Subtilisin-like Domain-Containing Protein (PfSDP), a Cross-Stage Antigen, Elicits Short-Lived Antibody Response Following Natural Infection with .

With the increasing detection of artemisinin resistance to front-line antimalarials in Africa and notwithstanding the planned roll-out of RTS'S and R21 in Africa, the search for new vaccines with high efficacy remains an imperative. Towards this endeavour, we performed in silico screening to identify gametocyte stage genes that could be targets of protection or diagnosis. Through the analysis we identified a gene, Pf3D7_1105800, coding for a subtilisin-like domain-containing protein (PfSDP) and thus dubbed the gene .

An expanded method for malaria parasite genetic surveillance using targeted nanopore sequencing.

Malaria causes around 250 million cases and over 600,000 deaths annually, with the heaviest burden falling on young children living in sub-Saharan Africa. Molecular surveillance of parasites and mosquito vectors are key components of effective malaria control decision-making. Previously, we have designed and implemented a nanopore-based workflow for targeted molecular surveillance in Ghana, which we call DRAG1 (drug resistance + antigen multiplex PCR).

Plasmodium falciparum isolates: ex vivo drug response.

Objectives: While artemisinin-based combination therapies (ACTs) are effective in sub-Saharan Africa, clinical isolates that are refractory to artemisinin derivatives are emerging in East Africa and ACT partner drugs are becoming less effective in West Africa. We investigated the ex vivo responses of Plasmodium falciparum clinical isolates to frontline antimalarials and the contribution of validated molecular markers of antimalarial drug resistance.

Methods: Ex vivo susceptibility was measured for 66 clinical isolates collected from uncomplicated malaria patients.

PfRH5 vaccine; from the bench to the vial.

The search for potent malaria vaccine candidate has seen several twists and turns. Here, we provide a perspective on the current state of PfRH5-based malaria vaccine development, the progress, existing challenges, and future research directions. We discuss the clinical trials in endemic regions, immune correlates of protection, prospects of integrating PfRH5 into multi-antigen vaccine strategies and considerations on the onward development/deployment of PfRH5 vaccine from the laboratory to endemic communities.

Disparate co-evolution and prevalence of sulfadoxine and pyrimethamine resistance alleles and haplotypes at dhfr and dhps genes across Africa.

Sulfadoxine-pyrimethamine (SP), despite emergence of mutations in dhfr and dhps genes associated with lower treatment efficacy, is still recommended for preventive malaria treatment. Therefore, it is important to understand the evolution of P. falciparum dhfr and dhps genes.

Bi-Allelic Variant Identified with Exome Sequencing in a Consanguineous Multiplex Ghanaian Family Segregating Non-Syndromic Hearing Loss.

Genetic studies and phenotypic expansion of hearing loss (HL) for people living in Africa are greatly needed. We evaluated the clinical phenotypes of three affected siblings presenting non-syndromic (NS) HL and five unaffected members of a consanguineous Ghanaian family. Analysis of exome sequence data was performed for all affected and one unaffected family members.

Differential susceptibility of and clinical isolates from Ghana and Mali to current and lead discovery candidate antimalarial drugs.

Unlabelled: Non-falciparum species causing malaria in humans are considered neglected in the fight toward malaria elimination. Recent data highlight the increasing contribution of to malaria morbidity and mortality. In this study, the susceptibility of and to current antimalarial drugs was compared to advanced lead candidate drugs using field isolates.

Spatiotemporal analysis of Plasmodium falciparum erythrocyte binding antigen-175 gene dimorphism in Ghana.

Background: Malaria remains a leading cause of death worldwide, claiming over 600,000 lives each year. Over 90% of these deaths, mostly among children under 5 years, occur in sub-Saharan Africa and are caused by Plasmodium falciparum. The merozoites stage of the parasite, crucial for asexual development invade erythrocytes through ligand-receptor interactions.

scRNA-seq reveals elevated interferon responses and TNF-α signaling via NFkB in monocytes in children with uncomplicated malaria.

Malaria causes significant morbidity and mortality worldwide, disproportionately impacting sub-Saharan Africa. Disease phenotypes associated with infection can vary widely, from asymptomatic to life-threatening. To date, prevention efforts, particularly those related to vaccine development, have been hindered by an incomplete understanding of which factors impact host immune responses resulting in these divergent outcomes.

Gossypol is a natural product with good antimalarial activity against Plasmodium falciparum clinical isolates.

Gossypol has demonstrated significant antimalarial activity against chloroquine-resistant and susceptible Plasmodium falciparum parasites. However, data on its potency in clinical isolates of P. falciparum remains limited.

Identification of complex Plasmodium falciparum genetic backgrounds circulating in Africa: a multicountry genomic epidemiology analysis.

