21367 research outputs found
Sort by
Controlled human infection with Mycobacterium tuberculosis:practical considerations for clinical trials
Full text linkControlled human infection models (CHIMs) can accelerate vaccine development for infectious diseases. Mycobacterium tuberculosis is a human-adapted pathogen that is the leading infectious cause of death worldwide. M tuberculosis infection results in a spectrum of clinical outcomes that are incompletely modelled in animals. To date, the risks of infection, prolonged treatment, and sequelae related to CHIMs with M tuberculosis have been considered ethically unacceptable. However, recent advances in bacterial engineering have resulted in safe strains that could permit M tuberculosis CHIM studies with reduced risks. In this Personal View, we address the practical considerations for conducting a pulmonary M tuberculosis CHIM study. We summarise the ethical issues of M tuberculosis CHIM studies in tuberculosis-endemic and non-endemic settings; describe safety considerations, such as optimising the challenge dose and minimising risks to third parties; and outline and prioritise clinical, microbiological, immunological, and radiological endpoints that would render such a model useful for vaccine development.</p
Preventing Liver Disease in Malawi: Population-Based Studies of Hepatitis B, Alcohol use, and Liver Disease Outcomes
No full text"We carried her in a wheelbarrow to the clinic": process evaluation of the AMETHIST intervention combining microplanning with self-help groups to improve HIV prevention and treatment among female sex workers in Zimbabwe
Full text linkIntegrated community-based versus facility-based care for people with HIV, diabetes, and hypertension in sub-Saharan Africa (INTE-COMM): an open-label, multicountry, cluster-randomised trial
Full text linkBackground In sub-Saharan Africa, the burden of diabetes and hypertension is high, alongside a high prevalence of HIV. Whether these conditions can be managed in an integrated way in the community is unknown. We aim to compare integrated community-based care with integrated facility-based care for people with HIV, diabetes, and hypertension in Tanzania and Uganda. Methods This open-label, multicountry, cluster-randomised trial was conducted in 14 primary care facilities across Tanzania and Uganda. Adults aged 18 years or older with a diagnosis of HIV, type 2 diabetes, or hypertension (or a combination); receiving regular care at the health facility for at least 6 months; considered clinically stable; living within the catchment area and planning to stay for at least 6 months; and willing to receive care in the community were enrolled. In each facility, patients were grouped into clusters of 8–14. Each group was randomly assigned (1:1) using an online data management system, to integrated facility care or community care. In facility care, participants shared the same registration and waiting areas, were managed by the same physicians and health-care workers, and used the same pharmacy and laboratory services. In community care, a nurse and a trained lay worker supported the groups at focal points in the community with groups meeting once per month. Follow-up was 12 months. The first coprimary endpoint was a composite of blood pressure or fasting glucose control (defined as blood pressure <140/90 mm Hg in participants with hypertension alone, fasting glucose <7·0 mmol/L in those with diabetes alone, or both indicators controlled in those with both conditions) and the second was plasma viral load suppression for participants with HIV alone (defined as <1000 copies per mL or undetectable viral load). Both endpoints were assessed in the intention-to-treat population. Generalised estimating equation models accounted for clustering. This trial was registered with the ISRCTN registry, ISRCTN15319595 (completed). Findings Between Jan 30 and Oct 6, 2023, 2940 patients with HIV, diabetes, or hypertension (or a combination of these conditions) who lived close enough together to be placed into a group were identified as having appointments to attend at the participating facilities. 765 (26·0%) patients were not screened and 2175 (74·0%) were screened for eligibility. 203 (9·3%) patients were ineligible, four (0·2%) did not consent, and 104 (4·8%) could not be grouped into viable clusters. 1864 (63·4%) patients were assigned into 124 groups, and groups were randomised (62 to community care and 62 to facility care). There were more females than males (1302 [76·6%] of 1700 vs 398 [23·4%]). Among those with diabetes or hypertension (or both), 38 (6·3%) of 602 in the community care group versus 43 (7·1%) of 609 in the facility care group were excluded, with nine (3·7%) of 242 versus ten (4·0%) of 247 excluded among participants with HIV. The composite of blood pressure or fasting glucose control did not significantly differ between the two groups in participants with hypertension or diabetes (or both; 317 [55·2%] of 574 in the community care group vs 304 [53·2%] of 571 in the facility care group; adjusted risk difference 1·80 [95% CI –4·52 to 8·12]; p=0·58), whereas most participants with HIV alone reached viral suppression (227 [99·1%] of 229 vs 229 (98·7%) of 232; adjusted risk difference 0·44 [–1·12 to 1·99]; pnon-inferiority<0·0001). There were seven deaths in each study group. Interpretation In sub-Saharan Africa, integrated community care could reach a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV. Funding National Institute for Health and Care Research.</p
