Swiss Tropical and Public Health Institute

Background The analysis and interpretation of pharmacovigilance data is an essential component of the continuous benefit-risk assessment of authorised medicinal products. Effective pharmacovigilance data analysis starts with data collection and involves critical activities, such as signal detection, that enable the generation of new information on marketed products, and inform safety-related regulatory actions. This real-time pharmacovigilance data analysis, which requires efficient collaboration and exchange of information between the key pharmacovigilance stakeholders, represents a challenge for many low- and middle-income countries (LMIC). Objectives To assess the capacity for analysis of pharmacovigilance data in LMIC and to identify mechanisms to strengthen data analysis, interpretation and evidence-based pharmacovigilance decision-making. Design We used a convergent parallel mixed-methods study design consisting of qualitative and quantitative methods. Methods Qualitative and quantitative methods consisted of semi-structured interviews and an online survey, respectively. Quantitative research was complemented by cross-sectional analyses of the number of adverse event reports from LMIC in VigiBase® from 2019 to 2023. Results Nine key informants from eight countries were interviewed and 50 respondents from 34 countries completed the online survey. Four major themes emerged from the data and are proposed as transformative actions to strengthen pharmacovigilance data analysis and interpretation in LMIC: build on existing pharmacovigilance data analysis capacity rather than create new or parallel mechanisms; implement standardised procedures to enable efficient data analysis; augment the work of the safety committees by assigning pharmacovigilance staff to data analysis; and implement mechanisms that allow benefit-risk evaluation and decision-making. Conclusions Findings from this research revealed that many LMIC have implemented procedures for reporting and collecting suspected adverse events, but a considerable proportion of the data collected is not analysed in-country due to a lack of requisite knowledge, processes and structures to support such analysis. Establishing the four essential elements proposed by this research will equip LMIC for efficient data analysis, thereby supporting consistent decision-making through pharmacovigilance.

Background The association between long-term ambient air pollution and adult lung function has been inconsistently reported. This systematic review and meta-analysis aimed to quantify the impact of long-term (≥1 year) ambient air pollution on adult lung function. Methods Original articles published between 1 January 2006 and 26 July 2024 were searched in PubMed, Embase and Web of Science. Random-effects models were used to assess the strength of associations of gaseous (nitrogen dioxide and ozone) and particulate matter (PM) pollutants with diameters ≤2.5 and 10 µg, with lung function (forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC ratio). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) approach. Results Of 25 064 potential papers, 27 were included, of which 12 were meta-analysed. There was low-certainty evidence that a 10 µg·m ⁻³ increase in long-term NO 2 exposure was associated with lower FEV 1 (−15.6 mL, 95% CI −25.0– −6.2; I ² =86%; p<0.01) and high-certainty evidence for FVC (−25.3 mL, 95% CI −36.7– −14.0; I ² =70%, p<0.01). Similar associations were observed for PM 2.5 , while long-term exposure to O 3 and PM 10 were associated with lower FEV 1 with high- and moderate-certainty evidence, respectively. Exposure to O 3 was associated with lower FEV 1 /FVC (high-certainty evidence). Interpretation Long-term exposure to ambient air pollution adversely impacts adult lung function. This emphasises the importance of ongoing commitments to mitigating air pollution levels to preserve optimum lung health and prevent premature lung function decline that can lead to earlier and avoidable respiratory diseases.

Background There has been notable progress in pharmacovigilance (PV) in low- and middle-income countries (LMIC) in the last decade. However, only a few of these PV systems are fully functional, unlike in high-income countries where stringent legislation, regulations and operational guidelines have enabled the establishment of effective PV systems. The key challenges faced in LMIC include organisational inefficiencies; weak infrastructure; inconsistent and poorly enforced regulations; and inadequate financing and shortage of trained personnel. Furthermore, low adverse event volume and poor data quality hinder the capacity for safety data generation and utilisation. With the increasing availability of essential and innovative medicines in LMIC, establishing robust PV systems is crucial for effective safety surveillance. Objectives This research aims to analyse the development of PV systems across high-, middle- and low-income countries and to carve out essential elements for functionality and sustainability of PV systems in LMIC. Design A convergent parallel mixed-methods design, combining qualitative and quantitative methods. Methods Qualitative and quantitative research consisted of semi-structured interviews and an online survey, respectively. Results Twelve key informants from 10 countries were interviewed and 52 respondents from 36 countries completed the online survey. From the qualitative and quantitative data, we identified nine essential elements for sustainable PV development in LMIC: understanding the drivers of PV development; adequately resolving core system challenges; implementing an efficient organisational structure and good governance; establishing procedures for PV activities; ensuring availability of qualified and trained staff; identifying alternate sources of financing; having a strategic development plan; adequately leveraging the health system; and effectively integrating the pharmaceutical sector in the national PV system. Conclusion Findings from this research indicate that significant efforts are still needed to upgrade PV systems in LMIC to meet global standards despite the progress achieved in recent years. Developing the different areas emerging from this research, within the framework of a holistic, fit-for-purpose PV system strengthening, would enable a comprehensive progression from basic to functional and thus sustainable PV systems in LMIC.

