The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
The umbilical cord, composed of blood vessels and connective tissue, connects the fetus to the placenta during pregnancy. After birth, the remaining cord stump may serve as an entry point for harmful bacteria, potentially leading to serious infection (neonatal sepsis) and death, particularly in low- and middle-income countries (LMICs). Applying antiseptics - substances that prevent the growth of microorganisms on living tissues - may help reduce the risk of infection through the umbilical stump. To evaluate the benefits and harms of the application of antiseptics on a newborn's umbilical cord versus no antiseptics for the prevention of morbidity and mortality in infants in low- or middle-income countries (LMICs), and high-income countries (HIC). We searched CENTRAL, MEDLINE, Embase, LILACS and trial registries in December 2025. We checked reference lists of included studies and/or studies/systematic reviews where subject matter related to the intervention or population examined in this review. We included individual and cluster-randomized controlled trials comparing any antiseptic with no antiseptic applied to the umbilical cord of newborns (0 to 28 days of life), regardless of gestational age, birthweight, delivery setting, or maternal infection risk. We excluded studies involving newborns with congenital malformations, quasi-randomized or observational designs, trials comparing different formulations or concentrations of the same antiseptic, and studies involving only topical antibiotics or antiseptic-antibiotic combinations. Our outcomes were all-cause neonatal mortality, omphalitis, and cord separation time. All the outcomes were measured during the neonatal period (i.e. from birth to 28 days of life). The risk of bias was assessed by using the Cochrane risk of bias tool (RoB 1). Two review authors independently assessed studies for inclusion and evaluated the risk of bias. One review author extracted the data, and a second author verified the extraction for accuracy. We analyzed studies conducted in low- and middle-income countries (LMICs) separately from those in high-income countries (HICs), given the differing baseline risks. Where appropriate, we synthesized results using random-effects meta-analysis. We assessed the certainty of the evidence for each outcome using the GRADE approach. We included 18 trials in the review (143,150 participants), two studies are awaiting classification and four studies are ongoing trials. The included studies evaluated antiseptics such as 70% alcohol, 4.0% chlorhexidine (CHX), silver sulfadiazine, and povidone iodine in LMICs. In HIC, the studies evaluated CHX and alcohol. Five population-based trials looking at CHX in LMICs reported data on all-cause mortality that comprised 2280 deaths in 129,381 participants. Combined results showed that topical application of CHX may lead to a small reduction in all-cause neonatal mortality from 18/1000 to 15/1000 participants (average risk ratio (RR) 0.86; 95% confidence interval (CI) 0.73 to 1.01; 129,381 participants, 5 studies; low-certainty evidence). Among the CHX studies that took place in an LMIC, the topical application of CHX likely reduces the risk of omphalitis from 87/1000 participants in the control group to 62/1000 participants in the CHX group (RR 0.71; 95% CI 0.60 to 0.85; 128,486 participants, 5 studies; moderate-certainty evidence). The topical application of CHX likely increases cord separation time by 1.85 days in the CHX group compared with control (mean difference (MD) 1.85 days; 95% CI 0.81 to 2.90; 47,533 participants, 6 studies; moderate-certainty evidence) in studies conducted in LMICs. One study evaluated CHX in a HIC and did not report all-cause neonatal mortality data. The evidence was very uncertain about the use of topical application of CHX for the prevention of omphalitis (RR 0.28; 95 % CI 0.06 to 1.35; 669 participants, 1 study; very low-certainty evidence), indicating that the findings should be interpreted with caution. Similarly, the effect on cord separation time (MD: -0.80; 95 % CI -1.21 to -0.39; 669 participants, 1 study; very low-certainty evidence) was very uncertain. Four studies in LMICs evaluated the topical application of alcohol but none of them reported data on all-cause mortality. The evidence for the prevention of omphalitis from topical application of alcohol is very uncertain based on two studies (RR 1.22; 95% CI 0.34 to 4.44; 270 participants, 2 studies; very low-certainty evidence). The effect of alcohol on cord separation time is very uncertain based on data from four trials (MD -0.00 days; 95% CI -1.75 to 1.75; 598 participants, 4 studies; very low-certainty evidence). Four studies conducted in a HIC evaluated the topical application of alcohol. The pooled results showed that cord separation time was likely increased by 1.63 days in the alcohol group compared to the control group (MD 1.63 days; 95 % CI 1.11 to 2.15; 2117 participants, 4 studies; moderate-certainty evidence). None of the four studies in HIC that evaluated the topical application of alcohol reported data on the prevention of all-cause mortality or omphalitis. Overall, the included studies had a moderate risk of selection and attrition bias, a high risk of detection and performance bias, and unclear risk of reporting bias. Topical application of 4.0% chlorhexidine to the umbilical cord likely reduces the risk of cord infection and may reduce neonatal mortality in low- and middle-income countries, though it probably delays cord separation by about two days. In high-income countries, evidence for chlorhexidine is very uncertain. For 70% alcohol, evidence from low- and middle-income countries is very uncertain for prevention of infection, and its use may result in little or no difference in cord separation time. In high-income countries, moderate-certainty evidence suggests that alcohol likely delays cord separation slightly. This Cochrane review had no dedicated funding. 2010 Protocol available doi.org/10.1002/14651858.CD008635 2013 published review available doi.org/10.1002/14651858.CD008635.pub2.