Start4All protocol for a Bayesian cost-effectiveness model of tuberculosis screening and diagnosis in seven high burden low-income and middle-income countries
Full text linkINTRODUCTION: High costs of screening and diagnostic tests remain a major barrier to timely tuberculosis (TB) identification in resource-limited settings. Evidence on the cost-effectiveness of scalable screening algorithms is limited. Start4All is a research project aimed at developing and evaluating algorithmic approaches to TB screening and diagnosis, with the goal of optimising technical and allocative efficiency when expanding diagnostic coverage to primary healthcare and community settings. METHODS AND ANALYSIS: Five screening and diagnostic tests will be evaluated: a capillary blood-based assay (C-reactive protein (CRP)), sputum-based rapid molecular tests (PCR; individual and pooled Xpert MTB/RIF Ultra assay (Xpert Ultra, Cepheid®, California, USA)), a lateral-flow urine-based test for lipoarabinomannan (LF-LAM), and digital chest X-rays with artificial intelligence-based computer-aided detection (CXR-CAD). A microbiological reference standard of positive culture using the mycobacteria growth indicator tube will be used to confirm TB disease. We will compare the cost and effectiveness of concurrent and sequential positive serial combinations (screening algorithms) of CRP, CXR-CAD, LF-LAM, individual and pooled Xpert Ultra. Diagnostic performance will be estimated using sensitivity, specificity, predictive values and proportions of positive results, with Bayesian inference used to derive these estimates. The analysis will include adults (15 years and older) only and will be stratified by HIV status and level of care, including facility and community-based case finding. Effectiveness will be assessed based on the number of people with TB detected. Cost analysis will be conducted from the provider perspective, incorporating commodity and implementation costs. A decision tree model will be developed to assess the cost per number of persons with confirmed TB detected across all countries. Probabilistic sensitivity analysis will be conducted to account for uncertainty in model parameters, incorporating willingness-to-pay and willingness-to-accept thresholds. ETHICS AND DISSEMINATION: WHO ethical review committee approval ERC.0003921. Data will be available on reasonable request to the principal investigator of the consortium. </p
Travel-associated carbapenem-resistant organisms at a time of increasing geopolitical instability:a UK perspective
Full text linkBackground: Conflict and catastrophe compromise multi-national healthcare delivery and present risks for the spread of carbapenem-resistant organisms (CROs). The risk of and ability to detect travel-associated CROs in the UK remain unclear. Methods: A 10-question survey was sent to microbiology/infection prevention and control (IPC) practitioners of 108 UK acute NHS Trusts/Regions/Boards, exploring recent experience and IPC practices for travel-associated CROs and approaches to extended-spectrum antimicrobial testing. Additionally, major trauma network centres were invited to review detected carbapenemase-producing organism (CPO) molecular data from March 2022 to April 2024, comparing associated travel by the World Health Organization global region using one-way analysis of variance. Results: Seventy-three surveys were returned. IPC approaches were highly variable, with 19 of 73 (26.0%) centres requiring modification to national screening guidelines. Twenty-four of 73 (32.9%) centres reported CROs associated with recent travel to major conflict areas. Twelve major trauma network centres contributed to review of detected CPOs, finding 297 of 1290 (23.0%) individuals with travel to 52 different countries. In total, 227 of 297 (76.4%) were screening results; 279 of 297 (93.9%) were Enterobacterales. A total of 112 of 297 (37.7%) had travelled to Europe, where carbapenemase diversity was greater than elsewhere (P < 0.001).Interpretation: A considerable range of UK centres are detecting CROs associated with travel to areas of current major conflict. A more didactic approach to travel history on the first contact with healthcare services is required to stratify CPO risk at admission. These data should be collected prospectively in parallel with projects which successfully embed taking an effective travel history to assess the risk of travel-associated infectious disease. This will allow clearer understanding of travel behaviours and trends, delineate risk and inform effective IPC.</p
