Search

Bacteria and their viral predators (phages) are constantly evolving to subvert one another. Many bacterial immune systems that inhibit phages are encoded on mobile genetic elements that can be horizontally transmitted to diverse bacteria. Despite the pervasive appearance of immune systems in bacteria, it is not often known if these immune systems function against phages that the host encounters in nature. Additionally, there are limited examples demonstrating how these phages counter-adapt to such immune systems. Here, we identify clinical isolates of the global pathogen Vibrio cholerae harboring a novel genetic element encoding the bacterial immune system DarTG and reveal the immune systems impact on the co-circulating lytic phage ICP1. We show that DarTG inhibits ICP1 genome replication, thus preventing ICP1 plaquing. We further characterize the conflict between DarTG-mediated defense and ICP1 by identifying an ICP1-encoded protein that counters DarTG and allows ICP1 progeny production. Finally, we identify this protein, AdfB, as a functional antitoxin that abrogates the toxin DarT likely through direct interactions. Following the detection of the DarTG system in clinical V. cholerae isolates, we observed a rise in ICP1 isolates with the functional antitoxin. These data highlight the use of surveillance of V. cholerae and its lytic phages to understand the co-evolutionary arms race between bacteria and their phages in nature.IMPORTANCEThe global bacterial pathogen Vibrio cholerae causes an estimated 1 to 4 million cases of cholera each year. Thus, studying the factors that influence its persistence as a pathogen is of great importance. One such influence is the lytic phage ICP1, as once infected by ICP1, V. cholerae is destroyed. To date, we have observed that the phage ICP1 shapes V. cholerae evolution through the flux of anti-phage bacterial immune systems. Here, we probe clinical V. cholerae isolates for novel anti-phage immune systems that can inhibit ICP1 and discover the toxin-antitoxin system DarTG as a potent inhibitor. Our results underscore the importance of V. cholerae and ICP1 surveillance to elaborate novel means by which V. cholerae can persist in both the human host and aquatic reservoir in the face of ICP1.

UNLABELLED: Vibrio cholerae, the causative agent of the diarrheal disease cholera, poses an ongoing health threat due to its wide repertoire of horizontally acquired elements (HAEs) and virulence factors. New clinical isolates of the bacterium with improved fitness abilities, often associated with HAEs, frequently emerge. The appropriate control and expression of such genetic elements is critical for the bacteria to thrive in the different environmental niches they occupy. H-NS, the histone-like nucleoid structuring protein, is the best-studied xenogeneic silencer of HAEs in gamma-proteobacteria. Although H-NS and other highly abundant nucleoid-associated proteins (NAPs) have been shown to play important roles in regulating HAEs and virulence in model bacteria, we still lack a comprehensive understanding of how different NAPs modulate transcription in V. cholerae. By obtaining genome-wide measurements of protein occupancy and active transcription in a clinical isolate of V. cholerae, harboring recently discovered HAEs encoding for phage defense systems, we show that a lack of H-NS causes a robust increase in the expression of genes found in many HAEs. We further found that TsrA, a protein with partial homology to H-NS, regulates virulence genes primarily through modulation of H-NS activity. We also identified few sites that are affected by TsrA independently of H-NS, suggesting TsrA may act with diverse regulatory mechanisms. Our results demonstrate how the combinatorial activity of NAPs is employed by a clinical isolate of an important pathogen to regulate recently discovered HAEs. IMPORTANCE: New strains of the bacterial pathogen Vibrio cholerae, bearing novel horizontally acquired elements (HAEs), frequently emerge. HAEs provide beneficial traits to the bacterium, such as antibiotic resistance and defense against invading bacteriophages. Xenogeneic silencers are proteins that help bacteria harness new HAEs and silence those HAEs until they are needed. H-NS is the best-studied xenogeneic silencer; it is one of the nucleoid-associated proteins (NAPs) in gamma-proteobacteria and is responsible for the proper regulation of HAEs within the bacterial transcriptional network. We studied the effects of H-NS and other NAPs on the HAEs of a clinical isolate of V. cholerae. Importantly, we found that H-NS partners with a small and poorly characterized protein, TsrA, to help domesticate new HAEs involved in bacterial survival and in causing disease. A proper understanding of the regulatory state in emerging isolates of V. cholerae will provide improved therapies against new isolates of the pathogen.

In 2023, the 7th cholera pandemic continued to surge, with 535 321 cases reported to WHO, up from 472 697 in 2022. Cholera cases were reported from 45 countries, territories [...]

Cholera is a global health problem with no targeted therapies. The Ca2+-sensing receptor (CaSR) is a regulator of intestinal ion transport and a therapeutic target for diarrhea, and Ca2+ is considered its main agonist. We found that increasing extracellular Ca2+ had a minimal effect on forskolin-induced Cl- secretion in human intestinal epithelial T84 cells. However, extracellular Mg2+, an often-neglected CaSR agonist, suppressed forskolin-induced Cl- secretion in T84 cells by 65% at physiological levels seen in stool (10 mM). The effect of Mg2+ occurred via the CaSR/Gq signaling that led to cAMP hydrolysis. Mg2+ (10 mM) also suppressed Cl- secretion induced by cholera toxin, heat-stable E. coli enterotoxin, and vasoactive intestinal peptide by 50%. In mouse intestinal closed loops, luminal Mg2+ treatment (20 mM) inhibited cholera toxin-induced fluid accumulation by 40%. In a mouse intestinal perfusion model of cholera, addition of 10 mM Mg2+ to the perfusate reversed net fluid transport from secretion to absorption. These results suggest that Mg2+ is the key CaSR activator in mouse and human intestinal epithelia at physiological levels in stool. Since stool Mg2+ concentrations in patients with cholera are essentially zero, oral Mg2+ supplementation, alone or in an oral rehydration solution, could be a potential therapy for cholera and other cyclic nucleotide-mediated secretory diarrheas.

