Biology subjects

Egyir-Yawson, A.

Publications and source records attributed to Egyir-Yawson, A..

8 recordsLinked to original sources

bioRxiv2025

Spatially-explicit genomics of An. gambiae s.l uncovers fine-scale population structure and mechanisms of insecticide resistance

Progress in malaria control in sub-Saharan Africa is stalling, partly due to the spread of insecticide resistance in Anopheles vectors. Monitoring the evolution of insecticide resistance alleles and their spatial heterogeneity is important for malaria control programmes, and genomic surveillance has emerged as a pivotal tool for this purpose. Earlier genomics research has typically employed convenience-based sampling, and research has yet to be performed to optimise sampling regimens for malaria vector genomics. In an earlier study, we developed a spatially explicit sampling framework that considers the underlying ecology to enable sampling mosquitoes with reduced bias. We applied this framework to sample and perform whole-genome sequencing on 485 individual specimens of An. gambiae s.l mosquitoes from Obuasi, central Ghana, an area with extensive gold mining activities. In this region, An. gambiae s.l have been documented as highly resistant to multiple insecticides, including pyrethroids used for the treatment of bed-nets. High resolution of fine-scale population structure enabled the detection of isolation-by-distance in An. coluzzii in Obuasi, whilst finding that at this scale, geographic distance, rather than the underlying habitat, drives population structure. We examine methods to estimate mosquito kinship, demonstrating that polymorphic chromosomal inversions significantly confound established analytical tools, while revealing how the mosquitos chromosome architecture generates high variance in genetic relatedness among kin. Using genome-wide selection scans and clustering, we discover the novel mutations Gste2-F120L and Cyp9K1-N224I in detoxification enzymes that are driving selective sweeps, likely in response to insecticidal pressure. We find that the frequencies of some resistance variants are associated with artisanal-gold mines, and elucidate the continued evolution of the Voltage-gated sodium channel, the target of pyrethroid insecticides. Overall, we show that sampling vectors strategically may enhance our ability to perform effective genomic surveillance.

genomics↗

bioRxiv2025

Targeted genomic surveillance of insecticide resistance in African malaria vectors

The emergence of insecticide resistance is threatening the efforts of malaria control programmes, which rely heavily on a limited arsenal of insecticidal tools, such as insecticide-treated bed nets. Importantly, genomic surveillance of malaria vectors can provide critical, policy-relevant insights into the presence and evolution of insecticide resistance, allowing us to maintain and extend the shelf life of these interventions. Yet the complex genetic architecture of resistance, combined with resource constraints in malaria-endemic settings, have thus far precluded the widespread use of genomics in routine surveillance. Meanwhile, stakeholders in sub-Saharan Africa are moving towards locally driven, decentralised generation of genomic data, underscoring the need for standardised and robust genomics workflows. To address this need, we demonstrate an approach to targeted genomic surveillance in Anopheles gambiae s.l with Illumina sequencing. We target 90 genomic loci in the Anopheles gambiae s.l genome, including 55 resistance-associated mutations and 35 ancestry informative markers. This protocol is coupled with advanced, automated software for accurate and reproducible variant analysis. We are able to elucidate population structure and ancestry in our cohorts and accurately identify most species in the An. gambiae species complex. We report frequencies of variants at insecticide-resistance loci and explore the continued evolution of the pyrethroid target site, the Voltage-gated sodium channel. Applying the platform to a recently established colony of field-caught resistant mosquitoes (Siaya, Kenya), we identified seven independent resistance-associated variants contributing to reduced efficacy of insecticide-treated nets in East Africa. Additionally, we leverage a machine learning algorithm (XGBoost) to demonstrate the possibility of predicting bioassay mortality using genotypes alone. This achieved high accuracy (75%), demonstrating the potential of targeted genomics to predictively monitor insecticide resistance. Together these tools provide a practical, scalable solution for resistance monitoring while advancing the goal of building local genomic surveillance capacity in sub-Saharan Africa.

genomics↗

bioRxiv2024

Copy number variants underlie the major selective sweeps in insecticide resistance genes in Anopheles arabiensis from Tanzania.

