Project Title

Investigating artemisinin resistance in Nigerian isolates of Plasmodium falciparum (MAR-Malaria)

EDCTP Project Call

Career Development Fellowship (CDF)

Project Objectives

(i) Assess the extent of polymorphisms in ap2mu, ubp1 and pfcoronin genes . (ii) Establish the status of artemisinin-induced dormancy in the parasite isolates.

Study Design

The study will use samples that will be collected in Ijede General Hospital in Lagos, Nigeria. We have selected Ijede because it is a sentinel site for malaria control programmes in Nigeria. In addition, from our 2016 AL field efficacy surveillance experience, the site is manageable and we can ensure proper monitoring and supervision of patients. Malaria is meso-endemic (prevalence of about 25%) in the community (12). Individuals (1–70 years), with deliberate inclusion of young children, presenting at the hospital with symptoms of uncomplicated malaria will be screened for Plasmodium falciparum, first by rapid diagnostic test (RDT), followed by microscopy. Microscope slides will be blindly read by two independent level-1 microscopists. For microscopy-based estimates of parasite density, we will calculate the average of the values provided by the microscopists which are within the margin of between-reader difference. Two readings are considered discrepant if their difference is outside the 95% range of the limits of agreement of previous paired readings. To protect against source bias, we will ensure significant representation of both genders in our recruitment. Age-wise, we will make deliberate inclusion of participants 1-5 years, 6 -14 years and ≥15 years old to protect against source bias, we will ensure significant representation of both genders in our recruitment. At least 35 participants will be recruited per age group.

Project Summary

This study will characterize field isolates of P. falciparum from Lagos, Nigeria and describe their genetic, physiological and in vivo response to artemisinin-based combination treatment. Specifically, we will assess the extent of polymorphisms in ap2mu, ubp1 and pfcoronin genes and correlate the genetic information with in vitro phenotypic response of the parasites to artemisinin. The proposed research is important as it will greatly advance our understanding of the mechanism of ART-resistance in Nigerian parasites and in the long term reveal potential targets of alternative treatment strategies before resistance reaches critical levels.

Host Organisation

Sites

Current Organisation

Nigerian Institute of Medical Research

Current Job Title

Senior Research Fellow

Biography