Transcriptome analysis reveals molecular targets of erythrocyte invasion phenotype diversity in natural isolates from Cameroon.

Further understanding of the molecular mediators of alternative RBC invasion phenotypes in endemic malaria parasites will support malaria blood-stage vaccine or drug development. This study investigated the prevalence of sialic acid (SA)-dependent and SA-independent RBC invasion pathways in endemic parasites from Cameroon and compared the schizont stage transcriptomes in these two groups to uncover the wider repertoire of transcriptional variation associated with the use of alternative RBC invasion pathway phenotypes. A two-color flow cytometry-based invasion-inhibition assay against RBCs treated with neuraminidase, trypsin, and chymotrypsin and deep RNA sequencing of schizont stages harvested in the first replication cycle in culture were employed in this investigation.

Immunogenicity of yellow fever vaccine co-administered with 13-valent pneumococcal conjugate vaccine in rural Gambia: A cluster-randomised trial.

Introduction: Because booster doses of pneumococcal conjugate vaccine (PCV) may be given at a similar time to yellow fever vaccine (YF), it is important to assess the immune response to YF when co-administered with PCV. This has been investigated during a reduced-dose PCV trial in The Gambia.

Methods: In this phase 4, parallel-group, cluster-randomized trial, healthy infants aged 0-10 weeks were randomly allocated to receive either a two-dose schedule of PCV13 with a booster dose co-administered with YF vaccine at age 9 months (1 + 1 co-administration) or YF vaccine administered separately at age 10 months (1 + 1 separate) or the standard three early doses of PCV13 with YF vaccine at age 9 months (3 + 0 separate).

Real-Life Diagnostic Accuracy and Clinical Utility of Hepatitis B Virus (HBV) Nucleic Acid Testing Using the GeneXpert Point-of-Care Test System from Fresh Plasma and Dry Blood Spot Samples in The Gambia.

The GeneXpert HBV Viral Load test is a simplified tool to scale up screening and HBV monitoring in resource-limited settings, where HBV is endemic and where molecular techniques to quantify HBV DNA are expensive and scarce. However, the accuracy of field diagnostics compared to gold standard assays in HBV-endemic African countries has not been well understood. We aim to validate the diagnostic performance of the GeneXpert HBV Viral Load test in freshly collected and stored plasma and dried blood spot (DBS) samples to assess turn-around-time (TAT) for sample processing and treatment initiation, to map GeneXpert machines and to determine limitations to its use in The Gambia.

Adjunctive ivermectin mass drug administration for malaria control on the Bijagos Archipelago of Guinea-Bissau (MATAMAL): a quadruple-blinded, cluster-randomised, placebo-controlled trial.

Background: Arthropod vectors feeding on the blood of individuals treated with ivermectin have substantially increased mortality. Whether this effect will translate into a useful tool for reducing malaria burden at scale is not clear. Our trial aimed to assess whether using ivermectin as an adjunct to mass drug administration (MDA) with dihydroartemisinin-piperaquine would further reduce malaria prevalence.

Innovative diagnostic technologies: navigating regulatory frameworks through advances, challenges, and future prospects.

Diagnostic tools are key to guiding patient management and informing public health policies to control infectious diseases. However, many diseases still do not have effective diagnostics and much of the global population faces restricted access to reliable, affordable testing. This limitation underscores the urgent need for innovation to enhance diagnostic availability and effectiveness.

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.

Clinical outcomes of untreated adults living with chronic hepatitis B in The Gambia: an analysis of data from the prospective PROLIFICA cohort study.

Background: Expanding antiviral therapy to people with chronic hepatitis B virus (HBV) infection who are ineligible to receive treatment under current international criteria has been increasingly debated. Evidence to support this approach is scarce, especially in Africa. We aimed to address this knowledge gap by analysing the clinical outcomes of people with chronic hepatitis B in The Gambia who were untreated and ineligible for antiviral therapy at diagnosis.

Respiratory rates among rural Gambian children: a community-based cohort study.

Normal respiratory rates (RR) for children under five in the tropics are well-documented, but data for older children are limited. This study tracked RR changes with age and examined associations with nutritional status and environmental factors. We monitored rural Gambian children aged 6 months to 14 years, recording RR during home visits twice weekly over two rainy seasons.

The PRECISE-DYAD Neurodevelopmental substudy protocol: neurodevelopmental risk in children of mothers with pregnancy complications.

Background: Over 250 million children are not reaching their developmental potential globally. The impact of prenatal factors and their interplay with postnatal environmental factors on child neurodevelopment, is still unclear-particularly in low- and middle-income settings. This study aims to understand the impact of pregnancy complications as well as environmental, psychosocial, and biological predictors on neurodevelopmental trajectories.

Mosquitocidal effect of ivermectin-treated nettings and sprayed walls on Anopheles gambiae s.s.

Ivermectin (IVM) has been proposed as a new tool for malaria control as it is toxic on vectors feeding on treated humans or cattle. Nevertheless, IVM may have a direct mosquitocidal effect when applied on bed nets or sprayed walls. The potential for IVM application as a new insecticide for long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) was tested in this proof-of-concept study in a laboratory and semi-field environment.

The PRECISE-DYAD protocol: linking maternal and infant health trajectories in sub-Saharan Africa.

Background: PRECISE-DYAD is an observational cohort study of mother-child dyads running in urban and rural communities in The Gambia and Kenya. The cohort is being followed for two years and includes uncomplicated pregnancies and those that suffered pregnancy hypertension, fetal growth restriction, preterm birth, and/or stillbirth.

Methods: The PRECISE-DYAD study will follow up ~4200 women and their children recruited into the original PRECISE study.

Household-level effects of seasonal malaria chemoprevention in the Gambia.

