MRC PhD students

Academic qualifications
M. Medical Science (Medical Microbiology) with the MRC Malaria Research Programme, University of University of KwaZulu-Natal.

Title of Research Project
The Efficacy and Safety of Artemisinin-based Combination Therapy for the treatment of uncomplicated Plasmodium falciparum malaria in non-pregnant adults and children. 

Background
Effective case management of malaria is severely crippled by the spread of parasite resistance to antimalarials. To counteract the impact of drug resistance, the World Health Organization has endorsed artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated Plasmodium falciparum malaria. Currently recommended ACTs are artemether-lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine, artesunate plus sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine.

Objective
This study sought to review evidence of the efficacy and safety of artesunate, artemether and dihydroartemisinin in combination with different conventional antimalarials for the treatment of uncomplicated Plasmodium falciparum malaria in non-pregnant adults and children.

Major Findings
Artesunate combined with amodiaquine had a statistically significant lower risk of treatment failure compared to the combination of artesunate with sulfadoxine-pyrimethamine [RR=0.48, 95% CI (0.26; 0.89), p=0.02]. In addition, treatment with artesunate plus mefloquine was significantly associated with more adequate clinical and parasitological response compared to artesunate plus azithromycin [RR=1.73, 95% CI (1.25; 2.38), p<0.001]. There was no statistically significant difference in the risk of treatment failure when either mefloquine or atovaquone-proguanil were combination partners to artesunate [RR=2.6, 95%CI (0.93; 7.24)]. In clearing fever artesunate plus chloroquine was quicker than artesunate plus sulfadoxine-pyrimethamine [WMD= -7.20, 95%CI (-12.53; -1.87)].

Conclusion and Public Health Significance
The findings of this study support the implementation of artemisinin-based combination therapy for the treatment of uncomplicated malaria. Most crucially, this review found a greater advantage of combining amodiaquine with artesunate compared to sulfadoxine-pyrimethamine. The efficacy artesunate plus mefloquine was also superior to that of artesunate plus azithromycin. Furthermore, the combination of artemisinins with chloroquine, primaquine and azithromycin has shown very low efficacy and these combination therapies cannot be recommended.

Supervisors: Dr. R. Maharaj, Dr. M. Mabaso (Malaria Research Programme) and Dr. T. Young (South African Cochrane Centre).