Developing genomics expertise at Copenhagen in order to examine to what extent dhps-431V mutation may influence the protective efficacy of IPTp-SP

Objectives

The aims are to detect P. falciparum positivity at delivery and pregnancy outcome in participants who must have received three or more doses of IPTp-SP. This study will attempt to check the presence of existing and new Pfdhps/Pfdhfr mutations in the samples positive for P. falciparum using a quantitative PCR (qPCR). The prevalence of novel Pfdhps-431V mutant and other Pfdhps/Pfdhfr resistance alleles among the study population will be estimated. The significance of the resistance genes on the efficacy of SP will be described by looking at its associations with the reported IPTp use, P. falciparum infection, maternal anaemia, low birth weight, and preterm delivery.

Principal Institution

Obafemi Awolowo University (OAU), Nigeria

Principal Investigators / Focal Persons

Adebanjo J. Adegbola

Partner Institutions

University of Copenhagen, Denmark

Rationale and Abstract

Evaluation of malaria prevention strategies during pregnancy relies on precise diagnosis of parasite and monitoring of antimalarial resistance using genomic techniques. However, the expertise on genomic is rare in the malaria-endemic sub-Saharan African. The aim is to advance Adegbola’s expertise in clinical research and malaria parasite genomics by attending a training at the Center for Medical Parasitology, University of Copenhagen, Denmark. During the placement at Copenhagen, he will enhance his expertise on techniques such as DNA isolation, PCR amplification and Sanqer sequencing. This is for the purpose of conducting a clinical investigation on sulphadoxine-pyrimethamine (SP) resistance. A pilot study will be set up and a small number of samples will be analysed (sample load of 100-150) to pinpoint the trends of newly emerging mutation, design qPCR and sequencing methods and to generate a small dataset to attract a bigger funding for the intended follow-on project. The proposal consists of a 3-month training in Copenhagen with a focus on receiving modern genomic techniques and participation in short course. Then transfering the skills to his home organization and introduce the skills to other colleagues through peer training and workshop. Malaria in pregnancy (MiP) continues to be a significant public health issue, particularly in sub-Saharan Africa. The coverage of pregnant women with three or more doses of intermittent preventive treatment using sulphadoxine-pyrimethamine (IPTp-SP) is recommended to prevent risks associated with MiP in moderate-to-high transmission settings. Evidence has recently become available supporting the emergence of a novel Pfdhps-431V mutation in Nigeria. This new mutation may further confound the existing SP-resistance; thus, the intended follow-on project aims to assess the influence of Pfdhps-431V mutation on the protective efficacy of SP during pregnancy. The plan is to design an observational study to be implemented after the preparatory fellowship among adult women attending the ante-natal clinic.

External reference

EDCTP Grants

Thematic Categories

Drug Resistance
Vulnerable Populations

Date

Aug 2020 — Nov 2021

Total Project Funding

$82,735

Funding Details

European and Developing Countries Clinical Trials Partnership (EDCTP), The Netherlands

EDCTP-AREF Preparatory Fellowships - 2018

Grant ID: TMA2018PF-2537