This systematic review and meta-analysis aimed to investigate the relationship between both short-term and long-term exposure to key outdoor air pollutants specifically particulate matter (PM10 and PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO) and the risk of stillbirth. An extensive literature search was performed using multiple databases, including PubMed, Web of Science, Scopus, and Embase, with studies considered up to August 20, 2024. The quality of the studies was assessed using established criteria. Twenty-two studies met the inclusion criteria, highlighting significant associations between outdoor air pollutants and stillbirth. Long-term exposure to NO2/NOx during the first, second, and third trimesters was linked to increased odds of stillbirth, with standardized ORs of 2.79 (95% CI: 1.26–6.14), 2.74 (95% CI: 1.25-6.00), and 2.63 (95% CI: 1.25–5.56), respectively.However, no significant association was observed for NO2/NOx exposure throughout the entire pregnancy (OR: 2.84, 95% CI: 0.89–9.08). Similarly, each 10 µg/m3 increase in PM10 during each trimester was associated with elevated stillbirth risk, yielding standardized ORs of 2.31 (95% CI: 1.44–3.68), 2.56 (95% CI: 1.51–4.35), and 2.73, (95% CI: 1.53–4.87), respectively. Additionally, PM10 exposure throughout the entire pregnancy showed increased risk, with a standardized OR of 2.78 (95% CI: 1.34–5.76). Likewise, a 10 µg/m3 increase in PM2.5 exposure was associated with higher stillbirth risk in each trimester, resulting in ORs of 2.53 (95% CI: 1.16–5.48), 2.69 (95% CI: 1.17–6.19), and 2.75 (95% CI: 1.12–6.73), respectively. A 10 µg/m3 increase in PM2.5 exposure over the entire pregnancy was linked to increased odds of stillbirth (OR: 2.92, 95% CI: 1.4–6.06). Short-term exposure, evaluated over multiple lag days, displayed varied risk patterns, particularly regarding CO and SO2, while PM2.5 effects showed inconsistencies across studies. Due to substantial heterogeneity in lag period definitions, exposure metrics, and effect estimate formats across studies, a quantitative meta-analysis for short-term exposure was not feasible; thus, evidence for short-term effects remains descriptive and preliminary. This review suggests that outdoor air pollution is associated with an increased stillbirth risk, highlighting the need for public health measures and standardized research.
Information on childhood cancer burden is crucial for effective cancer policy planning. Unfortunately, observed paediatric cancer data are not available in every country, and previous global burden estimates have not discretely reported several common cancers of childhood. We aimed to inform efforts to address childhood cancer burden globally by analysing results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, which now include nine additional cancer causes compared with previous GBD analyses. GBD 2023 data sources for cancer estimation included population-based cancer registries, vital registration systems, and verbal autopsies. For childhood cancers (defined as those occurring at ages 0-19 years), mortality was estimated using cancer-specific ensemble models and incidence was estimated using mortality estimates and modelled mortality-to-incidence ratios (MIRs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the standard life expectancy at the age of death. Prevalence was estimated using survival estimates modelled from MIRs and multiplied by sequelae-specific disability weights to estimate years lived with disability (YLDs). Disability-adjusted life-years (DALYs) were estimated as the sum of YLLs and YLDs. Estimates are presented globally and by geographical and resource groupings, and all estimates are presented with 95% uncertainty intervals (UIs). Globally, in 2023, there were an estimated 377 000 incident childhood cancer cases (95% UI 288 000-489 000), 144 000 deaths (131 000-162 000), and 11·7 million (10·7-13·2) DALYs due to childhood cancer. Deaths due to childhood cancer decreased by 27·0% (15·5-36·1) globally, from 197 000 (173 000-218 000) in 1990, but increased in the WHO African region by 55·6% (25·5-92·4), from 31 500 (24 900-38 500) to 49 000 (42 600-58 200) between 1990 and 2023. In 2023, age-standardised YLLs due to childhood cancer were inversely correlated with country-level Socio-demographic Index. Childhood cancer was the eighth-leading cause of childhood deaths and the ninth-leading cause of DALYs among all cancers in 2023. The percentage of DALYs due to uncategorised childhood cancers was reduced from 26·5% (26·5-26·5) in GBD 2017 to 10·5% (8·1-13·1) with the addition of the nine new cancer causes. Target cancers for the WHO Global Initiative for Childhood Cancer (GICC) comprised 47·3% (42·2-52·0) of global childhood cancer deaths in 2023. Global childhood cancer burden remains a substantial contributor to global childhood disease and cancer burden and is disproportionately weighted towards resource-limited settings. The estimation of additional cancer types relevant in childhood provides a step towards alignment with WHO GICC targets. Efforts to decrease global childhood cancer burden should focus on addressing the inequities in burden worldwide and support comprehensive improvements along the childhood cancer diagnosis and care continuum. St Jude Children's Research Hospital, Gates Foundation, and St Baldrick's Foundation.
