Epidemiology of Enteroaggregative, Enteropathogenic, and Shiga Toxin-Producing Escherichia coli Among Children Aged <5 Years in 3 Countries in Africa, 2015-2018: Vaccine Impact on Diarrhea in Africa (VIDA) Study.

Background: To address knowledge gaps regarding diarrheagenic Escherichia coli (DEC) in Africa, we assessed the clinical and epidemiological features of enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), and Shiga toxin-producing E.

Giardia Detection and Codetection With Other Enteric Pathogens in Young Children in the Vaccine Impact on Diarrhea in Africa (VIDA) Case-Control Study: 2015-2018.

Background: Giardia has been associated with reduced risk of diarrhea in children in low-resource settings, but the mechanism underlying this association is unknown. To assess whether Giardia may shape colonization or infection with other enteric pathogens and impact associations with diarrhea, we examined Giardia and enteric pathogen codetection among children <5 years old in Kenya, The Gambia, and Mali as part of the Vaccine Impact on Diarrhea in Africa study.

Methods: We tested for Giardia and other enteric pathogens using enzyme-linked immunosorbent assays and real-time polymerase chain reaction (PCR) on stool, respectively.

Drivers of Decline in Diarrhea Mortality Between GEMS and VIDA Studies.

Background: Statistical modeling suggests that decreasing diarrhea-associated mortality rates in recent decades are largely attributed to improved case management, rotavirus vaccine, and economic development.

Methods: We examined data collected in 2 multisite population-based diarrhea case-control studies, both conducted in The Gambia, Kenya, and Mali: the Global Enteric Multicenter Study (GEMS; 2008-2011) and Vaccine Impact on Diarrhea in Africa (VIDA; 2015-2018). Population-level diarrhea mortality and risk factor prevalence, estimated using these study data, were used to calculate the attribution of risk factors and interventions for diarrhea mortality using a counterfactual framework.

Moderate-to-Severe Diarrhea and Stunting Among Children Younger Than 5 Years: Findings From the Vaccine Impact on Diarrhea in Africa (VIDA) Study.

Background: Stunting affects >20% of children <5 years old worldwide and disproportionately impacts underserved communities. The Vaccine Impact on Diarrhea in Africa (VIDA) Study examined the association between an episode of moderate-to-severe diarrhea (MSD) and the risk of subsequent stunting in children <5 years living in 3 sub-Saharan African countries.

Methods: In this prospective, matched, case-control study among children <5 years, data were collected over 36 months from 2 groups.

Prevalence of Salmonella in Stool During the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

Background: Non-typhoidal Salmonella (NTS) is a common cause of gastroenteritis in young children, with limited data on NTS serovars and antimicrobial resistance in Africa.

Methods: We determined the prevalence of Salmonella spp. and frequency of antimicrobial resistance among serovars identified in stools of 0-59 month-old children with moderate-to-severe diarrhea (MSD) and controls enrolled in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in The Gambia, Mali, and Kenya in 2015-2018, and compared with data from the Global Enteric Multicenter Study (GEMS; 2007-2010) and the GEMS-1A study (2011).

A Description of the Statistical Methods for the Vaccine Impact on Diarrhea in Africa (VIDA) Study.

Background: Diarrheal diseases remain a health threat to children in low- and middle-income countries. The Vaccine Impact on Diarrhea in Africa (VIDA) study was a 36-month, prospective, matched case-control study designed to estimate the etiology, incidence, and adverse clinical consequences of moderate-to-severe diarrhea (MSD) in children aged 0-59 months. VIDA was conducted following rotavirus vaccine introduction at 3 censused sites in sub-Saharan Africa that participated in the Global Enteric Multicenter Study (GEMS) ∼10 years earlier.

Antibiotic-Prescribing Practices for Management of Childhood Diarrhea in 3 Sub-Saharan African Countries: Findings From the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

Background: Despite antibiotic prescription being recommended for dysentery and suspected cholera only, diarrhea still triggers unwarranted antibiotic prescription. We evaluated antibiotic-prescribing practices and their predictors among children aged 2-59 months in the Vaccine Impact on Diarrhea in Africa (VIDA) Study performed in The Gambia, Mali, and Kenya.

Methods: VIDA was a prospective case-control study (May 2015-July 2018) among children presenting for care with moderate-to-severe diarrhea (MSD).

Causes of death identified in neonates enrolled through Child Health and Mortality Prevention Surveillance (CHAMPS), December 2016 -December 2021.

Each year, 2.4 million children die within their first month of life. Child Health and Mortality Prevention Surveillance (CHAMPS) established in 7 countries aims to generate accurate data on why such deaths occur and inform prevention strategies.

Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data.

Background: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs).

Methods: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger.

Randomized Trial of Vaccines for Zaire Ebola Virus Disease.

Background: Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease.

Methods: We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group).

Mass drug administration of azithromycin: an analysis.

Background: WHO recommends mass drug administration (MDA) of the antibiotic azithromycin for children aged 1-11 months in areas with high rates of infant and child mortality. Notwithstanding the substantial potential benefits of lowering childhood mortality, MDA raises understandable concerns about exacerbating antibiotic resistance.

