Joint Clinical Research Centre

INTRODUCTION:The development of approaches and interventions to achieve HIV remission continues to accelerate. Children living with HIV who started antiretroviral therapy (ART) at a young age and sustain viral suppression are an ideal clinical trial population. Trials may require analytic treatment interruptions (ATIs). Paediatric trials depend on the willingness of guardians to consent to child participation, yet there are few data about guardian willingness or attitudes. Here, we investigated the opinions of guardians of children likely to be eligible for ATI trials. METHODS:Children and youth who started ART ≤ 3 months of age, and who remained well-controlled on ART older than 7 years, were recruited in South Africa, Mozambique, Uganda, Mali and Thailand. A survey was conducted among guardians of these paediatric participants. The survey utilized a vignette describing a trial with ATI and assessed attitudes and intentions (measured on 7-point scales) of the guardians regarding their children's participation in a hypothetical trial. RESULTS:Guardians of 99 children were recruited. Guardians' median age was 45 years (range 24-73) and most (89.9%) were female. The median age of the child or youth with HIV was 13.2 years (range 7-18.5 years). Most respondents endorsed a positive intention to enrol their child in a future HIV remission trial (mean 6.5 [SD:1.3] on a 7-point scale), with significant variation across the sites (p = 0.0024). Most respondents strongly endorsed a range of trial benefits, including better future HIV treatments (93.8%) and access to better care (88.0%). Some endorsed concern about the trial burden to themselves (33.3%) and the child (35.4%). Almost half strongly believed that the trial would result in the child no longer needing ART (48%) and the child being cured of HIV (46.5%). CONCLUSIONS:Across multiple countries, guardians of children and youth who were treated early were positive about participation in trials with ATI. Only a third expressed some concern about trial burden, while almost half had unrealistic expectations about potential benefits. Recruitment into trials involving ATI will need to include effective communication strategies to ensure that participants and caregivers are adequately informed about burden, potential risks and the likelihood of personal benefit.

The study analyses robust, causal evidence of transformational change. We approach this topic by systematically reviewing literature that has the potential to document causal evidence for transformational change across a broad set of interventions and outcomes. Our focus is on evidence found in developing countries to inform climate interventions. We approach this learning exercise directly by looking at the energy sector and indirectly by reviewing the evidence on behavioural change in the public health sector. Both sectors show examples of transformational change with scale, depth and duration. We identify lessons on transformational change from these two sectors relevant to policymakers.

Karamoja continues to experience a substantial TB burden, and supporting preventive treatment among high-risk groups such as household contacts is essential for reducing progression from latent infection to active TB. Despite national efforts, adult TPT uptake in the region remained low prior to 2022. This study explored factors associated with uptake among adult TB contacts at Matany Hospital.We carried out a cross-sectional assessment involving 357 adults aged 18 years and above who were listed as contacts of bacteriologically confirmed TB patients between May 2022 and May 2023. Data were obtained through structured questionnaires and medical record extraction. Initiation of any recommended TPT regimen constituted uptake. Analysis was performed using STATA 14.2, employing chi-square tests for preliminary associations and multivariable logistic regression for adjusted estimates.Of 357 participants (59.4% female; mean age 44.6 years), 277 (77.6%) had initiated TPT. Contacts whose index patient was still on treatment had higher odds of uptake (OR=2.93; 95% CI: 1.31–6.54). Waiting times between 15 minutes and one hour markedly decreased TPT initiation (OR=0.33; 95% CI: 0.15–0.73). Catholics were more likely to initiate TPT compared to Anglicans (OR=3.68; 95% CI: 1.36–9.92). Limited exposure to community sensitization campaigns and inadequate knowledge of TPT significantly lowered uptake.High TPT uptake in this pastoralist setting appears to be influenced by early engagement of contacts, strong faith-based networks, and active community awareness efforts. Addressing knowledge gaps, reducing waiting times, and partnering with religious institutions may strengthen TPT coverage in similar high-burden regions.

