Vδ2+ T cell response to malaria correlates with protection from infection but is attenuated with repeated exposure.

Vδ2+ γδ T cells are semi-innate T cells that expand markedly following P. falciparum (Pf) infection in naïve adults, but are lost and become dysfunctional among children repeatedly exposed to malaria. The role of these cells in mediating clinical immunity (i.e. protection against symptoms) to malaria remains unclear. We measured Vδ2+ T cell absolute counts at acute and convalescent malaria timepoints (n = 43), and Vδ2+ counts, cellular phenotype, and cytokine production following in vitro stimulation at asymptomatic visits (n = 377), among children aged 6 months to 10 years living in Uganda. Increasing age was associated with diminished in vivo expansion following malaria, and lower Vδ2 absolute counts overall, among children living in a high transmission setting. Microscopic parasitemia and expression of the immunoregulatory markers Tim-3 and CD57 were associated with diminished Vδ2+ T cell pro-inflammatory cytokine production. Higher Vδ2 pro-inflammatory cytokine production was associated with protection from subsequent Pf infection, but also with an increased odds of symptoms once infected. Vδ2+ T cells may play a role in preventing malaria infection in children living in endemic settings; progressive loss and dysfunction of these cells may represent a disease tolerance mechanism that contributes to the development of clinical immunity to malaria

Utilization of indigenous food plants in Uganda: A case study of south-western Uganda

The purpose of the study was to document and establish the traditional processin methods of indigenous food plants in Rukungiri district. In order to establish the status and level of utilization and processing of indigenous food plants in southwestern Uganda, a baseline survey was carried out using a participatory method of data collection. Respondents in Rukungiri district cited a total of 94 plants that were used for food. Some of the food plants were classified as indigenous to the area, while others were classified as exotic. The food types generally fell into five broad categories, namely; vegetables, fruits, roots/tubers, pulses and cereals. Vegetables and fruits were the most commonly used food plants and the Amaranths species were found to be the most popular vegetables, whereas wild plums (Carissa edulis) and gooseberries (Physalis minima) were cited among thepreferred fruit species. In spite of the fact that indigenous/traditional food plants have always ensured food security at the household level, the process of collecting them from the wild, their production,consumption and domestication was found to be on the decline in this area. This decline can be attributed to limited available knowledge on their nutritional content and to the emphasis that is placed on commercial, high yielding exotic plants by both the agricultural extension officers and farmers. The majority of farmers are only interested in the cultivation of crops from which they can earn an income, and because no one has cultivated indigenous food plants with the intention of earning an income from them, the plants have not proved their worth. Although the methods of utilization, especially food preparation, varied from one household to another, boiling, steaming and frying were very common and cross-cutting almost all the households. The principal mode of food preservation cited by households, especially for seeds, wassun drying

The roles and values of wild foods in agricultural systems

Almost every ecosystem has been amended so that plants and animals can be used as food, fibre, fodder, medicines, traps and weapons. Historically, wild plants and animals were sole dietary components for hunter–gatherer and forager cultures. Today, they remain key to many agricultural communities. The mean use of wild foods by agricultural and forager communities in 22 countries of Asia and Africa (36 studies) is 90–100 species per location. Aggregate country estimates can reach 300–800 species (e.g. India, Ethiopia, Kenya). The mean use of wild species is 120 per community for indigenous communities in both industrialized and developing countries. Many of these wild foods are actively managed, suggesting there is a false dichotomy around ideas of the agricultural and the wild: hunter–gatherers and foragers farm and manage their environments, and cultivators use many wild plants and animals. Yet, provision of and access to these sources of food may be declining as natural habitats come under increasing pressure from development, conservation-exclusions and agricultural expansion. Despite their value, wild foods are excluded from official statistics on economic values of natural resources. It is clear that wild plants and animals continue to form a significant proportion of the global food basket, and while a variety of social and ecological drivers are acting to reduce wild food use, their importance may be set to grow as pressures on agricultural productivity increase.</jats:p

A protocol paper: community engagement interventions for cardiovascular disease prevention in socially disadvantaged populations in the UK: an implementation research study

Background: Cardiovascular disorders (CVD) are the single greatest cause of mortality worldwide. In the UK, the National Health Service (NHS) has launched an initiative of health checks over and above current care to tackle CVD. However, the uptake of Health Checks is poor in disadvantaged communities. This protocol paper sets out a UK-based study (Sussex and Nottingham) aiming to co-produce a community delivered CVD risk assessment and coaching intervention to support community members to reduce their risk of CVD. The overall aim of the project is to implement a tailored-to-context community engagement (CE) intervention on awareness of CVD risks in vulnerable populations in high, middle and low-income countries. The specific objectives of the study are to enhance stakeholder' engagement; to implement lifestyle interventions for cardiovascular primary prevention, in disadvantaged populations and motivate uptake of NHS health checks. Methods: This study uses both qualitative and quantitative methods in three phases of evaluation, including pre-, per-and post-implementation. To ensure contextual appropriateness the 'Scaling-up Packages of Interventions for Cardiovascular disease prevention in selected sites in Europe and Sub-Saharan Africa: An implementation research' (SPICES) project will organize a multi-component community-engagement intervention. For the qualitative component, the pre-implementation phase will involve a contextual assessment and stakeholder mapping, exploring potentials for CVD risk profiling strategies and led by trained Community Health Volunteers (CHV) to identify accessibility and acceptability. The per-implementation phase will involve healthy lifestyle counselling provided by CHVs and evaluation of the outcome to identify fidelity and scalability. The post-implementation phase will involve developing sustainable community-based strategies for CVD risk reduction. All three components will include a process evaluation. A stepped wedge cluster randomised trial of the roll out will focus on implementation outcomes including uptake and engagement and changes in risk profiles. The quantitative component includes pre and post-intervention surveys. The theory of the socio-ecological framework will be applied to analyse the community engagement approach. Discussion: Based on the results ultimately a sustainable community engagement-based strategy for the primary prevention of CVD risk will be developed to enhance the performance of NHS health care in the UK. The Trial Registration number is ISRCTN68334579