Objectives: In this study, we aimed to evaluate the use of MDA using both quantitative and ethical considerations.

Prioritizing Health Care Strategies to Reduce Childhood Mortality.

Importance: Although child mortality trends have decreased worldwide, deaths among children younger than 5 years of age remain high and disproportionately circumscribed to sub-Saharan Africa and Southern Asia. Tailored and innovative approaches are needed to increase access, coverage, and quality of child health care services to reduce mortality, but an understanding of health system deficiencies that may have the greatest impact on mortality among children younger than 5 years is lacking.

Objective: To investigate which health care and public health improvements could have prevented the most stillbirths and deaths in children younger than 5 years using data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

Introduction of an Electronic Clinical Decision Support Tool to Inform Prescribing for Pediatric Diarrhea in Bangladesh and Mali: Do Provider Expectations Predict Experiences?

Nonindicated antibiotics for childhood diarrhea is a major contributor to global antimicrobial resistance. Electronic clinical decision support tools (eCDSTs) may reduce unnecessary antibiotics. This study examined how providers' expectations of an eCDST to predict diarrhea etiology compared with their experiences using the tool.

Associations Between Eight Earth Observation-Derived Climate Variables and Enteropathogen Infection: An Independent Participant Data Meta-Analysis of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics.

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined.

Distribution of serotypes and antibiotic resistance of invasive Pseudomonas aeruginosa in a multi-country collection.

Background: Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections and is frequently associated with healthcare-associated infections. Because of its ability to rapidly acquire resistance to antibiotics, P. aeruginosa infections are difficult to treat.

Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings: A Randomized Clinical Trial.

Importance: World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth.

Postmortem investigations and identification of multiple causes of child deaths: An analysis of findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

Background: The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition.

Pathogens Associated With Linear Growth Faltering in Children With Diarrhea and Impact of Antibiotic Treatment: The Global Enteric Multicenter Study.

Background: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment.

Methods: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia.

Deaths Attributed to Respiratory Syncytial Virus in Young Children in High-Mortality Rate Settings: Report from Child Health and Mortality Prevention Surveillance (CHAMPS).

Background: Lower respiratory tract infections are a leading cause of death in young children, but few studies have collected the specimens needed to define the role of specific causes. The Child Health and Mortality Prevention Surveillance (CHAMPS) platform aims to investigate causes of death in children aged <5 years in high-mortality rate settings, using postmortem minimally invasive tissue sampling and other advanced diagnostic techniques. We examined findings for deaths identified in CHAMPS sites in 7 countries in sub-Saharan Africa and south Asia to evaluate the role of respiratory syncytial virus (RSV).

The Etiology of Childhood Pneumonia in Mali: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.

Background: We present findings from the Pneumonia Etiology Research for Child Health (PERCH) site in Bamako, Mali.

Methods: Cases were patients 28 days to 59 months of age, admitted to hospital with severe or very severe pneumonia (2005 World Health Organization definition). Community controls were frequency matched by age.

Cost-effectiveness of infant respiratory syncytial virus preventive interventions in Mali: A modeling study to inform policy and investment decisions.

Importance: Low- and middle-income countries have a high burden of respiratory syncytial virus lower respiratory tract infections. A monoclonal antibody administered monthly is licensed to prevent these infections, but it is cost-prohibitive for most low- and middle-income countries. Long-acting monoclonal antibodies and maternal vaccines against respiratory syncytial virus are under development.

Epidemiology of the Rhinovirus (RV) in African and Southeast Asian Children: A Case-Control Pneumonia Etiology Study.

Rhinovirus (RV) is commonly detected in asymptomatic children; hence, its pathogenicity during childhood pneumonia remains controversial. We evaluated RV epidemiology in HIV-uninfected children hospitalized with clinical pneumonia and among community controls. PERCH was a case-control study that enrolled children (1-59 months) hospitalized with severe and very severe pneumonia per World Health Organization clinical criteria and age-frequency-matched community controls in seven countries.

Meningococcal Serogroup ACWYX Conjugate Vaccine in Malian Toddlers.

Background: serogroups A, B, C, W, X, and Y cause outbreaks of meningococcal disease. Quadrivalent conjugate vaccines targeting the A, C, W, and Y serogroups are available. A pentavalent vaccine that also includes serogroup X (NmCV-5) is under development.

The Operational Feasibility of Vaccination Programs Targeting Influenza Risk Groups in the World Health Organization (WHO) African and South-East Asian Regions.

Background: Influenza vaccination is uncommon in low-resource settings. We evaluated aspects of operational feasibility of influenza vaccination programs targeting risk groups in the World Health Organization (WHO) African (AFR) and South-East Asian (SEAR) Regions.

Methods: We estimated routine immunization and influenza vaccination campaign doses, doses per vaccinator, and cold storage requirements for 1 simulated country in each region using evidence-based population distribution, vaccination schedule, and vaccine volumes.