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Clinical Microbiology Reviews Sep 2022Cholera, caused by Vibrio cholerae, persists in developing countries due to inadequate access to safe water, sanitation, and hygiene. There are approximately 4 million... (Review)
Review
Cholera, caused by Vibrio cholerae, persists in developing countries due to inadequate access to safe water, sanitation, and hygiene. There are approximately 4 million cases and 143,000 deaths each year due to cholera. The disease is transmitted fecally-orally via contaminated food or water. Severe dehydrating cholera can progress to hypovolemic shock due to the rapid loss of fluids and electrolytes, which requires a rapid infusion of intravenous (i.v.) fluids. The case fatality rate exceeds 50% without proper clinical management but can be less than 1% with prompt rehydration and antibiotics. Oral cholera vaccines (OCVs) serve as a major component of an integrated control package during outbreaks or within zones of endemicity. Water, sanitation, and hygiene (WaSH); health education; and prophylactic antibiotic treatment are additional components of the prevention and control of cholera. The World Health Organization (WHO) and the Global Task Force for Cholera Control (GTFCC) have set an ambitious goal of eliminating cholera by 2030 in high-risk areas.
Topics: Anti-Bacterial Agents; Cholera; Cholera Vaccines; Disease Outbreaks; Humans; Water
PubMed: 35726607
DOI: 10.1128/cmr.00211-21 -
Nature Communications Apr 2021National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological,...
National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.
Topics: Adolescent; Adult; Age Factors; Caliciviridae Infections; Child; Child, Preschool; China; Diarrhea; Escherichia coli; Escherichia coli Infections; Gastroenteritis; Humans; Middle Aged; Norovirus; Rotavirus; Rotavirus Infections; Salmonella; Salmonella Infections; Shigella; Vibrio Infections; Vibrio parahaemolyticus; Young Adult
PubMed: 33927201
DOI: 10.1038/s41467-021-22551-z -
Nature Apr 2022Horizontal gene transfer can trigger rapid shifts in bacterial evolution. Driven by a variety of mobile genetic elements-in particular bacteriophages and plasmids-the...
Horizontal gene transfer can trigger rapid shifts in bacterial evolution. Driven by a variety of mobile genetic elements-in particular bacteriophages and plasmids-the ability to share genes within and across species underpins the exceptional adaptability of bacteria. Nevertheless, invasive mobile genetic elements can also present grave risks to the host; bacteria have therefore evolved a vast array of defences against these elements. Here we identify two plasmid defence systems conserved in the Vibrio cholerae El Tor strains responsible for the ongoing seventh cholera pandemic. These systems, termed DdmABC and DdmDE, are encoded on two major pathogenicity islands that are a hallmark of current pandemic strains. We show that the modules cooperate to rapidly eliminate small multicopy plasmids by degradation. Moreover, the DdmABC system is widespread and can defend against bacteriophage infection by triggering cell suicide (abortive infection, or Abi). Notably, we go on to show that, through an Abi-like mechanism, DdmABC increases the burden of large low-copy-number conjugative plasmids, including a broad-host IncC multidrug resistance plasmid, which creates a fitness disadvantage that counterselects against plasmid-carrying cells. Our results answer the long-standing question of why plasmids, although abundant in environmental strains, are rare in pandemic strains; have implications for understanding the dissemination of antibiotic resistance plasmids; and provide insights into how the interplay between two defence systems has shaped the evolution of the most successful lineage of pandemic V. cholerae.
Topics: Cholera; Genomic Islands; Humans; Pandemics; Plasmids; Vibrio cholerae
PubMed: 35388218
DOI: 10.1038/s41586-022-04546-y -
Annual Review of Microbiology Sep 2022Cholera is a severe diarrheal disease caused by the bacterium and constitutes a significant public health threat in many areas of the world. infection elicits potent... (Review)
Review
Cholera is a severe diarrheal disease caused by the bacterium and constitutes a significant public health threat in many areas of the world. infection elicits potent and long-lasting immunity, and efforts to develop cholera vaccines have been ongoing for more than a century. Currently available inactivated two-dose oral cholera vaccines are increasingly deployed to both prevent and actively curb cholera outbreaks, and they are key components of the global effort to eradicate cholera. However, these killed whole-cell vaccines have several limitations, and a variety of new oral and nonoral cholera vaccine platforms have recently been developed. Here, we review emerging concepts in cholera vaccine design and implementation that have been driven by insights from human and animal studies. As a prototypical vaccine-preventable disease, cholera continues to be an excellent target for the development and application of cutting-edge technologies and platforms that may transform vaccinology.
