Drug resistance studies
Drug Resistance Studies
1. Community based in vivo evaluation of the therapeutic efficacy of chloroquine in the three malarious provinces of South Africa
Chloroquine efficacy studies were carried out during the 1996/1997 malarial season in KwaZulu Natal, Mpumalanga and the Northern Province. The aims of these investigations were:
- to provide information about the sensitivity in vivo to first-line therapeutic drugs of P. falciparum at sentinel sites in these provinces towards effective drug management;
- to determine species composition of the Plasmodial populations in the three provinces;
- and to develop the capacity of provincial malaria control programmes to sustain sentinel sites for future evaluations of drug sensitivity.
Collaborators
Medical Research Council and Department of Health
Funding
Department of Health and Medical Research Council
2. Hospital based, randomised, single blind, in vivo drug sensitivity investigation
This study was conducted at Mosvold hospital, Ingwavuma district, comparing sulphadoxine-pyrimethamine and chloroquine in the treatment of malaria patients. In a randomised, single blind, in vivo drug sensitivity investigation conducted in the Ingwavuma district of KwaZulu Natal, subjects infected with P. falciparum were treated with either chloroquine or sulphadoxine-pyrimethamine. The in vivo response of the parasites to treatment was monitored for up to seven days as were various clinical parameters. During the follow-up period, subjects' blood was examined for the presence of parasites on days 14, 21 and 28. Genotyping of the isolates, by nested PCR of genes coding for MSP1 and GLURP, both prior to treatment and during the follow-up period, was carried out to differentiate between recrudescence and new infections. In vitro sensitivity to chloroquine and sulphadoxine/ pyrimethamine of P. falciparum parasites isolated from the trial subjects prior to treatment was determined using the WHO in vitro microtechnique.
Collaborators
Medical Research Council, Department of Health, World Health Organization and Roche Pharmaceutical
Funding
Medical Research Council and Private Sector Companies
3. Community based in vivo evaluation of the therapeutic efficacy of sulphadoxine/pyrimethamine in Mpumalanga Province of South Africa
The resistance of P. falciparum to antimalarial drugs is a serious impediment to control of malaria. Resistance of P. falciparum to antimalarial drugs has been reported in South Africa as in many other countries where transmission of P. falciparum occurs.
A recently concluded in vivo study in Mpumalanga Province showed an unacceptable level of chloroquine resistance in P. falciparum. These findings formed the basis for a decision to change from chloroquine to sulphadoxine-pyrimethamine (SP) as the first-line treatment of P. falciparum malaria in the province. However, sensitivity of P. falciparum to SP in Mpumalanga is unknown. It was therefore necessary to obtain baseline information on the in vivo sensitivity of P. falciparum in Mpumalanga to SP. This information will serve as a basis on which future monitoring and assessment of parasite response to the drug will be made.
Collaborators
Department of Health, Mpumalanga Province and Medical Research Council
Funding
Department of Health and Medical Research Council
4. Gene flow in Plasmodium falciparum populations
Sulphadoxine-pyrimethamine, the current first-line drug for the treatment of malaria in much of southern Africa, may be compromised by the rapid spread of resistance via mutations in the dihydrofolate reductase/ dihydropteroate synthase enzyme system of P. falciparum. Detection of frequency of these mutations within various parasite populations will allow some understanding of gene flow and facilitate evaluation and planning of combination therapy strategies which may extend the useful life of sulphadoxine-pyrimethamine.
Collaborators
Medical Research Council, Departments of Health (KwaZulu-Natal, Mpumalanga and Northern Province) and London Schoool of Hygiene and Tropical Medicine.
Funding
Medical Research Council and Department of Health