Search Results (556)

Several review studies have addressed the implications of improper waste management on urban livability conditions at large, but we still do not have an overall picture of the link between poor waste management in Sub-Saharan countries and short- and long-term health impacts. Considering that Sub-Saharan Africa is the location of 19 of the 50 biggest dumpsites in the world, it is important to better understand what we do and do not know so far about this public health–waste management link. This study, therefore, provides an overall understanding of health risks associated with improper waste disposal in Sub-Saharan Africa, with a focus on air, water and soil pollution. Employing a systematic review approach, this study utilized academic databases, including PubMed, ScienceDirect, and Google Scholar, to identify and analyze 27 relevant articles, covering eight Sub-Saharan countries. The review was undertaken by categorizing trends and characteristics under themes of solid waste disposal practices, pollution consequences, and reported health problems. The results showed that air pollution, which was the most widely studied in Sub-Saharan Africa, accounted for 155 deaths/100,000 people. Water pollution has led to outbreaks of cholera, typhoid, and diarrhea, especially in communities near waste sites, while contaminated soil poses long-term risks, including for cancer and developmental harm. The findings also revealed that children, waste workers, and communities living near dumpsites are the most vulnerable. Despite growing evidence of harm, gaps remain in our understanding of chronic and long-term effects due to a lack of longitudinal data and inconsistent methodologies to measure health effects. The study also identified inconsistency in distance-based exposure metrics, as studies used varying distances of residents from waste sites to measure health outcomes. Finally, it highlights the urgent need for improved waste infrastructure, clear landfill siting guidelines, and long-term epidemiological studies to inform health-focused waste policies in Sub-Saharan Africa. Full article

Botulinum neurotoxin injections are used off-label to treat chronic pain, but their efficacy is limited and paralytic effects restrict clinical utility in these applications. Here, we investigated whether combining the light chain and translocation domains of botulinum neurotoxin A (BoNT/A) with the GM1-binding B subunit of cholera toxin would be beneficial in silencing pain-associated sensory neurons. Chimeric ChoBot was assembled via a coiled-coil linking technology and was shown to retain the enzymatic activity of BoNT/A in vitro and in vivo. In cultured dorsal root ganglion neurons, ChoBot cleaved SNAP25 in a calcitonin gene-related peptide (CGRP)-rich subpopulation of sensory neurons, resulting in marked inhibition of CGRP release. ChoBot had a lesser effect on the compound muscle action potentials of the rat gastrocnemius muscle than BoNT/A following subcutaneous injections. In rat models of pain, including chemotherapy-induced peripheral neuropathy, intraplantar administration of ChoBot significantly attenuated mechanical allodynia. Immunohistochemical analysis confirmed SNAP25 cleavage in NF200- and CGRP-expressing sensory fibres in the epidermis following a single injection. ChoBot also mediated SNAP25 cleavage in human neuroblastoma cells in culture. Together, these findings indicate that ChoBot enables a silencing of pain-associated sensory pathways, providing a new strategy for the development of new long-lasting analgesics for chronic pain. Full article

Non-O1/non-O139 Vibrio cholerae strains are widely distributed in aquatic environments worldwide and are increasingly recognized as potential reservoirs of antimicrobial resistance and virulence-associated determinants. In this study, we performed an integrated phenotypic and genomic analysis of 116 V. cholerae isolates collected in 2024 from environmental and clinical sources in Jiaxing, China, including 106 non-O1/non-O139 isolates, 9 O1 isolates, and 1 O139 isolate. Antimicrobial susceptibility testing showed that most isolates remained susceptible to β-lactam/β-lactamase inhibitor combinations, third-generation cephalosporins, carbapenems, and tigecycline, whereas resistance was more frequently observed for ampicillin, streptomycin, nalidixic acid, and ciprofloxacin. Based on the non-susceptibility criteria of Maitrakas et al., 19 of 116 isolates (16.4%) were classified as multidrug-resistant, whereas none met the definition of extensively drug-resistant. Genomic analysis identified diverse resistance determinants, including plasmid-mediated quinolone resistance genes (qnrVC variants) and quinolone resistance-determining region mutations in gyrA and parC. Virulence-associated genes showed heterogeneous distributions: core regulatory and hemolysis-related genes were highly prevalent, whereas classical cholera toxin genes were largely absent. Several accessory virulence factors, including the RTX toxin operon, chxA, ninth, and makA, were detected in subsets of isolates. Core genome multilocus sequence typing revealed substantial genetic diversity, with environmental and clinical isolates distributed across multiple lineages and showing no clear clustering by isolation source. Overall, these data demonstrate the diverse antimicrobial resistance, virulence-associated gene repertoires, and population structure of the Jiaxing V. cholerae collection, with particular relevance to the predominant non-O1/non-O139 population. Full article