We previously established the selection-marker-free rice-based oral cholera vaccine (MucoRice-CTB) line 51A for human use by Agrobacterium-mediated co-transformation and conducted a double-blind, randomized, placebo-controlled phase I trial in Japan and the United States. Although MucoRice-CTB 51A was acceptably safe and well tolerated by healthy Japanese and U.S. subjects and induced CTB-specific antibodies neutralizing cholera toxin secreted by Vibrio cholerae, we were limited to a 6-g cohort in the U.S. trial because of insufficient production of MucoRice-CTB. Since MucoRice-CTB 51A did not grow in sunlight, we re-examined the previously established marker-free lines and selected MucoRice-CTB line 19A. Southern blot analysis of line 19A showed a single copy of the CTB gene. We resequenced the whole genome and detected the transgene in an intergenic region in chromosome 1. After establishing a master seed bank of MucoRice-CTB line 19A, we established a hydroponic production facility with LED lighting to reduce electricity consumption and to increase production capacity for clinical trials. Shotgun MS/MS proteomics analysis of MucoRice-CTB 19A showed low levels of α-amylase/trypsin inhibitor-like proteins (major rice allergens), which was consistent with the data for line 51A. We also demonstrated that MucoRice-CTB 19A had high oral immunogenicity and induced protective immunity against cholera toxin challenge in mice. These results indicate that MucoRice-CTB 19A is a suitable oral cholera vaccine candidate for Phase I and II clinical trials in humans, including a V. cholerae challenge study.

Background: Cholera continues to be a major public health threat, especially in regions with poor sanitation and limited access to clean water. Accurate prediction and management of cholera outbreaks are essential to reduce mortality and morbidity. This review focuses on the potential of polymerase chain reaction (PCR) cycle threshold (Ct) values as an innovative tool for early detection and control of cholera outbreaks, specifically highlighting its utility in predicting outbreaks and guiding public health responses. PCR Ct values offer a significant advantage in the early detection of Vibrio cholerae, the pathogen responsible for cholera, in both clinical and environmental samples. By providing quantitative data on bacterial load, lower Ct values indicate a higher concentration of the pathogen, signaling the potential for increased disease transmission. These values allow for more precise, real-time monitoring of cholera outbreaks and aid in targeting intervention strategies such as water sanitation improvements, vaccination campaigns, and antibiotic treatments. Moreover, the application of Ct values in environmental surveillance, particularly in monitoring water sources, offers a proactive approach to prevent the spread of cholera by identifying contamination risks before human cases arise. However, the implementation of PCR in low-resource settings faces significant challenges, including high costs, the need for advanced laboratory infrastructure, and a lack of technical expertise. Addressing these barriers through cost-effective innovations and capacity building initiatives is crucial for optimizing the use of PCR Ct values in cholera management. Conclusion: PCR Ct values hold great promise for improving cholera outbreak prediction and control. Despite challenges in adopting this technology in resource-limited settings, the integration of Ct value monitoring into public health frameworks can enhance early detection efforts and contribute to more effective cholera management strategies. [ABSTRACT FROM AUTHOR]

Cholera is a disease of poverty affecting people with inadequate access to safe water and basic sanitation. Conflict, unplanned urbanization and climate change all increase the risk of cholera. In this article, an optimal control deterministic mathematical model of cholera disease with cost-effectiveness analysis is developed and analyzed considering both direct and indirect contact transmission pathways. The model qualitative behaviors, such as the invariant region, the existence of a positive invariant solution, the two equilibrium points (disease-free and endemic equilibrium), and their stabilities (local as well as global stability) of the model are studied. Moreover, the basic reproduction number of the model is obtained. We also performed sensitivity analysis of the basic parameters of the model. Then an optimal control problem is designed with a control functional having five controls: vaccination, treatment, environment sanitation and personal hygiene, and water quality improvement program. We examined the existence and uniqueness of the optimal controls of the system. Through the implementation of Pontryagin's maximum principle, the characterization of the optimal controls optimality system is established. The numerical simulation results the integrated control strategies demonstrated that strategy 2, 7, and 12 are effective programs to combat cholera disease from the community. Based on the local circumstances, available funds, and resources, it is recommended to the government stakeholders and policymakers to execute any one of the three integrated intervention programs. [ABSTRACT FROM AUTHOR]

We propose, in this paper, a hybrid Cholera transmission model with phage to simulate the interaction between Vibrio cholerae and phages in the host population and environment, which is coupled with some reaction–diffusion equations and first-order partial differential equations. The precise formulation of basic reproduction number ( ℛ 0 ) is deduced, which characterizes the elimination or prevalence of this disease. Specifically, the disease-free steady state is globally asymptotically stable for ℛ 0 ≤ 1 but unstable for ℛ 0 > 1. Further, the phage invasion reproduction number ℛ 1 is also obtained, which portrays the impact of phages on Vibrio cholerae in the environment. That is, for ℛ 0 > 1 , the phage-free endemic steady state is globally asymptotically stable if ℛ 1 ≤ 1 , and the phage-present endemic steady state is globally asymptotically stable if ℛ 1 > 1. Numerical simulations are introduced for the purpose of verifying the main results. [ABSTRACT FROM AUTHOR]

Analysis of clinical and environmental Vibrio cholerae O1 strains obtained during 2008-2015 in Nigeria showed that lineages Afr9 and Afr12 carrying cholera toxin and Vibrio pathogenicity island 1 can be isolated from water. Our findings raise concerns about the role of the environment in maintenance and emergence of cholera outbreaks in Nigeria. [ABSTRACT FROM AUTHOR]

Nigeria accounts for a substantial cholera burden globally, particularly in its northeast region, where insurgency is persistent and widespread. We used participatory group model building workshops to explore enablers and barriers to implementing known cholera interventions, including water, sanitation and hygiene, surveillance and laboratory, case management, community engagement, oral cholera vaccine, and leadership and coordination, as well as exploring leverage points for interventions and collaboration. The study engaged key cholera stakeholders in the northeastern States of Adamawa and Bauchi, as well as national stakeholders in Abuja. Adamawa and Bauchi States' group modes building participants comprised 49 community members and 43 healthcare providers, while the 23 national participants comprised government ministry, department and agency staff, and development partners. Data were analysed thematically and validated via consultation with selected participants. The study identified four overarching themes regarding the enablers and barriers to implementing cholera interventions: (1) political will, (2) health system resources and structures, (3) community trust and culture, and (4) spill-over effect of COVID-19. Specifically, inadequate political will exerts its effect directly (e.g. limited funding for prepositioning essential cholera supplies) or indirectly (e.g. overlapping policies) on implementing cholera interventions. The healthcare system structure (e.g. centralization of cholera management in a State capital) and limited surveillance tools weaken the capacity to implement cholera interventions. Community trust emerges as integral to strengthening the healthcare system's resilience in mitigating the impacts of cholera outbreaks. Lastly, the spill-over effects of COVID-19 helped promote interventions similar to cholera (e.g. water, sanitation and hygiene) and directly enhanced political will. In conclusion, the study offers insights into the complex barriers and enablers to implementing cholera interventions in Nigeria's cholera-endemic settings. Strong political commitment, strengthening the healthcare system, building community trust and an effective public health system can enhance the implementation of cholera interventions in Nigeria. [ABSTRACT FROM AUTHOR]