Background The presence of a community effect in cluster randomized trials of malaria vector control interventions has led to the implementation of “buffer zones” around clusters to limit the potential for contamination between interventions. No consensus has been reached on how large these buffers need to be to encapsulate the effect. Methods Nested within a phase-III cluster randomized malaria vector control trial in Northwest Tanzania, this study aims to determine the presence and spatial range of community effects from long-lasting insecticidal net (LLIN) and indoor residual spraying (IRS) interventions on household-level malaria infection in trial clusters four months post-intervention. Effective spatial range estimates of intervention community effects were compared to the 300m buffer distance implemented to limit intervention spillover between clusters in the trial. Geographically-weighted adjusted odds of malaria infection in children aged 0.5–14 years were determined four months post community-level intervention with a randomized allocation comprising one of two LLIN products (OlysetTM LN: 1000mg/m² permethrin or OlysetTM Plus LN: 400 + permethrin 800mg/m²) with either IRS (Actellic®300CS: 1000mg/m² micro-encapsulated pirimiphos-methyl) or no IRS. Robust semivariances were calculated for each of 48 intervention clusters and fit to semivariogram models by Weighted Least Squares. Results 6440 children from 2785 households were included in the geographically-weighted logistic regression. Prevalence of Plasmodium falciparum infection was 45.9% in the study population. Twenty (20) clusters had significant residual effect ranges, 13 of which were fit to Sine Hole Effect models, indicating periodicity in the study area. Effective range estimates for the study area had a median value of 1210 m (IQR: 958–1691). Clusters with IRS had a higher median range value: 1535 m (IQR: 976–3398) than those without IRS: 1168m (IQR: 829–1504). Conclusions Significant semivariogram model range estimates extended beyond the trial buffer sizes by a median average of 868 m in LLIN intervention clusters and 1235 m for IRS clusters. This presents a contamination, or spillover, potential for all trialed intervention types that may reduce the statistical power to detect difference between trial arms. Future studies should consider the ranges of intervention effects and contamination potential between trial arms when designing buffer areas.

Background Installing insecticidal netting on open eaves, windows, and holes in walls of unimproved houses is a potential malaria control tool. It prevents mosquito house-entry, induces lethal and sub-lethal effects on malaria vectors, and may reduce malaria transmission. Therefore, a household epidemiological trial was conducted to assess the efficacy of insecticide-treated screening (ITS) on malaria infection and indoor vectors in Tanzania. Methods In Chalinze district, Tanzania, 421 households were randomized into two arms. In June-July 2021, one group of households’ houses was fitted with ITS (incorporated with deltamethrin and piperonyl butoxide) on eaves, windows, and wall holes, while the second group did not receive screening. After installation, consenting household members (aged ≥ 6 months) were tested for malaria infection using quantitative polymerase chain reaction after the long rainy season (June/July 2022, primary outcome) and the short rainy season (January/February 2022, secondary outcome). Secondary outcomes included indoor total mosquito per trap/night (June–July 2022), adverse effects after one month of ITS installation (August 2021), and chemical bioavailability and retention of ITS samples after one year of field use (June/July 2022). At the end of the trial, the control group received ITS. Results Malaria prevalence among residents in the ITS arm was 19.9% (50/251) and 28.3% (65/230) in the control arm after the long rains, however, this difference was not significant [adjusted odds ratio (OR) 0.67 (95% CI 0.35–1.28), p = 0.227]. Similarly, no protection was seen for ITS after the short rains, [OR 1.27 (95% CI 0.68–2.38), p = 0.452]. However, school-age children in the ITS arm had lower malaria after the long rains [OR 0.11 (95% CI 0.02–0.73), p = 0.022]. No serious adverse effects were reported. The mean number of female Anopheles mosquitoes caught per trap/night was not significantly different between arms [1.7 vs 2.4, crude relative risk: 0.71 (95% CI 0.16–3.09), p = 0.650]. ITS showed reduced chemical bioavailability and retention post-field use. The trial reported high household refusals (17–30%) in both arms in both surveys. Conclusion The trial was inconclusive because households' refusal resulted in low power. A large cluster randomized trial of the intervention, preferably with screens treated with longer-lasting insecticides installed in houses, is needed. Trial registry: The trial was registered at ClinicalTrials.gov (NCT05125133) on October 2021