Aquaponic systems are increasingly recognized as sustainable technologies for integrated fish and vegetable production. However, concerns remain regarding the potential internalization of human pathogens into vegetables grown in these systems. This study assessed the risk of pathogen internalization in lettuce leaves grown in aquaponic systems with Nile tilapia challenged with Escherichia coli or Vibrio cholerae. The system comprised nine fish tanks, eighteen hydroponic pipes, and eighty-one lettuce plants, with tanks assigned to three treatments. Samples of water, fish gut, fish blood, and lettuce leaves were collected. Microbiological analyses included selective culture, biochemical assays, and molecular identification. Although colonies consistent with E. coli and V. cholerae were recovered on selective media, molecular sequencing identified other bacterial species, including Aeromonas sp., Aeromonas caviae, Aeromonas veronii, Enterobacter hormaechei, and Citrobacter freundii. The findings indicate that conventional culture-based methods may produce false-positive results and highlight the importance of molecular confirmation. Notably, pathogenic bacteria associated with tilapia were detected and appeared capable of disseminating through the system and internalizing into lettuce tissues. This result highlights the need for biosecurity measures, contamination monitoring, and the combined use of conventional and molecular diagnostic tools to ensure accurate pathogen detection and compliance with international food safety standards. Full article

Klebsiella pneumoniae poses a severe global health threat due to its extensive antibiotic resistance. However, to date, no vaccine against this pathogen has been approved for clinical use worldwide. Although self-assembling nanocarriers present distinct advantages for vaccine design, their ability to effectively load polysaccharide antigens and further elicit mucosal immunity remains unclear. Here, we developed a modular, self-assembling nanovaccine (CNP-OPS_KpO1) against K. pneumoniae by loading of K. pneumoniae O1 polysaccharide antigen onto a cholera toxin B subunit (CTB)-based nanoparticle (CNP). After determining the safety of the vaccine via intranasal immunization, we further evaluated its immune efficacy. CNP-OPS_KpO1 elicited stronger systemic IgG and mucosal sIgA responses than non-nanoparticulate controls. In a non-lethal pulmonary infection model, CNP-OPS_KpO1 vaccination reduced lung bacterial burden by over 5 logs compared to controls, achieving near-complete bacterial clearance. Histopathological analysis further confirmed minimal lung damage in vaccinated animals. In addition, in a lethal pulmonary challenge model, it conferred 90% survival, whereas all mice in the antigen-alone control group died within 4 days. Our work not only provides a safe, effective, and adjuvant-free candidate vaccine against K. pneumoniae but also advances a versatile platform for developing broad-spectrum mucosal vaccines against other pathogens. Full article

Human organoids and organ-on-chip/microphysiological systems (OoC/MPS) are increasingly used as new-approach methodologies for biotoxin assessment. They retain human-relevant tissue organization and enable interpretable analysis of exposure geometry, barrier transport, perfusion, and (when needed) multi-organ coupling. In this review, we synthesize primary evidence across major toxin classes, including bacterial enterotoxins (e.g., cholera toxin, heat-stable enterotoxins, Shiga toxins), mycotoxins (e.g., aflatoxin B1, ochratoxin A, deoxynivalenol), and algal/cyanobacterial toxins (e.g., saxitoxin, domoic acid, microcystins, biliatresone). We emphasize studies that clearly define toxin identity and exposure context and that demonstrate mechanism-critical model competencies under assay conditions. We highlight decision-informative functional endpoints that align with the dominant pathophysiology. These include cystic fibrosis transmembrane conductance regulator (CFTR)-dependent secretion in human enteroids/colonoids, transporter-linked proximal tubular injury in kidney MPS, gut–kidney axis injury from Shiga toxin-producing E. coli in microfluidic systems, and multi-electrode array (MEA) network readouts in human 3D neural tissues. We then summarize best practices that improve cross-study comparability. These include reporting delivered versus nominal exposure, assessing recovery/mass balance and device/material interactions, applying proportional biological qualification (polarity, transporter/enzymatic competence, functional stability), defining a minimal comparable endpoint core, and preserving QIVIVE readiness in reporting. Finally, we outline near-term priorities for the field, including chronic low-dose and mixture designs, harmonized reference panels and acceptance criteria, and fit-for-purpose escalation to coupled OoC/MPS only when perfusion or organ–organ coupling is expected to change the interpretation. Full article

