Antibodies to PfEMP1 and variant surface antigens: Protection after controlled human malaria infection in semi-immune Kenyan adults.

Objectives: Acquisition of antibodies to Plasmodium falciparum variant surface antigens (VSA) expressed on infected red blood cells (iRBCs) is associated with naturally acquired immunity to malaria. We have previously shown that antibodies to VSA on iRBCs are associated with protection against parasite growth in the context of controlled human malaria infection (CHMI). This study explored whether antibodies to recombinant antigens derived from PfEMP1 domains were independently associated with protection during CHMI in semi-immune Kenyan adults.

A retrospective analysis of drug resistance markers detects an early (2016/17) high prevalence of the k13 C469Y mutation in asymptomatic infections in Northern Uganda.

The emergence of drug-resistant parasites in sub-Saharan Africa will substantially challenge malaria control. Here, we evaluated the frequency of common drug resistance markers among adolescents from Northern Uganda with asymptomatic infections. We used an established amplicon deep sequencing strategy to screen dried blood spot samples collected from 2016 to 2017 during a reported malaria epidemic within the districts of Kitgum and Pader in Northern Uganda.

A scoping review of ethics review processes during public health emergencies in Africa.

Background: The COVID-19 pandemic forced governments, multilateral public health organisations and research institutions to undertake research quickly to inform their responses to the pandemic. Most COVID-19-related studies required swift approval, creating ethical and practical challenges for regulatory authorities and researchers. In this paper, we examine the landscape of ethics review processes in Africa during public health emergencies (PHEs).

Bi-isotype immunoglobulins enhance antibody-mediated neutrophil activity against parasites.

Background: Malaria remains a major global health priority, and monoclonal antibodies (mAbs) are emerging as potential new tools to support efforts to control the disease. Recent data suggest that Fc-dependent mechanisms of immunity are important mediators of protection against the blood stages of the infection, but few studies have investigated this in the context of mAbs. We aimed to isolate mAbs agnostic to cognate antigens that target whole merozoites and simultaneously induce potent neutrophil activity measured by the level of reactive oxygen species (ROS) production using an antibody-dependent respiratory burst (ADRB) assay.

Designing and delivering bioinformatics project-based learning in East Africa.

Background: The Eastern Africa Network for Bioinformatics Training (EANBiT) has matured through continuous evaluation, feedback, and codesign. We highlight how the program has evolved to meet challenges and achieve its goals and how experiential learning through mini projects enhances the acquisition of skills and collaboration. We continued to learn and grow through honest feedback and evaluation of the program, trainers, and modules, enabling us to provide robust training even during the Coronavirus disease 2019 (COVID-19) pandemic, when we had to redesign the program due to restricted travel and in person group meetings.

Antibody-Dependent Respiratory Burst against Merozoites in Individuals Living in an Area with Declining Malaria Transmission.

Malaria transmission intensity affects the development of naturally acquired immunity to malaria. An absolute correlate measure of protection against malaria is lacking. However, antibody-mediated functions against correlate with protection against malaria.

Effect of depth of interaction resolution on the spatial resolution of SIAT aPET.

Spatial resolution is a crucial parameter for a positron emission tomography (PET) scanner. The spatial resolution of a high-resolution small animal PET scanner is significantly influenced by the effect of depth of interaction (DOI) uncertainty. The aim of this work is to investigate the impact of DOI resolution on the spatial resolution of a small animal PET scanner called SIAT aPET and determine the required DOI resolution to achieve nearly uniform spatial resolution within the field of view (FOV).

Development and performance of SIAT bPET: a high-resolution and high-sensitivity MR-compatible brain PET scanner using dual-ended readout detectors.

Purpose: Positron emission tomography/magnetic resonance imaging (PET/MRI) is a powerful tool for brain imaging, but the spatial resolution of the PET scanners currently used for brain imaging can be further improved to enhance the quantitative accuracy of brain PET imaging. The purpose of this study is to develop an MR-compatible brain PET scanner that can simultaneously achieve a uniform high spatial resolution and high sensitivity by using dual-ended readout depth encoding detectors.

Methods: The MR-compatible brain PET scanner, named SIAT bPET, consists of 224 dual-ended readout detectors.

Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.

Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes.

Evaluating effect modification by HIV testing history to understand the mechanisms behind the impact of announcing HIV self-testing availability in a clinic system in Kenya.

Background: In sub-Saharan Africa, truckers and female sex workers (FSWs) have high HIV risk and face challenges accessing HIV testing. Adding HIV self-testing (HIVST) to standard of care (SOC) programs increases testing rates. However, the underlying mechanisms are not fully understood.

Determinants of utilization of malaria preventive measures during pregnancy among women aged 15 to 49 years in Kenya: an analysis of the Malaria Indicator Survey 2020.

Background: Malaria is a significant cause of morbidity and mortality. Malaria infection in pregnancy can have severe consequences for the fetus and the mother. To fight against malaria infection in pregnancy, Kenya integrated the issuance of an insecticide-treated net (ITN) and intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTpSP) with antenatal care (ANC) for pregnant women.

