Search Results (43)

The National Adaptation Plan of Bangladesh identifies eleven climate-stressed zones, placing nearly 100 million people at high risk of climate-related hazards. Vulnerable groups such as the poor, floating populations, daily laborers, and slum dwellers are particularly affected. However, there is a lack of data on climate-sensitive diseases and related hospital visits in these areas. This study explored the prevalence of such diseases using the Delphi method through focus group discussions with 493 healthcare professionals from 153 hospitals in 156 upazilas across 21 districts and ten zones. Participants were selected by district Civil Surgeons. Key climate-sensitive diseases identified included malnutrition, diarrhea, pneumonia, respiratory infections, typhoid, skin diseases, hypertension, cholera, mental health disorders, hepatitis, heat stroke, and dengue. Seasonal surges in hospital visits were noted, influenced by factors like extreme heat, air pollution, floods, water contamination, poor sanitation, salinity, and disease vectors. Some diseases were zone-specific, while others were widespread. Regions with fewer hospital visits often had higher disease burdens, indicating under-reporting or lack of access. The findings highlight the need for area-specific adaptation strategies and updates to the Health National Adaptation Plan. Strengthening resilience through targeted investment and preventive measures is crucial to reducing health risks from climate change. Full article

Non-O1, non-O139 Vibrio cholerae (NOVC) extraintestinal infections are rare, but recently, several clinical incidents have been reported worldwide. Toxigenic V. cholerae is a well-known etiological agent of cholera, responsible for acute dehydrating watery diarrhea. Outbreaks occur in an epidemic seasonal pattern, particularly in countries with poverty and poor sanitation. Strains of NOVC are usually not involved in causing the epidemic or pandemic outbreaks seen with potential strains of V. cholerae serogroup O1 and O139. However, they can still cause severe sporadic cases of intestinal as well as extraintestinal infections. In this study, we investigated a case of extraintestinal infections associated with the NOVC serogroup isolated from a deep closed wound abscess. The isolate was screened for the presence of three major virulence genes, toxR, ctxA, and tcpA. The strain tested positive for the toxR gene encoding the regulatory protein and cholera toxin (ctx) gene and tested negative for the toxin-coregulated pilus (TCP) gene, which is essential for the colonization of the human intestine, causing the severe diarrheal disease cholera. To the best of our knowledge, this is the first case of extraintestinal infection caused by toxigenic Vibrio cholerae non-O1/non-O139 in a hospitalized patient in Saudi Arabia. Full article

The Cholera-Hospital-based-Intervention-for-7-Days (CHoBI7) mobile health (mHealth) program is a targeted water treatment and hygiene (WASH) program for the household members of diarrhea patients, initiated in the healthcare facility with a single in-person visit and reinforced through weekly voice and text messages for 3 months. A recent randomized controlled trial of the CHoBI7 mHealth program in urban Dhaka, Bangladesh, found that this intervention significantly increased WASH behaviors and reduced diarrhea prevalence. The objective of this present study was to conduct formative research using an implementation science framework to adapt the CHoBI7 mHealth program for scalable implementation in rural Bangladesh, and to promote construction of self-made handwashing stations (CHoBI7 Scale-up program). We conducted a 3-month multi-phase pilot with 275 recipients and 25 semi-structured interviews, 10 intervention planning workshops, and 2 focus group discussions with intervention recipients and program implementers. High appropriateness, acceptability, and adoption of the CHoBI7 Scale-up program was observed, with most recipients constructing self-made handwashing stations (90%) and chlorinating drinking water (63%) and 50% of participants observed handwashing with soap in the final pilot phase. At the recipient level, facilitators included weekly voice and text messages with videos on handwashing station construction, which served as reminders for the promoted water treatment and hand hygiene behaviors. Barriers included perceptions that self-made iron filters commonly used in households also removed microbial contamination from water and therefore chlorine treatment was not needed, and mobile messages not always being shared among household members. At the implementer level, facilitators for program implementation included follow-up phone calls to household members not present at the healthcare facility at the time of intervention delivery, and the promotion of multiple self-made handwashing station designs. Barriers included high patient volume in healthcare facilities, as well as the high iron in groundwater in the area that reduced chlorination effectiveness. These findings provide valuable evidence for adapting the CHoBI7 mHealth program for a rural setting, with a lower-cost, scalable design, and demonstrated the important role of formative research for tailoring WASH programs to new contexts. Full article