Freshwater ecosystems play an important role in human survival, ecosystem functioning, and biodiversity conservation, yet industrialisation and urbanisation dump over 80% of untreated sewage into them. This inadequate wastewater management leads to enteric pathogens like Escherichia coli, Salmonella, Shigella, Campylobacter, Vibrio cholerae, Pseudomonas aeruginosa, and Legionella pneumophila that are responsible for a wide range of waterborne human diseases globally with extensive morbidity and mortality. The World Health Organization (WHO) estimates that at least 2 billion individuals drink water contaminated with pathogens, resulting in illnesses like cholera, dysentery, and diarrhoea, and approximately 50,000 diarrheal deaths annually. Classical epidemiology approaches are the basis for determining disease burden in public health, but they are limited in their capacity to predict future health risks. Quantitative microbial risk assessment (QMRA) addresses this by estimating the potential health risks of any exposure to microbial pathogens in any environment using four key elements, which include the identification of the microbial hazards, human exposure to the hazard through diverse activities, dose–response relationships, and the estimated risk of the infection. This review summarises information on freshwater pathogens, their occurrence, sources and health implications. The methodological approaches of QMRA in freshwater systems are reviewed with examples drawn from recreational activities, drinking water, and wastewater-impacted environments. Global QMRA studies indicate a wide range of infection risk estimates, reflecting differences in water sources, pathogens, and exposure conditions. Thus, QMRA is known to be a valuable public health tool for freshwater ecosystems, linking microbial contamination dynamics to health risk estimates that support proactive management and policy-relevant decision-making. Full article

In this work, we consider a simple bistable motif constituted by a self-enhancing Transcription Factor (TF) and its mRNA with non-instantaneous dynamics. In particular, we mainly numerically investigated the impact of bounded stochastic perturbations of Sine–Wiener type affecting the degradation rate/binding rate constant of the TF on the phase-like transitions of the system. We show that the intrinsic exponential delay in the TF positive feedback, due to the presence of a mRNA with slow dynamics, deeply affects the above-mentioned transitions for long but finite times. We also show that, in the case of more complex delays in the feedback and/or in the translation process, the impact of the extrinsic stochasticity is further amplified. We also briefly investigate the power-law behavior (PLB) of the averaged energy spectrum of the TF by showing that, in some cases, the PLB is simply due to the filtering nature of the motif. A similar analysis can also be applied to biological models having a qualitatively similar structure, such as the well-known Capasso and Paveri–Fontana model of cholera spreading. Full article

Background/Objectives: Franz Tappeiner (1816–1902) is often celebrated as a pioneer of alpine medicine and the founder of Tappeiner Promenade in Meran (South Tyrol, Italy). However, his legacy extends far beyond the scenic infrastructure, encompassing a comprehensive vision of physical activity as a public health intervention. His multidisciplinary practice anticipated the principles of contemporary rehabilitation, preventive medicine, and climate-sensitive public health. Methods: This historical public health analysis, combining biographical, contextual, and material–spatial approaches, reinterprets Tappeiner’s writings, institutional engagements, and civic projects through the lens of modern public health frameworks. Drawing on primary materials (e.g., published articles, autobiographical fragments, and commemorative texts) and recent evidence from rehabilitation and environmental health research, these contributions were contextualized. Results: Tappeiner’s early focus on infectious disease prevention (e.g., cholera and tuberculosis) transitioned into a strategic emphasis on recovery and behavioral therapy through environmental design. The walking therapy model of Max Joseph Oertel, locally realized in the Tappeiner Promenade, prefigured modern concepts such as structured green rehabilitation, walkability, and urban-health citizenship. His systematic integration of graded walking into civic infrastructure represents one of the earliest documented examples of embedding physical activity promotion at the population level. He contributed substantial personal funds to the path’s construction, embedding therapeutic gradients, curating vegetation, and promoting inclusive design to support convalescence. Contemporary research supports the intuition that green, low- to moderate-intensity walking improves cardiometabolic health, psychological well-being, and functional capacity. Moreover, his integrative ethos, merging clinical medicine, civic ethics, and spatial intervention, parallels contemporary eco-social models of public health. Conclusions: Franz Tappeiner’s career exemplifies a still-relevant model of physician leadership that is empirically grounded, socially accountable, and ecologically attuned, with physical activity promotion embedded as a central element of his public health vision. His work invites reflection on how medical professionals can shape not only individual care but also urban environments and collective health futures. Full article