Background: Vibrio cholerae O1 El Tor, the etiological agent responsible for the last cholera pandemic, has become a well-established model organism for which some genetic tools are available. While CRISPRi technology has been applied to V. cholerae, improvements were necessary to upscale it and enable pooled screening by high-throughput sequencing in this bacterium. Results: In this study, we present a genome-wide CRISPR-dCas9 screen specifically optimized for the N16961 El Tor model strain of V. cholerae. This approach is characterized by a tight control of dCas9 expression and activity, as well as a streamlined experimental setup. Our library allows the depletion of 3,674 (98.9%) annotated genes from the V. cholerae genome. To confirm its effectiveness, we screened for genes that are essential during exponential growth in rich medium and identified 369 genes for which guides were significantly depleted from the library (log2FC < -2). Remarkably, 82% of these genes had previously been described as hypothetical essential genes in V. cholerae or in a closely related bacterium, V. natriegens. Conclusion: We thus validated the robustness and accuracy of our CRISPRi-based approach for assessing gene fitness in a given condition. Our findings highlight the efficacy of the developed CRISPRi platform as a powerful tool for high-throughput functional genomics studies of V. cholerae. [ABSTRACT FROM AUTHOR]

Background: Africa reports the highest number of outbreaks globally, accounting for 39% of all outbreaks in 2022. The Integrated Disease Surveillance and Response strategy in Kenya ensures the reporting of outbreaks up to the national level. We present a summary of the burden of reported disease outbreaks in Kenya, 2007–2022. Methods: We reviewed historical surveillance data, 2007–2022, summarized the annual caseload and deaths of reported outbreaks, and classified the outbreaks into 3 categories, that is high, moderate, and low burden. A nested Poisson regression model was fit to determine whether there was a significant increase in the number of diseases and counties reporting outbreaks over time. Results: Twenty-three diseases were reported. COVID-19, cholera, epidemic malaria, kala-azar, and measles were associated with a high disease burden. The highest number of diseases reported in a single year was 10. We observed an increase in the number of outbreaks over time (IRR = 1.26, 95% CI [1.22–1.29], p < 0.001), and an increase in the number of counties reporting outbreaks over time (r = 0.97, p < 0.001). Conclusion: There was an increase in the frequency and geographic occurrence of outbreaks. The differences in outbreak occurrence between counties necessitate targeted and enhanced preventive, preparedness, and response interventions at the sub-national level to reduce the burden of outbreaks. [ABSTRACT FROM AUTHOR]

In June 1849, James K. Polk died from cholera in Nashville, less than four months removed from the presidency. Seizing on a sensational column in the New York Herald, the editor of the Tennessee Baptist, J. R. Graves, used Polk’s hasty deathbed conversion to educate southerners about the inherent dangers they embraced when they joined Methodist and Presbyterian congregations. The ensuing debate offers a window into the sectarian edge of Nashville’s religious weeklies, revealing that far from fearing greed or secularization, they embraced competition from other Protestant denominations in a race to build a modern, denominational press that could evangelize the region. [ABSTRACT FROM AUTHOR]

In this work, we mechanistically formulate a generalized cholera model with nonlocal time delay to study the impact of bacterial hyperinfectivity on cholera epidemics in a spatially heterogeneous environment. Mathematical challenges lie in the fact that (i) the generalized cholera model considers the intrinsic growth of short-lived hyperinfectious (HI vibrios) state of V. cholerae and lower-infectious (LI vibrios) state of V. cholerae simultaneously; and (ii) this article originally derives the detailed classifications of spatial dynamics for the cholera model with some generally functional response functions, non-uniformness of diffusion rates and nonlocal time delay. We introduce three basic reproduction numbers: one is for HI state of V. cholerae , the other is for LI state of V. cholerae , and another is for the cholera disease in the host population. Based on these basic reproduction numbers, we further establish the global threshold dynamics. Under some conditions, the basic reproduction number of infection is strictly decreasing with respect to the diffusion coefficients of infectious hosts. [ABSTRACT FROM AUTHOR]

Introduction: John Snow, a British physician of the 19th century, played a pivotal role in challenging prevailing medical beliefs during his time. His groundbreaking studies on the cholera epidemic led to the rejection of the miasma theory and the establishment of the link between contaminated water and the spread of the disease. Aim: This study aims to explore the contributions of John Snow to the fields of anaesthesiology and epidemiology, focusing on his significant findings and methodologies. Material and methods: This study utilizes a literature review approach to examine John Snow's contributions to anaesthesiology and epidemiology. Searches were conducted in databases using relevant keywords, focusing on peer-reviewed articles and authoritative sources. The data was qualitatively synthesized to extract key insights into Snow's methodologies and findings, aiming to provide a brief overview of his impact on medical science. Results and discussion: John Snow (1813-1858) is celebrated as a pioneer in epidemiology and anaesthesiology. He identified contaminated water as the source of the 1854 cholera outbreak in London, establishing the basis for modern epidemiology. Snow's innovative mapping of cholera cases was crucial in controlling the epidemic. He also advanced anaesthetic techniques, notably using chloroform on Queen Victoria during childbirth, improving the safety of anaesthesia. His work remains influential in both fields. Conclusions: John Snow's pioneering work significantly impacted the development of anaesthesiology and epidemiology. His insights into cholera transmission and anaesthetic agents, along with his seminal publication On Chloroform and Other Anaesthetic, continue to inspire advancements in medical science. Snow's legacy underscores the importance of evidence-based medicine and the pursuit of knowledge in addressing public health challenges. [ABSTRACT FROM AUTHOR]

