Histo-Blood Group Antigen Null Phenotypes Associated With a Decreased Risk of Clinical Rotavirus Vaccine Failure Among Children <2 Years of Age Participating in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in Kenya, Mali, and the Gambia.

Background: Previously studied risk factors for rotavirus vaccine failure have not fully explained reduced rotavirus vaccine effectiveness in low-income settings. We assessed the relationship between histo-blood group antigen (HBGA) phenotypes and clinical rotavirus vaccine failure among children <2 years of age participating in the Vaccine Impact on Diarrhea in Africa Study in 3 sub-Saharan African countries.

Methods: Saliva was collected and tested for HBGA phenotype in children who received rotavirus vaccine.

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.

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.

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.

Characteristics of Salmonella Recovered From Stools of Children Enrolled in the Global Enteric Multicenter Study.

Background: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of nontyphoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates.

Methods: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole-genome sequence data.

The Clinical Presentation of Culture-positive and Culture-negative, Quantitative Polymerase Chain Reaction (qPCR)-Attributable Shigellosis in the Global Enteric Multicenter Study and Derivation of a Shigella Severity Score: Implications for Pediatric Shigella Vaccine Trials.

Background: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials.

Methods: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold <27.

Diarrhoeal disease and subsequent risk of death in infants and children residing in low-income and middle-income countries: analysis of the GEMS case-control study and 12-month GEMS-1A follow-on study.

Background: The Global Enteric Multicenter Study (GEMS) was a 3-year case-control study that measured the burden, aetiology, and consequences of moderate-to-severe diarrhoea (MSD) in children aged 0-59 months. GEMS-1A, a 12-month follow-on study, comprised two parallel case-control studies, one assessing MSD and the other less-severe diarrhoea (LSD). In this report, we analyse the risk of death with each diarrhoea type and the specific pathogens associated with fatal outcomes.

Impact of the addition of azithromycin to antimalarials used for seasonal malaria chemoprevention on antimicrobial resistance of Streptococcus pneumoniae.

Objective: A trial was conducted in Burkina Faso and Mali to investigate whether addition of azithromycin to the antimalarials used for seasonal malaria chemoprevention reduces mortality and hospital admissions of children. We tested the sensitivity of nasal isolates of Streptococcus pneumoniae obtained during this trial to azithromycin and other antibiotics.

Methods: Azithromycin or placebo was administered monthly, in combination with the antimalarials used for seasonal malaria chemoprevention, for four months, over the annual malaria transmission seasons of 2014, 2015, and 2016.

The incidence, aetiology, and adverse clinical consequences of less severe diarrhoeal episodes among infants and children residing in low-income and middle-income countries: a 12-month case-control study as a follow-on to the Global Enteric Multicenter Study (GEMS).

Background: Diarrheal diseases remain a leading cause of illness and death among children younger than 5 years in low-income and middle-income countries. The Global Enteric Multicenter Study (GEMS) has described the incidence, aetiology, and sequelae of medically attended moderate-to-severe diarrhoea (MSD) among children aged 0-59 months residing in censused populations in sub-Saharan Africa and south Asia, where most child deaths occur. To further characterise this disease burden and guide interventions, we extended this study to include children with episodes of less-severe diarrhoea (LSD) seeking care at health centres serving six GEMS sites.

Epidemiology, Risk Factors, and Outcomes of Respiratory Syncytial Virus Infections in Newborns in Bamako, Mali.

Background: Few studies describe the respiratory syncytial virus (RSV) burden in African populations, and most have utilized hospital-based surveillance. In Mali, no community-based studies exist of the incidence or epidemiology of RSV infection. This study provides the first estimates of RSV incidence in Mali.

Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS).

Background: Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites.

Maternal Influenza Vaccination and the Risk of Laboratory-Confirmed Influenza Among Household Contacts Under the Age of Five in Mali.

Influenza transmission is increased among household contacts. Vaccination decreases transmission; however it is unclear how vaccinating a single individual alters disease risk among household contacts, particularly in regions with low vaccination coverage. Pregnant women were randomized to influenza or control vaccination.

Characterization of Invasive Serogroup C1 Infections in Mali.

Nontyphoidal (NTS) are the leading cause of foodborne infections worldwide and a major cause of bloodstream infections in infants and HIV-infected adults in sub-Saharan Africa (SSA). Typhimurium (serogroup B) and Enteritidis (serogroup D) are the most common serovars in this region. However, data describing rarer invasive NTS serovars, particularly those belonging to serogroups C1 and C2, circulating in SSA are lacking.

Epidemiology of influenza in West Africa after the 2009 influenza A(H1N1) pandemic, 2010-2012.

