The Impact of Non-Dysentery Shigella Infection on the Growth and Health of Children over Time (INSIGHT)-A Prospective Case-Control Study Protocol.

(1) 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.

Evaluation of a rapid diagnostic test for detection of Vibrio cholerae O1 in the Democratic Republic of the Congo: Preventative intervention for cholera for 7 days (PICHA7 program).

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.

Comparative analysis of cholera serum vibriocidal antibodies from Convalescent and vaccinated adults in Zambia.

Cholera is responsible for 1.3 to 4.0 million cholera cases globally and poses a significant threat, with Zambia reporting 17,169 cases as of 4th February 2024.

Seroconversion and Kinetics of Vibriocidal Antibodies during the First 90 Days of Re-Vaccination with Oral Cholera Vaccine in an Endemic Population.

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.

Validation of a Human Challenge Model Using an LT-Expressing Enterotoxigenic Strain (LSN03-016011) and Characterization of Potential Amelioration of Disease by an Investigational Oral Vaccine Candidate (VLA1701).

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 (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.

New sequences from Eastern and Southern Africa alter our understanding of regional cholera transmission.

Despite ongoing containment and vaccination efforts, cholera remains prevalent in many countries in sub-Saharan Africa. Part of the difficulty in containing cholera comes from our lack of understanding of how it circulates throughout the region. To better characterize regional transmission, we generated and analyzed 118 genomes collected between 2007-2019 from five different countries in Southern and Eastern Africa.

Epidemiology of Enterotoxigenic among Children and Adults Seeking Care at Hospitals in Two Geographically Distinct Rural Areas in Bangladesh.

Enterotoxigenic (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.

The Antimicrobial Resistance of Enterotoxigenic from Diarrheal Patients and the Environment in Two Geographically Distinct Rural Areas in Bangladesh over the Years.

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 (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.

MecVax supplemented with CFA MEFA-II induces functional antibodies against 12 adhesins (CFA/I, CS1-CS7, CS12, CS14, CS17, and CS21) and 2 toxins (STa, LT) of enterotoxigenic (ETEC).

Enterotoxigenic (ETEC) strains that produce various adhesins and one or two enterotoxins are the leading causes of children's diarrhea and travelers' diarrhea. MecVax, a multivalent ETEC vaccine candidate, consists of two proteins, an adhesin multiepitope fusion antigen (MEFA) that stimulates antibodies to the seven most important ETEC adhesins (CFA/I and CS1-CS6) and a toxoid fusion antigen which stimulates antibodies against ETEC enterotoxins (heat-labile toxin and heat-stable toxin). CFA MEFA-II, another polyvalent MEFA protein, has been demonstrated to stimulate antibodies to another five important ETEC adhesins (CS7, CS12, CS14, CS17, and CS21).

Gut microbiota shifts favorably with delivery of handwashing with soap and water treatment intervention in a prospective cohort (CHoBI7 trial).

Background: Cholera can result in the expulsion of important microbiota from the gut and result in death if left untreated. The disease transmits mainly via drinking water carrying Vibrio cholerae; and household contacts (HHC) of cholera patients are at elevated risk during the first week of infection. The gut microbiota profiles of HHC-children of cholera patients at Dhaka city slums were investigated before (day 0) and after (day 8) delivery of chlorinated water as part of the major study 'CHoBI7 trial (cholera-hospital-based intervention for 7 days)'.

Efficacy of an Enterotoxigenic (ETEC) Vaccine on the Incidence and Severity of Traveler's Diarrhea (TD): Evaluation of Alternative Endpoints and a TD Severity Score.

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.

A broadly immunogenic polyvalent multiepitope fusion antigen protein protects against and lethal pulmonary challenges in mice.

There are no licensed vaccines for , a leading cause of children's diarrhea and a common etiology of travelers' diarrhea. To develop a cross-protective vaccine, in this study, we constructed a polyvalent protein immunogen to present conserved immunodominant epitopes of invasion plasmid antigens B (IpaB) and D (IpaD), VirG, GuaB, and Shiga toxins on backbone protein IpaD, by applying an epitope- and structure-based multiepitope-fusion-antigen (MEFA) vaccinology platform, examined protein ( MEFA) broad immunogenicity, and evaluated antibody function against invasion and Shiga toxin cytotoxicity but also protection against lethal challenge. Mice intramuscularly immunized with MEFA protein developed IgG responses to IpaB, IpaD, VirG, GuaB, and Shiga toxins 1 and 2; mouse sera significantly reduced invasion of , serotype 2a, 3a, or 6, and type 1 and neutralized cytotoxicity of Shiga toxins of and Shiga toxin-producing .

Prioritizing interventions for cholera control in Kenya, 2015-2020.

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.

Food Hygiene and Fecal Contamination on the Household Compound are Associated with Increased Pediatric Diarrhea in Urban Bangladesh (CHoBI7 Program).

