Call | Career Development Fellowship (CDF) |
Programme | EDCTP2 |
Start Date | 2021-01-01 |
End Date | 2023-12-31 |
Project Code | TMA2019CDF-2782 |
Status | Active |
Investigating artemisinin resistance in Nigerian isolates of Plasmodium falciparum (MAR-Malaria)
(i) Assess the extent of polymorphisms in ap2mu, ubp1 and pfcoronin genes . (ii) Establish the status of artemisinin-induced dormancy in the parasite isolates.
Institution | Country |
---|---|
Nigerian Institute of Medical Research (NIMR) | Nigeria |
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.
Ijede, Lagos, Nigeria |
Type | Name | Title | University | Start Date | End Date |
---|---|---|---|---|---|
PhD | Afolabi Owoloye | Mr | University of Lagos | 01/01/2021 | 2024 |
Nigerian Institute of Medical Research
Senior Research Fellow
2021 | NIH Emerging Global Leader Award |
Type | Name | Title | University | Start Date | End Date |
---|---|---|---|---|---|
PhD | Afolabi Owoloye | Tracking antimalarial drug resistance in Nigeria | University of Lagos | 2021 | 2024 |
Role | Committee/board | Start Date | End Date |
---|---|---|---|
Reviewer | AREF College of Experts |
Institution | Degree | Year |
---|---|---|
, |
Malaria Genomics Hematology Oncogenetics
Background: The devastating public health impact of malaria has prompted the need for effective interventions. Malaria control gained traction after the introduction of artemisinin-based combination therapy (ACT). However, the emergence of artemisinin (ART) partial resistance in Southeast Asia and emerging reports of delayed parasite sensitiv- ity to ACT in African parasites signal a gradual trend towards treatment failure. Monitoring the prevalence of muta- tions associated with artemisinin resistance in African populations is necessary to stop resistance in its tracks. Muta- tions in Plasmodium falciparum genes pfk13, pfcoronin and pfatpase6 have been linked with ART partial resistance.
Methods: Findings from published research articles on the prevalence of pfk13, pfcoronin and pfatpase6 polymor- phisms in Africa were collated. PubMed, Embase and Google Scholar were searched for relevant articles reporting polymorphisms in these genes across Africa from 2014 to August 2021, for pfk13 and pfcoronin. For pfatpase6, relevant articles between 2003 and August 2021 were retrieved.
Results: Eighty-seven studies passed the inclusion criteria for this analysis and reported 742 single nucleotide poly- morphisms in 37,864 P. falciparum isolates from 29 African countries. Five validated-pfk13 partial resistance markers were identified in Africa: R561H in Rwanda and Tanzania, M476I in Tanzania, F446I in Mali, C580Y in Ghana, and P553L in an Angolan isolate. In Tanzania, three (L263E, E431K, S769N) of the four mutations (L263E, E431K, A623E, S769N) in pfatpase6 gene associated with high in vitro IC50 were reported. pfcoronin polymorphisms were reported in Senegal, Gabon, Ghana, Kenya, and Congo, with P76S being the most prevalent mutation.
Conclusions: This meta-analysis provides an overview of the prevalence and widespread distribution of pfk13, pfcor- onin and pfatpase6 mutations in Africa. Understanding the phenotypic consequences of these mutations can provide information on the efficacy status of artemisinin-based treatment of malaria across the continent.