Enterovirus D68 (EV-D68) has been implicated in clusters of acute flaccid myelitis (AFM) and severe respiratory illness; however, the magnitude and consistency of association across settings and over time remain uncertain. We quantified the association between EV-D68 detection and acute neurologic outcomes (particularly AFM) and explored design- and time-related heterogeneity. Following PRISMA 2020 and MOOSE guidance, we systematically identified observational studies reporting associations between EV-D68 detection and neurologic outcomes. Random effects meta-analysis was performed using REML with Knapp-Hartung adjustment; heterogeneity was summarised with τ2 and I2. Prespecified moderators were examined with meta-regression. Small-study effects were evaluated using contour-enhanced funnel plots, Egger and Peters tests, and PET-PEESE bias-adjusted models. PROSPERO registration: 1152300. Across 98 studies, the pooled odds ratio (OR) was 1.39 (95% CI 1.14-1.69), with high heterogeneity (I2 = 98.9%; prediction interval 0.24-8.15). By design, respiratory surveillance studies showed stronger association (OR 1.59, 95% CI 1.35-1.86, k = 78) whereas AFM case-control studies did not (OR 0.86, 95% CI 0.40-1.86, k = 20). In multivariable meta-regression, study design and calendar year explained about 47% of inter-study variance. Predicted ORs declined from 2014 to 2022 across regions. Funnel asymmetry and small-study effects were suggested; PET-PEESE bias-adjusted estimates remained above the null. The EV-D68 outcome association is context-dependent and time-varying. Surveillance datasets enriched during outbreak waves drive the pooled signal, while AFM case-control designs yield attenuated estimates after adjustment. Standardising diagnostics and integrating design-specific surveillance will improve risk estimation and AFM preparedness.
Migrants are at increased risk of infections including HIV, tuberculosis and viral hepatitis, with poorer outcomes. Early diagnosis and management can reduce morbidity, mortality and onward transmission. This systematic review summarises prevalence of HIV, latent and active tuberculosis and hepatitis B and C among UK migrants and evaluates associated risk factors. PubMed/Medline, EMBASE, Web of Science and the Cochrane Library were systematically searched from 2004 to 11 June 2025. The review was conducted using PRISMA guidelines and registered with PROSPERO (registration CRD42024521191). Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. High heterogeneity (I2 = 95.2%, 99.2%, 87.2%, 96.9% and 91.6% for IGRA, active TB, HIV, HBV and HCV yields, respectively) indicated that meta-analysis was not appropriate. The impact of risk factors on prevalence was explored through meta-regression and descriptive analysis. Of 2033 identified records, 36 were included, reporting Interferon Gamma Release Assay (IGRA) (n = 13), active TB (n = 10), HIV (n = 12), HBV (n = 16) and HCV (n = 11) test yields. An additional two publications excluded from the main analysis for reporting duplicate study data were included in the risk factor analysis because they stratified prevalence by additional risk factors. Highest yield was for IGRA which, excluding one lower prevalence outlier (6.9% (n = 1617)), was 15.1%-22.1%. There was high heterogeneity in active TB prevalence: 62-1,484/100,000. HIV prevalence among larger studies (n > 200) was 0.18%-0.48%. HBV prevalence was 0.00%-8.93% (all studies) and 1.06%-4.75% for larger studies (n > 1000). HCV prevalence was lower: 0.00%-1.67%, with only two of 11 included estimates above 0.50%. There was considerable heterogeneity in risk factors analysed making comparisons difficult. Despite heterogeneity, infection prevalence was generally high, particularly IGRA yield and HBV. This underscores the need to maintain effective monitoring, testing and treatment for key infections among migrant populations, especially given the rapidly evolving epidemiological and demographic landscape for this population.
