resistance against the used drugs.

Testing of anti-malarial drugs revealed that CQ is not longer suitable for the treatment of malaria in Sudan. Over 40% of the people that were treated with this drug did not resolve the malaria infection and had to be treated with alternative drugs. In the case of treatment with SP a much better result was obtained: in only 2% of the cases a treatment failure was observed. This suggests that SP may be used as new first line drug in the treatment of uncomplicated malaria in Sudan. However, genetic analysis showed that almost 15% of the P. falciparum population had mutations that may result in resistance against SP. This indicates that SP resistance lies in wait in Sudan, and that alternative treatment is needed.

These findings were communicated to the National Malaria Control Programme (NMCP) and the Ministry of Health of Sudan. Based on our results, and those of other groups, the NMCP has developed a new treatment protocol for malaria in which the use of CQ has been abolished, and replaced by artemisinin-based combination therapy.

 

Projects


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Team members


Contact

For further information please contact Dr. Henk Schallig

Tags

malaria | disease control | infectious diseases | pharmaceuticals | research |

Royal Tropical Institute