Epstein-Barr virus type 2 infection is associated with higher viral loads in pediatric tonsils from western Kenya.

Epstein-Barr virus (EBV) is an etiologic agent of endemic Burkitt lymphoma (BL), a prevalent pediatric cancer in sub-Saharan Africa. There are two known types of EBV, EBV Type-1 (EBV-1) and EBV Type-2 (EBV-2), both found in eBL patients. To determine the EBV load and type dynamics within the tonsils, saliva, whole blood, and plasma, we enrolled 102 children aged 1-14 undergoing tonsillectomy in a malaria holoendemic region of western Kenya.

Factors associated with laboratory-confirmed SARS-Cov-2 infection among patients with severe respiratory illness (SRI): Findings from the COVID-19 vaccine effectiveness evaluation in Kenya and Mali, 2022-2023.

Background: Understanding the epidemiology of SARS-CoV-2 infection in settings with limited data, especially given the dynamic nature of the virus and the reported epidemiological heterogeneity across countries, is important. We used data from the COVID-19 Vaccine effectiveness evaluation to determine factors associated with SARS-COV-2 infection among patients (≥ 12 years) with severe respiratory illness (SRI) in Kenya and Mali.

Methods: SRI was defined as acute onset (≤ 14 days) of at least two of the following: cough, fever, chills, rigors, myalgia, headache, sore throat, fatigue, congestion or runny nose, loss of taste or smell, or pneumonia diagnosis.

Sustained activation induced cytidine deaminase (AID) expression in B cells following Plasmodium falciparum malaria infection in Kenyan children.

Burkitt lymphoma (BL) is characterized by elevated levels of the enzyme activation-induced cytidine deaminase (AID), an enzyme critical for MYC translocation that is the hallmark of BL. Both EBV and Plasmodium falciparum malaria are cofactors in the etiology of BL. However, how these 2 pathogens drive BL pathogenesis is not yet understood.

Factors associated with mortality among patients aged 12 years and above requiring hospitalization for severe respiratory illness (SRI): Findings from the COVID-19 vaccine effectiveness evaluation in Kenya and Mali, 2022-2023.

Background: Mortality attributed to respiratory illnesses is well characterized in children <5 years. However, there is paucity of data among older populations. Here, we leveraged data from the COVID-19 Vaccine Effectiveness Evaluation to establish the factors associated with mortality among patients with severe respiratory illness (SRI) in Kenya and Mali.

Transcriptome- and DNA methylation-based cell-type deconvolutions produce similar estimates of differential gene expression and differential methylation.

Background: Changing cell-type proportions can confound studies of differential gene expression or DNA methylation (DNAm) from peripheral blood mononuclear cells (PBMCs). We examined how cell-type proportions derived from the transcriptome versus the methylome (DNAm) influence estimates of differentially expressed genes (DEGs) and differentially methylated positions (DMPs).

Methods: Transcriptome and DNAm data were obtained from PBMC RNA and DNA of Kenyan children (n = 8) before, during, and 6 weeks following uncomplicated malaria.

Transcriptome- and DNA methylation-based cell-type deconvolutions produce similar estimates of differential gene expression and differential methylation.

Background: Changing cell-type proportions can confound studies of differential gene expression or DNA methylation (DNAm) from peripheral blood mononuclear cells (PBMCs). We examined how cell-type proportions derived from the transcriptome versus the methylome (DNAm) influence estimates of differentially expressed genes (DEGs) and differentially methylated positions (DMPs).

Methods: Transcriptome and DNAm data were obtained from PBMC RNA and DNA of Kenyan children (n = 8) before, during, and 6 weeks following uncomplicated malaria.

Clinical and immunological outcomes of HIV-exposed uninfected and HIV-unexposed uninfected children in the first 24 months of life in Western Kenya.

Background: Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life.

Methods: Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months.

Effects of Maternal HIV Infection on Early Kaposi Sarcoma-Associated Herpesvirus Seroconversion in a Kenyan Mother-Infant Cohort.