Mapping resilience in conflict and recovery: A systems analysis of the health sector in Ethiopia’s Tigray region (2020–2025)
Full text linkThis study explores the resilience of the health system in Tigray (Ethiopia) in the period during and following the most recent conflict (2020–2025). The aim is to gain an understanding of the dynamic ways in which the health system has responded to the crisis and early recovery, highlighting elements of its resilience, including the resilience strategies (adaptation, absorption and transformation), resilience capacities (i.e., underlying broader capacities that the health system must have in place in order to deploy specific approaches) and resilience pathways. The study is grounded in a resilience framework and adopts a systems thinking approach, drawing on data from a documentary review, key informant interviews and focus groups in Tigray. The findings illustrate the impact of the war on elements of the health system, and the resilience strategies adopted within each element to sustain some extent the health system functionality during the conflict as well as the (longer-term) health system recovery. Based on the findings, a Causal Loop Diagram is developed, which helps to identify key emerging resilience capacities (the motivation, dedication and individual coping strategies of health workers; community trust in healthcare providers; and the regional health authority’s leadership), highlighting causal, balancing or reinforcing loops and pathways between elements, and critically exploring how resilience strategies, capacities and pathways connect and interrelate, sustaining some elements of the health system, preventing collapse and potentially supporting a return to a fully functioning healthcare system. Findings provide evidence that could support the reconstruction and recovery efforts in Tigray, and might inform recovery planning in other settings post-conflict
Chlorfenapyr bednets effectively overcome pyrethroid resistance escalation in highly resistant Anopheles malaria vectors in Uganda
Full text linkEscalating insecticide resistance threatens the efficacy of LLINs, undermining malaria control in Africa. We conducted the first experimental hut trials in Uganda using highly resistant free-flying wild Anopheles mosquitoes and F2 hybrids of FANG and Uganda An. funestus to evaluate the performance of bednets. The interceptor G2 (chlorfenapyr) bednet demonstrated superior efficacy compared to Interceptor (pyrethroid-only) net [mortality odds ratio (OR): 18.7 (8.05–48.6) P < 0.0001], achieving an overall mortality rate of 70.6% and 63.2% against An. funestus and An. gambiae respectively. In contrast, PermaNet 3.0 and Olyset Plus (piperonyl butoxide (PBO)) and Royal Guard (pyriproxyfen (PPF)-treated) bednets exhibited significantly lower mortality against An. funestus [Olyset Plus: 36.1%, PermaNet 3.0: 31.0% and Royal Guard (37.6%], though performance against An. gambiae was moderate [PermaNet 3.0: 61.4%, Olyset Plus: 50.0%, Royal Guard: 51.6%]. Interceptor net produced the lowest mortality (~ 25%) against both species. Regarding blood-feeding inhibition (BFI), PBO nets, particularly Olyset Plus, outperformed Interceptor G2 and Royal Guard, while Interceptor produced minimal BFI (< 36%). Further evaluation of Royal Guard’s PPF effect on oviposition revealed no significant reduction in oviposition rates compared to controls with An. funestus (63.9% vs. 63.3%, P > 0.05). Genetic analysis using the hybrid crosses revealed that pyrethroid resistance markers (4.3 Kb-SV and G454A-Cyp9K1) were significantly associated with mosquito survival and blood-feeding success against PermaNet 2.0 (pyrethroid-only) and PermaNet 3.0 but showed no significant association with Interceptor G2 net. These findings support Interceptor G2 as a promising intervention for regions dominated by both highly resistant An. funestus s.l. and An. gambiae s.l. Piperonyl butoxide and PPF nets emerge as a good alternative for areas mostly dominated by resistant An. gambiae s.l. populations. Critically, the demonstrated variable impact of insecticide resistance on bednet efficacy underscores the imperative need for a comprehensive vector distribution mapping, continuous field efficacy assessments, and systematic resistance monitoring. This evidence-based triad should guide strategic LLIN distribution and rotations to sustain malaria control efficacy in resistance-prone settings.</p