Background: The population structure of the malaria parasite Plasmodium falciparum can reveal underlying adaptive evolutionary processes. Selective pressures to maintain complex genetic backgrounds can encourage inbreeding, producing distinct parasite clusters identifiable by population structure analyses.

Methods: We analysed population structure in 3783 P falciparum genomes from 21 countries across Africa, provided by the MalariaGEN Pf7 dataset.

Low nucleotide diversity of the Plasmodium falciparum AP2-EXP2 gene among clinical samples from Ghana.

Background: PfAP2-EXP2 is located within chromosome 6 of Plasmodium falciparum recently identified to be undergoing an extensive selective sweep in West African isolates. The gene encoding this transcription factor, PfAP2-EXP2, is essential and thus likely subject to purifying selection that limits variants in the parasite population despite its genomic location.

Methods: 72 Plasmodium falciparum field samples and 801 clinical sequences from the Pf6 MalariaGEN dataset of Ghanaian origin, were integrated and analysed.

Towards integrated malaria molecular surveillance in Africa.

Integrated malaria molecular surveillance (iMMS) systems are essential for Africa's expanding malaria genomics initiatives. Here we highlight a few initiatives and demonstrate how iMMS can support evidence-based decisions and policies for National Malaria Programs and other malaria control stakeholders. We conclude with key considerations for advancing these malaria genomics initiatives towards sustainable iMMS.

Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny.

The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites.

Drug resistance and vaccine target surveillance of Plasmodium falciparum using nanopore sequencing in Ghana.

Malaria results in over 600,000 deaths annually, with the highest burden of deaths in young children living in sub-Saharan Africa. Molecular surveillance can provide important information for malaria control policies, including detection of antimalarial drug resistance. However, genome sequencing capacity in malaria-endemic countries is limited.

Co-infection of Plasmodium falciparum and Schistosoma mansoni is associated with anaemia.

Background: Malaria and schistosomiasis persist as major public health challenge in sub-Saharan Africa. These infections have independently and also in polyparasitic infection been implicated in anaemia and nutritional deficiencies. This study aimed at assessing asymptomatic malaria, intestinal Schistosoma infections and the risk of anaemia among school children in the Tono irrigation area in the Kassena Nankana East Municipal (KNEM) in the Upper East Region of Northern Ghana.

The global transcriptome of mid-stage gametocytes (stages II-IV) appears largely conserved and gametocyte-specific gene expression patterns vary in clinical isolates.

Our overall understanding of the developmental biology of malaria parasites has been greatly enhanced by recent advances in transcriptomic analysis. However, most of these investigations rely on laboratory strains (LS) that were adapted into culture many years ago, and the transcriptomes of clinical isolates (CI) circulating in human populations have not been assessed. In this study, RNA-seq was used to compare the global transcriptome of mid-stage gametocytes derived from three short-term cultured CI, with gametocytes derived from the NF54 reference laboratory strain.

Recent increase in low complexity polygenomic infections and sialic acid-independent invasion pathways in Plasmodium falciparum from Western Gambia.

Background: The malaria parasite Plasmodium falciparum utilizes multiple alternative receptor-ligand interactions for the invasion of human erythrocytes. While some P. falciparum clones make use of sialic acid (SA) residues on the surface of the human glycophorin receptors to invade the erythrocyte, others use alternative receptors independent of sialic acid residues.

Pf7: an open dataset of genome variation in 20,000 worldwide samples.

We describe the MalariaGEN Pf7 data resource, the seventh release of genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.

Global Distribution of Founder Variants Associated with Non-Syndromic Hearing Impairment.

The genetic etiology of non-syndromic hearing impairment (NSHI) is highly heterogeneous with over 124 distinct genes identified. The wide spectrum of implicated genes has challenged the implementation of molecular diagnosis with equal clinical validity in all settings. Differential frequencies of allelic variants in the most common NSHI causal gene, gap junction beta 2 (), has been described as stemming from the segregation of a founder variant and/or spontaneous germline variant hot spots.

Plasmodium malariae structure and genetic diversity in sub-Saharan Africa determined from microsatellite variants and linked SNPs in orthologues of antimalarial resistance genes.

Plasmodium malariae, a neglected human malaria parasite, contributes up to 10% of malaria infections in sub-Saharan Africa (sSA). Though P. malariae infection is considered clinically benign, it presents mostly as coinfections with the dominant P.

A novel autosomal dominant GREB1L variant associated with non-syndromic hearing impairment in Ghana.

Background: Childhood hearing impairment (HI) is genetically heterogeneous with many implicated genes, however, only a few of these genes are reported in African populations.

Methods: This study used exome and Sanger sequencing to resolve the possible genetic cause of non-syndromic HI in a Ghanaian family.

Results: We identified a novel variant c.