Background: In 2022 the WHO recommended the discretionary expansion of the eligible age range for seasonal malaria chemoprevention (SMC) to children older than 4 years. Older children are at lower risk of clinical disease and severe malaria so there has been uncertainty about the cost-benefit for national control programmes. However, emerging evidence from laboratory studies suggests protecting school-age children reduces the infectious reservoir for malaria and may significantly impact on transmission.

Impact of Intrapartum Azithromycin on the Carriage and Antibiotic Resistance of Escherichia coli and Klebsiella pneumoniae in Mothers and Their Newborns: A Substudy of a Randomized, Double-Blind Trial Conducted in The Gambia and Burkina Faso.

Background: Limited data exist on the effects of intrapartum azithromycin on the prevalence of carriage and antibiotic resistance of Enterobacterales.

Methods: We conducted a randomized trial in The Gambia and Burkina Faso where women received intrapartum azithromycin (2 g) or placebo. We determined the impact of treatment on the prevalence of carriage and antibiotic resistance of Escherichia coli and Klebsiella pneumoniae by analyzing rectal swabs (RS), nasopharyngeal swabs (NPS), breast milk, and rectovaginal swabs (RVS).

The effect of physical barriers under a raised house on mosquito entry: an experimental study in rural Gambia.

Background: Anopheles gambiae, the major malaria mosquito in sub-Saharan Africa, feed largely indoors at night. Raising a house off the ground with no barriers underneath reduces mosquito-house entry. This experiment tested whether walling off the space under an elevated hut affects mosquito-hut entry.

The Enterics for Global Health (EFGH) Surveillance Study in The Gambia.

Background: The Gambia, located in West Africa, is one of 7 country sites conducting the Enterics for Global Health (EFGH) Surveillance Study to establish incidence and consequence of -associated medically attended diarrhea among children 6-35 months old.

Methods: Here we describe the study site and research experience, sociodemographic characteristics of the study catchment area, facilities of recruitment for diarrhea case surveillance, and known care-seeking behavior for diarrheal illness. We also describe The Gambia's healthcare system and financing, current vaccine schedule and vaccine adaptation, local diarrhea management guidelines and challenges, and antibiotic resistance patterns in the region.

Tobacco smoking clusters in households affected by tuberculosis in an individual participant data meta-analysis of national tuberculosis prevalence surveys: Time for household-wide interventions?

Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB.

Risk factors for non-participation in ivermectin and dihydroartemisinin-piperaquine mass drug administration for malaria control in the MASSIV trial.

Background: Mass Drug Administration (MDA) has become a mainstay for the control of several diseases over the last two decades. Successful implementation of MDA programmes requires community participation and can be threatened by systematic non-participation. Such concerns are particularly pertinent for MDA programmes against malaria, as they require multi-day treatment over several consecutive months.

Practical Guidelines for Standardised Resolution of Important Protocol Deviations in Clinical Trials Conducted in Sub-Saharan Africa.

A clinical trial is any research on human subjects that involves an investigational medicinal product or device. Investigational medicinal products include unlicensed drugs or drugs used outside the product license (e.g.

A Perspective on the Strategy for Advancing ETVAX, An Anti-ETEC Diarrheal Disease Vaccine, into a Field Efficacy Trial in Gambian Children: Rationale, Challenges, Lessons Learned, and Future Directions.

For the first time in over 20 years, an Enterotoxigenic (ETEC) vaccine candidate, ETVAX, has advanced into a phase 2b field efficacy trial for children 6-18 months of age in a low-income country. ETVAX is an inactivated whole cell vaccine that has gone through a series of clinical trials to provide a rationale for the design elements of the Phase 2b trial. This trial is now underway in The Gambia and will be a precursor to an upcoming pivotal phase 3 trial.

Asymptomatic Plasmodium falciparum carriage at the end of the dry season is associated with subsequent infection and clinical malaria in Eastern Gambia.

Background: Chronic carriage of asymptomatic low-density Plasmodium falciparum parasitaemia in the dry season may support maintenance of acquired immunity that protects against clinical malaria. However, the relationship between chronic low-density infections and subsequent risk of clinical malaria episodes remains unclear.

Methods: In a 2-years study (December 2014 to December 2016) in eastern Gambia, nine cross-sectional surveys using molecular parasite detection were performed in the dry and wet season.

Treat All versus targeted strategies to select HBV-infected people for antiviral therapy in The Gambia, west Africa: a cost-effectiveness analysis.

Background: Global elimination of hepatitis B virus (HBV) requires expanded uptake of antiviral therapy, potentially by simplifying testing algorithms, especially in resource-limited countries. We evaluated the effectiveness, cost-effectiveness, and budget impact of three strategies that determine eligibility for anti-HBV treatment, as compared with the WHO 2015 treatment eligibility criteria, in The Gambia.

Methods: We developed a microsimulation model of natural history using data from the Prevention of Liver Fibrosis and Cancer in Africa programme (known as PROLIFICA) in The Gambia, for an HBV-infected cohort of individuals aged 20 years.

Plasmodium falciparum population structure and genetic diversity of cell traversal protein for ookinetes and sporozoites (CelTOS) during malaria resurgences in Dielmo, Senegal.

The ability to accurately measure the intensity of malaria transmission in areas with low transmission is extremely important to guide elimination efforts. Plasmodium falciparum Cell-traversal protein for ookinetes and sporozoites (PfCelTOS) is an important conserved sporozoite antigen reported as one of the promising malaria vaccine candidates, and could be used to estimate malaria transmission intensity. This study aimed at determining whether the diversity of PfCelTOS gene reflects the changes in malaria transmission that occurred between 2007 and 2014 in Dielmo, a Senegalese village, before and after the implementation of insecticide treated bed nets (ITNs).

Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys.

Background: Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities.