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Antimicrobial resistance (AMR) is a global health threat with 1.27 million and 4.95 million deaths attributable to and associated with bacterial AMR, respectively, in 2019. Our aim is to estimate the vaccine avertable bacterial AMR burden based on existing and future vaccines at the regional and global levels by pathogen and infectious syndromes. We developed a static proportional impact model to estimate the vaccination impact on 15 bacterial pathogens in terms of reduction in age-specific AMR burden estimates for 2019 from the Global Research on Antimicrobial Resistance project in direct proportion to efficacy, coverage, target population for protection, and duration of protection of existing and future vaccines. The AMR burden avertable by vaccination in 2019 was highest for the WHO Africa and South-East Asia regions, for lower respiratory infections, tuberculosis, and bloodstream infections by infectious syndromes, and for and by pathogen. In the baseline scenario for vaccination of primary age groups against 15 pathogens, we estimated vaccine-avertable AMR burden of 0.51 (95% UI 0.49-0.54) million deaths and 28 (27-29) million disability-adjusted life-years (DALYs) associated with bacterial AMR, and 0.15 (0.14-0.17) million deaths and 7.6 (7.1-8.0) million DALYs attributable to AMR globally in 2019. In the high-potential scenario for vaccination of additional age groups against seven pathogens, we estimated vaccine-avertable AMR burden of an additional 1.2 (1.18-1.23) million deaths and 37 (36-39) million DALYs associated with AMR, and 0.33 (0.32-0.34) million deaths and 10 (9.8-11) million DALYs attributable to AMR globally in 2019. Increased coverage of existing vaccines and development of new vaccines are effective means to reduce AMR, and this evidence should inform the full value of vaccine assessments.

Cholera is a significant health risk for low- and middle-income countries (LMIC), and the threat of outbreaks is likely to increase due to climate change. To keep up to date with the link between water quality and cholera, we conducted a systematic review and meta-analysis to update a previous review while only focusing on water-related exposures. We searched Embase, Web of Science and PubMed for literature published between 2016 and 2022. Search terms were consistent with the previous review. Study quality was assessed using the Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E). Water-related exposures were categorized according to the WHO/UNICEF Joint Monitoring Program for Water Supply, Sanitation and Hygiene (JMP) and further divided by the service ladder. Odds ratios were extracted and pooled by performing random-effects meta-analysis. We identified 22 new eligible studies and analysed them in addition to the 45 studies included in the previous review. Analyses revealed higher odds of cholera when consuming sachet water (OR = 1.69, 95% CI: 1.13 to 2.52), unimproved water (OR = 2.91, 95% CI: 1.21 to 7.02), surface water (OR = 3.40, 95% CI: 2.52 to 4.58), and untreated water (OR = 2.51, 95% CI: 2.03 to 3.10). Meanwhile, treating water (OR = 0.42, 95% CI: 0.27 to 0.65) by boiling (OR = 0.38, 95% CI: 0.17 to 0.84) or chlorination (OR = 0.37, 95% CI: 0.17 to 0.83), and drinking basic water (OR = 0.44, 95% CI: 0.27 to 0.69) showed protection. Water-related exposures were prioritized to synthesize the evidence on cholera transmission through drinking water, with sanitation and hygiene as additional risk factors. While the JMP service ladder provided a useful classification framework, context-specific differences in infrastructure and interpretation should be considered when evaluating these findings. Pooled estimates changed with updated evidence while qualitative insights on the protective or risk factors remain valid. Relatively low-cost methods like boiling or chlorinating water provide good protection comparable to providing basic water to the public.

Background Water, sanitation, and hygiene (WASH) play a pivotal role in controlling typhoid fever, as it is primarily transmitted through oral-fecal pathways. Given our constrained resources, staying current with the most recent research is crucial. This ensures we remain informed about practical insights regarding effective typhoid fever control strategies across various WASH components. We conducted a systematic review and meta-analysis of case-control studies to estimate the associations of water, sanitation, and hygiene exposures with typhoid fever. Methods We updated the previous review conducted by Brockett et al. We included new findings published between June 2018 and October 2022 in Web of Science, Embase, and PubMed. We used the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for risk of bias (ROB) assessment. We classified WASH exposures according to the classification provided by the WHO/UNICEF Joint Monitoring Programme for Water Supply, Sanitation, and Hygiene (JMP) update in 2015. We conducted the meta-analyses by only including studies that did not have a critical ROB in both Bayesian and frequentist random-effects models. Results We identified 8 new studies and analyzed 27 studies in total. Our analyses showed that while the general insights on the protective (or harmful) impact of improved (or unimproved) WASH remain the same, the pooled estimates of OR differed. Pooled estimates of limited hygiene (OR = 2.26, 95% CrI: 1.38 to 3.64), untreated water (OR = 1.96, 95% CrI: 1.28 to 3.27) and surface water (OR = 2.14, 95% CrI: 1.03 to 4.06) showed 3% increase, 18% decrease, and 16% increase, respectively, from the existing estimates. On the other hand, improved WASH reduced the odds of typhoid fever with pooled estimates for improved water source (OR = 0.54, 95% CrI: 0.31 to 1.08), basic hygiene (OR = 0.6, 95% CrI: 0.38 to 0.97) and treated water (OR = 0.54, 95% CrI: 0.36 to 0.8) showing 26% decrease, 15% increase, and 8% decrease, respectively, from the existing estimates. Conclusions The updated pooled estimates of ORs for the association of WASH with typhoid fever showed clear changes from the existing estimates. Our study affirms that relatively low-cost WASH strategies such as basic hygiene or water treatment can be an effective tool to provide protection against typhoid fever in addition to other resource-intensive ways to improve WASH. Trial registration PROSPERO 2021 CRD42021271881.

Urea is a problematic pollutant in reclaimed water for ultrapure water (UPW) production. The sulfate radical-based advanced oxidation process (SR-AOP) has been recognized as an effective method for urea degradation. However, conventional metal-based catalysts for peroxymonosulfate (PMS) activation are unsuitable for UPW production due to issues related to metal ion leaching. In this study, the use of powdered activated carbon (PAC) was investigated for the removal of urea from reclaimed water. The PAC exhibited a high degree of defects (I D /I G  = 1.709) and various surface oxygen functional groups (C–OH, C=O, and C–O), which greatly enhanced its catalytic capability. The PAC significantly facilitated PMS activation in the PMS + PAC system, leading to the complete urea decomposition. The PMS + PAC system demonstrated excellent urea removal efficiency within a wide pH range, except for pH < 3. Among the various anions present, the CO 3 2− and PO 4 3− inhibited urea degradation, while the coexistence of Cl − promoted urea removal. Furthermore, the feasibility test was evaluated using actual reclaimed water. The quenching test revealed that SO 4 − · , · OH, and O 2 − · played crucial roles in the degradation of urea in the PAC-assisted SR-AOP. The oxygen functional groups (C–OH and O–C=O) and defect sites of PAC clearly contributed to PMS activation.

ObjectivesThe global disease burden of Salmonella infections in 2017 included 135 900 deaths caused by Salmonella Typhi and Paratyphi and 77 500 deaths caused by invasive non-typhoidal Salmonella, with increasing antimicrobial resistance (AMR) exacerbating morbidity, mortality and costs. The aim of our systematic review and meta-analysis is to estimate the length of hospital stay and associated treatment costs for patients with susceptible and antibiotic-resistant Salmonella Typhi, Paratyphi and non-typhoidal Salmonella infections.DesignSystematic review and meta-analysis.Data sourcesWe searched EMBASE, Medline/PubMed, Scopus, Hinari and LILACS databases for studies published between 1 January 2005 and 15 May 2024, with no language restrictions.Eligibility criteriaWe included 30 studies that reported the length of hospital stay or treatment costs for patients with susceptible or antibiotic-resistant Salmonella Typhi, Paratyphi and non-typhoidal Salmonella infections. We excluded studies with sample sizes of less than 30 patients, those focused on non-human subjects and those not reporting our outcomes of interest.Data extraction and synthesisTwo reviewers independently screened studies and extracted data on the length of hospital stay and associated costs, with monetary values converted to 2019 USD. We aggregated data according to GDP per capita quantiles using a random-effects meta-analysis. We conducted a quality assessment using an adapted Joanna Briggs Institute tool.ResultsPatients with drug-resistant Salmonella infections had longer hospital stays, with an additional 0.5–2.2 days compared with drug-susceptible Salmonella infections. Based on our meta-analysis, the mean hospital stay for typhoidal Salmonella infections was 6.4 days (95% CI 4.9 to 7.8) for drug-susceptible cases and 8.4 days (95% CI 5.1 to 11.7) for resistant cases in the lowest income quartiles. While there were insufficient data to perform a pooled analysis, individual studies inferred that treatment costs for resistant typhoidal Salmonella infections were higher than for susceptible infections, and resistant non-typhoidal Salmonella infections had longer hospital stays and higher costs compared with susceptible infections. Data were scarce from high-Salmonella-burden countries, particularly in sub-Saharan Africa and parts of Asia.ConclusionsPatients with antibiotic-resistant Salmonella infections experience a greater healthcare burden in terms of hospitalisation length and direct costs compared with those with susceptible infections. We highlight the economic burden of AMR in Salmonella infections and emphasise the need for preventive measures.

With more than 1.2 million illnesses and 29,000 deaths in sub-Saharan Africa in 2017, typhoid fever continues to be a major public health problem. Effective control of the disease would benefit from an understanding of the subnational geospatial distribution of the disease incidence. We collated records of the incidence rate of typhoid fever confirmed by culture of blood in Africa from 2000 to 2022. We estimated the typhoid incidence rate for sub-Saharan Africa on 20 km × 20 km grids by exploring the association with geospatial covariates representing access to improved water and sanitation, health conditions of the population, and environmental conditions. We identified six published articles and one pre-print representing incidence rate estimates in 22 sites in 2000-2022. Estimated incidence rates showed geospatial variation at sub-national, national, and regional levels. The incidence rate was high in Western and Eastern African subregions followed by Southern and Middle African subregions. By age, the incidence rate was highest among 5-14 yo followed by 2-4 yo, > 14 yo, and 0-1 yo. When aggregated across all age classes and grids that comprise each country, predicted incidence rates ranged from 43.7 (95% confidence interval: 0.6 to 591.2) in Zimbabwe to 2,957.8 (95% CI: 20.8 to 4,245.2) in South Sudan per 100,000 person-years. Sub-national heterogeneity was evident with the coefficient of variation at the 20 km × 20 km grid-level ranging from 0.7 to 3.3 and was generally lower in high-incidence countries and widely varying in low-incidence countries. Our study provides estimates of 20 km × 20 km incidence rate of typhoid fever across sub-Saharan Africa based on data collected from 2000 through 2020. Increased understanding of the subnational geospatial variation of typhoid fever in Africa may inform more effective intervention programs by better targeting resources to heterogeneously disturbed disease risk.

Irritable bowel syndrome (IBS) is a chronic disease that causes abdominal pain and an imbalance of defecation patterns due to gastrointestinal dysfunction. The cause of IBS remains unclear, but intestinal-brain axis problems and neurotransmitters have been suggested as factors. In this study, chanoclavine, which has a ring structure similar to 5-hydroxytryptamine (5-HT), showed an interaction with the 5-HT3A receptor to regulate IBS. Although its derivatives are known to be involved in neurotransmitter receptors, the molecular physiological mechanism of the interaction between chanoclavine and the 5-HT3A receptor is unknown. Electrophysiological experiments were conducted using a two-electrode voltage-clamp analysis to observe the inhibitory effects of chanoclavine on Xenopus oocytes in which the h5-HT3A receptor was expressed. The co-application of chanoclavine and 5-HT resulted in concentration-dependent, reversible, voltage-independent, and competitive inhibition. The 5-HT3A response induced by 5-HT was blocked by chanoclavine with half-maximal inhibitory response concentration (IC50) values of 107.2 µM. Docking studies suggested that chanoclavine was positioned close F130 and N138 in the 5-HT3A receptor-binding site. The double mutation of F130A and N138A significantly attenuated the interaction of chanoclavine compared to a single mutation or the wild type. These data suggest that F130 and N138 are important sites for ligand binding and activity. Chanoclavine and ergonovine have different effects. Asparagine, the 130th amino acid sequence of the 5-HT3A receptor, and phenylalanine, the 138th, are important in the role of binding chanoclavine, but ergonovine has no interaction with any amino acid sequence of the 5-HT3A receptor. The results of the electrophysiological studies and of in silico simulation showed that chanoclavine has the potential to inhibit the hypergastric stimulation of the gut by inhibiting the stimulation of signal transduction through 5-HT3A receptor stimulation. These findings suggest chanoclavine as a potential antiemetic agent for excessive gut stimulation and offer insight into the mechanisms of 5-HT3A receptor inhibition.