This article explores the representation of wrath in relation to the topic of shipwreck in literary texts from 17th-century Spain. As seen in the emblematic genre of the time, as well as in novellas and theatre plays, wrath is represented as the shipwreck of reason. Lack of control and the destruction of the mind as consequences of anger are associated with the capsizing of ships in marine storms. From the Renaissance and well into the late 17th-century, a sound mind is figuratively equivalent to the tranquil voyage in which the ship is in control of the maritime space. By contrast, the reckless and uncontrollable mind is comparable to the ship tossed and destroyed by the tempest, unable to return from the abyss of the ocean depths. As demonstrated in the literary texts of the time, to let the mind be taken over by the passions, particularly wrath and love, was frequently correlated with madness and, thus, with moral decline, as under contemporaneous thought, insanity was connected to ethical degeneration and conversely, sanity with Christian virtues. Moreover, the symbolic implication of the shipwreck motif in Early Modern Spanish literature also reflected the medical notions of the time—namely those related to the bodily humors. Within these sociocultural coordinates, wrath and unrequited love are correlated to choleric and melancholic natures that can lead to madness and social unrest. In sum, the connection of wrath to nautical devastation is an effective means to convey social and political commentary and transmit didactic messages. [ABSTRACT FROM AUTHOR]

Recurrent cholera outbreak in Nigeria signifies a problem of water and sanitation. However, there is so much implication of open defecation and surface water pollution with little emphasis on the ground water which are predominantly sources of drinking water. The aim of this study was to carry out a pilot risk assessment of water sources in selected communities from four local government areas of Bida, Gbako, Katcha, and Lavun that experienced 2018 cholera outbreak in Niger State, Nigeria. The risk assessment was based on the guidelines for Assessing the Risk to Groundwater from On-Site Sanitation (ARGOSS). Our result showed that about 63% of the ground water sources in the study areas are of significant risk. The results also showed that the type of ground water sources did not determine the outcome of the risk assessment (Pearson's Chi-squared test, p > 0.05). However, the subsoil type of the sources affects or is associated with the outcome of the risk assessment (Pearson's Chi-squared test, p < 0.05). Generally, the Vibrio species counts of the water sources are in order of rivers/streams>> open wells>boreholes. The Vibrio species counts did not show any seasonal variation (t. test, p > 0.05). Also, there was no combined effect of the type of water sources and risk determination outcome on the Vibrio species counts (ANOVA, p > 0.05). This study can serve as basis for enforcement of well/borehole-pit latrine/septic tank distance limit in Nigeria. [ABSTRACT FROM AUTHOR]

Waterborne and foodborne illnesses caused by bacterial pathogens are major public health concerns, especially in developing countries like Nigeria—waterborne pathogens such as Escherichia coli, Salmonella spp. and Klebsiella spp. Contribute to the spread of health challenges, primarily due to poor sanitation, contaminated drinking water, and inadequate hygiene. Similarly, foodborne pathogens, including Escherichia coli, Listeria monocytogenes and Salmonella spp., are major causes of human illness, with animal-based foods often acting as transmission vectors. This review examines the current state of diagnosis, highlighting that most household water sources in Nigeria are vulnerable to contamination, with significant microbial loads exceeding WHO standards. It raises the need for effective interventions such as improved hygiene practices, water supply, sanitation and food safety management systems. Furthermore, this review discusses the impact of these pathogens on public health, noting that waterborne and foodborne diseases result in substantial mortality and economic burdens. Also, implementing good hygienic practices, Hazard Analysis Critical Control Point (HACCP) systems, and public health education are essential strategies for reducing the incidence of these diseases. This review concludes by calling for a collaborative effort among governments, policymakers, stakeholders, and researchers to develop and implement multifaceted interventions to combat these pervasive health threats. [ABSTRACT FROM AUTHOR]

Background: Vibrio cholerae is a primary cause of severe dehydrating diarrhea and remains a serious public health problem in low- and middleincome countries (LMICs) with insufficient water, sanitation, and hygiene. Cholera remains a public health threat the worldwide, mainly in countries with poor access to safe water and sanitation facilities. According to estimates, there are 21,000-143,000 deaths and 1.3-4 million cases of cholera annual. Objective: This study aims to carry out an analysis of the available information on cholera outbreaks in Diyala province, 2022. Patients and Methods: A descriptive study conducted in the department of public health using the data of cases reported from eight sectors in province. The data was collected from the surveillance unit, communicable control division of the public health department in Diyala province, IRAQ in 2022. Results: The total number of confirmed cases of cholera was (n = 139), female (72) 52 % and male (67) 48%, death reported for two of these cases. According to the date of onset, the registration of cases began from July 19 to October 25, 2022. However, the case fatality ratio (CFR) was 1.4%, while the attack rate in the governorate is 7.6 per 100,000 populations during 2022, the highest attack rate in Khanaqin district was (77 cases) 46, while the lowest attack rate in Baldruze, Al-Mansuria, and Al-Khalis districts was (1 case) 0.3,0.6, and 0.8 respectively. The age mean of patients was (38.7 ± 17.14 years) and the occurrence of the disease is more incidence in the age group 30-44 and females more than males. Conclusion: Occurrence Cholera outbreak during year 2022 without confirmed cases recorded since 2015 and the occurrence of cholera cases in governorate is greater during the months of August and September and most of the cases were from Khanaqin district. [ABSTRACT FROM AUTHOR]

This document is a compilation of research articles in the field of immunology, focusing on advancements in immunology research through the use of new approach methods (NAMs) as alternatives to traditional animal models. NAMs aim to accurately replicate the complex and dynamic nature of the immune system, bridging the gap between animal studies and human clinical trials. The document highlights specific advancements in NAMs, such as using postmortem tissues for immunological studies and modeling vascular inflammation using a microfluidic platform. These developments contribute to a better understanding of immune responses and disease progression, offering a more ethical and potentially more accurate alternative to traditional animal-based research. [Extracted from the article]

