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Content archived on 2024-05-07

Detection of plasmodium falciparum resistant to antifolate and sulphonamide drugs, and assessment of the efficacy of drug treatment using molecular methods

Objective

To evaluate molecular methods for the detection of antifolate and sulphonamide resistant malaria parasites, and to apply these methods to an epidemiological investigation of the prevalence of genes conferring resistance in populations of Plasmodium falciparum. The ultimate aim of the work is to contribute towards a rational use of such drugs in control strategies against the disease.
Expected Outcome

The results will show the prevalence of antifolate and sufadoxine resistant malaria parasites in malaria patients in Kenya and Zimbabwe. The prevalence of resistant strains is expected to be high in Kenya and low in Zimbabwe. In Kenya, MS-PCR will be applied on samples collected during the second and third year of the study and in Zimbabwe the method will be applied on samples collected in the first, second and third year. This will show whether the prevalence changes in times and whether chains harbouring different mutations will arise.
In situ PCR will provide insight in the prevalence of mixed infections.
The NASBA results will provide information on the treatment efficacy of antifolates and sulphonamides.
Information will be obtained on the relative sensitivities of the different assays in determining drug-treatment efficacy.
* To evaluate the sensitivity and specificity of a molecular assay - mutation specific polymerase chain reaction (MS-PCR) and in situ PCR - for the detection of antifolate (pyrimethamine) and sulphonamide (sulfadoxine) resistant mutants of Plasmodium falciparum.
* To evaluate the technique of semi-quantitative nucleic acid sequence based amplification (Q NASBA) for the detection of low levels of malaria parasites and for the determining of the efficacy of drug-treatment.
* To apply these assays for epidemiological monitoring of drug-resistant mutants of P. falciparum in different populations, and to evaluate and compare the efficacy of different drug-treatment regimens by parasitological and clinical criteria and by the analysis of the kinetics and degree of parasite clearance by NASBA.
* To increase and improve the local research capacity by providing training in molecular detection methods for the epidemiological and diagnostic investigation of drug-resistance of P. falciparum.

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Funding Scheme

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Coordinator

ROYAL TROPICAL INSTITUTE
EU contribution
No data
Address
39,Meibergdreef 39
1105 AZ AMSTERDAM
Netherlands

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Total cost

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Participants (3)

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