Background Persistent global health security risks require countries to establish effective, standards-aligned biosafety and biosecurity systems. Sub-Saharan Africa carries a disproportionate burden of infectious disease threats, yet systematic laboratory biorisk management (BRM) remains nascent in most low-income countries. Uganda's National Health Laboratory and Diagnostic Services (NHLDS) launched a national, risk- and performance-based BRM programme spanning the human health, animal health, water, and environmental laboratory sectors. This article describes the programme design, implementation trajectory, and outcomes between 2022 and 2025. Methods A national implementation evaluation employing a repeated cross-sectional design with a within-facility matched-cohort sub-analysis was conducted across Uganda’s One Health laboratory sectors. Four national BRM instruments were developed and validated: a biosafety and biosecurity manual, a training curriculum, a structured mentorship toolkit, and an ISO 35001:2019/ISO 15190:2020-aligned assessment checklist. Capacity was built through a three-tier cascade training model. Compliance assessments were conducted in 200 laboratories generating 337 assessment events. Within-facility change was analyzed for 29 mentored laboratories with paired 2023–2025 data; statistical testing used the paired t-test and Wilcoxon signed-rank test. Results The programme trained more than 1,500 laboratory personnel, including 25 national master trainers, 41 mentors, and 27 ISO 19011-certified auditors, and provided structured mentorship to 80 laboratories. System-level mean BRM compliance increased from 26.3% in 2022 to 48.7% in 2025 across all assessed laboratories. Within the matched mentored cohort (n = 29), mean compliance rose from 57.2% to 66.3% (within-facility mean change + 9.1 percentage points; 95% CI + 2.0 to + 16.3; p = 0.019; Wilcoxon p = 0.024; Cohen’s d = 0.46). The proportion of mentored laboratories classified as Low Risk or better (≥ 65%) increased from 21% to 55%. An inverse gradient was observed between baseline performance and subsequent gain. Conclusion A standardized, ISO-aligned BRM framework is operationally feasible at national scale in a low-resource, One Health setting. Structured multi-cycle mentorship, cascade training, and engaged leadership were associated with measurable within-facility performance gains. The programme provides a replicable model for countries seeking to operationalize international BRM standards across heterogeneous laboratory sectors.

Abstract Crimean-Congo haemorrhagic fever virus (CCHFV) causes a viral zoonotic disease transmitted through tick bites and direct contact with infected blood or tissue of infected animals. Socio-ecological and behavioural risk factors for CCHFV exposure in Uganda remain poorly understood, which can lead to the omission of key risk factors in quantitative survey design and limit our wider understanding. In this study, we explored human-animal-tick interaction transmission risks in Uganda. We conducted 24 focus group discussions (FGDs) and 31 key-informant interviews (KIIs) across six environmentally and socio-ecologically diverse districts, between October 2023 and March 2024. Study sites were selected using K-prototype analysis, which combined environmental and socio-ecological variables to identify distinct clusters within Uganda. FGDs were conducted separately with groups of community leaders, men, women and teenagers with stratified purposive sampling. Medical doctors, veterinarians, traditional healers, district surveillance officers, and herdsmen were individually interviewed as key informants and purposively sampled. Data were transcribed and translated into English, and analysed thematically using iterative categorisation in NVivo 14. Most participants reported tick bites, some as frequently as every day. Close contact with animals was common, including sleeping next to them in the same building, largely due to concerns about animal theft. Less frequent but notable practices included slaughtering animals for consumption or sacrifice and interactions with wild animals during hunting. Slaughtering and butchering an animal which was sick or had died was reportedly performed by participants in most districts. Plucking and roasting engorged ticks was a practice described in the Kaabong and Arua districts of Northern Uganda. These practices and behaviours highlight potential key risks of CCHFV transmission and underscore the need for future studies to address specific behaviours, to quantify if, and to what extent, they present an exposure risk. Further work should include underlying reasons for the behaviours, which would help ensure that culturally appropriate interventions are targeted.