Objectives Adolescent health is critical for achieving Sustainable Development Goal 3, ‘health for all at all ages’. In sub-Saharan Africa (SSA), mining projects hold promise for social and economic development. Yet, the extent to which the health and well-being of adolescents are impacted by industrial mining is poorly understood. In this paper, we aim to investigate how adolescent health and well-being is perceived by key informants and caregivers in communities that have been affected by industrial mining projects in Mozambique. Design and settings A qualitative study was implemented from May–July 2022 in two rural districts in Mozambique’s northern and central regions. Both districts have large industrial mining projects: a coal mine in Moatize district and a mineral sands mine in Moma district. Participants A total of 21 key informant interviews (KIIs) were conducted with a range of stakeholders, including health professionals and civil society and private sector representatives. In addition, four focus group discussions (FGDs) were conducted with adolescents’ caregivers. Results Through the combined results from the KIIs and FGDs, four main health concerns affecting adolescents in mining areas were identified: sexually transmitted infections, respiratory tract infections, diarrhoeal diseases and malaria. Mining activities were perceived to exacerbate negative health effects and contribute to poor health outcomes among adolescents. Although mining companies invested in public infrastructure, most participants did not perceive this investment as a positive contribution to the health and well-being of adolescents. Conclusion Our study sheds light on the multifaceted challenges perceived by stakeholders that adolescents residing in mining communities in Mozambique face. Insufficient priority is given to effective interventions that specifically target adolescent health in the two study mining areas. In order to leave no one behind, as stipulated by the sustainable development agenda, more emphasis should be placed on the role and responsibility of mining companies in adequately addressing adolescents’ unique health needs in mining settings in SSA.

Non-communicable diseases (NCDs) account for most of global deaths, with rising prevalence in low-and middle-income countries. Metabolic syndrome (MetS) is a cluster of interrelated NCD risk factors, including obesity, dyslipidaemia, hypertension, and hyperglycaemia, that amplify NCD risk. Four leading modifiable factors driving NCDs are physical inactivity, tobacco and alcohol use, and an unhealthy diet. Teachers in under-resourced schools face significant health challenges, with their wellbeing often overlooked in South Africa. The prevalence and severity of MetS, adherence to physical activity guidelines, and associations with modifiable NCD risk factors were assessed. This study, part of the ‘KaziBantu: Healthy Schools for Healthy Communities’ project, included 168 teachers (aged 21–72, mean = 47 years) from 8 under-resourced schools in Gqeberha, South Africa. Data collection included MetS markers, device-measured physical activity, tobacco and alcohol use, and total fat, saturated fat, sugar, and sodium intake. Covariates included age, sex, race, education, and household income. MetS was observed in 58% of participants, with central obesity (79%) being the most prevalent component, followed by hypertension (59%). The largest proportion of participants (26%) had 3 MetS components, followed by 4 components (20%), while 12% had all 5 components. Nearly half (44%) of teachers were physically inactive and 53% exceeded total fat intake recommendations. Bayesian multilevel logistic regression revealed key predictors of MetS: age (per year increase; odds ratio[OR]=1.15, 95% credible interval[CrI] [1.07, 1.24]) and high daily total fat intake (OR=3.37, 95%CrI [1.03, 11.96]) were positively associated, while hours spent in moderate-to-vigorous intensity physical activity per week (OR=0.73, 95%CrI [0.55, 0.95]) and higher monthly household income (OR=0.14, 95%CrI [0.02, 0.72]) were protective. Addressing physical inactivity and unhealthy diets through tailored interventions is crucial to reducing MetS prevalence and improving the health of teachers working in low-resourced settings. Effective solutions should empower healthier lifestyles while tackling structural barriers to health equity.