Vibrio fluvialis is an emerging foodborne pathogenic bacterium that can cause severe cholera-like diarrhea and various extraintestinal infections, posing challenges to public health and food safety worldwide. The arginine deiminase (ADI) pathway plays an important role in bacterial environmental adaptation and pathogenicity. However, the biological functions and regulatory mechanisms of the pathway in V. fluvialis remain unclear. In this study, we demonstrate that L-arginine upregulates the expression of the ADI gene cluster and promotes the growth of V. fluvialis. The ADI gene cluster, which we proved to be comprised of two operons, arcD and arcACB, significantly enhances the survival of V. fluvialis in acidic environments both in vitro (in culture medium and in macrophage) and in vivo (in mice). The mRNA level and reporter gene fusion analyses revealed that ArgR, a transcriptional factor, is necessary for the activation of both arcD and arcACB transcriptions. Bioinformatic analysis predicted the existence of multiple potential ArgR binding sites at the arcD and arcACB promoter regions that were further confirmed by electrophoretic mobility shift assay, DNase I footprinting, or point mutation analyses. Together, our study provides insights into the important role of the ArgR-ADI pathway in the survival of V. fluvialis under acidic conditions and the detailed molecular mechanism. These findings will deepen our understanding of how environmental changes and gene expression interact to facilitate bacterial adaptations and virulence. Full article

Healthcare-acquired infections are a major problem in healthcare facility settings around the world. The Democratic Republic of the Congo (DRC) has over 2 million diarrhea patients hospitalized each year. These healthcare settings become high-risk environments for spreading diarrheal illnesses such as cholera. The objective of the Preventative Intervention for Cholera for 7 Days (PICHA7) program is to develop evidence-based water, sanitation, and hygiene (WASH) interventions to reduce cholera and other severe diarrheal diseases in the DRC. The study objective was to evaluate the effectiveness of PICHA7 program delivery in increasing handwashing with a cleansing agent at stool/vomit- and food-related events in a healthcare facility setting among diarrhea patients and patient attendants. A pilot of the PICHA7 program was conducted among 284 participants in 27 healthcare facilities from March 2020 to November 2021 in urban Bukavu in the South Kivu Province of the DRC. The standard arm received the standard message provided in the DRC to diarrhea patients on the use of oral rehydration solution and a basic WASH message at healthcare facility discharge. The PICHA7 arm received the PICHA7 WASH pictorial module delivered by a health promoter focused on handwashing with a cleansing agent at the bedside of the diarrhea patient in the healthcare facility and provision of a soapy water bottle (water and detergent powder). Within 24 h of intervention delivery, a three-hour structured observation of handwashing practices at stool/vomit- and food-related events (key events) was conducted in healthcare facilities of diarrhea patients and their attendants. Compared to the standard arm, there was significantly more handwashing with a cleansing agent at key events in the PICHA7 arm (40% vs. 15%) (odds ratio: 5.04; (95% confidence interval (CI): 2.01, 12.7)). These findings demonstrate that delivery of the PICHA7 WASH pictorial module and provision of a soapy water bottle to diarrhea patients and their attendants presents a promising approach to increase handwashing with a cleansing agent among this high-risk population in healthcare facilities in the eastern DRC. Full article

In this study, we develop a comprehensive mathematical model to analyze the dynamics of epidemic cholera, characterized by acute diarrhea due to pathogen overabundance in the human body. The model is first developed from a deterministic point of view, and then it is modified to include the randomness by stochastic differential equations. The study selected Lévy noise above other well-known types of noise, emphasizing its importance in epidemic modeling. Besides presenting a biological justification for the stochastic system, we demonstrate that the equivalent deterministic model exhibits possible equilibria. The introduction is followed by theoretical analysis of the model. Through rigorous analysis, we establish that the stochastic model ensures a unique global solution. Lyapunov function theory is applied to construct necessary conditions, which on average, guarantee the model’s stability for ${\mathbb{R}}_0^s>1$. Our findings suggest the likelihood of eradicating the disease when ${\mathbb{R}}^s$ is below one, a significant insight supported by graphical simulations of the model. Graphical illustrations were generated from simulating the model in order to increase the analytical results’ robustness. This work provides a strong theoretical framework for a thorough comprehension of a range of such diseases. This research not only provides a deeper understanding of cholera dynamics but also offers a robust theoretical framework applicable to a range of similar diseases, alongside a novel approach for constructing Lyapunov functions for nonlinear models with random disturbances. Full article