The global rise in antimicrobial resistance (AMR) among environmental bacteria poses an escalating threat to public health, particularly in developing regions where antibiotic use in agriculture, aquaculture, and clinical settings remains poorly regulated. This study characterized antibiotic resistance patterns, virulence traits, and antibiotic resistance genes (ARGs) of Escherichia coli isolated from 24 major inland water bodies across Sri Lanka. A total of 120 isolates were recovered and subjected to susceptibility testing against seven clinically and agriculturally relevant antibiotics: amoxicillin (AMX), cloxacillin (CLOX), tetracycline (TET), oxytetracycline (OTC), piperacillin (PIP), cefotaxime (CTX), and ceftazidime (CAZ). Isolates were confirmed using standard biochemical tests and Gram staining, and minimum inhibitory concentrations (MICs) were determined via the agar dilution method (60 to 360 µg/mL). Multiple antibiotic resistance (MAR) indices were calculated to assess prior antibiotic exposure at each sampling site. PCR assays detected resistance genes (tetA, tetM) and virulence genes (eae, stx1, stx2). Widespread resistance was observed against AMX (100%) and CLOX (100%), while most isolates remained susceptible to the third-generation cephalosporins CTX and CAZ, suggesting the absence of extended-spectrum β-lactamase activity. MAR indices exceeded 0.2 across all sites, indicating pervasive prior antibiotic exposure. Resistance genes tetA (8.3%) and tetM (6.0%) were detected at moderate prevalence, consistent with widespread TET use in agricultural and veterinary contexts. Virulence genes eae and stx2 were absent; nevertheless, stx1 was detected in 2.0% of isolates from Minneriya Canal and Mahakandarawa Tank, indicating the presence of Shiga toxin-producing E. coli (STEC) with pathogenic potential. These findings demonstrate that Sri Lankan inland water bodies serve as critical reservoirs for ARG dissemination and potentially pathogenic strains, posing direct risks to communities dependent on these waters for domestic use, irrigation, and food production. Furthermore, this study provides a replicable methodological framework for future AMR surveillance studies in environmental and freshwater contexts. Systematic AMR surveillance, enhanced wastewater management, and targeted public health interventions are urgently needed, in alignment with One Health priorities and the United Nations Sustainable Development Goals.
INTRODUCTION: In the global context, healthcare-associated infections (HCAIs) are the most prevalent outcome of substandard patient care. There is a lack of data from developing regions, except for developing countries such as China and India, where reports from the World Health Organization (WHO) demonstrate a more substantial presence. This systematic review aims to investigate geographical disparities in HCAI occurrence in developing and developed countries. It also focuses on healthcare-associated infections, especially infectious endocarditis (IE) from implantable cardiac devices in high-income countries. METHODS: A literature review was conducted according to a pre-designed protocol. A search was performed in Embase, Ovid Medline, and PubMed for reports published between 2000 and 2024. No language restrictions were applied, and older, highly cited studies were retained. The search process retrieved 6,928 abstracts, of which 263 met eligibility criteria. The primary endpoint was to ascertain extant empirical research on the epidemiology of HCAIs in developing countries, with a focus on bacterial infections. The secondary endpoint investigated infections associated with transcatheter aortic valve replacement (TAVR) and cardiac implantable electronic devices (CIED) in developed countries. RESULTS: The primary endpoint revealed a HCAI rate in adult ICUs that is at least three times the USA rate. Surgical site infections were the most prevalent type of infection, with rates significantly higher than in developed countries. Gram-negative bacilli caused the most hospital infections. Methicillin-resistant Staphylococcus aureus was detected in many cases. The secondary endpoint demonstrated that Staphylococcus aureus is responsible for approximately one-third of healthcare-associated IE cases. In the United States, the percentage increased from 24% to 32%. Healthcare-associated IE carries a higher in-hospital mortality rate than community-acquired IE (31.1% vs. 20.3%; p < 0.01). Comparisons between TAVR and surgical aortic valve replacement are few and mixed. Large national registries and pooled PARTNER-trial data show comparable IE rates for both procedures. CIEDs-IE have a lower three-year survival rate (53.8% vs. 33% for pacemakers, 47.7% vs. 31.6% for implantable cardioverter-defibrillators, and 50.8% vs. 36.5% for cardiac resynchronization therapy). CONCLUSION: Surveillance HCAIs is essential for tracking disease and evaluating interventions. Focusing on key procedural steps can improve adherence and intervention impact. IE after TAVR and CIED is rare but severe, with high in-hospital mortality.
Biofilms formed by foodborne pathogens pose a significant threat to food safety, as they enhance microbial resistance to disinfectants and environmental stress. Understanding the relationship between their intricate structure and macroscopic mechanical properties is crucial for developing effective control strategies. This review systematically investigates how the combined application of confocal laser scanning microscopy (CLSM) and rheology provides a powerful solution to this problem. CLSM technology reveals biofilm structure and extracellular polymeric substance (EPS) distribution through high-resolution 3D imaging and multi-component fluorescence labeling. Rheology quantitatively analyzes key mechanical parameters such as viscoelasticity and yield stress. Their integration establishes a multidimensional "structure-function-mechanics" research framework, enabling cross-scale correlations from microscopic features to macroscopic mechanical responses. Additionally, this review analyzes current biofilm removal strategies, fluorescent labeling methods for EPS components, and the composition and functions of EPS in typical bacterial biofilms. We further explore optimized technical approaches to overcome food matrix interference, applications in cleaning process optimization, and future standardization directions integrated with artificial intelligence. This comprehensive methodology provides a systematic and efficient paradigm for understanding biofilm mechanisms and developing control strategies, holding significant implications for biofilm prevention in the food industry.