Maintaining fitness is an important consideration when mosquitoes are mass‐reared for the deployment of genetic interventions that are designed to suppress populations because released mosquitoes need to compete with wild‐type mosquitoes. Late‐hatching mosquitoes are more suitable for transportation to remote field sites. Here, we investigated the fitness of late‐hatching phenotypes in Anopheles coluzzii . Selected lines of the VK strain (from Burkina Faso) were created through bidirectional selection for early and late hatching, over 20 generations. These were compared with each other and the established Mopti reference strain from Mali, reared in the lab for >16 years. Significant differences in life‐history traits were found between Mopti and VK strains but few differences were found between the selected VK lines. Considering that late‐hatching VK lines showed no evidence of fitness costs, our results suggest that the late selected VK lines, which start hatching after 4 days, are an alternative option for egg shipment for mass mosquito releases over the well‐established Mopti that hatches within 2 days and has lower adult survival.

Background SARS-CoV-2 (COVID-19) has emerged as a significant global public health challenge, revealing critical vulnerabilities within health systems worldwide. While extensive data on COVID-19 is available from high-income countries, information remains scarce in lower-income regions, particularly regarding its impact on pregnant women. This study aims to evaluate the burden of COVID-19 among pregnant women and its effects on maternal and birth outcomes during the third wave in Benin. Methods A cross-sectional, hospital-based survey was conducted from May 19 to September 19, 2022, at the Lagune Mother and Child Teaching Hospital. A standardized questionnaire was administered, and nasal swabs along with serological analysis were performed on 437 pregnant women. Multivariate logistic regression was used to assess risk factors and evaluate the impact of previous or current COVID-19 exposure on maternal and birth adverse outcomes. Results SARS-CoV-2 was detected in less than 1% of pregnant women through PCR testing of nasal swab samples. Among the study population, 14.4% of women were vaccinated against COVID-19. A total of 81.1% of women tested positive for antibodies, suggesting prior exposure or infection to SARS-CoV-2 or vaccination. Notably, 78.6% of unvaccinated women had detectable antibodies, which serves as a more accurate proxy for infection prevalence. No significant association was found between prior COVID-19 exposure and adverse maternal and birth outcomes (aOR: 0.48, 95% CI 0.15–1.51). Conclusions Although PCR testing revealed a low incidence of active SARS-CoV-2 infection, the high prevalence of IgG antibodies among pregnant women suggests widespread prior exposure or infection. Vaccination was identified as a strong predictor of detectable IgG antibodies. Notably, despite the presence of antibodies, no significant association was found between prior COVID-19 exposure and adverse maternal or birth outcomes. These findings highlight the need for further research to explore the potential long-term effects of COVID-19 infection on pregnancy outcomes and to better understand the relationship between antibody presence and maternal and fetal health. Supplementary Information The online version contains supplementary material available at 10.1186/s13690-025-01633-0.

Digital clinical decision support algorithms (CDSAs) that guide healthcare workers during consultations can enhance adherence to guidelines and the resulting quality of care. However, this improvement depends on the accuracy of inputs (symptoms and signs) entered by healthcare workers into the digital tool, which relies mainly on their clinical skills, often limited, especially in resource-constrained primary care settings. This study aimed to identify and characterize potential clinical skill gaps based on CDSA data patterns and clinical observations. We retrospectively analyzed data from 20,085 pediatric consultations conducted using an IMCI-based CDSA in 16 primary health centers in Rwanda. We focused on clinical signs with numerical values: temperature, mid-upper arm circumference (MUAC), weight, height, z-scores (MUAC for age, weight for age, and weight for height), heart rate, respiratory rate and blood oxygen saturation. Statistical summary measures (frequency of skipped measurements, plausible and implausible values) and their variation in individual health centers compared to the overall average were used to identify 10 health centers with irregular data patterns signaling potential clinical skill gaps. We subsequently observed 188 consultations in these health centers and interviewed healthcare workers to understand potential error causes. Observations indicated basic measurements not being assessed correctly in most children; weight (70%), MUAC (69%), temperature (67%), height (54%). These measures were predominantly conducted by minimally trained non-clinical staff in the registration area. More complex measures, done by healthcare workers in the consultation room, were often skipped: respiratory rate (43%), heart rate (37%), blood oxygen saturation (33%). This was linked to underestimating the importance of these signs in child management, especially in context of high patient loads at primary care level. Addressing clinical skill gaps through in-person training, eLearning and regular personalized mentoring tailored to specific health center needs is imperative to improve quality of care and enhance the benefits of CDSAs.

