Molecular Epidemiology of Plasmodium Falciparum in Ashanti Region, Ghana in a Setting of Artesunate-Amodiaquine Use

The approach to making antimalarial drugs available in the community and ensuring that they are used appropriately is now well established through WHO/TDR-supported multi-country studies using Chloroquine. The use of ART-AMQ combination treatment for home management of childhood malaria is a new area of research and programme implementation. Natural populations of P. falciparum are heterogeneous mixtures of individuals with different, genetically determined degrees of drug response during treatments. The first part of this study was, therefore, aimed at determining the effectiveness of treatments and molecular epidemiology of P. falciparum in a setting of ART-AMQ use in the home setting in a rural district in Ghana. Community Drug Distributors (CDDs) in the study communities in the Ejisu-Juaben Municipal District were trained to examine children presenting with fevers and those suspected to be due to malaria, were treated presumptively with unit-dose prepacked ART-AMQ over three days. CDDs from these communities were also trained to take finger-prick blood samples prior to treatment for polymerase chain reaction (PCR) analysis and parasitological confirmation and those confirmed positive were enrolled into the study. Febrile children treated were followed up and had their blood samples taken on days 14 and 28 after the start of treatment to assess the effect of treatment on peripheral parasitaemia. Of the 836 blood samples collected, 71% of the presumptive treatments were confirmed microscopically to have malaria parasites whilst 29% were without the parasites. Parasitological failure by day 28 in children treated at home was 27.8% whilst parasitological failure corrected for re-infections using merozoite surface protein-2 (msp2) and glutamine-rich protein (glurp) markers was 11.6%. Over 50% of the febrile children treated at home had multiple infections using both glurp and msp2 markers. In msp2 marker, over 80% of the children had P. falciparum clones belonging to the IC/3D7 allelic family with only 2% having both FC27 and IC/3D7 allelic families. Twenty different IC/3D7 family alleles and four different FC27 families were detected. The accuracy of the CDDs and caregivers was quiet high implying that febrile children had early and appropriate home care of malaria although not all of them had malaria parasites. However, the parasitological failure rate of 11.6% for ART-AMQ use at home, calls for search for alternative treatment regimen. The high level of polymorphism, antigenic variation, multiplicity of infections and the frequency of infections had contributed to the treatment outcomes. The second part of the study was to compare in-vivo field trial of ACTs with Artesunate-Amodiaquine in the treatment of uncomplicated malaria in school pupils. The failure of Chloroquine has necessitated the re-examination of the potential of combinations of existing products and the development of new combination drugs. Hence, school pupils were screened microscopically in two surveys and those that were positive were enrolled and followed up for 28 days. In all, 56.8% (476) pupils were positive and were subsequently randomized into seven different treatment groups of ACTs. School pupils were followed up for 28 days period and had their blood samples taken on days 14 and 28 after the start of treatment to assess the effect of treatment on peripheral parasitaemia and on haemoglobin concentrations. Parasitological failure by day 28 in pupils treated with various ACTs was 28.4%, 18.2%, 12.0%, 38.1%, 30.8%, 33.3% and 7.1% for Artesunate-Sulfadoxine-Pyrimethamine, Artesunate-Amodiaquine, Artesunate-Mefloquine, Artesunate-Chlorproguanil-Dapsone, Arthemeter-Lumefantrine, Artesunate-Chloroquine and AMOTEX (co-formulation of ART-AMQ) treatment groups respectively. The change in mean haemoglobin over the baseline haemoglobin by days 14 and 28 were 0.7g/dl and 0.9g/dl respectively (p<0.001). The burden of malaria and anaemia among school children is high and warrants investment to reduce these levels. In this study, AMOTEX had the least failure rate (7.1%) by day 28, but was the least tolerated among the pupils. However, Artesunate-Mefloquine combination has demonstrated a high potential alternative option to ART-AMQ since it was well tolerated and has high parasite clearance among study pupils.

Source: KNUST