Bacteria in the genus Vibrio are ubiquitous in estuarine and coastal waters. Some species (including Vibrio cholerae and Vibrio vulnificus) are known human pathogens causing ailments like cholera, diarrhea, or septicemia. Notably, V. vulnificus can also cause a severe systemic infection (known as vibriosis) in eels raised in aquaculture facilities. Water samples were periodically collected from the estuary of the Asahi River, located in the southern part of Okayama City, Japan. These samples were directly plated onto CHROMagar Vibrio plates, and colonies displaying turquoise-blue coloration were selected. Thereafter, polymerase chain reaction was used to identify V. cholerae and V. vulnificus. A total of 30 V. cholerae strains and 194 V. vulnificus strains were isolated during the warm season when the water temperature (WT) was higher than 20 °C. Concurrently, an increase in coliforms was observed during this period. Notably, V. vulnificus has two genotypes, designated as genotype 1 and genotype 2. Genotype 1 is pathogenic to humans, while genotype 2 is pathogenic to both humans and eels. The loop-mediated isothermal amplification method was developed to rapidly determine genotypes at a low cost. Of the 194 strains isolated, 80 (41.2%) were identified as genotype 1 strains. Among the 41 strains isolated when the WTs were higher than 28 °C, 25 strains (61.0%) belonged to genotype 1. In contrast, of the 32 strains isolated when the WTs were lower than 24 °C, 27 strains (84.4%) belonged to genotype 2. These results suggest that the distribution of the two genotypes was influenced by WT. Full article

In recent years, the number of foodborne infections with non-O1 and non-O139 Vibrio cholerae (NOVC) has increased worldwide. These have ranged from sporadic infection cases to localized outbreaks. The majority of case reports describe self-limiting gastroenteritis. However, severe gastroenteritis and even cholera-like symptoms have also been described. All reported diarrheal cases can be traced back to the consumption of contaminated seafood. As climate change alters the habitats and distribution patterns of aquatic bacteria, there is a possibility that the number of infections and outbreaks caused by Vibrio spp. will further increase, especially in countries where raw or undercooked seafood is consumed or clean drinking water is lacking. Against this background, this review article focuses on a possible infection pathway and how NOVC can survive in the human host after oral ingestion, colonize intestinal epithelial cells, express virulence factors causing diarrhea, and is excreted by the human host to return to the environment. Full article

Controlled human infection models are important tools for the evaluation of vaccines against diseases where an appropriate correlate of protection has not been identified. Enterotoxigenic Escherichia coli (ETEC) strain LSN03-016011/A (LSN03) is an LT enterotoxin and CS17-expressing ETEC strain useful for evaluating vaccine candidates targeting LT-expressing strains. We sought to confirm the ability of the LSN03 strain to induce moderate-to-severe diarrhea in a healthy American adult population, as well as the impact of immunization with an investigational cholera/ETEC vaccine (VLA-1701) on disease outcomes. A randomized, double-blinded pilot study was conducted in which participants received two doses of VLA1701 or placebo orally, one week apart; eight days after the second vaccination, 30 participants (15 vaccinees and 15 placebo recipients) were challenged with approximately 5 × 10⁹ colony-forming units of LSN03. The vaccine was well tolerated, with no significant adverse events. The vaccine also induced serum IgA and IgG responses to LT. After challenge, 11 of the placebo recipients (73.3%; 95%CI: 48.0–89.1) and 7 of the VLA1701 recipients (46.7%; 95%CI: 24.8–68.8) had moderate-to-severe diarrhea (p = 0.26), while 14 placebo recipients (93%) and 8 vaccine recipients (53.3%) experienced diarrhea of any severity, resulting in a protective efficacy of 42.9% (p = 0.035). In addition, the vaccine also appeared to provide protection against more severe diarrhea (p = 0.054). Vaccinees also tended to shed lower levels of the LSN03 challenge strain compared to placebo recipients (p = 0.056). In addition, the disease severity score was lower for the vaccinees than for the placebo recipients (p = 0.046). In summary, the LSN03 ETEC challenge strain induced moderate-to-severe diarrhea in 73.3% of placebo recipients. VLA1701 vaccination ameliorated disease severity, as observed by several parameters, including the percentage of participants experiencing diarrhea, as well as stool frequency and ETEC severity scores. These data highlight the potential value of LSN03 as a suitable ETEC challenge strain to evaluate LT-based vaccine targets (NCT03576183). Full article