Animal Assisted Interventions (AAIs) have been shown to have several effects in humans but the underlying cerebral mechanisms are still widely unknown. This research explored the neurological aspects of human–animal interactions. Specifically, we focused on frontal alpha asymmetry (FAA), a feature indicating differences in alpha power between the left and right frontal cortex, which is recognized as a correlate of approach motivation and positive affect. Twenty-nine healthy adults participated in this study, in which we used electroencephalography to measure their brain activity. The study comprised five phases: baseline measurements, interaction with a real dog, interaction with a replica dog, interaction with a plant, and a neutral phase. Participants had both physical and visual contact with the real dog, the replica and the plant, and the procedure was repeated three times for each participant. We also assessed participants’ subjective experiences of mental states and intrinsic motivation through the Multidimensional Well-Being and the Intrinsic Motivation Inventory questionnaires. The objective measurements of motivation and positive affect through FAA did not show a significant difference between interactions with a real dog and control conditions, but the subjective assessments differed. Participants reported significantly higher motivation and a more positive state of mind after interacting with a real dog compared to the control conditions. These results could be considered in therapeutic settings when determining whether to incorporate an animal into a treatment plan. In summary, this study highlights the complexity of human–animal interactions (HAI) and shows an intricate interplay between objective and subjective measurements. Our findings emphasize the importance of considering both neural markers and subjective experiences for understanding the nuanced mechanisms involved in the meaningful connections humans have with animals.

Plasmodione is a potent early antiplasmodial compound. A metabolic study on mice treated with plasmodione revealed that 6-hydroxy–plasmodione was the main metabolite eliminated in the urine of treated mice. To block the metabolic pathway in the host, the introduction of fluorine at C-6 of the 3-benzylmenadione core was applied and showed potent antiplasmodial activity similar to that of the plasmodione analogue in vitro. In this work, a library of 38 6-fluoro-3-benzylmenadione analogues (a series) was constructed by incorporating structurally diverse groups in place of the 4-(trifluoromethyl) substituent present in the antiplasmodial plasmodione, via three synthetic routes. All new compounds were tested against the P. falciparum NF54 strain and for cytotoxicity with the rat L6 line. With a fluorine atom at C-6, A-a-21 was revealed to be the only compound from the a series, superior to the 6-H- analogue from the b series, with an IC50 value of 70 nM versus 200 nM. Then, five other fluorine-based 3-benzylmenadiones, in which the fluorine was introduced in various positions of the 3-benzylmenadione core, were synthetized to assist our understanding of the impact of fluorine on antiplasmodial potencies in vitro; in particular, the aim here was to compare the effects of human serum and P. berghei species in these drug screens. This was also conducted in vivo with the P. berghei-infected mouse model. In the P. berghei species assay, PD and the 4′-fluoro-3′-trifluoromethyl-benzylmenadione A-b-9 exhibited a similar antiplasmodial behavior toward P. falciparum versus P. berghei. In the human serum versus Albumax assays, only the 6-fluoro–plasmodione showed a lower shift factor between Albumax assays and human serum conditions, suggesting a lower protein binding for the 6-F-PD compared to plasmodione or A-b-9. In vivo, 6-fluoro–plasmodione proved to be the most potent 3-benzylmenadione, reducing parasitemia by 50% after oral administration at 50 mg/kg.