IntroductionAntibiotic resistance (ABR) may increase hospital costs, utility loss and mortality risk per patient. Understanding these losses at national, regional and global scales is necessary for efficiently tackling ABR. Our aim is to estimate the global economic burden of antibiotic-resistant infections and the potential for bacterial vaccines to mitigate this burden.MethodsWe take healthcare system and labour productivity perspectives. Hospital cost-per-case and length-of-stay estimates were calculated through meta-analyses and reviewing published systematic reviews. Unit labour productivity losses were estimated through a human capital approach. Modelled estimates were used where secondary data were missing. Death and incidence data were combined with unit cost data to estimate the economic burden associated with ABR in 2019, and the potential costs averted (in 2019 US$) based on uptake scenarios of vaccines that currently exist or are likely to be developed.ResultsMultidrug-resistant tuberculosis had the highest mean hospital cost attributable to ABR per patient, the range was US$3000 in lower-income settings to US$41 000 in high-income settings, with carbapenem-resistant infections associated with a high cost-per-case of US$3000–US$7000 depending on syndrome. ABR was associated with a median value of US$693 billion (IQR: US$627 bn–US$768 bn) in hospital costs globally, with US$207 bn (IQR: US$186 bn–US$229 bn) potentially avertable by vaccines. Productivity losses were quantified at almost US$194 billion, with US$76 bn avertable by vaccines.ConclusionsThe economic burden of ABR is associated with high levels of hospital bed-days occupied, hospital spending and labour productivity losses globally and should, therefore, remain high on national and international policy agendas. Vaccines against Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae would avert a substantial portion of the economic burden associated with ABR. More robust evidence, particularly in low-income countries, on the hospital costs, associated with and attributable to ABR, is needed.

Abstract OP 37: Health Status 3, B210 (FCSH), September 5, 2025, 11:30 - 12:30 Aims Labour migration is a growing global phenomenon, with most research to date focusing on low-skilled labour migrants entering Europe and North America. Despite high prevalence of labour migration within the Asian Pacific region, little is known about their health and social status to inform targeted health interventions. We conducted a systematic review to explore the morbidity and mortality of international migrant workers and their transnational families in the Asia-Pacific region. Methods Studies published between 1 January 2000 to 1 April 2024 were searched in MEDLINE, Embase, PsycINFO, and Ovid Global Health without language limitation. Grey literature and non-English reports were searched manually. We used narrative synthesis to assess health outcomes of the study population. Results Ultimately, 54 studies with 86,620 participants from 17 countries were included. Findings show the active labour migration in the Asia-Pacific region where 68,320 migrant workers move across 30 countries. Five countries send and receive labourers concurrently. Key health concerns: mental health problems, Musculoskeletal disorders (MSDs), infection diseases, mixed health outcomes of physical and psychological illness, chronic disease, and occupational injury. Reports suggested high prevalence of illness and death. 48,128 migrant workers reported occupational injuries, and 1,973 reported MSDs symptoms. Mental health problems affect both migrant workers (n = 1,975) and their transnational families(n = 3,902). Overwork, poor working conditions, and workplace hazards impacted health outcomes in these populations. Conclusion Multi-sector interventions are needed in countries with high numbers of migrant workers to protect their health and safety, including policies to regulate working hours, improve occupational health and safety, and increase access to healthcare. Governments in both sending and destination locations with international agencies should take greater responsibility for this important and often essential workforce.

Monoamine serotonin is a major neurotransmitter that acts on a wide range of central nervous system and peripheral nervous system functions and is known to have a role in various processes. Recently, it has been found that 5-HT is involved in cognitive and memory functions through interaction with cholinergic pathways. The natural flavonoid kaempferol (KAE) extracted from Cudrania tricuspidata is a secondary metabolite of the plant. Recently studies have confirmed that KAE possesses a neuroprotective effect because of its strong antioxidant activity. It has been confirmed that KAE is involved in the serotonergic pathway through an in vivo test. However, these results need to be confirmed at the molecular level, because the exact mechanism that is involved in such effects of KAE has not yet been elucidated. Therefore, the objective of this study is to confirm the interaction of KAE with 5-HT3A through electrophysiological studies at the molecular level using KAE extracted from Cudrania tricuspidata. This study confirmed the interaction between 5-HT3A and KAE at the molecular level. KAE inhibited 5-HT3A receptors in a concentration-dependent and voltage-independent manner. Site-directed mutagenesis and molecular-docking studies confirmed that the binding sites D177 and F199 are the major binding sites of human 5-HT3A receptors of KAE.