Background: Diverse bacterial group behaviors are controlled by quorum sensing, a regulatory network of bacterial gene expression based on cell density, and involving communication through chemical signal molecules called autoinducers. Multidisciplinary research in toxigenic Vibrio cholerae the etiologic agent of cholera, appear to suggest group behavior in the ecology, epidemiology, pathogenesis and transmission of the pathogen. This review summarizes latest advances and known aspects of quorum regulated environmental survival form of V. cholerae, and their role in cholera outbreaks, as well as the significance of this knowledge in tracking the pathogen for prevention of cholera. Main body: Pathogenic V. cholerae naturally exists in aquatic reservoirs, and infects humans, often leading to epidemic outbreaks of cholera. Effective detection and monitoring of the pathogen in surface waters have been a research focus in preventing cholera outbreaks. However, in the aquatic reservoirs, V. cholerae persists mostly in a quiescent state referred to as viable but non-culturable (VBNC), or conditionally viable environmental cells (CVEC), which fail to grow in routine bacteriological culture. The presence of CVEC can, however, be observed by fluorescent antibody based microscopy, and they appear as clumps of cells embedded in an exopolysaccharide matrix. Current studies suggest that CVEC found in water are derived from in-vivo formed biofilms excreted by cholera patients. The transition to CVEC occurs when dilution of autoinducers in water blocks quorum-mediated regulatory responses that would normally disperse the cellular aggregates. Consequently, CVEC are resuscitated to actively growing cells if autoinducers are replenished, either in the laboratory, or naturally by other environmental bacteria or the intestinal microbiota when CVEC are ingested by humans or aquatic animals. Conclusion: Quorum sensing plays a crucial role in the environmental persistence of toxigenic V. cholerae in a latent state, and their periodic emergence to cause cholera outbreaks. Furthermore, the autoinducer driven resuscitation of these cells may be a basis for improving the detection of V. cholerae in water samples, and monitoring V. cholerae in their aquatic reservoirs in cholera endemic areas. [ABSTRACT FROM AUTHOR]

In Bangladesh, Vibrio cholerae lineages are undergoing genomic evolution, with increased virulence and spreading ability. However, our understanding of the genomic determinants influencing lineage transmission and disease severity remains incomplete. Here, we developed a computational framework using machine-learning, genome scale metabolic modelling (GSSM) and 3D structural analysis, to identify V. cholerae genomic traits linked to lineage transmission and disease severity. We analysed in-patients isolates from six Bangladeshi regions (2015-2021), and uncovered accessory genes and core SNPs unique to the most recent dominant lineage, with virulence, motility and bacteriophage resistance functions. We also found a strong correlation between V. cholerae genomic traits and disease severity, with some traits overlapping those driving lineage transmission. GSMM and 3D structure analysis unveiled a complex interplay between transcription regulation, protein interaction and stability, and metabolic networks, associated to lifestyle adaptation, intestinal colonization, acid tolerance and symptom severity. Our findings support advancing therapeutics and targeted interventions to mitigate cholera spread. Cholera continues to cause significant mortality in endemic regions such as Bangladesh where diverse lineages circulate. Here, the authors investigate genomic features that are associated with linage transmission dynamics and disease severity using machine learning, genome-scale metabolic modelling, and 3D structural analysis. [ABSTRACT FROM AUTHOR]

This review traces the development of vaccines from ancient times to the present, highlighting major milestones and challenges. It covers the significant impact of vaccines on public health, including the eradication of diseases such as smallpox and the reduction of others such as polio, measles, and influenza. The review provides an in-depth look at the COVID-19 vaccines, which were developed at unprecedented speeds due to the urgent global need. The study emphasizes the ongoing potential of vaccine development to address future global health challenges, demonstrating the critical role vaccines play in disease prevention and public health. Moreover, it discusses the evolution of vaccine technology, from live-attenuated and inactivated vaccines to modern recombinant and mRNA vaccines, showcasing the advancements that have enabled rapid responses to emerging infectious diseases. The review underscores the importance of continued investment in research and development, global collaboration, and the adoption of new technologies to enhance vaccine efficacy and coverage. By exploring historical and contemporary examples, the article illustrates how vaccines have transformed medical practice and public health outcomes, providing valuable insights into future directions for vaccine innovation and deployment. [ABSTRACT FROM AUTHOR]

Epidemics and Pandemics (disease outbreaks) are the occurrence of cases of disease in excess of what would be normally expected. Epidemic-prone diseases, including emerging and re-emerging diseases, constitute the greatest threat to public health security and disruption of social and economic development. When outbreaks are diagnosed in specific areas, an outbreak response is triggered to stop the spread rapidly. In the past 20 years, the sub-Saharan region has witnessed a marked increase in the number of outbreaks in pandemics, such as cholera, dengue, A/H5N 1 influenza among others. While efforts toward containment have been individually studied, we have no recent studies that examine them collectively in order to draw appropriate comparisons, no recent studies that have especially focused on hard-to-reach areas, and none that have applied a health systems lens. This study thus details a scoping review of short-term health system responses to epidemics across hard-to-reach areas in sub-Saharan Africa. The scoping review will be undertaken following PRISMA guidelines. A modified Donabedian framework will be used to understand the different approaches used while responding to epidemics. The review will focus on published and unpublished studies that report short-term health systems responses to epidemics in hard to reach areas. These will be gleaned from PubMed, google scholar and Cochrane, supplemented by a Google advanced search. In addition, manual searches will be carried out through related articles and websites. Data will be charted, coded, and narratively synthesized. our exclusion criteria will include; protocols, book chapters and countries not identified as hard to reach areas in SSA. We anticipate developing a document that will show the different approaches health systems in different countries used when responding to epidemics. The information generated will contribute to strengthening future epidemic responses by identifying best practices and innovative ideas as well as highlighting knowledge gaps. [ABSTRACT FROM AUTHOR]