Background Schistosomiasis is a disease of poverty. Integrated interventions are recommended for its elimination. Despite major prevalence reductions over the past decades, hotspot areas with persistent or recurring moderate or high prevalence remain. We aimed to assess the contribution of multidisciplinary interventions that were adapted to the local micro-epidemiology for schistosomiasis elimination in Pemba, Tanzania, and to identify drivers for the occurrence of hotspot areas. Methodology From 2020 to 2024, annual cross-sectional surveys were conducted in schools and communities in 20 implementation units (IUs) to assess the Schistosoma haematobium prevalence and monitor the impact of interventions. Based on the prevalence, the IUs were annually re-stratified into hotspot and low-prevalence IUs. In hotspots, mass drug administration in schools and communities, snail control and behavior change measures were implemented. Low-prevalence areas received surveillance-response interventions. With a random effects model, the association between S. haematobium infections and environmental and economic factors were assessed. Using risk layers based on the random effects model, hotspot areas were determined geographically. Principal findings The overall S. haematobium prevalence in the 20 IUs changed from 1.2% (26/2200, 95% Confidence Interval (CI): 0.5-1.9%) in 2021 to 1.0% (27/2752, 95% CI: 0.4-1.6%) in 2024 in schools, and from 0.8% (31/3885, 95% CI: 0.4-1.2%) in 2021 to 1.2% (43/3711, 95% CI: 0.3-2.0%) in 2024 in communities. Across the study period, 8 IUs were considered a hotspot. The number of hotspot IUs decreased from 5 in 2021, to 4 in 2022, to 3 in 2023 but increased again to 5 in 2024. Some of the hotspot IUs resurged once interventions were adapted to surveillance-response. S. haematobium infections were significantly associated with the standardized kernel density of water bodies with Bulinus presence (Odds Ratio (OR): 2.3; 95% CI: 1.6-3.4), a very low economic score (OR: 4.1; 95% CI: 1.7-9.9) and living far away from a road (OR: 4.7; 95% CI: 2.1-10.6). Conclusion Adaptive multidisciplinary interventions maintained the very low prevalence in Pemba but failed to interrupt S. haematobium transmission within 4 years. A comprehensive integrated intervention package contributed to reducing the number of hotspot IUs. However, some hotspots persisted also intense interventions or resurged once interventions were adapted to surveillance-response. To achieve complete elimination in Pemba and elsewhere, poverty needs to be reduced, and investments in global health equity, including the water sanitation and hygiene infrastructure, are essential. Trial registration ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493.

The risk and prognosis of tuberculosis (TB) are influenced by a complex interplay between human and bacterial genetic factors. While previous genomic studies have largely examined human and bacterial genomes separately, we adopted an integrated approach to uncover host–pathogen interactions. We leveraged paired human and Mycobacterium tuberculosis (M.tb) genomic data from 1000 adult TB patients from Tanzania and used a “genome-to-genome” approach to search for associations between human and M.tb genetic variants and to identify interacting genetic loci. Our analyses revealed two significant host–pathogen genetic associations. The first significant association (p = 4.7e-11) links a human intronic variant in PRDM15 (rs12151990), a gene involved in apoptosis regulation, with an M.tb variant in Rv2348c (I101M), which encodes a T cell-stimulating antigen. The second significant association (p = 6.3e-11) connects a human intergenic variant near TIMM21 and FBXO15 (rs75769176) – also associated with TB severity (p = 0.04) – with an M.tb variant in FixA (T67M). While FBXO15 is involved in the regulation of antigen processing and TIMM21 affects mitochondrial function, FixA's role remains undefined due to limited functional characterization. Additionally, we observed that a group of M.tb T cell epitope variants were significantly associated with HLA-DRB1 variation, suggesting that, despite their rarity, certain epitopes may still be subjected to immune selective pressure. Together, these findings identify previously unknown sites of genomic conflicts between humans and M.tb, advancing our understanding of how this pathogen evades selection pressure and persist in human populations.

Introduction & aim Intraoperative adverse events (iAEs) increase postoperative complications, which are devastating to patients and costly to healthcare systems. To optimise patient outcomes, the WHO Surgical Safety Checklist (WHO SSC) was introduced in 2008, but adherence, especially to its third part (sign-out), is low, and iAEs are currently not routinely assessed. This gap between evidence supporting the use of the WHO SSC, current inconsistent sign-out practice and the lack of standardised reporting of iAEs warrants applying an implementation science approach. Hence, this project aims to simultaneously evaluate the effectiveness and implementation of the sign-out, including systematic recording and discussion of iAEs during the sign-out. Methods & analysis Using a hybrid effectiveness-implementation approach, this prospective before-and-after-cohort project includes five surgical disciplines within nine Swiss hospitals. Following an extensive context analysis, this project is set up in three phases: (1) recruitment of 40 patients per surgical discipline and site (approx. 900 in total) for baseline assessment; (2) implementation based on a multifaceted, tailored implementation strategy (including formation of implementation teams, comprehensive education of healthcare professionals, top-down leadership, regular feedback rounds and tailoring implementation to local needs); and (3) recruitment of 40 patients per discipline to assess the changes after implementation (approx. 900). Implementation (eg, checklist fidelity composed of completion and quality) and effectiveness outcomes (ie, clinical patient outcomes) will be analysed using a mixed regression model. Discussion & conclusion By enhancing adherence to the WHO SSC sign-out, including standardised reporting of iAEs, we expect to further improve perioperative patient outcomes. Based on the context analysis, we will provide a widely applicable implementation plan to support and sustain the required behavioural change, which will support roll-out in further hospitals. Meanwhile, clinical and implementation science expertise is meeting the challenges of the complex environment of perioperative care.