Improving nutrition with agricultural biodiversity

This guide describes the process and procedures for collecting important information required to assess local farming systems and agrobiodiversity, household food consumption norms and the nutritional status of vulnerable groups within a given population using specific indicators. Additionally, this guide provides a framework for practical implementation of a holistic program that focuses on creating a customized intervention based on community-specific data. The manual strives to combine perspectives from the following models and approaches: 1. Farming Systems Model (FAO/WB) 2. Agroecological Model (NAFRI, FAO) 3. Indigenous Food Culture Documentation (CINE/IDRC/FAO) 4. Measuring Nutritional Functional Diversity (Columbia EI) 5. Positive Deviance Model (The Positive Deviance Initiative) 6. FANTA Nutritional Assessment Guides (USAID) 7. Food Security and Livelihoods Model (ACF International) 8. Ethnobotanical Documentation: A User’s Model (ICH/UNESCO) The development of this manual also could not have been possible without the guidance of previously published manuals by the World Health Organization (WHO), the World Food Programme (WFP) and the Centre for Indigenous Peoples’ Nutrition and Environment CINE. This manual recommends a 7 phase process to approach communities of focus holistically and with a trajectory of long-term improvement

Subtypes A1 and D, and recombinant HIV-1 natural polymorphisms associated with lenacapavir drug resistance in Uganda

BackgroundLenacapavir, a novel HIV-1 capsid inhibitor, shows promise for treating MDR HIV-1, as well as for pre-exposure prophylaxis (PrEP) in prevention of HIV infection. Its unique mechanism and lack of cross-resistance with other antiretroviral classes make lenacapavir a significant addition to HIV therapy. The clinical trials CALIBRATE and CAPELLA have demonstrated high viral suppression rates in both ART-naive individuals and individuals with MDR HIV-1. Lenacapavir-associated resistance mutations, such as M66I and Q67H, rarely seen as natural polymorphisms in lenacapavir-naive populations, are predominantly studied in subtype B HIV-1.ObjectivesOur study aimed to investigate the prevalence of lenacapavir resistance-associated mutations in HIV-1 subtypes A1 and D in a cohort of individuals living with HIV-1 from southwestern Uganda.MethodsUtilizing plasma samples from ART-naive adults living in Uganda, HIV-1 Gag p24 (capsid) sequences were analysed for lenacapavir resistance mutations.ResultsAmong 546 lenacapavir-naive participants, no major lenacapavir resistance-associated mutations were found. Minor mutations were present in 1.6% of participants, with T107A being the most common. Longitudinal data indicated the persistence of T107A for at least 3 years post-ART initiation in one participant. Phylogenetic analysis indicated individuals carrying T107A were found independently in distinct locations within the tree, suggesting that T107A might have arisen from multiple distinct base substitution events. Shannon entropy analysis showed high variability in certain capsid sites, but none overlapped with known lenacapavir resistance sites.ConclusionsThese findings suggest a low prevalence of naturally occurring lenacapavir resistance mutations in Uganda, supporting lenacapavir's potential efficacy in this region

Adverse Events Reported During Weekly Isoniazid-Rifapentine (3HP) Tuberculosis Preventive Treatment Among People With Human Immunodeficiency Virus in Uganda

BackgroundShort-course tuberculosis (TB) prevention regimens, including 12 weeks of isoniazid and rifapentine (3HP), are increasingly used in high-TB-burden countries. Despite established safety and tolerability in efficacy trials, 3HP-related adverse events (AEs) could differ in routine settings. Real-world data on AE type, frequency, and timing are crucial for health systems considering 3HP programmatic scale-up.MethodsWe reviewed AEs among people with human immunodeficiency virus (HIV) participating in a pragmatic implementation trial of facilitated 3HP taken by directly observed therapy (DOT) or self-administered therapy (SAT) in Kampala, Uganda, and classified them using the Common Terminology Criteria for Adverse Events. We assessed AE timing and summarized related clinical actions including laboratory tests, diagnoses made, medications prescribed, and treatment interruptions.ResultsAmong 1655 people with HIV treated between July 2020 and September 2022, 270 (16.3%) reported 451 events; main issues included general (7%), nervous system (6%), musculoskeletal (5%), gastrointestinal (5%), and dermatologic (3%) disorders. Most (61%) occurred within 6 weeks of initiating 3HP. Among those with events, 211 (78%) required further clinician evaluation, 202 (75%) required laboratory testing, 102 (38%) had medications prescribed, 40 (15%) had treatment paused, and 14 (5%) discontinued 3HP. Women, those multidimensionally impoverished, and DOT recipients were more likely to report an AE. SAT users and later enrollees were more likely to have 3HP interrupted or stopped due to an AE.ConclusionsIn a routine setting, 3HP was safe, with 16% of people with HIV reporting AEs and only 3% requiring temporary or permanent treatment interruption. These findings support 3HP expansion in routine HIV/AIDS care settings for TB prevention. Clinical Trials Registration. NCT03934931