18 July 2018
Despite the reduction in burden, malaria remains one of the main infectious diseases afflicting sub-Saharan Africa. Malaria cases are treated with antimalarial drugs. However, the malaria parasite may become resistant to them and this is why it is very important to monitor their efficacy. This is necessary for the prompt detection of emerging resistance and to review treatment policies.
In an effort to better understand drug resistance, Plasmodium falciparum parasite isolates were collected from malaria patients in The Gambia between 2012 and 2015. Each isolate was tested in the laboratory against several antimalarial drugs, especially components of the artemisinin combination treatments (ACTs). These parasites were also investigated to identify mutations in their genome that confer resistance to antimalarial drugs. During this period, we observed an increase in the concentration of lumefantrine and other quinolines needed to kill the malaria parasites. However, during the same period the concentrations of artemisinin derivatives needed to kill parasites decreased.
The study was led by Dr Alfred Amambua-Ngwa with the help of co-investigators Dr Joseph Okebe, Haddijatou Mbye, Fatoumatta Bojang, Sukai Ceesay, Abdullahi Ahmed, Aminata Jawara, Bakary Danso, Dr Muna Affara, Dr Davis Nwakanma and Professor Umberto D’Alessandro. In a parallel study, we compared the genomic structure of parasite isolates collected at different time points between 2012 and 2015 to isolates collected before 2012. This led to the identification of new genetic mutations that may be related to tolerance to certain antimalarial drugs such as Lumefantrine. The mechanism by which these genetic markers mediate drug tolerance is the focus of the PhD thesis research of Haddijatou Mbye, funded by the Wellcome Trust DELTAS programme.
The monitoring of the response of malaria parasites to antimalarial drugs will continue at least until the end of 2018. Two new approaches based on advanced technologies will be implemented. The first approach will involve Next Generation sequencing to characterise all the genetic markers in parasite isolates tolerant to antimalarial drugs. The second approach by flow cytometry will precisely determine the stage at which parasite isolates adapt to drugs. This work would allow us to characterise the mechanisms of antimalarial drug resistance and identify genetic markers. We will then establish their occurrence among clinical malaria cases and in the general population.