To keep ahead of the evolution of resistance to insecticides in mosquitoes, national malaria control programmes must make use of a range of insecticides, both old and new, while monitoring resistance mechanisms. Knowledge of the mechanisms of resistance remains limited in Anopheles arabiensis, which in many parts of Africa is of increasing importance because it is apparently less susceptible to many indoor control interventions. Furthermore, comparatively little is known in general about resistance to non-pyrethroid insecticides such as pirimiphos-methyl (PM), which are crucial for effective control in the context of resistance to pyrethroids. We performed a genome-wide association study to determine the molecular mechanisms of resistance to deltamethrin (commonly used in bednets) and PM, in An. arabiensis from two regions in Tanzania. Genomic regions of positive selection in these populations were largely driven by copy number variants (CNVs) in gene families involved in resistance to these two insecticides. We found evidence of a new gene cluster involved in resistance to PM, identifying a strong selective sweep tied to a CNV in the Coeae2g-Coeae6g cluster of carboxylesterase genes. Using complementary data from An. coluzzii in Ghana, we show that copy number at this locus is significantly associated with PM resistance. Similarly, for deltamethrin, resistance was strongly associated with a novel CNV allele in the Cyp6aa / Cyp6p cluster. Against this background of metabolic resistance, target site resistance was very rare or absent for both insecticides. Mutations in the pyrethroid target site Vgsc were at very low frequency in Tanzania, yet combining these samples with three An. arabiensis individuals from West Africa revealed a startling diversity of evolutionary origins of target site resistance, with up to 5 independent origins of Vgsc-995 mutations found within just 8 haplotypes. Thus, despite having been first recorded over 10 years ago, Vgsc resistance mutations in Tanzanian An. arabiensis have remained at stable low frequencies. Overall, our results provide a new copy number marker for monitoring resistance to PM in malaria mosquitoes, and reveal the complex picture of resistance patterns in An. arabiensis.

genomics↗

bioRxiv2024

Parallel evolution in mosquito vectors - a duplicated esterase locus is associated with resistance to pirimiphos-methyl in An. gambiae

The primary control methods for the African malaria mosquito, Anopheles gambiae, are based on insecticidal interventions. Emerging resistance to these compounds is therefore of major concern to malaria control programmes. The organophosphate, pirimiphos-methyl, is a relatively new chemical in the vector control armoury but is now widely used in indoor residual spray campaigns. Whilst generally effective, phenotypic resistance has developed in some areas in malaria vectors. Here, we used a population genomic approach to identify novel mechanisms of resistance to pirimiphos-methyl in Anopheles gambiae s.l mosquitoes. In multiple populations, we found large and repeated signals of selection at a locus containing a cluster of detoxification enzymes, some of whose orthologs are known to confer resistance to organophosphates in Culex pipiens. Close examination revealed a pair of alpha-esterases, Coeae1f and Coeae2f, and a complex and diverse pattern of haplotypes under selection in An. gambiae, An. coluzzii and An. arabiensis. As in Cx. pipiens, copy number variation seems to play a role in the evolution of insecticide resistance at this locus. We used diplotype clustering to examine whether these signals arise from parallel evolution or adaptive introgression. Using whole-genome sequenced phenotyped samples, we found that in West Africa, a copy number variant in Anopheles gambiae is associated with resistance to pirimiphos-methyl. Overall, we demonstrate a striking example of contemporary parallel evolution which has important implications for malaria control programmes.

evolutionary biology↗

bioRxiv2024

Signatures of adaptation at key insecticide resistance loci in Anopheles gambiae in Southern Ghana revealed by low-coverage WGS.

Resistance to insecticides and adaptation to a diverse range of environments present challenges to Anopheles gambiae s.l. mosquito control efforts in sub-Saharan Africa. Whole-genome-sequencing is often employed for identifying the genomic basis underlying adaptation in Anopheles, but remains expensive for large-scale surveys. Low-coverage whole-genome-sequencing (lcWGS) can identify regions of the genome involved in adaptation at a lower cost, but is currently untested in Anopheles mosquitoes. Here, we use lcWGS to investigate population genetic structure and identify signatures of local adaptation in Anopheles mosquitoes across southern Ghana. In contrast to previous analyses, we find no structuring by ecoregion, with Anopheles coluzzii and Anopheles gambiae populations largely displaying the hallmarks of large, unstructured populations. However, we find signatures of selection at insecticide resistance (IR) loci that appear ubiquitous across ecoregions in An. coluzzii, and strongest in forest ecoregions in An. gambiae. In the IR gene Cyp9k1, we find species-specific alleles under selection, suggesting interspecific variation in the precise mechanism of resistance conferred by Cyp9k1. Our study highlights resistance candidate genes in this region, and validates lcWGS, potentially to very low coverage levels, for population genomics and exploratory surveys for adaptation in Anopheles taxa.

evolutionary biology↗

bioRxiv2023

Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae s.l.

Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of the most widespread tools currently used to control malaria. The genetic underpinnings of resistance are still only partially understood, with much of the variance in resistance phenotype left unexplained. We performed a multi-country large scale genome-wide association study of resistance to two insecticides widely used in malaria control: deltamethrin and pirimiphos-methyl. Using a bioassay methodology designed to maximise the phenotypic difference between resistant and susceptible samples, we sequenced 969 phenotyped female An. gambiae and An. coluzzii from ten locations across four countries in West Africa (Benin, Cote dIvoire, Ghana and Togo), identifying single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) segregating in the populations. The patterns of resistance association were highly multiallelic and variable between populations, with different genomic regions contributing to resistance, as well as different mutations within a given region. While the strongest and most consistent association with deltamethrin resistance came from the region around Cyp6aa1, this resistance was based on a combination of several independent CNVs in An. coluzzii, and on a non-CNV bearing haplotype in An. gambiae. Further signals involved a range of cytochrome P450, mitochondrial, and immunity genes. Similarly, for pirimiphos-methyl, while the strongest signal came from the region of Ace1, more widespread signals included cytochrome P450s, glutathione S-transferases, and a subunit of the nAChR target site of neonicotinoid insecticides. The regions around Cyp9k1 and the Tep family of immune genes were associated with resistance to both insecticide classes, suggesting possible cross-resistance mechanisms. These locally-varying, multigenic and multiallelic patterns highlight the challenges involved in genomic monitoring and surveillance of resistance, and form the basis for improvement of methods used to detect and predict resistance. Based on simulations of resistance variants, we recommend that yet larger scale studies, exceeding 500 phenotyped samples per population, are required to better identify associated genomic regions.

genomics↗

bioRxiv2020

Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus

Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Cote dIvoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 and substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa probably due to cross-resistance with previously used insecticides. Our findings highlight the phenotypic value of this complex resistance haplotype and clarify its evolutionary history, providing tools to understand the current and future effectiveness of pirimiphos-methyl based interventions.

genomics↗

bioRxiv2018

Haematological parameters and plasma levels of 8-iso-prostaglandin F2α in malaria-sickle cell co-morbidity: A cross sectional study

IntroductionMalaria and sickle cell disease (SCD) co-morbidity have previously been reported in Ghana. However, there is paucity of data on haematological profiles and oxidative stress in comorbidity states. This study identified novel inflammatory biomarkers associated with malaria in SCD and analyzed the levels of 8-iso-prostaglandin F2 oxidative stress biomarker in malaria-SCD co-morbidity in Ghanaian patients.\n\nMethodsBlood (5ml) was collected from malaria patients into K3-EDTA tube. Malaria parasites speciation and quantification were then done according WHO guidelines. All eligible samples were assayed for haematological profile, sickle cell phenotyping, infectious markers (hepatitis B, hepatitis C, syphilis and HIV 1&2) and plasma levels of 8-epi-prostaglandin F2..\n\nResultsPrevalence of malaria in SCD (malaria-SCD) was 13.4% (45/335). Male: female ratio was 0.8:1 (X2=1.43, p=0.231). Mean ages for malaria in normal haemoglobin type (malaria-HbAA) and malaria-SCD were 12.79{+/-}4.91 and 11.56{+/-}3.65 years respectively (p=0.048). Geometric mean of parasite density was higher in malaria-HbAA (20394 parasites/l vs. 9990 parasites/l, p=0.001) whilst mean body temperature was higher in malaria-SCD (39.0{+/-}0.87{degrees}C vs. 37.9{+/-}1.15{degrees}C, p=0.001). Mean leukocytes, lymphocytes, eosinophils, monocytes, platelets and platelet indices values were significantly elevated in malaria-SCD. Significant reduction in RBC and RBC indices in malaria-SCD were also observed. Eosinophils-to-basophils ratio (EBR) and monocytes-to-basophils ratio (MBR) were novel cellular inflammatory biomarkers which could predict malaria in SCD. The sensitivities of cut-off values of EBR>14, MBR>22 and combined use of EBR>14 and MBR>22 were 79.55%, 84.09% and 91.11% respectively. Mean 8-iso-prostaglandin F2 was 338.1pg/ml in malaria-HbAA and 643.8pg/ml in malaria-SCD (p=0.001). 8-iso-prostaglandin F2 correlated with parasite density (r=0.787, p=0.001), temperature (r=0.566, p=0.001) and leucocytes (r=0.573, p=0.001) and negatively correlated with RBC (r=-0.476, p=0.003), haemoglobin (r=-0.851, p=0.001) and haematocrit (r=-0.735, p=0.001).\n\nConclusionPlasmodium falciparum parasitaemia increases oxidative damage and causes derangement haematological parameters. Cut of values of EBR>14 and MBR>22 could predict malaria in SCD.

immunology↗