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Household members of diarrhea patients are at higher risk of developing diarrheal diseases (>100 times for cholera) than the general population during the 7 days after the diarrhea patient is admitted at a health facility. There is growing evidence demonstrating that theory-driven water, sanitation, and hygiene (WASH) interventions are likely to yield greater behavior change than those based on health education alone. The Cholera Hospital-Based Intervention for 7-Days (CHoBI7) mobile health (mHealth) program is a theory-driven WASH intervention initially delivered to a diarrhea patient by a health promoter during a health facility visit and reinforced through weekly voice and text messages. In the recent randomized controlled trial (RCT) of the CHoBI7-mHealth program in Bangladesh, this intervention significantly reduced diarrheal disease and stunting, and increased handwashing with soap and stored drinking water quality over the 12-month program period. The aim of this study was to assess the underlying mechanism of change of this intervention. Handwashing with soap was measured by 5-hour structured observation. Stored drinking water quality was assessed by the presence of Escherichia coli during unannounced spot checks. Psychosocial factors were measured among 1,468 participants in the CHoBI7-mHealth RCT. Perceived susceptibility, response efficacy, self-efficacy, dirt reactivity, and diarrhea knowledge were mediators of the CHoBI7-mHealth program's effect on stored drinking water quality at the 1-week follow-up. Self-efficacy, response efficacy, and diarrhea knowledge were mediators of the intervention's effect on handwashing with soap habit maintenance and stored drinking water quality at the 12-month follow-up. This study demonstrates how theory-driven approaches for intervention design can facilitate WASH behavior change.

(1) Shigella spp. (Shigella) is known for causing dysentery with blood in stool, but most children infected with Shigella have non-dysentery Shigella-associated diarrhea (NDSD). The World Health Organization recommends the use of antibiotics when diarrhea is bloody, leaving most NDSD cases untreated. The absence of dysentery may not indicate a low risk of death and severe morbidity. Rapid diagnosis and treatment of shigellosis in vulnerable, young children may be lifesaving. INSIGHT aims to determine the potential benefit of identifying NDSD cases (n = 296) and their outcomes compared to cases of Shigella dysentery [DS (n = 148)] and non-Shigella watery diarrhea [WD (n = 148)]. (2) Children seeking care at hospitals in Bangladesh will be enrolled and followed for 1 year (NDSD and DS) or 90 days (WD). We will determine the impact of NDSD on morbidity, mortality, gut health, nutritional status, and cognitive development compared to DS and WD in children and whether the simple "Rapid LAMP-based Diagnostic Test (RLDT)" can accelerate the detection and treatment of shigellosis in the clinical settings of rural Bangladesh. (3) INSIGHT will determine the impact of NDSD in children and determine if the treatment guidelines of shigellosis need to be revisited to improve clinical outcomes and the development of these children. [ABSTRACT FROM AUTHOR]

Objective: Globally, there are estimated to be 2.9 million cholera cases annually. Early detection of cholera outbreaks is crucial for resource allocation for case management and for targeted interventions to be delivered to stop the spread of cholera. In resource limited settings such as Eastern Democratic Republic of the Congo (DRC), there is often limited laboratory capacity for analysing stool samples for cholera by bacterial culture. Therefore, rapid diagnostic tests (RDTs) for cholera present a promising tool to rapidly test stool samples in a health facility setting for cholera. Our objective is to evaluate the Crystal VC O1 RDT for cholera detection compared with bacterial culture and polymerase chain reaction (PCR) for Vibrio cholerae. Methods: From March 2020 to December 2022, stool samples were collected from 644 diarrhoea patients admitted to 94 health facilities in Bukavu in Eastern DRC. Patient stool samples were analysed by Crystal VC O1 RDT for cholera and by bacterial culture and PCR for V. cholerae O1. Results: Twenty six percent of diarrhoea patients (166/644) had stool samples positive for cholera by RDT, and 24% (152/644) had stool samples positive for V. cholerae O1 by bacterial culture or PCR. The overall specificity and sensitivity of the Crystal VC O1 RDT by direct testing was 94% (95% confidence interval [CI]: 92%–96%) and 90% (95% CI, 84%–94%), respectively, when compared with either a positive result by bacterial culture or PCR. Conclusion: Our findings suggest that the Crystal VC O1 RDT presents a promising tool for cholera surveillance in this cholera endemic setting in sub‐Saharan Africa. [ABSTRACT FROM AUTHOR]