Cholera is an exceptionally aggressive infectious disease characterized by the potential to induce acute, copious, watery diarrhea of considerable severity and renal inflammation. Diabetic nephropathy is a serious complication of diabetes mellitus that can lead to kidney failure through inflammation; thus, anti-inflammatory agents are promising therapies for diabetic nephropathy. Previous studies have shown that the essential oil of Zanthoxylum myriacanthum var. pubescens Huang, Maqian essential oil (MQEO), exhibits potent antibacterial, anti-inflammatory, and renoprotective activities in diabetic mice and has emerged as a potential therapeutic drug for the treatment of diabetic nephropathy complications. Therefore, the present study was carried out to screen the potential inhibition of cholera toxin and the diabetic renoprotective activity of MQEO through computational approaches. Twelve chemical constituents derived from MQEO were docked with cholera toxin and the target proteins involved in diabetic nephropathy, namely, TXNIP, Nrf2, and DPP IV, and, subsequently, the predictions of molecular dynamic simulations, the drug-likeness properties, and the ADMET properties were performed. α-terpineol showed high binding affinities toward the cholera toxin protein. For TXNIP, among all the chemical constituents, α-phellandrene and p-cymene showed strong binding affinities with the TXNIP protein and displayed relatively stable flexibility at the hinge regions of the protein, favorable physicochemical properties in the absence of hepatotoxicity, and low cytotoxicity. For Nrf2, α-terpineol exhibited the highest binding affinity and formed a very stable complex with Nrf2, which displayed high pharmacokinetic properties. All compounds had low free-binding energies when docked with the DPP IV protein, which suggests potent biological activity. In conclusion, based on a computational approach, our findings reveal that MQEO constituents have inhibitory activity against cholera toxin and are promising therapeutic agents for suppressing diabetic inflammation and for the treatment of diabetic nephropathy complications. Full article

Introduction: Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea in travelers as well as for children living in low- to middle-income countries. ETEC adhere to intestinal epithelium via colonization factors (CFs). CFA/I, a common CF, is composed of a polymeric stalk and a tip-localized minor adhesive subunit, CfaE. Vaccine delivery by the transcutaneous immunization of dscCfaE was safe but was poorly immunogenic in a phase 1 trial when administered to volunteers with LTR(192G) and mLT. To potentially enhance the immunogenicity of CfaE while still delivering via a cutaneous route, we evaluated the safety and immunogenicity of two CfaE constructs administered intradermally (ID) with or without mLT. Methods: CfaE was evaluated as a donor strand-complemented construct (dscCfaE) and as a chimeric construct (Chimera) in which dscCfaE replaces the A1 domain of the cholera toxin A subunit and assembles non-covalently with the pentamer of heat-labile toxin B (LTB). Subjects received three ID vaccinations three weeks apart with either dscCfaE (1, 5, and 25 µg) or Chimera (2.6 and 12.9 µg) with and without 0.1 µg of mLT. Subjects were monitored for local and systemic adverse events. Immunogenicity was evaluated by serum and antibody-secreting cell (ASC) responses. Results. The vaccine was well-tolerated with predominantly mild and moderate local vaccine site reactions characterized by erythema, induration and post-inflammatory hyperpigmentation. High rates of serologic and ASC responses were seen across study groups with the most robust responses observed in subjects receiving 25 µg of dscCfaE with 0.1 mcg of LT(R192G). Conclusion: Both ETEC adhesin vaccine prototypes were safe and immunogenic when co-administered with mLT by the ID route. The observed immune responses induced with the high dose of dscCfaE and mLT warrant further assessment in a controlled human infection model. Full article

While emerging evidence highlights the significance of gut microbiome in gastrointestinal infectious diseases, treatments like Fecal Microbiota Transplantation (FMT) and probiotics are gaining popularity, especially for diarrhea patients. However, the specific role of the gut microbiome in different gastrointestinal infectious diseases remains uncertain. There is no consensus on whether gut modulation therapy is universally effective for all such infections. In this comprehensive review, we examine recent developments of the gut microbiome’s involvement in several gastrointestinal infectious diseases, including infection of Helicobacter pylori, Clostridium difficile, Vibrio cholerae, enteric viruses, Salmonella enterica serovar Typhimurium, Pseudomonas aeruginosa Staphylococcus aureus, Candida albicans, and Giardia duodenalis. We have also incorporated information about fungi and engineered bacteria in gastrointestinal infectious diseases, aiming for a more comprehensive overview of the role of the gut microbiome. This review will provide insights into the pathogenic mechanisms of the gut microbiome while exploring the microbiome’s potential in the prevention, diagnosis, prediction, and treatment of gastrointestinal infections. Full article