Gastrointestinal carriage of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) presents a critical public health threat globally. However, in resource-constrained countries with poor sanitation, inadequate drinking water, and limited microbiology laboratories like Kenya, epidemiological data of these strains is limited. This study assessed the gastrointestinal carriage of ESBL-E and the risk factors for colonization among children (≤ 5 years) in the inpatient department (IPD) and outpatient department (OPD). This was a hospital-based cross-sectional study at Thika Level 5 Hospital, Kenya, from February to June 2023. In total, 540 participants (OPD: 270, IPD: 270) were recruited, using systematic random sampling and consecutive sampling in OPD and IPD, respectively. Children admitted for less than 48 h in the paediatrics ward and those with a prior history of hospitalization (≤ 3 months) in OPD were excluded. Demographic data were collected using a well-structured questionnaire. Following the standard microbiology methods, stool or rectal swab samples were cultured, with the identity and antimicrobial susceptibility of isolates elucidated by automated platforms. The overall ESBL-E gastrointestinal carriage rate was 35.4% (191/540), and was highest among outpatients at 40.4% (109/270). Isolates demonstrated co-resistance to aminoglycosides (43–52%), quinolones (52–62%), carbapenems (44–50%), and sulfonamides (92–97%). They were more susceptible to piperacillin/tazobactam (67–95%) and colistin (96–99%). Carbapenemase-producing Enterobacterales (CPE) co-carriage rate was 17.6% (16/91), with similar rates for inpatients (50%, 8/16) and outpatients (50%, 8/16). Escherichia coli was the predominant ESBL-E overall (82.2%, 157/191), among outpatients (83.5%, 91/109), and inpatients (80.5%, 66/82), and was also the main CPE (overall: 81.3%, 13/16; OPD: 75%, 6/8; IPD: 87.5%, 7/8). Independent predictors of colonization included child age (adjusted odds ratio (OR): 1.60, p = 0.045) and a history of antimicrobial use from retail pharmacies without a clinician’s prescription (adjusted OR: 0.18, p = 0.047). This study demonstrates a substantial burden of gastrointestinal carriage of ESBL-E and CPE co-carriage among children (≤ 5 years), with E. coli being the predominant organism. Age less than two years and a history of exposure to non-prescribed antimicrobials were independent factors for colonization. Efforts to limit exposure to contaminated environments and targeted antimicrobial stewardship initiatives are required to mitigate AMR in the current study setting.
Avian Pathogenic Escherichia coli (APEC) causes colibacillosis in poultry, which leads to tremendous economic losses. Traditional control methods, including antibiotics and conventional vaccines, are less effective due to the genetic diversity of APEC and developing antimicrobial resistance (AMR). Novel epitope- and peptide-based vaccines, supported by machine learning (ML), hold high promise. This meta-analysis and systematic review evaluated the effectiveness of epitope- and peptide-vaccine-based candidates against APEC-related morbidity and mortality, production factors, and AMR, and the use of ML in vaccine development. Ten studies were included. Outcomes assessed were prevention of mortality, morbidity, immunogenicity, production performance, and reduction in AMR. The random-effects model was applied for meta-analysis, and the use of ML was summarized descriptively. Vaccines prevent mortality (RR = 1.49; 95% CI: 1.30-1.68, p < 0.001, I2 = 5.55%) and morbidity (RR = 1.50; 95% CI: 0.64-2.35, p < 0.001, I2 = 49.55%) significantly. More sophisticated formulations, such as outer membrane vesicles (OMVs) and nanoparticle-conjugated platforms, induced substantial immune responses and cross-serotype protection. The available evidence showed variability, which needs further validation. The interventions may reduce bacterial load and, potentially, antibiotic consumption. ML provided exciting potential that may improve epitope prediction and delivery strategies. Epitope- and peptide-vaccines showed significant but variable efficacy, while ML demonstrated promising potential in improving the control of APEC. Their utility needs to be established through large field trials and economic analysis.