Background: Over the last decade, capacity for influenza surveillance and research in West Africa has strengthened. Data from these surveillance systems showed influenza A(H1N1)pdm09 circulated in West Africa later than in other regions of the continent.

Methods: We contacted 11 West African countries to collect information about their influenza surveillance systems (number of sites, type of surveillance, sampling strategy, populations sampled, case definitions used, number of specimens collected and number of specimens positive for influenza viruses) for the time period January 2010 through December 2012.

Meningococcal carriage within households in the African meningitis belt: A longitudinal pilot study.

Objectives: Carriers of Neisseria meningitidis are a key source of transmission. In the African meningitis belt, where risk of meningococcal disease is highest, a greater understanding of meningococcal carriage dynamics is needed.

Methods: We randomly selected an age-stratified sample of 400 residents from 116 households in Bamako, Mali, and collected pharyngeal swabs in May 2010.

Direct Detection of Shigella in Stool Specimens by Use of a Metagenomic Approach.

The underestimation of species as a cause of childhood diarrhea disease has become increasingly apparent with quantitative PCR (qPCR)-based diagnostic methods versus culture. We sought to confirm qPCR-based detection of via a metagenomics approach. Three groups of samples were selected from diarrheal cases from the Global Enteric Multicenter Study: nine culture-positive and qPCR-positive (culture qPCR) samples, nine culture-negative but qPCR-positive (culture qPCR) samples, and nine culture-negative and qPCR-negative (culture qPCR) samples.

Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial Comparing the Reactogenicity and Immunogenicity of a Single Standard Dose to Those of a High Dose of CVD 103-HgR Live Attenuated Oral Cholera Vaccine, with Shanchol Inactivated Oral Vaccine as an Open-Label Immunologic Comparator.

Reactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically naive individuals during virgin soil epidemics, when cholera reaches immunologically naive populations that have not experienced cholera for decades, would facilitate cholera control. One dose of attenuated O1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing ≥2 × 10 CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S.

Evaluation of Pneumococcal Load in Blood by Polymerase Chain Reaction for the Diagnosis of Pneumococcal Pneumonia in Young Children in the PERCH Study.

Background.: Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia.

Detection of Pneumococcal DNA in Blood by Polymerase Chain Reaction for Diagnosing Pneumococcal Pneumonia in Young Children From Low- and Middle-Income Countries.

Background.: We investigated the performance of polymerase chain reaction (PCR) on blood in the diagnosis of pneumococcal pneumonia among children from 7 low- and middle-income countries.

Methods.

The Effect of Antibiotic Exposure and Specimen Volume on the Detection of Bacterial Pathogens in Children With Pneumonia.

Background.: Antibiotic exposure and specimen volume are known to affect pathogen detection by culture. Here we assess their effects on bacterial pathogen detection by both culture and polymerase chain reaction (PCR) in children.

Standardization of Laboratory Methods for the PERCH Study.

The Pneumonia Etiology Research for Child Health study was conducted across 7 diverse research sites and relied on standardized clinical and laboratory methods for the accurate and meaningful interpretation of pneumonia etiology data. Blood, respiratory specimens, and urine were collected from children aged 1-59 months hospitalized with severe or very severe pneumonia and community controls of the same age without severe pneumonia and were tested with an extensive array of laboratory diagnostic tests. A standardized testing algorithm and standard operating procedures were applied across all study sites.

Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study.

Background: Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS).

Methods: GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia.

Genomic diversity of EPEC associated with clinical presentations of differing severity.

Enteropathogenic Escherichia coli (EPEC) are diarrhoeagenic E. coli, and are a significant cause of gastrointestinal illness among young children in developing countries. Typical EPEC are identified by the presence of the bundle-forming pilus encoded by a virulence plasmid, which has been linked to an increased severity of illness, while atypical EPEC lack this feature.

Evolution of atypical enteropathogenic E. coli by repeated acquisition of LEE pathogenicity island variants.

Atypical enteropathogenic Escherichia coli (aEPEC) is an umbrella term given to E. coli that possess a type III secretion system encoded in the locus of enterocyte effacement (LEE), but lack the virulence factors (stx, bfpA) that characterize enterohaemorrhagic E. coli and typical EPEC, respectively.

Aeromonas-Associated Diarrhea in Children Under 5 Years: The GEMS Experience.

We report the clinical findings, epidemiology, and risk factors for moderate-to-severe diarrhea (MSD) associated with Aeromonas species in children 0-59 months of age, from the Global Enteric Multicenter Study, conducted at three sites in south Asia and four sites in sub-Saharan Africa. Children with MSD were enrolled along with controls matched for age, gender, and neighborhood. Pooled, age-stratified conditional logistic regression models were applied to evaluate the association of Aeromonas infection controlling for coinfecting pathogens and sociodemographic variables.