Background: We identified whether maternal human immunodeficiency virus (HIV) infection during pregnancy affects transplacental transfer of Kaposi sarcoma-associated herpesvirus (KSHV)-specific antibodies and subsequent infant infection.

Methods: We followed pregnant Kenyan women through delivery and their infants until age 2 years. Children were classified as HIV-exposed uninfected (HEU) or HIV-unexposed uninfected (HUU) based on maternal HIV status.

Clinical and Immunological Outcomes of HIV-Exposed Uninfected and HIV-Unexposed Uninfected Children in the First 24 Months of Life in Western Kenya.

Background: Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life.

Methods: Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months.

Macrophages drive KSHV B cell latency.

Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong infection and persists in latently infected B cells. Paradoxically, in vitro B cell infection is inefficient, and cells rapidly die, suggesting the absence of necessary factor(s). KSHV epidemiology unexpectedly mirrors that of malaria and certain helminthic infections, while other herpesviruses are ubiquitous.

Effect of Malaria Infection on Epstein-Barr Virus Persistence in Kenyan Children.

Background: The 2 cofactors in the etiology of Burkitt lymphoma (BL) are Epstein-Barr virus (EBV) and repeated Plasmodium falciparum malaria infections. This study evaluated EBV loads in mucosal and systemic compartments of children with malaria and controls. Age was analyzed as a covariate because immunity to malaria in endemic regions is age dependent.

Molecular characterization and genotype distribution of thioester-containing protein 1 gene in Anopheles gambiae mosquitoes in western Kenya.

Background: Evolutionary pressures lead to the selection of efficient malaria vectors either resistant or susceptible to Plasmodium parasites. These forces may favour the introduction of species genotypes that adapt to new breeding habitats, potentially having an impact on malaria transmission. Thioester-containing protein 1 (TEP1) of Anopheles gambiae complex plays an important role in innate immune defenses against parasites.

Monocyte epigenetics and innate immunity to malaria: yet another level of complexity?

Children under the age of 5 years living in areas of moderate to high malaria transmission are highly susceptible to clinical malaria with fever that prompts treatment of blood stage infection with anti-malarial drugs. In contrast, older school age children frequently experience subclinical malaria, i.e.

Rare Alleles and Signatures of Selection on the Immunodominant Domains of Pfs230 and Pfs48/45 in Malaria Parasites From Western Kenya.

Malaria elimination and eradication efforts can be advanced by including transmission-blocking or reducing vaccines (TBVs) alongside existing interventions. Key transmission-blocking vaccine candidates, such as domain one and domain 3, should be genetically stable to avoid developing ineffective vaccines due to antigenic polymorphisms. We evaluated genetic polymorphism and temporal stability of domain one and domain three in parasites from western Kenya.

Intimate partner violence among pregnant women attending prenatal care in Bondo sub-county, Western Kenya.

Objectives: To investigate prevalence and factors that contribute to intimate partner violence among pregnant women attending prenatal care in Bondo sub-county, Western Kenya.

Methods: This cross-sectional analysis was conducted in three health facilities in Bondo, Western Kenya, from August 2020 to August 2021. Using systematic sampling 360 pregnant women attending prenatal care were selected.

Signatures of selection and drivers for novel mutation on transmission-blocking vaccine candidate Pfs25 gene in western Kenya.

Background: Leading transmission-blocking vaccine candidates such as Plasmodium falciparum surface protein 25 (Pfs25 gene) may undergo antigenic alterations which may render them ineffective or allele-specific. This study examines the level of genetic diversity, signature of selection and drivers of Pfs25 polymorphisms of parasites population in regions of western Kenya with varying malaria transmission intensities.

Methods: Dry blood spots (DBS) were collected in 2018 and 2019 from febrile outpatients with malaria at health facilities in malaria-endemic areas of Homa Bay, Kisumu (Chulaimbo) and the epidemic-prone highland area of Kisii.

Maternal HIV Infection as a Risk Factor for Primary Epstein-Barr Virus Infection in Kenyan Infants.