Non-O157 Shiga Toxin–Producing Escherichia coli (non-O157 STEC) pathogens cause considerable debilities and were reviewed for its prevalence, antimicrobial Resistance, and clinical outcomes in Africa from a One Health perspective. Following the PRISMA guidelines, studies reporting non-O157 STEC in human, animal, environmental and food samples from African countries were retrieved from African Journals Online, Scopus, Google Scholar, Web of Science, and PubMed. Retrieved data were analyzed using random-effects model by the DerSimonian–Laird method and assessment of risk-of-bias for individual studies, with Egger’s test. Of 22 included studies, most were conducted in Northern Africa (59%, n = 13). The most frequently reported STEC serogroups were O26 (26.60%), O45 (8.21%), O111 (7.6%), O121 (3.34%), O145 (4.10%), O78 and O91 (4.10%). Virulence genes including Stx1 (24.9%), stx2 (19.7%), and eae were commonly detected in isolates from human samples than in isolates from other sources. Pooled prevalence of non-O157 STEC in African countries was 20.7% (95% CI: 11.1–30.2, I2 = 97.4%, p = 0.0001) with combined human-animal sources pooled prevalence of 27.3% (95% CI: 9.2–45.3; I2 = 98.6%; p = 0.0001). More than 10% pooled resistance to commonly used antibiotics and high proportion of strains harboring blaTEM, blaVIM, blaNDM, blaCTX, blaOXA encoding ESBLs, tet variants for tetracycline, sul1 and sul2 encoding resistance for sulphamethoxaole, and qnrS (for fluoroquinolone resistance) were recorded. Non-O157 STEC associated infections showing clinical presentations characterized by diarrhea, gastroenteritis, and UTI which were mostly observed in children < 5 years. The prevalence rates and antimicrobial resistance pattern of non-O157 STEC serogroups is a growing concern to African populations and clinical outcomes. There is a need for public enlightenment on prevention of non-O157 STEC with One Health approach.
The epidemiology of invasive fungal infections (IFIs) among patients receiving Bruton tyrosine kinase inhibitors (BTKIs) remains incompletely characterized. We conducted a systematic review and meta-analysis of 88 studies including 23 737 patients to evaluate the prevalence and risk factors for IFIs in this population. Among 16 studies that applied the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium consensus definitions of IFIs, the pooled prevalence of proven/probable IFIs was 2.83% (95% confidence interval [CI], 1.97-4.06), with the highest prevalence observed in patients with central nervous system lymphoma (9.02%). Aspergillosis was the most frequently reported IFI (1.76%), followed by pneumocystosis, candidiasis, and cryptococcosis. The risk factors significantly associated with proven/probable IFIs were concurrent corticosteroid use (odds ratio [OR], 5.03; 95% CI, 2.31-10.92) and ≥3 previous lines of therapy (OR, 3.26; 95% CI, 1.54-6.88). Across clinical trials, the prevalence of fungal infections varied across BTKI agents, ranging from 2.50% with tirabrutinib, to 0.62% with pirtobrutinib. Data on antifungal and Pneumocystis jirovecii pneumonia prophylaxis were limited and inconclusive. Among clinical trials that reported fungal infections as adverse events, the prevalence of IFI was the highest in patients treated with tirabrutinib (2.50%), followed by zanubrutinib (2.13%), ibrutinib (1.75%), acalabrutinib (1.31%), orelabrutinib (1.08%), and pirtobrutinib (0.62%). Although some findings suggest a potential benefit in selected patients, current evidence remains insufficient to support broad prophylaxis recommendations. These results underscore the need for individualized risk assessment and further research to inform prevention strategies.
Fleas are holometabolous, blood-feeding ectoparasites capable of transmitting diverse pathogens of significant veterinary and public health concerns. Their occurrence and abundance within a given habitat depend on environmental factors and the availability of suitable hosts. In Pakistan, research on flea fauna and their associated pathogens has been neglected. To date, no reports have documented the molecular characterization of Ctenocephalides felis felis and their associated bacteria in Pakistan. In the present study, three hundred and eighty morphologically identified C. felis felis specimens-comprising 184 collected from free roaming (stray) dogs (n = 69) and 196 from cats (n = 86), were subjected to DNA extraction followed by amplification of the cytochrome oxidase subunit 1 gene (cox1) and citrate synthase gene (gltA) for flea identity confirmation and screening for the presence of associated bacteria, respectively. Amplicons of appropriate base pair sizes were sequenced and submitted to BLASTn and subsequently subjected to phylogenetic analyses. The obtained cox1 sequence from the morphologically identified C. felis felis in this study showed 100% identity and phylogenetically clustered with C. felis felis sequences from India, Australia, Thailand, China, and Laos in GenBank. Similarly, gltA sequences showed 100% identity with the Wolbachia endosymbiont of C. felis reported from the United Kingdom. This study provides the first genetic characterization of C. felis felis infesting dogs and cats, and their associated Wolbachia endosymbiont in Khyber Pakhtunkhwa (KP), Pakistan. These findings provide baseline molecular data and highlight the need for systematic surveillance and management measures to mitigate any potential veterinary and public health threats.
