The National Institute for Medical Research (commonly abbreviated to NIMR), was a medical research institute based in Mill Hill, on the outskirts of north London, England. It was funded by the Medical Research Council (MRC);In 2016, the NIMR became part of the new Francis Crick Institute, which was constructed next to St Pancras railway station in the Camden area of central London.
BACKGROUND:People living with HIV and hospitalised with sepsis in Africa are at risk of death due to tuberculosis but diagnostics for tuberculosis might be delayed or inaccessible for people presenting for critical care. We aimed to compare the effects of immediate empirical and high-dose antituberculosis therapy on 28-day mortality in adult people living with HIV with sepsis in east Africa. METHODS:ATLAS was a phase 3, open-label, randomised, controlled, 2 × 2 factorial, superiority trial conducted at four hospitals in Tanzania and Uganda. Participants were aged 18 years or older, living with HIV, and had been admitted to hospital with sepsis with two or more modified quick Sequential Organ Failure Assessment score criteria. Exclusion criteria were active tuberculosis or receipt of antituberculosis therapy within 6 months of hospitalisation, pregnancy or lactation, allergies to antituberculosis therapy, another investigational drug within the past month, chronic liver disease, heavy alcohol use, positive serum cryptococcal antigen, or anticipated significant drug-drug interaction with rifampicin. A computer-generated permuted-block algorithm with allocation concealment and random block sizes of four and eight randomly assigned participants (1:1) to receive either immediate or diagnosis-dependent antituberculosis therapy, and (1:1) to receive either high-dose or conventional WHO-recommended weight-based dose antituberculosis therapy. Allocation was stratified by country and the presence of altered mental status at the time of randomisation. Participants randomly assigned to conventional-dose antituberculosis therapy received fixed-dose combination tablets of rifampicin approximately 10 mg/kg, isoniazid approximately 5 mg/kg, pyrazinamide, and ethambutol, plus pyridoxine 50 mg orally. Participants randomly assigned to receive high-dose antituberculosis therapy received rifampicin approximately 30 mg/kg and isoniazid approximately 7·5 mg/kg as a combination of single formulation tablets and fixed-dose combination tablets that included WHO-recommended weight-based doses of pyrazinamide and ethambutol, plus pyridoxine. Participants continued immediate antituberculosis therapy for 28 days. All medications were administered daily. Participants in the diagnosis-dependent antituberculosis therapy groups received treatment based on a clinical or microbiological diagnosis of tuberculosis. All participants received 2 g intravenous ceftriaxone daily for 7 days. The primary endpoint was 28-day mortality analysed in the modified intention-to-treat population and in the subgroup with later confirmed tuberculosis. We defined the survival time for each participant as the time from randomisation until death, discharged (alive) by day 28, or censored (alive) at day 28. We graded adverse events according to recommendations from the National Institutes of Health Division of AIDS. This study was registered with ClinicalTrials.gov, NCT04618198, and is completed. FINDINGS:Between Jan 5, 2022, and Dec 9, 2024, 707 people were screened for eligibility and 437 were randomly assigned (110 to immediate conventional-dose, 112 to immediate high-dose, 107 to diagnosis-dependent conventional-dose, and 108 to diagnosis-dependent high-dose antituberculosis therapy). 395 patients (226 [57%] of whom were female and 169 [43%] were male; all participants were Black) received study intervention and were analysed for the primary outcome of 28-day mortality. We confirmed tuberculosis in 204 (52%) patients. There was no evidence of differences in 28-day mortality in immediate antituberculosis therapy groups (50 deaths [25%] in 198 patients) compared with diagnosis-dependent groups (50 deaths [25%] in 197 patients; adjusted hazard ratio [aHR] 0·99 [95% CI 0·67-1·46]; p=0·95), or in high-dose antituberculosis therapy groups (51 deaths [26%] in 199 patients) compared with conventional-dose groups (49 deaths [25%] in 196 patients; aHR 1·07 [0·72-1·59]; p=0·73). In patients with microbiologically confirmed tuberculosis, the 28-day mortality relative to the diagnosis-dependent conventional-dose group (18 deaths [34%] in 53 patients) was lower for the immediate conventional-dose group (six deaths [12%] in 51 participants; aHR 0·32 [95% CI 0·13-0·82]; p=0·015); for the diagnosis-dependent high-dose group (11 deaths [20%] in 56 patients) was 0·51 (0·24-1·08; p=0·079); and for the immediate high-dose group (11 deaths [26%] in 43 patients) was 0·63 (0·29-1·36; p=0·24). No significant differences in adverse events occurred between treatment groups but numerically more events of drug-induced liver injury occurred in the immediate high-dose group compared with any other group. INTERPRETATION:Among all participants with HIV-related sepsis, 28-day mortality was not significantly reduced with immediate or high-dose antituberculosis therapy. In the subgroup with later confirmed tuberculosis, immediate conventional-dose antituberculosis therapy significantly reduced 28-day mortality, suggesting, as in other forms of bacterial sepsis, that hours to active treatment might determine survival. FUNDING:US National Institutes of Health.