Malaria attributable fractions with changing transmission intensity: Bayesian latent class vs logistic models.

Background: Asymptomatic carriage of malaria parasites is common in high transmission intensity areas and confounds clinical case definitions for research studies. This is important for investigations that aim to identify immune correlates of protection from clinical malaria. The proportion of fevers attributable to malaria parasites is widely used to define different thresholds of parasite density associated with febrile episodes.

A framework for managing health research capacity strengthening consortia: addressing tensions and enhancing capacity outcomes.

There has been a steady increase in health research capacity strengthening (HRCS) consortia and programmes. However, their structures and management practices and the effect on the capacity strengthening outcomes have been underexamined. We conducted a case study involving three HRCS consortia where we critically examined the consortia's decision-making processes, strategies for resolving management tensions and the potential implications for consortia outcomes.

Pandemic preparedness and responsiveness of research review committees: lessons from review of COVID-19 protocols at KEMRI Wellcome Trust Research Programme in Kenya.

: The scale of the COVID-19 pandemic and novelty of SARS-CoV-2 presented unprecedented challenges in the review of COVID-19 protocols. We investigated how research at the KEMRI Wellcome Trust Research Programme (KWTRP) was reviewed, including by institutional and national level committees. A document review and in-depth interviews with researchers, regulators and research reviewers were conducted.

Breadth of Antibodies to Variant Surface Antigens Is Associated With Immunity in a Controlled Human Malaria Infection Study.

Background: variant surface antigens (VSAs) contribute to malaria pathogenesis by mediating cytoadhesion of infected red blood cells to the microvasculature endothelium. In this study, we investigated the association between anti-VSA antibodies and clinical outcome in a controlled human malaria infection (CHMI) study.

Method: We used flow cytometry and ELISA to measure levels of IgG antibodies to VSAs of five heterologous and one homologous parasite isolates, and to two PfEMP1 DBLβ domains in blood samples collected a day before the challenge and 14 days after infection.

Transmission networks of SARS-CoV-2 in Coastal Kenya during the first two waves: A retrospective genomic study.

Background: Detailed understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) regional transmission networks within sub-Saharan Africa is key for guiding local public health interventions against the pandemic.

Methods: Here, we analysed 1139 SARS-CoV-2 genomes from positive samples collected between March 2020 and February 2021 across six counties of Coastal Kenya (Mombasa, Kilifi, Taita Taveta, Kwale, Tana River, and Lamu) to infer virus introductions and local transmission patterns during the first two waves of infections. Virus importations were inferred using ancestral state reconstruction, and virus dispersal between counties was estimated using discrete phylogeographic analysis.

Increasing diversity in genomics requires investment in equitable partnerships and capacity building.

Calls for diversity in genomics have motivated new global research collaborations across institutions with highly imbalanced resources. We describe practical lessons we have learned so far from designing multidisciplinary international research and capacity-building programs that prioritize equity in two intertwined programs — the NeuroGAP-Psychosis research study and GINGER training program — spanning institutions in Ethiopia, Kenya, South Africa, Uganda and the united States.

The burden of neurological impairments and disability in older children measured in disability-adjusted life-years in rural Kenya.

Neurological impairment (NI) and disability are common in sub-Saharan Africa (SSA), but the overall burden in terms of morbidity and mortality in older children remains unknown. We estimated the burden of NI in disability-adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs) for older children in a defined rural setting in Kenya. We used empirical and literature estimates to model the overall burden for children aged 5-14 years in five domains: epilepsy (lifetime and active) and moderate/severe cognitive, hearing, motor, and visual impairments.

Neurological impairment and disability in children in rural Kenya.

Aim: To investigate geographical change over time in the burden of neurological impairments in school-aged children in a demographic surveillance area.

Method: We investigated changes in neurological impairment prevalence in five domains (epilepsy and cognitive, hearing, vision, and motor impairments) using similar two-phase surveys conducted in 2001 (n=10 218) and 2015 (n=11 223) and determined changes in location-level prevalence, geographical clustering, and significant risk factors for children aged 6 to 9 years (mean 7y 6mo, SD 1y) of whom 50.4% were males.

Tracking the introduction and spread of SARS-CoV-2 in coastal Kenya.

Genomic surveillance of SARS-CoV-2 is important for understanding both the evolution and the patterns of local and global transmission. Here, we generated 311 SARS-CoV-2 genomes from samples collected in coastal Kenya between 17 March and 31 July 2020. We estimated multiple independent SARS-CoV-2 introductions into the region were primarily of European origin, although introductions could have come through neighbouring countries.

protGear: A protein microarray data pre-processing suite.

Protein microarrays are versatile tools for high throughput study of the human proteome, but systematic and non-systematic sources of bias constrain optimal interpretation and the ultimate utility of the data. Published guidelines to limit technical variability whilst maintaining important biological variation favour DNA-based microarrays that often differ fundamentally in their experimental design. Rigorous tools to guide background correction, the quantification of within-sample variation, normalisation, and batch correction specifically for protein microarrays are limited, require extensive investigation and are not centrally accessible.