Migraine is a disabling neurological disorder with limited tolerability and cardiovascular limitations associated with traditional acute therapies such as triptans. Rimegepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist, has emerged as a promising treatment option. This meta-analysis evaluated the efficacy and safety of a single 75 mg oral dose of rimegepant for acute preventive treatment of migraine. A systematic search of PubMed, Scopus, and Web of Science was conducted from inception to October 2025. Only randomized controlled trials (RCTs) evaluating oral rimegepant 75 mg for acute migraine in adults were included. Primary outcomes included pain freedom and pain relief at 2, 24, and 48 h. Secondary outcomes included freedom from associated migraine symptoms, return to normal function, rescue medication use, and adverse events. A random-effects model was applied for pooled analysis. Nine RCTs involving 7,198 participants were included. Participants received a single 75 mg oral dose of rimegepant per migraine attack. Rimegepant demonstrated significantly greater 2-hour pain freedom compared with placebo (RR = 1.77; 95% CI: 1.5-2.1). Two-hour pain relief was similarly improved (RR = 1.35; 95% CI: 1.28-1.42). Safety outcomes were comparable to placebo, with no significant differences in total adverse events (RR = 1.10) or serious adverse events. A single 75 mg oral dose of rimegepant is an effective and well-tolerated therapeutic option for both acute and preventive migraine treatment, offering meaningful clinical improvement and a favorable safety profile. Its non-vasoconstrictive mechanism provides a valuable alternative for patients unable to use triptans or those who respond inadequately to existing therapies.
Bovine deep tissue lymph nodes (DTLNs) are retained in bench trimmings during carcass fabrication and enter the ground beef supply, making Salmonella contamination in DTLNs a recognized food safety concern. To characterize this contamination and provide quantitative inputs for microbial risk assessment, this study applied systematic review and meta-analysis to synthesize evidence on Salmonella prevalence and concentration in bovine DTLNs. Of 490 records initially retrieved from two bibliographic databases and grey literature, 33 were identified as relevant and included in meta-analyses. The pooled Salmonella prevalence in DTLNs was 10.8% (95% CI [7.5, 14.5]), with significant heterogeneity between studies. Subgroup analyses revealed higher prevalence during the warm season compared to the cool season (10.7% vs. 3.8%), in feedlot cattle compared to cull cattle (13.5% vs. 3.4%), and in subiliac lymph nodes (18%). The most prevalent serotypes were Anatum, Reading, Montevideo, Dublin, Typhimurium, Cerro, and Kentucky. Antimicrobial resistance (AMR) data was sparse and methodologically inconsistent. Among the two largest studies, most isolates were pan-susceptible (80.6-86%), with multidrug resistance in a minority (8.3-10.7%); resistance to tetracycline, streptomycin, and chloramphenicol was most common, while resistance to antibiotics used for treating human salmonellosis was lower but present. Concentration data were substantially underreported, with only two studies providing sufficient data for a preliminary quantitative synthesis. Overall, dominant serotypes, seasonal patterns, and major AMR profiles in DTLNs were consistent with those reported in beef products. These findings provide a quantitative foundation for risk assessment and evaluation of DTLN-targeted interventions to mitigate salmonellosis risks associated with ground beef consumption.
Three actinomycete strains, WSLK1-3T, WSLK1-4, and WSLK1-5, associated with scabby potato tuber, were characterized using polyphasic and genome-based taxonomy. All strains were found to be Gram-stain-positive, filamentous bacteria, including LL-diaminopimelic acid in cell-wall peptidoglycan. Whole-cell sugars were glucose, mannose, rhamnose, and ribose. MK-9(H6) and MK-9(H10) were major menaquinones; C16:0, isoC16:0, anteiso-C15:0, and anteiso-C17:0 were major cellular fatty acids; diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, and phosphatidylinositol mannoside were major phospholipids; and DNA G + C contents were 71.5 mol%. Phylogenetic analysis based on 16S rRNA gene and genome sequences indicated that strains WSLK1-3T, WSLK1-4, and WSLK1-5 are closely related to Streptomyces canus DSM 40017T (=JCM 4212T), and S. pseudovenezuelae DSM 40212T (=JCM 11516T), respectively. The 16S rRNA gene sequences, average nucleotide identity based on BLAST (ANIb) and MUMmer (ANIm), and digital DNA-DNA hybridization (dDDH) values among the three strains were 100%, 99.12%, 99.33%, and 94.3%, respectively, indicating that these strains belong to the same species. Strains WSLK1-3T, WSLK1-4, and WSLK1-5 showed 88.54-90.62% ANIb, 90.99-92.27% ANIm, and 40.4-45.1% to their closely related type strains: S. canus JCM 4212T, and S. pseudovenezuelae JCM 11516T. All novel strains were pathogenic, causing necrosis on potato tuber slices, inhibiting plant seedlings, and inducing superficial to raised scab lesions on potato tubers. Based on the phenotypic, chemotaxonomic, pathogenic, and genomic data, strains WSLK1-3T, WSLK1-4, and WSLK1-5 could be assigned to the novel species within the genus Streptomyces for which the name Streptomyces tuberiscabiei sp. nov. is proposed. The type strain is WSLK1-3T (=TBRC 19150T = LMG 33893T).
