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Dr Alfred Ngwa

Professor

United Kingdom

My research team applies in vitro cell assays and analysis of genomic variation to determine response of the major malaria parasite Plasmodium falciparum to changes in its environment including response to drugs and transmission. We explore genetic variation in parasite, human and vector populations across Africa that may determine variance in outcome of exposure and infection with Plasmodium species.

Affiliations

MRC Unit The Gambia at LSHTM

Teaching

I teach a practical module with Prof David Conway in the MSc in Pathogen Genomics

Research

My main interest is to understand how malaria parasite populations adapt to changes in the environment brought about by various interventions targeting parasite and the vector populations as well as natural processes in the host such as immunity. I work within the malaria research programme at MRC, The Gambia to employ targeted and whole genome sequencing of selected malaria endemic populations. Some more specific interests are in the following areas;

• Determining the relationship between invasion, virulence and drug susceptibility phenotypes and specific mutations in the genome of Plasmodium falciparum.

o We seek to understand the co-evolution of parasite and host genes as a step towards the selection of the immunogenic candidate genes for vaccine development. We have so far focused on genes showing signatures of balancing selection assumed to be a consequence of immune selection. However, several surface genes of both immune cells and erythrocytes show signs of balancing selection. Hence balancing selection in the pathogen could be a co-evolutionary process needing further studies. I will like to apply this thesis to other pathogens such as helminths that are co-endemic with malaria in developing countries.

o We track the accumulation of mutations that confer adaptation to drug intervention pressure from whole genome and targeted sequencing of retrospective samples collected over the quarter of a century. We hypothesise that drug resistance becomes more effective following successive accumulation of mutations contributing to the development of the phenotype.

o We believe variance in transmission can be determined from the micro-ecology of parasite in endemic populations. This natural variance can be perturbed by interventions that disrupt natural population structure and allow for selection of fit ‘strains’. With intensive cover of intervention such selection allows for the expansion of such strains creating hotspots of transmission in generally low endemic areas. We use genetic tools to determine and tract dynamics in such hotspots. We map the flow of isolates across The Gambia and Africa using identity-by-decent and other pairwise genetic similarity matrices.

• In am interested in developing technical alternatives and methods to locally analyse both SNP and structural variations on the Plasmodium genome. For example employing various alignment algorithms to optimise the calling of microsatellite and indel variants from next generation sequencing short reads. We believe that the more rapid evolution of STR variants will enable early determination of regions in the genome that may be under directional selection from new chemotherapeutic interventions.

• We wish to develop non-expert tools for analysis of population genetic data to uncover patterns in rarely accessed populations. The exploration of genetic data especially those generated from NGS analysis has been limited by the need for computer programming and quantitative skills that are mostly deficient in pathogen endemic communities. Development of a combination of low-spec computers and softwares for easy manipulation of genetic variables will broaden our understanding of many more parasite populations as it will rapidly integrate local researchers into population genetic research.

Research Area
Chemotherapy
Clinical trials
Drug resistance
Global Health
Parasites
Protozoa
Surveillance
Biochemistry
Bioinformatics
Cell biology
Genetic Epidemiology
Genetics
Genomics
Immunoepidemiology
Molecular epidemiology
Parasitology
Disease and Health Conditions
Malaria
Infectious diseases
Country
Cameroon
Gambia
Nigeria
Region
Sub-Saharan Africa (all income levels)