Introduction: Tongue weakness and atrophy can lead to deficits in the vital functions of breathing and swallowing in patients with motor neuron diseases (MNDs; e.g., amyotrophic lateral sclerosis (ALS) and pseudobulbar palsy), often resulting in aspiration pneumonia, respiratory failure, and death. Available treatments for patients with MNDs are largely palliative; thus, there is a critical need for therapies targeting preservation of upper airway function and suggesting a role for tongue exercise in patients with MNDs. Here, we leveraged our inducible rodent model of hypoglossal (XII) motor neuron degeneration to investigate the effects of a strength endurance tongue exercise program on upper airway structure and function. Our model was created through intralingual injection of cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue to induce targeted death of XII motor neurons. Methods: Rats in this study were allocated to 4 experimental groups that received intralingual injection of either CTB-SAP or unconjugated CTB + SAP (i.e., control) +/- tongue exercise. Following tongue exercise exposure, we evaluated the effect on respiratory function (via plethysmography), macrostructure [via magnetic resonance imaging (MRI) of the upper airway and tongue], and ultrafine structure [via ex vivo magnetic resonance spectroscopy (MRS) of the tongue] with a focus on lipid profiles. Results: Results showed that sham exercise-treated CTB-SAP rats have evidence of upper airway restriction (i.e., reduced airflow) and structural changes present in the upper airway (i.e., airway compression) when compared to CTB-SAP + exercise rats and control rats +/- tongue exercise, which was ameliorated with tongue exercise. Additionally, CTB-SAP + sham exercise rats have evidence of increased lipid expression in the tongue consistent with previously observed tongue hypertrophy when compared to CTB-SAP + exercise rats or control rats +/- tongue exercise. Conclusion: These findings provide further evidence that a strength endurance tongue exercise program may be a viable therapeutic treatment option in patients with XII motor neuron degeneration in MNDs such as ALS. Future directions will focus on investigating the underlying mechanism responsible for tongue exercise-induced plasticity in the hypoglossal-tongue axis, particularly inflammatory associated factors such as BDNF. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 24-year-old man who was admitted with fever, cough, shortness of breath, and chest pain, ultimately diagnosed with a respiratory viral infection, likely influenza, complicated by a bacterial superinfection. Topics discussed include the historical context of the 1918 influenza pandemic, advancements in the identification and vaccination against influenza, and the development of early surveillance systems and their impact on public health responses.

Background: Indian subcontinent being an important region in the fight to eliminate cholera needs better cholera surveillance. Current methods miss most infections, skewing disease burden estimates. Triangulating serosurvey data, clinical cases, and risk factors could reveal India's true cholera risk. Methods: We synthesized data from a nationally representative serosurvey, outbreak reports and risk factors like water, sanitation and the Multidimensional Poverty Index, to create a composite vulnerability index for assessing state-wise cholera risk in India. We tested 7,882 stored sera samples collected during 2017–18 from individuals aged 9–45 years, for vibriocidal antibodies to Vibrio cholerae O1 using a cut-off titre ≥320 defining as elevated titre. We also extracted data from the 2015–19 Integrated Disease Surveillance Programme and published cholera reports. Results: Overall, 11.7% (CI: 10.4–13.3%) of the sampled population had an elevated titre of cholera vibriocidal antibodies (≥320). The Southern region experienced the highest incidence (16.8%, CI: 12.1–22.8), followed by the West (13.2%, CI: 10.0–17.3) and North (10.7%, CI: 9.3–12.3). Proportion of samples with an elevated vibriocidal titre (≥320) was significantly higher among individuals aged 18–45 years (13.0% CI: 11.2–15.1) compared to children 9–17 years (8.6%, CI 7.3–10.0, p<0.05); we found no differences between sex or urbanicity. Between 2015–2019, the Integrated Disease Surveillance Program (IDSP) reported 29,400 cases of cholera across the country. Using the composite vulnerability index, we found Karnataka, Madhya Pradesh, and West Bengal were the most vulnerable states in India in terms of risk of cholera. Conclusion: The present study showed that cholera infection is present in all five regions across India. The states with high cholera vulnerability could be prioritized for targeted prevention interventions. Author summary: Cholera remains a significant public health threat in areas with inadequate water, sanitation, and hygiene (WASH). The World Health Organization's Global Task Force on Cholera Control (GTFCC) launched "Ending Cholera: A Global Roadmap to 2030" to reduce cholera deaths and eliminate the disease in 20 countries by 2030 through targeted interventions, including improved WASH practices and disease surveillance. cholera surveillance, especially in developing countries seldom poses difficulty in terms of the need for laboratory infrastructure, and other resource constraints. Thereby, in this study, we utilized a viable approach with serosurvey data from 2017, cholera outbreak data, WASH indicators, and the Multidimensional Poverty Index (MPI) to create a composite vulnerability index for cholera risk in India. Overall, 11.7% of the sampled population had detectable levels of cholera antibodies reflecting previous infection. The Southern region of India experienced the highest incidence, followed by the West and North. the study showed that cholera infection is present in all five regions across India. Further, the vulnerability index which we built could be utilized in other settings so that effective tailored interventions could be applied in identified priority areas. [ABSTRACT FROM AUTHOR]

Duck pasteurellosis also called as Duck cholera is a highly contagious disease of ducks caused by Pasteurella multocida. It has been found to be most commonly occurring bacterial disease among semi-mature and mature birds with 5 to 100 % morbidity and 0.5 to 80 % mortality rates. The present study was conducted to investigate the suspected outbreak of pasteurellosis in a duck farm. The samples were collected from morbid and dead birds after conducting post-mortem examinations and processed for further isolation, identification and molecular characterization. The samples were found to be positive for Pasteurella multocida by cultural and biochemical tests and confirmed as Pasteurella multocida by using Pasteurella multocida species specific KMT1 primers and capsular type A specific primers. It was further processed for virulence-associated ompH gene. The purified Pasteurella multocida species specific KMT1 product was sequenced and based on nucleotides homology and phylogenetic analysis, the sample was having 99.76 % homology to Pasteurella multocida strain VP161 chromosome. Based on nucleotides homology and phylogenetic analysis of the capsular type-specific hyaDhyaC gene partial nucleotide sequences, the sample was having 98.60% homology to Pasteurella multocida strain PMISC1 HyaD (hyaD) gene specific for capsular type A. [ABSTRACT FROM AUTHOR]

A quiz concerning a notable scientist honored by a tickborne protozoan infection focuses on Victor Babeș (1854–1926), who made significant contributions to pathology and microbiology, including his pioneering work in rabies vaccine development.