Persistent SARS-CoV-2 transmission, ongoing mpox outbreaks, and the continued spread of endemic diseases such as typhoid fever and cholera underscore the urgent need for global, multiomics surveillance. In this Personal View, we present Project ODIN, a consortium of European and African partners launched in 2023 that aims to meet this challenge by deploying innovative systems for near real-time pathogen detection and actionable public health insights. The project is a collaboration between high-income and low-income countries in northern Europe and sub-Saharan Africa. Focusing on low-income and middle-income countries, ODIN integrates metagenomics with mobile laboratory systems for comprehensive pathogen monitoring across diverse environments. ODIN emphasises standardised sampling, bioinformatics pipelines, and data-sharing protocols to ensure reliable, interoperable results while addressing infrastructure and resource limitations. By bridging gaps in genomic surveillance, these initiatives seek to strengthen outbreak preparedness, improve pathogen detection, monitor antimicrobial resistance, and provide a holistic approach to One Health challenges. Together, these innovations could advance global surveillance capacity-particularly in under-resourced regions-paving the way for effective disease control and evidence-based policy making.
Abstract Background Despite decades of control efforts. malaria burden in Tanzania remains high, with marked heterogeneity in transmission intensity across regions. Insecticide-treated bed nets (ITNs) are a core malaria intervention and are distributed through multiple channels in Tanzania to promote equitable access and use, yet disparities in ITNs ownership and use persist. This study evaluated socio-demographic predictors of ITNs ownership and use among rural communities from five regions with varying malaria endemicity. Methods A community-based cross-sectional survey covering individuals aged ≥ 6 months was conducted from July to August 2023 in 15 villages across five districts from five regions of Mainland Tanzania (Kagera, Kigoma, Njombe, Ruvuma, and Tanga). Data on demographics, malaria prevention practices, anthropometrics and socio-economic status (SES) were collected using structured questionnaires installed in tablets, run with Open Data Kit (ODK) software. Socio-demographic predictors of ITNs ownership and use were assessed using logistic regression analysis. The results were reported as crude (cOR) and adjusted odds ratios (aOR) with 95% confidence intervals (CI) and a p-value < 0.05 was considered statistically significant. Results Among the 10,228 enrolled participants, 7939 (77.6%) and 7899 (77.2%) reported owning and using ITNs, respectively. ITNs ownership and use varied significantly across districts (p < 0.001), with the highest rates observed in Nyasa (Ruvuma) and the lowest in Kyerwa (Kagera). Females had higher odds of both ITNs ownership and use than males (aOR = 1.27, 95% CI 1.12–1.45, p < 0.001 for both outcomes). Under-fives were more likely to own (aOR = 1.83, 95%CI 1.56–2.15, p < 0.001) and use ITNs (aOR = 2.26, 95%CI 1.62–3.15, p < 0.001) than adults. Participants from Nyasa (Ruvuma), Ludewa (Njombe), Muheza (Tanga) and Buhigwe (Kigoma) districts exhibited higher odds of ITNs ownership and use compared to those from Kyerwa (Kagera) (p < 0.001). Higher education attainment and household SES were independently associated with increased ITNs ownership and use (p < 0.001). Conclusion Although ITNs ownership and use were relatively higher across the surveyed communities, coverage remained below the national target of 80% (projected for 2023). Higher ITNs ownership and use were reported among females, under-fives, participants with higher education and those from households with high SES. Disparities by sex, age groups, household SES and education status persist and should be explicitly addressed through ITNs distribution strategies to enable equitable access and use of ITNs across all population groups to expedite progress toward malaria elimination in Tanzania.
Tuberculosis (TB) remains a major public health challenge in Tanzania, with both drug-sensitive and drug-resistant strains contributing to significant mortality. This study presents a mathematical model to analyze TB transmission dynamics from 2018 to 2023, incorporating treatment interventions, nutritional supplements, and community awareness as control strategies. A cost-effectiveness analysis of three optimal control strategies is conducted using numerical simulations. Results show that combined treatment with appropriate drugs for both TB strains is the most cost-effective approach, significantly reducing infection rates. In contrast, single interventions offer limited impact. The findings emphasize the importance of timely, targeted, and combined interventions to effectively control TB spread. Therefore, the study suggests that to attain effective control of TB, both infected groups should be treated accordingly and simultaneously which will significantly lead to the decline rate of exposed and infectious, and hence the disease infection spread will be controlled.
Tuberculosis (TB) remains a major global health problem, and its control is increasingly challenged by the rise of drug-resistant Mycobacterium tuberculosis (MTB). This study investigates the development and spread of resistance to the first-line drugs isoniazid and rifampicin using resistance data collected from Tanzania. A two-hypercubic dynamical model was developed that represents all possible pathways of resistance acquisition and used the data to estimate the model parameters. Local and global sensitivity analyses were then carried out to identify the parameters with the greatest influence on resistance dynamics. Phase portrait analysis was used to explore interactions among the model compartments, revealing important patterns in resistance transitions. In addition, several treatment and intervention scenarios were simulated to examine their potential impact on reducing drug resistance. The results provide useful insights into how resistance evolves, identify key factors that drive resistance, and offer evidence-based guidance for improving TB treatment strategies. Overall, the study highlights the importance of data-driven modelling in supporting public health decision-making for drug-resistant TB.