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individuals resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled and re-vaccinated with two doses of Shanchol™, regardless of previous vaccination, and followed-up for 90 days. Bloods were collected at baseline before re-vaccination, at day 14 prior to second dosing, and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60, and 90 days across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly, irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) infections undeniably continue to have substantial morbidity and mortality in younger children; however, limited data are available on the disease burden of older children and adults and on ETEC epidemiology by geographical location at the subnational level. Facility-based surveillance over the years was established to identify patients with ETEC diarrhea in two geographically distinct areas in rural Bangladesh, Chhatak in the north and Mathbaria in the southern coastal area. ETEC was highly prevalent in both areas, while the proportions, toxin types and colonization factors varied by location, season and age groups. Children < 5 years old and adults between 20 and 60 years old were at the highest risk of ETEC diarrhea which required urgent care. This study underscores the importance of capturing subnational and seasonal variations in ETEC epidemiology. ETEC vaccine developers and public health stakeholders may need to target adults between 20 and 60 years of age in addition to young children as new vaccines currently under development become licensed and introduction begins. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is an unprecedented global health challenge, involving the transfer of bacteria and genes between humans and the environment. We simultaneously and longitudinally determined the AMR of enterotoxigenic Escherichia coli (ETEC) strains isolated from diarrheal patients and an aquatic environment over two years from two geographically distinct locations, Coastal Mathbaria and Northern Chhatak in Bangladesh. A total of 60% and 72% of ETEC strains from the patients in Mathbaria and Chhatak, respectively, were multi-drug resistant (MDR) with a high proportion of ETEC resistant to nalidixic acid (80.7%), macrolides (49.1–89.7%), ampicillin (57.9–69%), and trimethoprim/sulfamethoxazole (55.2%). From the surface water, 68.8% and 30% of ETEC were MDR in Mathbaria and Chhatak, respectively, with a high proportion of ETEC strains resistant to macrolides (87.5–100%), ampicillin (50–75%), ceftriaxone (62.5%), and nalidixic acid (40%). Notably, 80–100% of the ETEC strains were susceptible to tetracycline and quinolones (ciprofloxacin and norfloxacin), both in clinical and aquatic ETEC. The AMR varied by the ETEC toxin types. The patterns of excessive or limited consumption of drugs to treat diarrhea over time in Bangladesh were reflected in the ETEC AMR from the patients and the environment. The high prevalence of MDR-ETEC strains in humans and the environment is of concern, which calls for vaccines and other preventative measures against ETEC. [ABSTRACT FROM AUTHOR]

Background. Enterotoxigenic E. coli (ETEC) is a principal cause of diarrhea in travelers, deployed military personnel, and children living in low to middle-income countries. ETEC expresses a variety of virulence factors including colonization factors (CF) that facilitate adherence to the intestinal mucosa. We assessed the protective efficacy of a tip-localized subunit of CF antigen I (CFA/I), CfaE, delivered intradermally with the mutant E. coli heat-labile enterotoxin, LTR192G, in a controlled human infection model (CHIM). Methods. Three cohorts of healthy adult subjects were enrolled and given three doses of 25 μg CfaE + 100 ng LTR192G vaccine intradermally at 3-week intervals. Approximately 28 days after the last vaccination, vaccinated and unvaccinated subjects were admitted as inpatients and challenged with approximately 2 × 107 cfu of CFA/I+ ETEC strain H10407 following an overnight fast. Subjects were assessed for moderate-to-severe diarrhea for 5 days post-challenge. Results. A total of 52 volunteers received all three vaccinations; 41 vaccinated and 43 unvaccinated subjects were challenged and assessed for moderate-to-severe diarrhea. Naïve attack rates varied from 45.5% to 64.7% across the cohorts yielding an overall efficacy estimate of 27.8% (95% confidence intervals: −7.5–51.6%). In addition to reducing moderate–severe diarrhea rates, the vaccine significantly reduced loose stool output and overall ETEC disease severity. Conclusions. This is the first study to demonstrate protection against ETEC challenge after intradermal vaccination with an ETEC adhesin. Further examination of the challenge methodology is necessary to address the variability in naïve attack rate observed among the three cohorts in the present study. [ABSTRACT FROM AUTHOR]

Inadequate hand hygiene is estimated to result in nearly 300,000 deaths annually, with the majority of deaths being among children younger than 5 years. In an effort to promote handwashing with soap and water treatment behaviors among highly susceptible household members of cholera patients, we recently developed the Cholera-Hospital-Based Intervention-for-7-Days (CHoBI7); "chobi" means picture in Bengali. This 1-week handwashing with soap and water treatment intervention is delivered by a promoter in the hospital and the home to cholera patients and their household members. In our randomized controlled trial of this intervention, we observed a significant reduction in symptomatic cholera infections during the 1-week intervention period compared to the control arm and sustained high uptake of observed handwashing with soap behaviors up to 12 months postintervention. The aim of the present study was to assess the underlying mechanism of change that led to the high handwashing with soap behavior observed among participants who received the CHoBI7 intervention. Handwashing with soap was measured using 5-hour structured observation, and psychosocial factors were assessed using a structured questionnaire among 170 intervention and 174 control household members enrolled in the CHoBI7 trial. To investigate potential mediators of the CHoBI7 intervention effect, mediation models were performed. Response efficacy was found to mediate the intervention's effect on habit formation for handwashing with soap at the 1-week follow-up, and disgust, convenience, and cholera awareness were mediators of habit maintenance at the 6- to 12-month follow-up. These results support the use of theory-driven approaches for the development and implementation of handwashing with soap interventions.

