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Publications (607)
Cholera remains a significant public health burden in many countries in sub-Saharan Africa, though the exact mechanisms of bacterial emergence and spread remain largely undefined. We generated genomic data from 728 Vibrio cholerae O1 isolates predominantly collected between 2019-2024 to create the largest dataset of V. cholerae genomes sequenced lo...
(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...
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 ofte...
ABTRACT Background: Currently, the Global Cholera Control Roadmap recommends two doses OCV vaccination campaign as one of cholera control strategies in cholera hotspots and to repeat this campaign after about 03 years in these hotspots to boost population immunization. However, data are needed to guide the efficient planning and implementation of t...
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...
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-e...
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 Vibrio cholerae genomes coll...
Enterotoxigenic Escherichia coli (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...
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 esta...
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 individual’s resident in cholera hotspot areas remains unclear. Using...
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 ge...
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 t...
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...
There are no licensed vaccines for Shigella , a leading cause of children’s diarrhea and a common etiology of travelers’ diarrhea. To develop a cross-protective Shigella vaccine, in this study, we constructed a polyvalent protein immunogen to present conserved immunodominant epitopes of Shigella invasion plasmid antigens B (IpaB) and D (IpaD), VirG...
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...
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 2017, the Global Task Force for Cholera Control (GTFCC) set a goal to eliminate cholera from ≥ 20 countries and to reduce cholera deaths by 90% by 2030. Many countries have included oral cholera vaccine (OCV) in their cholera control plans. We felt that a simple, user-friendly monitoring tool would be useful to guide national progress toward cho...
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 base...
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...
Introduction: We analyzed the multilocus variable tandem repeat analysis (MLVA) genotypes from DNA of toxigenic Vibrio cholerae O1 patient isolates from Nigeria collected by the Nigerian Institute of Medical Research between 2016 to 2021. Findings: Sixty distinct MLVA genotypes were observed among the 144 Isolates. There were two large clonal compl...
Using epitope- and structure-based multiepitope fusion antigen vaccinology platform, we constructed a polyvalent protein immunogen that presents antigenic domains (epitopes) of Vibrio cholerae toxin-coregulated pilus A, cholera toxin (CT), sialidase, hemolysin A, flagellins (B, C, and D), and peptides mimicking lipopolysaccharide O-antigen on a fla...
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 O...
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...
Background
This research aims to evaluate the feasibility of using avian immunoglobulins (IgY) raised against adhesion factors of enterotoxigenic Escherichia coli (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. Ther...
(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 WA...
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 km ² in a smal...
to theeditor—We thank Dr Nalin for pointing out the high case fatality rates (CFR) reported from Cameroon in our recent article about cholera in Africa [1]. Clearly these rates are much higher than are expected for cholera, a disease which is effectively treated with rehydration and antibiotics. Antibiotic resistance was not reported during these o...
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....
There are no vaccines licensed for enterotoxigenic Escherichia coli (ETEC), a leading bacterial cause of children’s diarrhea and travelers’ diarrhea. MecVax, a multivalent E. coli vaccine candidate composed of two epitope- and structure-based polyvalent proteins (toxoid fusion 3xSTa N12S -mnLT R192G/L211A and CFA/I/II/IV MEFA), is to induce broad a...
Enterotoxigenic Escherichia coli (ETEC) strains are a leading cause of children’s and travelers’ diarrhea. Developing effective vaccines against this heterologous group has proven difficult due to the varied nature of toxins and adhesins that determine their pathology. A multivalent candidate vaccine was developed using a multi-epitope fusion antig...
Abstract Background Monitoring and Evaluation (M&E) is essential in ensuring population’s access to immunization. Surveys are part of this M&E approach but its timing limits the use of its results to improve the coverage of the evaluated campaign. An oral cholera vaccination campaign was organized in a health district of the Far North region of Cam...