Formal infectious disease surveillance in Ukraine has been disrupted by Russia’s 2022 invasion, leading to challenges with tracking and containing epidemics. To analyze the effects of the war on infectious disease epidemiology, we used open-source data from EPIWATCH, an artificial intelligence early-warning system. We analyzed patterns of infectious diseases and syndromes before (November 1, 2021–February 23, 2022) and during (February 24–July 31, 2022) the conflict. We compared case numbers for the most frequently reported diseases with numbers from formal sources and found increases in overall infectious disease reports and in case numbers of cholera, botulism, tuberculosis, HIV/AIDS, rabies, and salmonellosis during compared with before the invasion. During the conflict, although open-source intelligence captured case numbers for epidemics, such data (except for diphtheria) were unavailable/underestimated by formal surveillance. In the absence of formal surveillance during military conflicts, open-source data provide epidemic intelligence useful for infectious disease control. [ABSTRACT FROM AUTHOR]

The occurrence of Vibrio cholerae, Vibrio metschnikovii and Vibrio fluvialis, important aquatic human pathogens of genus Vibrio, were determined in the surface water of the Danube River in Bratislava. The isolates were identified by biochemical tests. Biochemical characteristics of environmental isolates could be slightly different from reference and clinical strains which is reflected in dissimilarity rate, which was in our case not sufficient. A molecular method called amplified ribosomal DNA restriction analysis was used for confirmation of phenotypic identification. The species identity of 19 out of 22 isolates was confirmed, in the case of 3 misidentified ones, the identity of the genus did not change. The identity of all V. cholerae isolates was confirmed by PCR using species-specific gene called ompW. Also, main virulence factors of these isolates were determined. None of the isolates possessed all three virulence factors necessary for the induction of cholera. [ABSTRACT FROM AUTHOR]

This commentary discusses the impact of the COVID-19 pandemic on low- and middle-income countries, referred to as "have not" countries. These countries have faced challenges in obtaining and affording pandemic vaccines and antiviral agents. The author suggests an alternative approach of treating the host response to infection with a combination of generic statins and ACE inhibitors or ARBs, which target the endothelial dysfunction underlying COVID-19. Observational studies and clinical trials are needed to better prepare these countries for treating COVID-19 and future pandemics. The commentary also highlights the need for a pluralistic approach that considers both randomized controlled trials and observational studies in understanding treatment efficacy. The availability of inexpensive generic drugs in "have not" countries could have a significant impact on global equity. [Extracted from the article]

Copyright of Bylye Gody is the property of Cherkas Global University Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this study, we presented a modified SIR-SI model to investigate the dynamics and potential controls for cholera transmission, with an incident rate equipped with a saturation factor to investigate the combined impact of three vital measures which include effective surveillance, vaccination campaign and proper treatment in case severity. We established among other things, the qualitative analysis of the model to validate the results. Furthermore, the reproduction number (R0) was found to be less than unity (1), through the stability analysis. Additionally, finite different scheme was utilized in solving the differential equations of the model. MATLAB software was used for the numerical simulation to examine the effect of these control measures on the population density, findings from the graphical solutions depicts that these measures will aid in flattening the curve Cholera propagation in the population if properly implemented. [ABSTRACT FROM AUTHOR]

The lack of a universally accepted definition of a pandemic hinders a comprehensive understanding of and effective response to these global health crises. Current definitions often lack quantitative criteria, rendering them vague and limiting their utility. Here, we propose a refined definition that considers the likelihood of susceptible individuals contracting an infectious disease that culminates in widespread global transmission, increased morbidity and mortality, and profound societal, economic, and political consequences. Applying this definition retrospectively, we identify 22 pandemics that occurred between 165 and 2024 AD and were caused by a variety of diseases, including smallpox (Antonine and American), plague (Justinian, Black Death, and Third Plague), cholera (seven pandemics), influenza (two Russian, Spanish, Asian, Hong Kong, and swine), AIDS, and coronaviruses (SARS, MERS, and COVID-19). This work presents a comprehensive analysis of past pandemics caused by both emerging and re-emerging pathogens, along with their epidemiological characteristics, societal impact, and evolution of public health responses. We also highlight the need for proactive measures to reduce the risk of future pandemics. These strategies include prioritizing surveillance of emerging zoonotic pathogens, conserving biodiversity to counter wildlife trafficking, and minimizing the potential for zoonotic spillover events. In addition, interventions such as promoting alternative protein sources, enforcing the closure of live animal markets in biodiversity-rich regions, and fostering global collaboration among diverse stakeholders are critical to preventing future pandemics. Crucially, improving wildlife surveillance systems will require the concerted efforts of local, national and international entities, including laboratories, field researchers, wildlife conservationists, government agencies and other stakeholders. By fostering collaborative networks and establishing robust biorepositories, we can strengthen our collective capacity to detect, monitor, and mitigate the emergence and transmission of zoonotic pathogens. [ABSTRACT FROM AUTHOR]

Introduction: Cholera remains a substantial public health challenge in Somalia. Ongoing droughts in the country have caused significant outbreaks which have negatively affected the lives of many individuals and overwhelmed health facilities. We aimed to estimate the costs associated with cholera cases for households and health facilities in Somalia. Methods: This cost-of-illness study was conducted in five cholera treatment centres in Somalia and 400 patients treated in these facilities. Data collection took place during October and November 2023. Given that a significant portion of the patients were children, we interviewed their caregivers to gather cost data. We interviewed staff at the centres and the patients. The data obtained from the household questionnaire covered direct (medical and non-medical) and indirect (lost wages) costs, while direct costs were estimated for the health facility (personnel salaries, drugs and consumables used to treat a patient, and utility expenses). All costs were calculated in US dollars (USD), using 2023 as the base year for the estimation. Results: The average total cost of a cholera episode for a household was US$ 33.94 (2023 USD), with 50.4% (US$ 17.12) being direct costs and 49.6% (US$ 16.82) indirect costs. The average total cost for a health facility to treat an episode of cholera was US$ 82.65. The overall average cost to households and health facilities was US$ 116.59. The average length of stay for a patient was 3.08 days. In the households, patients aged 41 years and older incurred the highest mean total cost (US$ 73.90) while patients younger than 5 years had the lowest cost (US$ 21.02). Additionally, 61.8% of households had to use family savings to cover the cost of the cholera episode, while 14.5% had to borrow money. Most patients (71.8%) were younger than 16 years– 45.3% were 5 years or younger– and 94.0% had never received a cholera vaccine. Conclusion: Our study suggests that preventing one cholera episode in Somalia could avert substantial losses for both the households and cholera treatment centres. The findings shed light on the expenses associated with cholera that extend beyond healthcare, including substantial direct and indirect costs borne by households. Preventing cholera cases could lead to a decrease in this economic burden, consequently our study supports the need for preventive measures. [ABSTRACT FROM AUTHOR]

