Current Challenges of Malaria Chemotherapy in Africa: Prospects of Novel Drugs and Combination Therapies

T Mengesha; E Makonnen

T Mengesha Ethiopian Health and Nutrition Research Institute, P. 0. Box 1242, Addis Ababa, Ethiopia
E Makonnen Department of Pharmacology, Faculty of Medicine, Addis Ababa University, P.O. Box 9086, Addis Ababa, Ethiopia

Abstract

The objective of this study was to point out recent undertakings on novel and standard drugs,as single, or combination therapy. The study design was based on aggregation and analysis of data generated in clinical and safety trials, using standard or widely used dosage regimen, acquired through primary publications, secondary or textual and Med-line references. The factors used in data extraction and compilation was length of visit to endemic areas, age, pregnancy, lactation, and idiosyncracy for Malaria chemoprophylaxis; and modes of action, clinical efficacy, safety and structural similarities of antimalarial compounds for chemotherapy. Proguanil/chloroquine combination was thus, found to be a comparatively safe prophylaxis, where there is chloroquine failure. In treatment schedules, chloroquine or artesunate in combination with sulfadoxine/pyrimethamine (S/P) is shown to increase the clinical efficacy of the latter, which reduces drug pressure on quinine. The C-5' modification of pyronaridine and amodiaquine leads to increased potency on one hand and reduced toxicity on the other. This modification is found to be one of the positive developments in drug design. The possibility of development of cross-resistance in structurally modified drugs and their congeners, however, cannot be ruled out. Combination therapies based on the synergistic modes of action as in the case of dapsone/proguanil, and on the complementary kinetics as in the case of artemisinin/mefloquine are recommended. By so doing, recrudescence is avoided and resistance emergence delayed. In conclusion, combining the analgesic/antipyretic features of chloroquine or artesunate with S/P is considered a useful strategy. Prospective prophylaxis and treatment with novel drugs as single or combination therapy are positive developments in face of the challenge in malaria chemotherapy. In line with the experience of quinine and artemisinin, research on herbal medicines is also worth considering.