In this prospective cohort study, we explored individual- and household-level risk factors associated with diarrheal diseases among 251 children younger than 5 years in slum areas of urban Dhaka, Bangladesh. During the 3-month study period, diarrhea surveillance was conducted monthly, and spot checks of the household compound were performed at baseline to assess the presence of feces (animal or human) in the household compound and in cooking and food storage areas, and to assess whether cooked food was covered and refrigerated. We also collected caregiver reports on child mouthing behaviors.

Reduced Diarrhea Prevalence and Improvements in Handwashing with Soap and Stored Drinking Water Quality Associated with Diarrheal Disease Awareness Measured by Interactive Voice Response Messages in the CHoBI7 Mobile Health Program.

The Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7) mobile health program promotes water, sanitation, and hygiene (WASH) behaviors through interactive voice response (IVR), voice, and text messages to reduce diarrheal diseases in Bangladesh. The objective of this study was to investigate the relationship between responses to CHoBI7 WASH IVR quiz messages and subsequent diarrhea and WASH behaviors. Fourteen CHoBI7 IVR quiz messages on handwashing with soap and treatment of stored water were sent to 517 households with 1,777 participants during the 12-month program period.

A polyvalent multiepitope protein cross-protects against infection in rabbit colonization and passive protection models.

Using epitope- and structure-based multiepitope fusion antigen vaccinology platform, we constructed a polyvalent protein immunogen that presents antigenic domains (epitopes) of toxin-coregulated pilus A, cholera toxin (CT), sialidase, hemolysin A, flagellins (B, C, and D), and peptides mimicking lipopolysaccharide O-antigen on a flagellin B backbone. Mice and rabbits immunized intramuscularly with this polyvalent protein immunogen developed antibodies to all of the virulence factors targeted by the immunogen except lipopolysaccharide. Mouse and rabbit antibodies exhibited functional activities against CT enterotoxicity, CT binding to GM ganglioside, bacterial motility, and in vitro adherence of O1, O139, and non-O1/non-O139 serogroup strains.

An Age-stratified, Randomized Immunogenicity Trial of Killed Oral Cholera Vaccine with Delayed Second Dose in Cameroon.

The recommended schedule for killed oral cholera vaccine (OCV) is two doses, 2 weeks apart. However, during vaccine campaigns, the second round is often delayed by several months. Because more information is needed to document antibody responses when the second dose is delayed, we conducted an open-label, phase 2, noninferiority clinical trial of OCV.

Feasibility of avian antibodies as prophylaxis against enterotoxigenic escherichia coli colonization.

Background: This research aims to evaluate the feasibility of using avian immunoglobulins (IgY) raised against adhesion factors of enterotoxigenic (ETEC) as prophylaxis of diarrheal illness caused by these pathogens. ETEC requires adhesion to human intestinal epithelial cells as a primary step in establishing enteric infection. Therefore, inhibition of adhesion may prevent such infections and reduce clinical burdens of diarrheal illness.

Randomized Controlled Trial of the Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7) Cholera Rapid Response Program to Reduce Diarrheal Diseases in Bangladesh.

(a) Objective: To build an evidence base on effective water, sanitation, and hygiene interventions to reduce diarrheal diseases in cholera hotspots, we developed the CHoBI7 Cholera Rapid Response Program. (b) Methods: Once a cholera patient (confirmed by bacterial culture) is identified at a health facility, a health promoter delivers a targeted WASH intervention to the cholera hotspot (households within 20 m of a cholera patient) through both in-person visits during the first week and bi-weekly WASH mobile messages for the 3-month program period. A randomized controlled trial of the CHoBI7 Cholera Rapid Response Program was conducted with 284 participants in 15 cholera hotspots around cholera patients in urban Dhaka, Bangladesh.

Temporal and Spatial Differences between Symptomatic and Asymptomatic Malaria Infections in the Chittagong Hill Districts, Bangladesh.

Mapping asymptomatic malaria infections, which contribute to the transmission reservoir, is important for elimination programs. This analysis compared the spatiotemporal patterns of symptomatic and asymptomatic Plasmodium falciparum malaria infections in a cohort study of ∼25,000 people living in a rural hypoendemic area of about 179 km2 in a small area of the Chittagong Hill Districts of Bangladesh. Asymptomatic infections were identified by active surveillance; symptomatic clinical cases presented for care.

Nontoxigenic Vibrio cholerae Challenge Strains for Evaluating Vaccine Efficacy and Inferring Mechanisms of Protection.

Human challenge studies are instrumental for testing cholera vaccines, but these studies use outdated strains and require inpatient facilities. Here, we created next-generation isogenic Ogawa and Inaba O1 V. cholerae challenge strains (ZChol strains) derived from a contemporary Zambian clinical isolate representative of current dominant pandemic V.