Health systems in low- and middle-income countries often face severe resource constraints and are implementing reforms to improve accountability and efficiency. Healthcare managers and governance structures are key for the successful implementation of these reforms. This study aimed to examine the implementation of the Direct Health Facility Financing (DHFF), focusing on the perspectives of health facility in-charges and members of Council Health Management Teams (CHMTs). This study employed a cross-sectional web-based questionnaire administered to all heads of public health facilities and members of CHMTs in the Kilimanjaro and Morogoro. First, we analyzed the demographics of healthcare managers, characteristics of health facilities, and the reported implementation of DHFF governance. We then performed multivariate ordered logistic regressions analyses to examine the associations between healthcare managers’ perceptions of DHFF implementation, reported changes, and resource allocation changes while controlling for health managers and facility characteristics. 348 health managers participated in the study. 23% of health facility in-charges had received DHFF-related training in the previous 12 months. 76% reported that supportive supervision explicitly includes DHFF considerations. 92% of CHMTs reported a decrease in administrative workload following DHFF implementation, compared to 80% of facility managers. Positive perceptions of autonomy in planning, budgeting and fund management were widespread (88% facility in-charge and 95% CHMTs). Health managers with higher levels of education reported positive perceptions of strong DHFF governance. Urban facilities were more likely to report higher overall DHFF governance. As the number of staff trained in DHFF increased, the positive perceptions of challenges also increased. Facility managers with a university degree perceived a successful impact of DHFF in increasing their financial resources. This study suggests that the implementation of the DHFF was positively received by health facility managers. The DHFF appears to have led to improvements in resource mobilization and financial incentives potentially contributing to overall efficiencies.

Background Globally, tuberculosis (TB) is the leading cause of death from a single infectious agent. In 2023, an estimated 2.7 million cases of TB were undiagnosed or unreported. To address missing cases, the World Health Organization recommends systematic screening for TB. This is synonymous to active case finding (ACF) and involves provider-initiated screening and testing for TB. Despite the high incidence and prevalence of TB among people who use drugs (PWUD), there is a significant gap in data, on their perspectives, regarding the implementation of TB ACF services. This study aimed to explore facilitators and barriers to implementing peer-led TB ACF, as perceived by both, current and potential service users. Methods We conducted in-depth interviews among purposively selected adult PWUD in Dar-es-Salaam region, Tanzania. Study participants included: (1) peer PWUD with prior history of illicit drug use and medication-assisted treatment (MAT) (n = 10), (2) current medication-assisted treatment service users receiving clinic-based daily methadone (n = 8), and (3) community PWUD not on MAT recruited from various community locations (n = 4). All peer PWUD were experienced in TB ACF. Thematic content analysis was utilized with the support of NVivo12. Results Our findings are presented into two categories: individual and structural, with three main themes pertaining to peer-led TB ACF: (1) facilitators (2) facilitators for targeted improvement and optimization and (3) barriers. A critical facilitator was the acceptability of peer PWUD in providing TB ACF services. Key facilitators for targeted improvement and optimization included the TB screening tool, mobile TB diagnostic services, integrated methadone/TB services, and monetary incentives to peer PWUD. Barriers included inadequate adherence to infection prevention and control (IPC) measures when providing TB ACF services resulting in a reluctance to wear face masks due to stigma, misconceptions that prior TB preventive therapy among peers negates their need for continued IPC adherence, high mobility of PWUD and the fear of withdrawal symptoms associated with the use of anti-TB medication. Due to this fear, many PWUD preferred not to take anti-TB, as they were concerned about the potential severity of withdrawal symptoms. Conclusion Our findings highlight the crucial role of peer-led approaches in enhancing TB ACF among PWUD. Peer acceptance as service providers highlights the potential of community-driven interventions. Strengthening facilitators and addressing challenges is key to optimizing these services. Future research should explore the feasibility of providing peer-supported TB diagnosis and treatment services at friendly drop-in centers. Recommendations 1. Strengthen mobile diagnostic services by increasing their frequency and coverage, enabling timely diagnosis and treatment. 2. Enhance the TB symptom screening tool by including a symptom-independent test, such as a chest X-ray, as the symptoms of illicit drug use can mask and mimic TB symptoms making diagnosis challenging. 3. Address stigma and misconceptions through peer-led education and awareness campaigns that utilize audio-visual materials tailored to PWUD. This will promote adherence to IPC measures and create a more supportive environment for TB ACF activities. 4. Use anti-TB with minimal interactions with opiates or shorter TB treatment regimens to prevent withdrawal symptoms and improve adherence.