Human immunodeficiency virus (HIV) infection is known to be associated with EBV shedding in saliva suggesting an increased risk of EBV transmission to infants born to mothers with HIV at an earlier age. In this study we investigated (i) whether maternal HIV status was a risk factor for EBV in blood at delivery or for shedding in saliva and breast milk of 6- and 10-weeks post-partum mothers, (ii) if there was a difference in EBV strains shed between HIV+ and HIV- mothers, and (iii) if maternal HIV status was a determinant of EBV viral load in their infants. Samples were collected as part of a prospective cohort study that followed HIV-positive (HIV+) and HIV-negative (HIV-) pregnant women in Western Kenya through delivery and post-partum period.

Hyper-prevalence of submicroscopic Plasmodium falciparum infections in a rural area of western Kenya with declining malaria cases.

Background: The gold standard for diagnosing Plasmodium falciparum infection is microscopic examination of Giemsa-stained peripheral blood smears. The effectiveness of this procedure for infection surveillance and malaria control may be limited by a relatively high parasitaemia detection threshold. Persons with microscopically undetectable infections may go untreated, contributing to ongoing transmission to mosquito vectors.

Genetic diversity and population structure of the human malaria parasite Plasmodium falciparum surface protein Pfs47 in isolates from the lowlands in Western Kenya.

Plasmodium falciparum parasites have evolved genetic adaptations to overcome immune responses mounted by diverse Anopheles vectors hindering malaria control efforts. Plasmodium falciparum surface protein Pfs47 is critical in the parasite's survival by manipulating the vector's immune system hence a promising target for blocking transmission in the mosquito. This study aimed to examine the genetic diversity, haplotype distribution, and population structure of Pfs47 and its implications on malaria infections in endemic lowlands in Western Kenya.

Determinants of the uptake of intermittent preventive treatment of malaria in pregnancy with sulphadoxine pyrimethamine in Sabatia Sub County, Western Kenya.

Background: Annually, 125.2 million pregnant women worldwide risk contracting malaria, including 30.3 million and 1.

IFN-λ4 genetic variants influence clinical malaria episodes in a cohort of Kenyan children.

Background: Interferon (IFN)- λ4, a type III IFN, production is controlled by a dinucleotide frameshift variant (rs368234815-dG/TT) within the first exon of the IFNL4 gene. Carriers of the IFNL4-dG allele but not the IFNL4-TT allele are able to produce the IFN-λ4 protein. Patients with hepatitis C virus that do not produce the IFN-λ4 protein have higher rates of viral clearance suggesting a potential inhibitory role of IFN-λ4 in liver-tropic infections.

Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children.

Background: Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya.

Increased investment in gametocytes in asymptomatic Plasmodium falciparum infections in the wet season.

Background: Transmission stemming from asymptomatic infections is increasingly being recognized as a threat to malaria elimination. In many regions, malaria transmission is seasonal. It is not well understood whether Plasmodium falciparum modulates its investment in transmission to coincide with seasonal vector abundance.

Malaria during pregnancy and transplacental transfer of Kaposi sarcoma-associated herpesvirus (KSHV) antibodies: a cohort study of Kenyan mother and child pairs.

Background: Kaposi sarcoma-associated herpesvirus (KSHV) seroprevalence in sub-Saharan African children can range up to 50% by age 2 years but factors affecting early age of KSHV infection are not well understood. Malaria during pregnancy has been associated with hindered transplacental transfer of antibodies to several pathogens but whether it affects transplacental transfer of KSHV antibodies is unknown. We aimed to determine if in utero malaria exposure reduced the transfer of KSHV antibodies across the placenta.

Malaria Is Associated With Kaposi Sarcoma-Associated Herpesvirus Seroconversion in a Cohort of Western Kenyan Children.

Background: We aimed to determine whether Plasmodium falciparum infection affects age of Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion in Kenyan children.

Methods: Kenyan children (n = 144) enrolled at age 1 month, from 2 sites with different levels of malaria transmission (stable/high vs unstable/low) were followed to age 24 months. Plasma was tested for KSHV antibodies using enzyme-linked immunosorbent assay (ELISA; K8.