This study examines the historical relationship between water management and epidemic diseases in the Region of Murcia (Southeast Spain) between the 16th and 19th centuries. It focuses on two major pathologies—yellow fever and cholera—which, despite differing transmission mechanisms (vector-borne and waterborne, respectively), both depended critically on aquatic and semi-endorheic ecosystems. By analysing archival records, parish death registers, and historical reports of floods and droughts, the paper demonstrates how inadequate hydraulic infrastructure and poor sanitation practices intensified epidemic outbreaks. At least five large-scale epidemic episodes (1804, 1834, 1854, 1865, and 1885) coincided with extreme hydrological events, indicating a clear correlation between water governance failures and mortality peaks. Conversely, periods of effective state intervention through regulation and infrastructure maintenance reveal a marked reduction in disease incidence. The results highlight that water governance was not only a technical challenge but also a socio-political determinant of public health. These historical insights remain relevant today, particularly as climate change exacerbates water-related risks worldwide. Understanding the long-term interactions between ecology, infrastructure, and disease contributes to current debates on environmental resilience and sustainable management of water resources as key components of collective health and social stability. Full article

The highly chitinolytic marine bacterium Vibrio jasicida KMM 6832, which exhibits potent antifungal activity, possesses an atypical Glycosyl Hydrolase family 19 (GH19) chitinase (ChitVjs). This is the first report of a GH19 gene in V. jasicida, an enzyme generally absent in this species and rare within the Harveyi clade. Phylogenetically, ChitVjs-like enzymes from the genera Vibrio and Aeromonas form a distinct cluster, separate from typical plant and bacterial GH19 counterparts. Despite high sequence identity (80–94%) with characterized homologs from V. parahaemolyticus and V. cholerae, ChitVjs is distinguished by its obligate halophilicity (optimum 0.3–0.4 M NaCl), an acidic isoelectric point (pI 4.72), and a broader cation-activation profile (K⁺, Ni²⁺, Ca²⁺, Cu²⁺, Co²⁺). The recombinant ChitVjs was produced in E. coli as a soluble 63 kDa protein. It functions as a stable, salt-dependent endo-chitinase/chitosanase, exhibiting optimal activity at 40 °C and pH 7.0. The enzyme displays high affinity for colloidal chitin (K_M 0.377 mg·mL⁻¹), is activated by DTT and Tween 80, and shows moderate stability in organic solvents. Furthermore, unlike its primarily catabolic relatives, ChitVjs suppresses conidial germination in marine-derived Aspergillus strains. These findings suggest that ChitVjs significantly contributes to the competitive fitness of V. jasicida KMM 6832 in high-salinity marine environments through both nutrient acquisition and antagonism. Full article

The October 2023 to 2024 cholera outbreak demonstrates significant challenges related to water quality and sanitation, especially in peri-urban areas with limited access to clean water. This study assesses the presence of faecal coliforms and Escherichia coli (E. coli) in drinking water sources across five townships, identified as cholera transmission hotspots, two months post the cholera outbreak in the Lusaka District. A total of 169 water samples were collected from protected sources, treated piped water, and unprotected sources, including dams and shallow wells. Faecal coliforms and E. coli were detected across all source types. Among unprotected sources, 92.3% (12/13) of samples contained ≥100 CFU/100 mL of both faecal coliforms and E. coli. Protected sources showed variable contamination, with 18.3% exceeding ≥100 CFU/100 mL for faecal coliforms and 15.4% for E. coli. Treated water sources showed the lowest contamination, with 88.5% of samples having no detectable faecal coliforms and 90.4% having no detectable E. coli. Zero-inflated negative binomial regression showed that treated water sources were associated with substantially lower faecal coliform counts compared with protected sources (PR = 0.11, 95% CI: 0.03–0.35), while unprotected sources exhibited higher contamination intensity (PR = 1.77, 95% CI: 0.94–3.31). Treated sources were significantly more likely to be structurally free of contamination, whereas unprotected sources had an extremely low probability of yielding zero counts. These findings indicate that current water safety conditions in Lusaka’s cholera hotspot areas remain inadequate for preventing faecal-oral transmission. Full article