Topics: Animals; Cholera; Cholera Vaccines; Humans; Vaccines, Inactivated; Vibrio cholerae
PubMed: 35759873
DOI: 10.1146/annurev-micro-041320-033201 -
Journal of Bacteriology Nov 2020is a large and diverse genus of bacteria, of which most are nonpathogenic species found in the aquatic environment. However, a subset of the genus includes several... (Review)
Review
is a large and diverse genus of bacteria, of which most are nonpathogenic species found in the aquatic environment. However, a subset of the genus includes several species that are highly pathogenic, either to humans or to aquatic animals. In recent years, , commonly known as the zebrafish, has emerged as a major animal model used for studying nearly every aspect of biology, including infectious diseases. Zebrafish are especially useful because the embryos are transparent, larvae are small and facilitate imaging studies, and numerous transgenic fish strains have been constructed. Zebrafish models for several pathogenic species have been described, and indeed a fish model is highly relevant for the study of aquatic bacterial pathogens. Here, we summarize the zebrafish models that have been used to study pathogenic species to date.
Topics: Animals; Disease Models, Animal; Humans; Vibrio; Vibrio Infections; Virulence; Zebrafish
PubMed: 32778562
DOI: 10.1128/JB.00165-20 -
Gut Microbes 2021The bacterium is the etiologic agent of the severe human diarrheal disease cholera. The gut microbiome, or the native community of microorganisms found in the human... (Review)
Review
The bacterium is the etiologic agent of the severe human diarrheal disease cholera. The gut microbiome, or the native community of microorganisms found in the human gastrointestinal tract, is increasingly being recognized as a factor in driving susceptibility to infection, fitness, and host interactions of this pathogen. Here, we review a subset of the emerging studies in how gut microbiome structure and microbial function are able to drive virulence gene regulation, metabolism, and modulate host immune responses to cholera infection and vaccination. Improved mechanistic understanding of commensal-pathogen interactions offers new perspectives in the design of prophylactic and therapeutic approaches for cholera control.
Topics: Animals; Bacterial Proteins; Cholera; Gastrointestinal Microbiome; Gene Expression Regulation, Bacterial; Humans; Vibrio cholerae
PubMed: 34180341
DOI: 10.1080/19490976.2021.1937015 -
MSphere Nov 2019is a noninvasive pathogen that colonizes the small intestine and produces cholera toxin, causing severe secretory diarrhea. Cholera results in long lasting immunity,... (Review)
Review
is a noninvasive pathogen that colonizes the small intestine and produces cholera toxin, causing severe secretory diarrhea. Cholera results in long lasting immunity, and recent studies have improved our understanding of the antigenic repertoire of Interactions between the host, , and the intestinal microbiome are now recognized as factors which impact susceptibility to cholera and the ability to mount a successful immune response to vaccination. Here, we review recent data and corresponding models to describe immune responses to infection and explain how the host microbiome may impact the pathogenesis of In the ongoing battle against cholera, the intestinal microbiome represents a frontier for new approaches to intervention and prevention.
Topics: Animals; Cholera; Disease Models, Animal; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Immunity, Innate; Microbial Interactions; Vibrio cholerae
PubMed: 31776240
DOI: 10.1128/mSphere.00597-19 -
The Lancet. Microbe Apr 2023Vibriocidal antibodies are currently the best characterised correlate of protection against cholera and are used to gauge immunogenicity in vaccine trials. Although...
BACKGROUND
Vibriocidal antibodies are currently the best characterised correlate of protection against cholera and are used to gauge immunogenicity in vaccine trials. Although other circulating antibody responses have been associated with a decreased risk of infection, the correlates of protection against cholera have not been comprehensively compared. We aimed to analyse antibody-mediated correlates of protection from both V cholerae infection and cholera-related diarrhoea.