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. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) infections are highly prevalent in developing countries, where clinical presentations range from asymptomatic colonization to severe cholera-like illness. The molecular basis for these varied presentations, which may involve strain-specific virulence features as well as host factors, has not been elucidated. We demonstrate that, when challenged with ETEC strain H10407, originally isolated from a case of cholera-like illness, blood group A human volunteers developed severe diarrhea more frequently than individuals from other blood groups. Interestingly, a diverse population of ETEC strains, including H10407, secrete the EtpA adhesin molecule. As many bacterial adhesins also agglutinate red blood cells, we combined the use of glycan arrays, biolayer inferometry, and noncanonical amino acid labeling with hemagglutination studies to demonstrate that EtpA is a dominant ETEC blood group A-specific lectin/ hemagglutinin. Importantly, we have also shown that EtpA interacts specifically with glycans expressed on intestinal epithelial cells from blood group A individuals and that EtpA-mediated bacterial-host interactions accelerate bacterial adhesion and effective delivery of both the heat-labile and heat-stable toxins of ETEC. Collectively, these data provide additional insight into the complex molecular basis of severe ETEC diarrheal illness that may inform rational design of vaccines to protect those at highest risk., Introduction Enterotoxigenic Escherichia coli (ETEC) is a major cause of infectious diarrhea in the developing world (1, 2). These organisms are estimated to be responsible for millions of infections and [...]

Kenya has experienced cholera outbreaks since 1971, with the most recent wave beginning in late 2014. Between 2015–2020, 32 of 47 counties reported 30,431 suspected cholera cases. The Global Task Force for Cholera Control (GTFCC) developed a Global Roadmap for Ending Cholera by 2030, which emphasizes the need to target multi-sectoral interventions in priority cholera burden hotspots. This study utilizes the GTFCC's hotspot method to identify hotspots in Kenya at the county and sub-county administrative levels from 2015 through 2020. 32 of 47 (68.1%) counties reported cholera cases during this time while only 149 of 301 (49.5%) sub-counties reported cholera cases. The analysis identifies hotspots based on the mean annual incidence (MAI) over the past five-year period and cholera's persistence in the area. Applying a MAI threshold of 90th percentile and the median persistence at both the county and sub-county levels, we identified 13 high risk sub-counties from 8 counties, including the 3 high risk counties of Garissa, Tana River and Wajir. This demonstrates that several sub-counties are high level hotspots while their counties are not. In addition, when cases reported by county versus sub-county hotspot risk are compared, 1.4 million people overlapped in the areas identified as both high-risk county and high-risk sub-county. However, assuming that finer scale data is more accurate, 1.6 million high risk sub-county people would have been misclassified as medium risk with a county-level analysis. Furthermore, an additional 1.6 million people would have been classified as living in high-risk in a county-level analysis when at the sub-county level, they were medium, low or no-risk sub-counties. This results in 3.2 million people being misclassified when county level analysis is utilized rather than a more-focused sub-county level analysis. This analysis highlights the need for more localized risk analyses to target cholera intervention and prevention efforts towards the populations most vulnerable. Author summary: Kenya has experienced recurrent cholera outbreaks from 1971 through today and constraints on resources make it essential to target multi-sectoral interventions to high priority areas. Using surveillance data from 2015–2020, this study identifies high priority areas for cholera intervention in Kenya following guidance from the Global Task Force on Cholera Control. We identified that roughly 3 million people (6% of the population) in 13 sub-counties live in high priority areas in Kenya, where the mean annual incidence exceeded 70 cases per 100,000 population and over 35% of weeks reported at least one suspected cholera case. Further, 1.6 million people living in high priority sub-counties would have been de-prioritized had the analysis been performed only at the county scale. Cholera interventions in Kenya should target high priority sub-counties, and future countries undergoing cholera control planning should carefully consider operational implementation when determining the spatial scale of their prioritization analysis. [ABSTRACT FROM AUTHOR]

In December 2013, violence erupted in Juba, South Sudan, and quickly spread throughout the country. By the end of 2014, one in five persons within the country had been displaced, [...]

Severe cholera without adequate rehydration kills up to half of affected persons (1). The World Health Organization estimates that 3-5 million cholera cases occur worldwide each year (2). Studies have [...]