Acute respiratory infections are a leading cause of morbidity and mortality among young children globally. The objective of this study was to evaluate the impact of the Cholera-Hospital-Based-Intervention-for-7-days (CHoBI7) handwashing with soap and water treatment mobile health (mHealth) program on respiratory illness among diarrhea patients and...
BACKGROUND:
Diarrhea is a leading cause of death in children under five. Molecular methods exist for the rapid detection of enteric pathogens; however, the logistical costs of storing stool specimens limit applicability. We sought to demonstrate that dried filter paper specimen preservation can identify diarrheal diseases causing significant morbid...
The controlled human infection model (CHIM) for enterotoxigenic Escherichia coli (ETEC) has been instrumental in defining ETEC as a causative agent of acute watery diarrhea, providing insights into disease pathogenesis and resistance to illness, and enabling preliminary efficacy evaluations for numerous products including vaccines, immunoprophylact...
Studies of the epidemiology of cholera in the Ganges Delta led to understanding cholera’s transmission patterns, risk groups, seasonality, and the relationship of cholera with the environment. In Bangladesh and West Bengal cholera is seasonal, transmission occurs consistently every year with only brief periods without cases. By contrast, in most Af...
Background
After a multi-country Asian outbreak of cholera due to Vibrio cholerae serogroup O139 which started in 1992, it is rarely detected from any country in Asia and has not been detected from patients in Africa.
Methodology/Principal findings
We extracted surveillance data from the Dhaka and Matlab Hospitals of International Centre for Diarr...
Campylobacter jejuni infection is a leading cause of foodborne disease, common to children, adult travelers, and military populations in low- to middle-income countries. In the absence of a licensed vaccine, efforts to evaluate prophylactic agents are underway. The prophylactic efficacy of a twice-daily, 550 mg dose of the antibiotic rifaximin demo...
Cholera is endemic in Nigeria, and Kano State reports outbreaks yearly with a case fatality rate (CFR) of 3.3% from 2010 to 2019. The lack of data at ward level has enabled the disease to evade focused interventions. The goal of this study was to describe the geographic distributions, care-seeking behaviors, Spatio-temporal cluster patterns of the...
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 pa...
Two-dose killed oral cholera vaccines (OCV) are currently being used widely to control cholera. The standard dose-interval for OCV is 2 weeks; however, during emergency use of the vaccine, it may be more appropriate to use the available doses to quickly give a single dose to more people and give a delayed second dose when more vaccine becomes avail...
There are no vaccines licensed for enterotoxigenic Escherichia coli (ETEC), a leading cause of diarrhea for children in developing countries and international travelers. Virulence heterogeneity among strains and difficulties identifying safe antigens for protective antibodies against STa, a potent but poorly immunogenic heat-stable toxin which play...
Background
Cholera has been present and recurring in Zambia since 1977. However, there is a paucity of data on genetic relatedness and diversity of the Vibrio cholerae isolates responsible for these outbreaks. Understanding whether the outbreaks are seeded from existing local isolates or if the outbreaks represent separate transmission events can i...
We investigated the environmental and individual-level risk factors for diarrheal disease among young children in slum areas of Dhaka, Bangladesh. A prospective cohort study was conducted among 884 children under 5 years of age. Caregiver reports were collected on sociodemographic factors and hygiene behaviors. Diarrhea surveillance data was collec...
The Republic of Burundi first reported cholera cases in 1978 and outbreaks have been occurring nearly every year since then. From 2008–2020, 6949 cases and 43 deaths were officially reported. To evaluate Burundi’s potential to eliminate cholera, we identified hotspots using cholera incidence and disease persistence as suggested by the Global Task F...
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 yi...
Cholera is a severe acute, highly transmissible diarrheal disease which affects many low- and middle-income countries. Outbreaks of cholera are confirmed using microbiological culture, and additional cases during the outbreak are generally identified based on clinical case definitions, rather than laboratory confirmation. Many low-resource areas wh...
Background
Diarrheal diseases are a leading cause of global morbidity and mortality affecting all ages, but especially children under the age of five in resource-limited settings. Shigella is a leading contributor to diarrheal diseases caused by bacterial pathogens and is considered a significant antimicrobial resistance threat. While improvements...