BackgroundYemen continues to endure cholera outbreaks during ongoing conflict and destructive environmental events. Air raids have been used throughout the conflict to target military and civilian infrastructure. We aimed to assess the association between air raids and cholera incidence while taking into account geographical, environmental, economic, and demographic factors that drive outbreaks.MethodsIn this ecological modelling study, we used data from Sept 12, 2016, to Dec 29, 2019, for the number of air raids, vegetation coverage, surface water, precipitation, temperature, economic variables, and cholera case and population data to model the association between conflict and the weekly incidence of cholera (per 100 000 people) in Yemen. Data were transformed into weekly intervals and governorates were categorised according to air raid severity (the number of raids in the previous 3 months). We used a negative binomial generalised additive model that accounted for geographical location and environmental, temporal, economic, and demographic variables to estimate incidence rate ratios for the association between air raid severity and cases of cholera.FindingsDuring the study period, 2 107 912 cases of cholera were reported in Yemen, and a minimum of 11 366 air raids were recorded. After controlling for relevant factors, compared with no air raids, all other levels of air raid severity were significantly associated with cholera incidence. The largest effect was noted in governorates with severe air raid levels (ie, ≥76 during the previous 3 months), which had an incidence rate ratio of 2·06 (95% CI 1·59-2·69; p

Abstract Background Cholera continues to be a major public health threat, especially in regions with poor sanitation and limited access to clean water. Accurate prediction and management of cholera outbreaks are essential to reduce mortality and morbidity. This review focuses on the potential of polymerase chain reaction (PCR) cycle threshold (Ct) values as an innovative tool for early detection and control of cholera outbreaks, specifically highlighting its utility in predicting outbreaks and guiding public health responses. Main body of abstract PCR Ct values offer a significant advantage in the early detection of Vibrio cholerae, the pathogen responsible for cholera, in both clinical and environmental samples. By providing quantitative data on bacterial load, lower Ct values indicate a higher concentration of the pathogen, signaling the potential for increased disease transmission. These values allow for more precise, real-time monitoring of cholera outbreaks and aid in targeting intervention strategies such as water sanitation improvements, vaccination campaigns, and antibiotic treatments. Moreover, the application of Ct values in environmental surveillance, particularly in monitoring water sources, offers a proactive approach to prevent the spread of cholera by identifying contamination risks before human cases arise. However, the implementation of PCR in low-resource settings faces significant challenges, including high costs, the need for advanced laboratory infrastructure, and a lack of technical expertise. Addressing these barriers through cost-effective innovations and capacity building initiatives is crucial for optimizing the use of PCR Ct values in cholera management. Conclusion PCR Ct values hold great promise for improving cholera outbreak prediction and control. Despite challenges in adopting this technology in resource-limited settings, the integration of Ct value monitoring into public health frameworks can enhance early detection efforts and contribute to more effective cholera management strategies.

This article explores the representation of wrath in relation to the topic of shipwreck in literary texts from 17th-century Spain. As seen in the emblematic genre of the time, as well as in novellas and theatre plays, wrath is represented as the shipwreck of reason. Lack of control and the destruction of the mind as consequences of anger are associated with the capsizing of ships in marine storms. From the Renaissance and well into the late 17th-century, a sound mind is figuratively equivalent to the tranquil voyage in which the ship is in control of the maritime space. By contrast, the reckless and uncontrollable mind is comparable to the ship tossed and destroyed by the tempest, unable to return from the abyss of the ocean depths. As demonstrated in the literary texts of the time, to let the mind be taken over by the passions, particularly wrath and love, was frequently correlated with madness and, thus, with moral decline, as under contemporaneous thought, insanity was connected to ethical degeneration and conversely, sanity with Christian virtues. Moreover, the symbolic implication of the shipwreck motif in Early Modern Spanish literature also reflected the medical notions of the time—namely those related to the bodily humors. Within these sociocultural coordinates, wrath and unrequited love are correlated to choleric and melancholic natures that can lead to madness and social unrest. In sum, the connection of wrath to nautical devastation is an effective means to convey social and political commentary and transmit didactic messages.

Abstract Background Diverse bacterial group behaviors are controlled by quorum sensing, a regulatory network of bacterial gene expression based on cell density, and involving communication through chemical signal molecules called autoinducers. Multidisciplinary research in toxigenic Vibrio cholerae the etiologic agent of cholera, appear to suggest group behavior in the ecology, epidemiology, pathogenesis and transmission of the pathogen. This review summarizes latest advances and known aspects of quorum regulated environmental survival form of V. cholerae, and their role in cholera outbreaks, as well as the significance of this knowledge in tracking the pathogen for prevention of cholera. Main body Pathogenic V. cholerae naturally exists in aquatic reservoirs, and infects humans, often leading to epidemic outbreaks of cholera. Effective detection and monitoring of the pathogen in surface waters have been a research focus in preventing cholera outbreaks. However, in the aquatic reservoirs, V. cholerae persists mostly in a quiescent state referred to as viable but non-culturable (VBNC), or conditionally viable environmental cells (CVEC), which fail to grow in routine bacteriological culture. The presence of CVEC can, however, be observed by fluorescent antibody based microscopy, and they appear as clumps of cells embedded in an exopolysaccharide matrix. Current studies suggest that CVEC found in water are derived from in-vivo formed biofilms excreted by cholera patients. The transition to CVEC occurs when dilution of autoinducers in water blocks quorum-mediated regulatory responses that would normally disperse the cellular aggregates. Consequently, CVEC are resuscitated to actively growing cells if autoinducers are replenished, either in the laboratory, or naturally by other environmental bacteria or the intestinal microbiota when CVEC are ingested by humans or aquatic animals. Conclusion Quorum sensing plays a crucial role in the environmental persistence of toxigenic V. cholerae in a latent state, and their periodic emergence to cause cholera outbreaks. Furthermore, the autoinducer driven resuscitation of these cells may be a basis for improving the detection of V. cholerae in water samples, and monitoring V. cholerae in their aquatic reservoirs in cholera endemic areas.