Vibrio is a genus of ubiquitous bacteria found in a wide variety of aquatic and marine habitats; of the >100 described Vibrio spp., ~12 cause infections in humans. Vibrio cholerae can cause cholera, a severe diarrhoeal disease that can be quickly fatal if untreated and is typically transmitted via contaminated water and person-to-person contact. Non-cholera Vibrio spp. (for example, Vibrio parahaemolyticus, Vibrio alginolyticus and Vibrio vulnificus) cause vibriosis - infections normally acquired through exposure to sea water or through consumption of raw or undercooked contaminated seafood. Non-cholera bacteria can lead to several clinical manifestations, most commonly mild, self-limiting gastroenteritis, with the exception of V. vulnificus, an opportunistic pathogen with a high mortality that causes wound infections that can rapidly lead to septicaemia. Treatment for Vibrio spp. infection largely depends on the causative pathogen: for example, rehydration therapy for V. cholerae infection and debridement of infected tissues for V. vulnificus-associated wound infections, with antibiotic therapy for severe cholera and systemic infections. Although cholera is preventable and effective oral cholera vaccines are available, outbreaks can be triggered by natural or man-made events that contaminate drinking water or compromise access to safe water and sanitation. The incidence of vibriosis is rising, perhaps owing in part to the spread of Vibrio spp. favoured by climate change and rising sea water temperature.

The factors that enhance the transmission of pathogens during epidemic spread are ill defined. Water-borne spread of the diarrhoeal disease cholera occurs rapidly in nature, whereas infection of human volunteers with bacteria grown in vitro is difficult in the absence of stomach acid buffering. It is unclear, however, whether stomach acidity is a principal factor contributing to epidemic spread. Here we report that characterization of Vibrio cholerae from human stools supports a model whereby human colonization creates a hyperinfectious bacterial state that is maintained after dissemination and that may contribute to epidemic spread of cholera. Transcriptional profiling of V. cholerae from stool samples revealed a unique physiological and behavioural state characterized by high expression levels of genes required for nutrient acquisition and motility, and low expression levels of genes required for bacterial chemotaxis.

The facultative pathogen Vibrio cholerae can exist in both the human small bowel and in aquatic environments. While investigation of the infection process has revealed many factors important for pathogenesis, little is known regarding transmission of this or other water-borne pathogens. Using a temporally controlled reporter of transcription, we focus on bacterial gene expression during the late stage of infection and identify a unique class of V. cholerae genes specific to this stage. Mutational analysis revealed limited roles for these genes in infection. However, using a host-to-environment transition assay, we detected roles for six of ten genes examined for the ability of V. cholerae to persist within cholera stool and/or aquatic environments. Furthermore, passage through the intestinal tract was necessary to observe this phenotype. Thus, V. cholerae genes expressed prior to exiting the host intestinal tract are advantageous for subsequent life in aquatic environments.

SummaryBackgroundKilled whole-cell oral cholera vaccines (kOCVs) are becoming a standard cholera control and prevention tool. However, vaccine efficacy and direct effectiveness estimates have varied, with differences in study design, location, follow-up duration, and vaccine composition posing challenges for public health decision making. We did a systematic review and meta-analysis to generate average estimates of kOCV efficacy and direct effectiveness from the available literature.MethodsFor this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Review Library on July 9, 2016, and ISI Web of Science on July 11, 2016, for randomised controlled trials and observational studies that reported estimates of direct protection against medically attended confirmed cholera conferred by kOCVs. We included studies published on any date in English, Spanish, French, or Chinese. We extracted from the published reports the primary efficacy and effectiveness estimates from each study and also estimates according to number of vaccine doses, duration, and age group. The main study outcome was average efficacy and direct effectiveness of two kOCV doses, which we estimated with random-effect models. This study is registered with PROSPERO, number CRD42016048232.FindingsSeven trials (with 695 patients with cholera) and six observational studies (217 patients with cholera) met the inclusion criteria, with an average two-dose efficacy of 58% (95% CI 42–69, I2=58%) and effectiveness of 76% (62–85, I2=0). Average two-dose efficacy in children younger than 5 years (30% [95% CI 15–42], I2=0%) was lower than in those 5 years or older (64% [58–70], I2=0%; p<0·0001). Two-dose efficacy estimates of kOCV were similar during the first 2 years after vaccination, with estimates of 56% (95% CI 42–66, I2=45%) in the first year and 59% (49–67, I2=0) in the second year. The efficacy reduced to 39% (13 to 57, I2=48%) in the third year, and 26% (−46 to 63, I2=74%) in the fourth year.InterpretationTwo kOCV doses provide protection against cholera for at least 3 years. One kOCV dose provides at least short-term protection, which has important implications for outbreak management. kOCVs are effective tools for cholera control.FundingThe Bill & Melinda Gates Foundation.

How Vibrio cholerae spreads around the world and what determines its seasonal peaks in endemic areas are not known. These features of cholera have been hypothesized to be primarily the result of environmental factors associated with aquatic habitats that can now be identified. Since 1997, fortnightly surveillance in 4 widely separated geographic locations in Bangladesh has been performed to identify patients with cholera and to collect environmental data. A total of 5670 patients (53% <5 years of age) have been studied; 14.3% had cholera (10.4% due to V. cholerae O1 El Tor, 3.8% due to O139). Both serogroups were found in all locations; outbreaks were seasonal and often occurred simultaneously. Water-use patterns showed that bathing and washing clothes in tube-well water was significantly protective in two of the sites. These data will be correlated with environmental factors, to develop a model for prediction of cholera outbreaks.