Background Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Current TB treatments are inadequate, requiring participants closely adhere to multi-drug regimens that are long, complex, and often poorly tolerated. In addition to these well-recognized shortcomings, current TB treatments, particularly those for rifampicin-resistant tuberculosis, leave a majority of cured participants with permanent, clinically significant lung impairment and radiographic evidence of bronchiectasis and fibrosis. This project will determine if two adjunctive host-directed therapies (HDTs) can prevent these poor outcomes. Methods Three hundred thirty participants with RIF-R TB and baseline risk factors for poor outcome will be enrolled in a randomized, controlled, 3-armed multi-centre trial, with clinical sites in Romania, Moldova, Georgia, Mozambique, and South Africa. All participants will receive standard multidrug therapy according to national guidelines. Those participants randomized to the experimental arms will in addition receive either CC-11050 (dovramilast) or metformin. Co-primary efficacy endpoints will examine effects on lung function (measured by spirometry) and infection (measured as time to stable sputum culture conversion). A sub-study will examine quantitative change in lung radiodensity by CT scan. Discussion These selected host-directed therapies candidates represent two complementary strategies: reducing inflammation vs inducing host cell anti-microbial activity, respectively. Both candidates are supported by data from preclinical and clinical studies. If successful, this ground-breaking project will increase Europe’s capacity to control drug resistant tuberculosis by developing new treatments that increase the likelihood of cure and reduce the risk of life-long disability. Trial registration EudraCT Number: 2020–004295-18. South African National Clinical Trial Registration (SANCTR) Number: DOH-27–042021-8345.

The disease burden from Legionella spp. infections has been increasing in many industrialized countries and, despite decades of scientific advances, ranks amongst the highest for waterborne diseases. We review here several key research areas from a multi-disciplinary perspective and list critical research needs to address some of the challenges of Legionella spp. management in engineered environments. These include: (1) A consideration of Legionella species diversity and co-occurrence, beyond Legionella pneumophila only; (2) An assessment of their environmental prevalence and clinical relevance, and how that may affect legislation, management and intervention prioritization; (3) A consideration of Legionella spp. sources, their definition and prioritization; (4) The factors affecting Legionnaires’ disease seasonality, how they link to sources, Legionella spp. proliferation and ecology, and how these may be affected by climate change; (5) The challenge of saving energy in buildings while controlling Legionella spp. with high water temperatures and chemical disinfection; (6) The ecological interactions of Legionella spp. with other microbes, and their potential as a biological control strategy. Ultimately, we call for increased inter-disciplinary collaboration between multiple research domains, as well as trans-disciplinary engagement and collaboration across government, industry and science as the way towards controlling and reducing Legionella-derived infections.

Functional Health Information Systems are critical to provide decision-makers with reliable and quality data for real-time adaptation of the health system. The District Health Information System (DHIS) 2, the world’s largest Health Information Management System (HMIS), facilitates routine health data collection and reporting in many countries globally through its flexible digital platform. In a majority of low and middle income countries (LMICs), there is usually a good availability of indicators on communicable diseases, and maternal and child health. However, although LMICs now face a rapid epidemiological transition with the growing burden of cardiovascular diseases, their HMIS have generally not been adapted to systematically integrate quality data on non-communicable diseases (NCDs) which is essential to quality of care and to assess health systems performance along the chronic disease continuum of care. Here we describe the steps that Senegal took to develop and implement a systematic data collection system for hypertension data using DHIS2. We draw important lessons on opportunities and challenges for integration of NCD data into HMIS and discuss future perspectives for the continued improvement and sustainability of cardiovascular population health data management.