Cholera outbreaks are prevalent in coastal regions, where hydroclimatic factors play a critical role. However, evidence on their associations with different genotypes remains limited, and global projection remains lacking. We compiled cholera data from EnteroBase and WHO weekly reports covering 110 coastal countries from 1980 to 2022. A generalized additive model was used to examine the associations between hydroclimatic factors and different cholera serotypes and genotypes. We further projected future cholera occurrences for each coastal country under three climate change scenarios from 2025 to 2100. During the study period, Wave 3 of O1 replaced Wave 1 as the predominant genotype of cholera, while cholera O139 remained at low levels and only occurred in Asia. At the country–year level, each 1 °C increase in sea surface temperature (SST) was significantly associated with cholera occurrence (OR: 1.032, 95% CI: 1.023 to 1.040) and Wave 3 of O1 (OR: 1.149, 95% CI: 1.097 to 1.203). Drainage density (m/km²) and coastline ratio (%) were positively related to cholera, with ORs of 1.067 (95% CI: 1.046 to 1.087) and 1.022 (95% CI: 1.019 to 1.027). For future projections, five trend patterns were identified under different emission scenarios, with most countries showing increased cholera risk due to global hydroclimatic changes, peaking under the SSP585 scenario. Our findings reveal associations between hydroclimatic factors and different cholera genotypes and project future cholera risk across coastal countries, thereby providing evidence to inform genotype-specific surveillance and targeted prevention strategies at the global scale. Full article

Introduction: Cholera remains a major public health threat in endemic settings, and oral cholera vaccine (Shanchol™) campaigns are increasingly used amid constrained global supply. However, practical decisions on revaccination require clearer, setting-specific estimates of how rapidly vaccine-induced vibriocidal antibodies peak and wane. Methods: We conducted a prospective cohort kinetics analysis in Lukanga Swamps (Central Province, Zambia), enrolling adults (18–65 years) stratified by prior Shanchol™ exposure (0, 1, or 2 previous doses). All participants received two Shanchol™ doses 14 days apart, with serum collected at baseline and days 14, 28, 60, and 90 (end of follow-up). Ogawa and Inaba vibriocidal titres were measured using a complement-based assay and analysed on the log10 scale. Serotype-specific mixed-effects models with natural cubic splines for time (knots: 14, 28, 60 days) assessed trajectories by prior-dose strata, adjusting for age, sex, and HIV status. Peak timing and post-peak half-life were derived from model-based predictions with participant-level bootstrap CIs (1000 replications). Results: The analysis included 225 participants: 68 (30.2%) with zero prior doses, 89 (39.6%) with one, and 68 (30.2%) with two; median age was 33 years (IQR 25–49), 56.4% were female, and 19.2% were HIV-positive. Modelled titres for both serotypes rose steeply after vaccination, peaking around day 36–37 across prior-dose strata. Ogawa titres reached half of peak by about day 73–78, corresponding to post-peak half-lives of 37–41 days; Inaba declined more slowly with half-lives of 42–46 days. Confidence intervals overlapped across prior-dose strata, indicating minimal differences by vaccination history. Conclusions: In this cholera-endemic adult population, Shanchol™ induced vibriocidal responses that peaked at ~5 weeks and waned over the following 5–7 weeks, with broadly similar kinetics regardless of prior vaccination and slightly slower decay for Inaba than Ogawa. These parameters can inform booster timing in hotspot settings. Full article

Mucosal-associated invariant T (MAIT) cells exist in high numbers in the body and have a unique and highly conserved T cell receptor (TCR). They can be activated in a TCR-dependent manner by ligands presented on the monomorphic protein MHC class I-related protein 1 (MR1) which is found on many cell types, including professional antigen presenting cells (APCs) and epithelial cells. This has sparked interest in the potential to exploit the MR1-MAIT cell axis for the development of vaccines against infectious disease. Within this context an MR1 ligand, typically 5-(2-oxopropylideneamino)-d-ribitylaminouracil (5-OP-RU), is administered with or without a Toll-like receptor (TLR) ligand or cytokine in a pan vaccination approach that would prime the immune response to provide protection against a variety of bacterial and viral pathogens. This strategy has led to enhanced protection in murine models of Legionella longbeachae, Francisella tularensis, Klebsiella pneumoniae, Streptococcus pneumoniae and influenza infection. However, studies against Mycobacterium tuberculosis infection have proven less successful. The second vaccination approach involves pairing the MR1 ligand with more conventional antigens that could activate CD4⁺ and/or CD8⁺ T cells. This approach has been successful in murine models of cholera, influenza, and SARS-CoV-2, including in the context of subunit vaccines. However, there are several challenges when using MR1-MAIT cell-mediated vaccine adjuvants. These include the inherent instability of 5-OP-RU and the need for more advanced studies to better understand how the use of MR1 ligands would translate to applications in humans. This review will discuss these aspects and highlight the mechanistic studies that have been undertaken to understand how MAIT cells might elicit their effects within the context of MAIT cell-mediated vaccines for infectious disease. Full article