Wastewater-based surveillance (WBS) of microbial pathogens has become an increasingly useful approach to monitor public health at the population level. However, these efforts varied widely in scope, methodology and focus within the GCC region. It remains unclear how WBS is being used across the region, and to what extent it can inform decision-making or contribute to long-term surveillance infrastructure within the GCC. This review aimed to critically assess WBS studies conducted across GCC and to provide perspective on how to further strengthen the ability of WBS to inform and provide early detection on the emergence of health concerns arising from microbial contaminants that are circulating in the community. This review was conducted following the PRISMA extension for scoping reviews guidance, aiming to identify and critically evaluate peer-reviewed studies that applied WBS across GCC between January 2015 and October 2025. A structured English-language literature search was carried out on the Web of Science, Scopus, and Google Scholar. Search results were screened against predefined inclusion and exclusion criteria. A survey was conducted with GCC stakeholders involved in the execution of wastewater surveillance, and their responses were studied to align actual WBS activities against that reported in the literature. A total of 26 studies met the inclusion criteria for this review, with uneven distribution of studies published across the GCC countries (n = 6). The main targets reported in the WBS studies are antimicrobial resistance (AMR) and SARS-CoV-2. Majority of the studies report qualitative presence of microbial targets and lack quantitative measurements that are required to facilitate decision-making and intervention measures. Emerging methods and technology that can enable WBS were discussed to facilitate future WBS effort in GCC. Although WBS holds significant promises to enhance public health surveillance in the GCC, its potential remains underutilized. Moving forward, addressing capacity training and providing sustainable long-term funding mechanisms, standardizing methodological differences and/or providing a guideline that detail the best practices, promoting a consortium-based surveillance system and initiating research that can facilitate the utilization of WBS data to inform decision-making processes would be crucial for the successful integration of WBS into the region's public health framework.
The escalating release of toxic heavy metals and emerging contaminants into ecosystems necessitates sustainable, high-efficiency remediation strategies. Nanocellulose is emerging as a promising material for bioremediation technologies, due to its unique features like renewability, and high binding affinity. Derived from diverse renewable sources, nanocellulose can be functionalized to improve heavy metal adsorption, offering a versatile platform for pollutant removal. Despite extensive research on the environmental application of nanocellulose, limited studies have applied preferred reporting items for systematic review and meta-analysis (PRISMA) analysis to provide a comprehensive account of the bioremediation potential of nanocellulose. To this end, the objective of this study was to conduct a systematic review by following PRISMA guidelines, to assess recent advancements in the development of nanocellulose-based biomaterials for the removal of heavy metals, and other pollutants. From a total of 326 articles screened, only 132 studies met the inclusion criteria. The selected reports revealed that nanocellulose-based aerogels, membranes, and composites demonstrate significant potential for diverse environmental applications, including wastewater treatment, desalination, and oil-water separation. The bibliometric analysis revealed a surge in research on the topic since 2021, yet many knowledge gaps persist in translation of laboratory-scale innovations to industrial applications. Particularly, the challenges of production scalability, material stability under dynamic conditions, and cost-effectiveness impede large-scale adoption of nanocellulose for pollutant removal. Overall, this PRISMA analysis identified key areas for future research, guiding innovation to improve efficacy and scalability of nanocellulosic biomaterials in environmental applications.
Legumes establish a mutualistic interaction with nitrogen-fixing rhizobia. Lotus japonicus is a model for studying this symbiosis; however, only a limited number of rhizobial species nodulating this host have been taxonomically described. Here, we characterise four Mesorhizobium strains (DC-1.1T, Qj1B1, DC-1.5T, and Qj2B2) isolated from root nodules of Lotus japonicus and Lotus burttii. Multi-locus phylogeny and phylogenomic analyses resolved these isolates into two well-supported monophyletic clades. Genome-based comparisons supported their classification as distinct taxa, with strains DC-1.1T and Qj1B1 showing 95.2% average nucleotide identity (ANI) and 62.9-63.5% digital DNA-DNA hybridisation (dDDH) values relative to Mesorhizobium newzealandense ICMP 19545T, whereas DC-1.5T and Qj2B2 exhibited 92.5-92.8% ANI and 49.9-50.5% dDDH compared with Mesorhizobium waimense ICMP 19557T. Together with chemotaxonomic and physiological traits, these data support the proposal of two novel species, Mesorhizobium bavaricum sp. nov. (DC-1.1T and Qj1B1) and Mesorhizobium monacense sp. nov. (DC-1.5T and Qj2B2). Metagenomic analyses predicted high environmental prevalence for these novel taxa, particularly within soil habitats. Isolates DC-1.1T, Qj1B1, and DC-1.5T effectively nodulated Lotus burttii and significantly promoted plant growth, whereas Qj2B2 neither nodulated nor enhanced growth. Comparative genomic analysis revealed that the nodulating isolates harbour symbiotic genes (nod, fix, and nif) on symbiotic plasmids, a rare feature in Mesorhizobium strains, whereas Qj2B2 lacks essential nod and nif genes. Consistent with these genomic features, symbiotaxonomic analysis assigned the nodulating isolates to symbiovar loti. These results highlight the potential of these isolates as models for comparative analyses of symbiotic plasmid evolution and horizontal gene transfer.