In South Asia and Africa, an estimated 88.5 million diarrhea episodes are attributed to Shigella infections annually (1). Shigellosis occurs most often in children < 5 years of age (2,3). [...]

Introduction Cholera continues to be a threat in many countries. Cases and deaths continue in Hispaniola, Africa and Asia. Each year, the WER provides an update of these numbers as [...]

Objective To describe and analyse the characteristics of oral cholera vaccination campaigns; Including location, target population, logistics, vaccine coverage and delivery costs. Methods We searched PubMed, the World Health Organization (WHO) website and the Cochrane database with no date or language restrictions. We contacted public health personnel, experts In the field and in ministries of health and did targeted web searches. Findings A total of 33 documents were included In the analysis. One country, Viet Nam, incorporates oral cholera vaccination into its public health programme and has administered approximately 10.9 million vaccine doses between 1997 and 2012. In addition, over 3 million doses of the two WHO pre-qualified oral cholera vaccines have been administered in more than 16 campaigns around the world between 1997 and 2014. These campaigns have either been pre-emptive or reactive and have taken place under diverse conditions, such as in refugee camps or natural disasters. Estimated two-dose coverage ranged from 46 to 88% of the target population. Approximate delivery cost per fully immunized person ranged from 0.11-3.99 United States dollars. Conclusion Experience with oral cholera vaccination campaigns continues to Increase. Public health officials may draw on this experience and conduct oral cholera vaccination campaigns more frequently. Objectif Decrire et analyser les caracteristiques des campagnes de vaccination orale contre le cholera; y compris le site, la population cible, la logistique, la couverture vaccinale et les couts de distribution. Methodes Nous avons effectue des recherches dans PubMed, le site Internet de l'Organisation mondiale de la Sante (OMS) et la base de donnees Cochrane sans aucune restriction de date ou de langue. Nous avons contacte des membres du personnel de la sante publique, des experts travaillant dans le domaine et dans les ministeres de la Sante et nous avons cible les recherches sur Internet. Resultats Nous avons inclus 33 documents au total dans l'analyse. Un seul pays, le Viet Nam, inclut la vaccination orale anticholerlque dans son programme de sante publique et a administre environ 10,9 millions de doses de vacclns entre 1997 et 2012. En outre, plus de 3 millions de doses des deux vaccins oraux anticholeriques prequalifies de I'OMS ont ete administres dans plus de 16 campagnes de vaccination dans le monde entier entre 1997 et 2014. Ces campagnes ont ete menees en prevention ou en reaction et ont eu lieu dans diverses conditions, comme dans des camps de refugies ou lors de catastrophes naturelles. La couverture estimee des deux doses etait comprise entre 46 et 88% de la population cible. Les frais de distribution approximatifs par personne entierement vaccinee sont compris entre 0,11 et 3,99 dollars. Conclusion L'experience avec les campagnes de vaccination orale contre le cholera continue a se developper. Les responsables de la sante publique peuvent tirer profit de cette experience et mener plus frequemment des campagnes de vaccination orale contre le cholera. Objetivo Describir y analizar las caracteristicas de las campanas de vacunacion oral contra el colera, incluyendo la ubicacion, la poblacion objetivo, la logistica, los costes de cobertura y la entrega de vacunas. Metodos Realizamos busquedas en PubMed, la pagina web de la Organizacion Mundial de la salud (OMS) y la base de datos Cochrane sin restricciones de fechas ni idioma. Nos pusimos en contacto con el personal de salud publica, expertos del sector y los ministerios de salud, y realizamos busquedas especificas en la web. Resultados Se incluyo un total de 33 documentos en el analisis. Un pais, Viet Nam, incorpora vacunas orales contra el colera en su programa de salud publica y ha administrado aproximadamente 10,9 millones de dosis de vacunas entre 1997 y 2012. Ademas, se han administrado mas 3 de millones de dosis de las dos vacunas orales contra el colera orales que cumplen con los requisitos de la OMS en mas de 16 campanas en todo el mundo realizadas entre 1997 y 2014. Estas campanas han sido preventivas o reactivas, y se han llevado a cabo en diversas condiciones, como en campamentos de refugiados o desastres naturales. La cobertura estimada de dos dosis oscilo entre el 46 y 88% de la poblacion objetivo. El coste aproximado del suministro por persona completamente inmunizada oscilo entre 0,11 y 3,99 dolares de los Estados Unidos. Conclusion La experiencia con las campanas de vacunacion oral contra el colera sigue aumentando. Los funcionarios de salud publica pueden aprovechar esta experiencia y realizar campanas de vacunacion orales contra el colera con mayor frecuencia., Introduction Vibrio cholerae O1 and O139 causes severe diarrhoea and the main strategies to prevent the disease are to promote hygiene and to ensure safe water and sanitation. These basic [...]