The efficacy of an Oral Whole Cell ETEC Vaccine (OEV) against Travelers’ Diarrhea (TD) was reexamined using novel outcome and immunologic measures. More specifically, a recently developed disease severity score and alternative clinical endpoints were evaluated as part of an initial validation effort to access the efficacy of a vaccine intervention for the first time in travelers to an ETEC endemic area. A randomized, double-blind, placebo-controlled trial followed travelers to Guatemala or Mexico up to 28 days after arrival in the country following vaccination (two doses two weeks apart) with an ETEC vaccine. Fecal samples were collected upon arrival, departure, and during TD for pathogen identification. Serum was collected in a subset of subjects to determine IgA cholera toxin B subunit (CTB) antibody titers upon their arrival in the country. The ETEC vaccine’s efficacy, utilizing a TD severity score and other alternative endpoints, including the relationship between antibody levels and TD risk, was assessed and compared to the per-protocol primary efficacy endpoint. A total of 1435 subjects completed 7–28 days of follow-up and had available data. Vaccine efficacy was higher against more severe (≥5 unformed stools/24 h) ETEC-attributable TD and when accounting for immunologic take (PE ≥ 50%; p < 0.05). The vaccine protected against less severe (3 and 4 unformed stools/24 h) ETEC-attributable TD when accounting for symptom severity or change in activity (PE = 76.3%, p = 0.01). Immunologic take of the vaccine was associated with a reduced risk of infection with ETEC and other enteric pathogens, and with lower TD severity. Clear efficacy was observed among vaccinees with a TD score of ≥4 or ≥5, regardless of immunologic take (PE = 72.0% and 79.0%, respectively, p ≤ 0.03). The vaccine reduced the incidence and severity of ETEC, and this warrants accelerated evaluation of the improved formulation (designated ETVAX), currently undergoing advanced field testing. Subjects with serum IgA titers to CTB had a lower risk of infection with ETEC and Campylobacter jejuni/coli. Furthermore, the TD severity score provided a more robust descriptor of disease severity and should be included as an endpoint in future studies. Full article

Cholera is a bacterial disease that is commonly transmitted through contaminated water, leading to severe diarrhea and rapid dehydration that can prove fatal if left untreated. The complexity of the disease spread arises from the convergence of several distinct and interrelated factors, which previous research has often failed to consider. A significant scientific limitation of the existing literature is the simplistic assumption of linear or logistic dynamics of the disease spread, thereby impeding a thorough assessment of the effectiveness of control strategies. Since environmental factors are the most influential determinant of Vibrio bacterial growth in nature and are responsible for the resurgence, propagation, and disappearance of cholera epidemics, we have proposed a S-I-R-S model that combines bacterial dynamics with the Allee effect. This model takes into account the environmental influence and allows for a better understanding of the disease dynamics. Our results have revealed the phenomenon of bi-stability, with backward and forward bifurcation. Furthermore, our findings have demonstrated that the Allee effect provides a robust framework for characterizing fluctuations in bacterial populations and the onset of cholera outbreaks. This framework can be used for assessing the effectiveness of control strategies, including regular environmental sanitation programs, adherence to hygiene protocols, and monitoring of unfavorable weather conditions. Full article

Background. Quinolones are commonly used for reducing the duration of diarrhea, infection severity, and limiting further transmission of disease related to Vibrio cholerae, but V. cholerae susceptibility to quinolone decreases over time. In addition to mutations in the quinolone-resistance determining regions (QRDRs), the presence of qnr and other acquired genes also contributes to quinolone resistance. Results. We determined the prevalence of quinolone resistance related genes among V. cholerae O139 strains isolated in China. We determined that eight strains carried qnrVC, which encodes a pentapeptide repeat protein of the Qnr subfamily, the members of which protect topoisomerases from quinolone action. Four qnrVC alleles were detected: qnrVC1, qnrVC5, qnrVC12, and qnrVC9. However, the strains carrying qnrVC1, qnrVC5, and qnrVC12 were ciprofloxacin (CIP)-sensitive. Contrastingly, the strain carrying qnrVC9 demonstrated high CIP resistance. qnrVC9 was carried by a small plasmid, which was conjugative and contributed to the high CIP resistance to the receptor V. cholerae strain. The same plasmid was also detected in V. vulnificus. The qnrVC1, qnrVC5, and qnrVC12 were cloned into expression plasmids and conferred CIP resistance on the host V. cholerae O139 strain. Conclusions. Our results revealed the contribution of quinolone resistance mediated by the qnrVC9 carried on the small plasmid and its active horizontal transfer among Vibrio species. The results also suggested the different effects of qnrVC alleles in different V. cholerae strains, which is possibly due to differences in sequences of qnrVC alleles and even the genetic characteristics of the host strains. Full article