Background
Shigellosis is a major cause of moderate to severe diarrhoea and dysentery in children under 5 years of age in low and middle-income countries. The Flexyn2a vaccine conjugates the O-polysaccharide of Shigella flexneri 2a to Pseudomonas aeruginosa exotoxin A. We describe a Phase 2b proof-of-concept challenge study that evaluated safety, i...
During 2016 to 2019, cholera outbreaks were reported commonly to the Ministry of Health from refugee settlements. To further understand the risks cholera posed to refugees, a review of surveillance data on cholera in Uganda for the period 2016–2019 was carried out. During this 4-year period, there were seven such outbreaks with 1,495 cases and 30 d...
Nigeria is endemic for cholera since 1970, and Kano State report outbreaks annually with high case fatality ratios ranging from 4.98%/2010 to 5.10%/2018 over the last decade. However, interventions focused on cholera prevention and control have been hampered by a lack of understanding of hotspot Local Government Areas (LGAs) that trigger and sustai...
Recent studies have gained a better appreciation of the potential impacts of enteric infections beyond symptomatic diarrhea. It is recognized that infections by several enteropathogens could be associated with growth deficits in children and intestinal and systemic inflammation may play an important underlying role. With enterotoxigenic E. coli (ET...
Objectives
To evaluate the quality and coverage of the campaign to distribute oral cholera vaccine (OCV) during a cholera outbreak in Hoima, Uganda to guide future campaigns of cholera vaccine.
Design
Survey of communities targeted for vaccination to determine vaccine coverage rates and perceptions of the vaccination campaign, and a separate surve...
A fundamental, clinical and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophag...
Background
The Cholera-Hospital-Based-Intervention-for-7-days (CHoBI7) mobile health (mHealth) program was a cluster-randomized controlled trial of diarrhea patient households conducted in Dhaka, Bangladesh.
Methods
Patients were block-randomized to three arms: standard recommendation on oral rehydration solution use; health facility delivery of C...
Objective
The objective of the study was to investigate potential risk factors for growth faltering among children under 5 years of age.
Method
We conducted a prospective cohort study of 553 children under 5 years from diarrhoea patient households in urban Dhaka, Bangladesh. Height and weight measurements were obtained at baseline and at a 12‐mont...
Objective
The Cholera‐Hospital‐Based Intervention for 7‐days (CHoBI7) mobile health (mHealth) program delivers mobile messages to diarrhoea patient households promoting water treatment and handwashing with soap. The randomised controlled trial (RCT) of the CHoBI7 mHealth program demonstrated this intervention was effective in significantly reducing...
Background:
Water is the most abundant resource on earth, however water scarcity affects more than 40% of people worldwide. Access to safe drinking water is a basic human right and is a United Nations Sustainable Development Goal (SDG) 6. Globally, waterborne diseases such as cholera are responsible for over two million deaths annually. Cholera is...
Objective
The Cholera‐Hospital‐Based‐Intervention‐for‐7‐days (CHoBI7) is a water treatment and handwashing with soap intervention for diarrhoea patients and their household members which is initially delivered in a healthcare facility setting. This study evaluated the effectiveness of CHoBI7 program delivery in increasing handwashing with soap in a...
Objective
To characterise childhood mouthing and handling behaviours and to assess the association between hand‐to‐object and object‐to‐mouth contacts and diarrhoea prevalence in young children in urban Dhaka, Bangladesh.
Methods
A prospective cohort study was conducted among 494 children under 5 years of age in Dhaka, Bangladesh. This study was n...
Introduction
In 2017, amidst insecurity and displacements posed by Boko Haram armed insurgency, cholera outbreak started in the Muna Garage camp for Internally Displaced Persons (IDPs) in Borno State, Nigeria. In response, the Borno Ministry of Health and partners determined to provide oral cholera vaccine (OCV) to about 1 million people in IDP cam...