Selected Publications

Long-distance transmission patterns modelled from SNP barcodes of Plasmodium falciparum infections in The Gambia.
AMAMBUA-NGWA, A; JEFFRIES, D; Mwesigwa, J; Seedy-Jawara, A; Okebe, J; ACHAN, J; DRAKELEY, C; Volkman, S; D'ALESSANDRO, U;
2019
Scientific reports
Major subpopulations of Plasmodium falciparum in sub-Saharan Africa.
AMAMBUA-NGWA, A; Amenga-Etego, L; Kamau, E; Amato, R; Ghansah, A; Golassa, L; Randrianarivelojosia, M; Ishengoma, D; Apinjoh, T; Maïga-Ascofaré, O; Andagalu, B; Yavo, W; Bouyou-Akotet, M; Kolapo, O; Mane, K; Worwui, A; JEFFRIES, D; Simpson, V; D'ALESSANDRO, U; Kwiatkowski, D; Djimde, AA;
2019
SCIENCE
Consistent signatures of selection from genomic analysis of pairs of temporal and spatial Plasmodium falciparum populations from The Gambia.
AMAMBUA-NGWA, A; JEFFRIES, D; Amato, R; Worwui, A; Karim, M; Ceesay, S; Nyang, H; Nwakanma, D; Okebe, J; Kwiatkowski, D; CONWAY, DJ; D'ALESSANDRO, U;
2018
Scientific reports
Sustained Ex Vivo Susceptibility of Plasmodium falciparum to Artemisinin Derivatives but Increasing Tolerance to Artemisinin Combination Therapy Partner Quinolines in The Gambia.
AMAMBUA-NGWA, A; Okebe, J; Mbye, H; Ceesay, S; El-Fatouri, F; Joof, F; Nyang, H; JANHA, R; Affara, M; Ahmad, A; Kolly, O; NWAKANMA, D; D'ALESSANDRO, U;
2017
Antimicrobial agents and chemotherapy
Exceptionally long-range haplotypes in Plasmodium falciparum chromosome 6 maintained in an endemic African population.
AMAMBUA-NGWA, A; Danso, B; Worwui, A; Ceesay, S; Davies, N; JEFFRIES, D; D'ALESSANDRO, U; CONWAY, D;
2016
Malaria journal
Prevalence of Malaria Infection in Pregnant Women Attending Antenatal Clinics in Southern Senegal.
Diouf, MP; Kande, S; Oboh, MA; Manga, IA; Tairou, F; Seck, A; Diallo, A; Lo, AC; Sow, D; Sylla, K; Ndiaye, M; Tine, RC; Faye, B; Merle, C; AMAMBUA-NGWA, A; Miligan, P; Ndiaye, J-LA;
2024
The American journal of tropical medicine and hygiene
Plasmodium falciparum population structure and genetic diversity of cell traversal protein for ookinetes and sporozoites (CelTOS) during malaria resurgences in Dielmo, Senegal.
Wotodjo, AN; Oboh, MA; Sokhna, C; Diagne, N; Diène-Sarr, F; Trape, J-F; Doucouré, S; AMAMBUA-NGWA, A; D'ALESSANDRO, U;
2023
Infection, genetics and evolution
Rebound of multiple infections and prevalence of anti-malarial resistance associated markers following malaria upsurges in Dielmo village, Senegal, West Africa
Wotodjo, AN; Oboh, MA; Doucoure, S; Diagne, N; Diène-Sarr, F; Niang, M; Trape, J-F; Sokhna, C; AMAMBUA-NGWA, A; D'ALESSANDRO, U;
2023
Malaria journal
Malaria in adults after the start of Covid-19 pandemic: an analysis of admission trends, demographics, and outcomes in a tertiary hospital in the Gambia.
Bittaye, SO; Jagne, A; Jaiteh, LE S; AMAMBUA-NGWA, A; SESAY, AK; Ekeh, B; NADJM, B; Ramirez, WE; Ramos, A; Okeahialam, B; Effa, E; Nyan, O; Njie, R;
2023
Malaria journal
Recent increase in low complexity polygenomic infections and sialic acid-independent invasion pathways in Plasmodium falciparum from Western Gambia.
Nganyewo, NN; Bojang, F; ORIERO, EC; Drammeh, NF; Ajibola, O; Mbye, H; Jawara, AS; Corea, S; Awandare, GA; D'ALESSANDRO, U; Amenga-Etego, LN; AMAMBUA-NGWA, A;
2023
Parasites & vectors
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