METHODS
We conducted a systems serology study that analysed 58 serum antibody biomarkers as correlates of protection against V cholerae O1 infection or diarrhoea. We used serum samples from two cohorts: household contacts of people with confirmed cholera in Dhaka, Bangladesh, and cholera-naive volunteers who were recruited at three centres in the USA, vaccinated with a single dose of CVD 103-HgR live oral cholera vaccine, and then challenged with V cholerae O1 El Tor Inaba strain N16961. We measured antigen-specific immunoglobulin responses against antigens using a customised Luminex assay and used conditional random forest models to examine which baseline biomarkers were most important for classifying individuals who went on to develop infection versus those who remained uninfected or asymptomatic. V cholerae infection was defined as having a positive stool culture result on days 2-7 or day 30 after enrolment of the household's index cholera case and, in the vaccine challenge cohort, was the development of symptomatic diarrhoea (defined as two or more loose stools of ≥200 mL each, or a single loose stool of ≥300 mL over a 48-h period).
FINDINGS
In the household contact cohort (261 participants from 180 households), 20 (34%) of the 58 studied biomarkers were associated with protection against V cholerae infection. We identified serum antibody-dependent complement deposition targeting the O1 antigen as the most predictive correlate of protection from infection in the household contacts, whereas vibriocidal antibody titres ranked lower. A five-biomarker model predicted protection from V cholerae infection with a cross-validated area under the curve (cvAUC) of 79% (95% CI 73-85). This model also predicted protection against diarrhoea in unvaccinated volunteers challenged with V cholerae O1 after vaccination (n=67; area under the curve [AUC] 77%, 95% CI 64-90). Although a different five-biomarker model best predicted protection from the development of cholera diarrhoea in the challenged vaccinees (cvAUC 78%, 95% CI 66-91), this model did poorly at predicting protection against infection in the household contacts (AUC 60%, 52-67).
INTERPRETATION
Several biomarkers predict protection better than vibriocidal titres. A model based on protection against infection among household contacts was predictive of protection against both infection and diarrhoeal illness in challenged vaccinees, suggesting that models based on observed conditions in a cholera-endemic population might be more likely to identify broadly applicable correlates of protection than models trained on single experimental settings.
FUNDING
National Institute of Allergy and Infectious Diseases and National Institute of Child Health and Human Development, National Institutes of Health.
Topics: Child; Humans; Cholera; Antibodies, Bacterial; Bangladesh; Vibrio cholerae; Diarrhea
PubMed: 36907197
DOI: 10.1016/S2666-5247(22)00391-3 -
Frontiers in Cellular and Infection... 2020, the causative agent of cholera, could proliferate in aquatic environment and infect humans through contaminated food and water. Enormous microorganisms residing in... (Review)
Review
, the causative agent of cholera, could proliferate in aquatic environment and infect humans through contaminated food and water. Enormous microorganisms residing in human gastrointestinal tract establish a special microecological system, which immediately responds to the invasion of , through "colonization resistance" mechanisms, such as antimicrobial peptide production, nutrients competition, and intestinal barrier maintenances. Meanwhile, could quickly sense those signals and modulate the expression of relevant genes to circumvent those stresses during infection, leading to successful colonization on the surface of small intestinal epithelial cells. In this review, we summarized the crosstalks profiles between gut microbiota and in the terms of Type VI Secretion System (T6SS), Quorum Sensing (QS), Reactive Oxygen Species (ROS)/pH stress, and Bioactive metabolites. These mechanisms can also be applied to molecular bacterial pathogenesis of other pathogens in host.
Topics: Bacterial Proteins; Cholera; Gastrointestinal Microbiome; Gene Expression Regulation, Bacterial; Humans; Intestines; Type VI Secretion Systems; Vibrio cholerae
PubMed: 33194819
DOI: 10.3389/fcimb.2020.582554 -
Vaccine Feb 2020
Topics: Cholera; Cholera Vaccines; Clinical Trials as Topic; Endemic Diseases; Global Health; Humans
PubMed: 31402237
DOI: 10.1016/j.vaccine.2019.07.071