Longevity of immune response after a single dose of typhoid conjugate vaccine against Salmonella Typhi among children in Hyderabad, Pakistan.

Objectives: Typhoid remains a persistent contributor to childhood morbidity in communities lacking sanitation infrastructure. Typhoid conjugate vaccine (TCV) is effective in reducing disease risk in vaccinees; however, the duration of protection is unknown. This study measured the longevity of immune response to TCV in children aged under 10 years in Hyderabad, Pakistan, where an outbreak of extensively drug-resistant typhoid has been ongoing.

Cost-effectiveness and public health impact of typhoid conjugate vaccine introduction strategies in Bangladesh.

Purpose: Typhoid fever causes substantial morbidity and mortality in Bangladesh. The government of Bangladesh plans to introduce typhoid conjugate vaccines (TCV) in its expanded program on immunization (EPI) schedule. However, the optimal introduction strategy in addition to the costs and benefits of such a program are unclear.

Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Typhi genomes.

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000).

Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch.

Seroepidemiology for Enteric Fever: Emerging Approaches and Opportunities.

Safe and effective typhoid conjugate vaccines (TCVs) are available, but many countries lack the high-resolution data needed to prioritize TCV introduction to the highest-risk communities. Here we discuss seroepidemiology-an approach using antibody response data to characterize infection burden-as a potential tool to fill this data gap. Serologic tests for typhoid have existed for over a hundred years, but only recently were antigens identified that were sensitive and specific enough to use as epidemiologic markers.

Seroincidence of Enteric Fever, Juba, South Sudan.

We applied a new serosurveillance tool to estimate typhoidal Salmonella burden using samples collected during 2020 from a population in Juba, South Sudan. By using dried blood spot testing, we found an enteric fever seroincidence rate of 30/100 person-years and cumulative incidence of 74% over a 4-year period.

Incidence of typhoid and paratyphoid fever in Bangladesh, Nepal, and Pakistan: results of the Surveillance for Enteric Fever in Asia Project.

Background: Precise enteric fever disease burden data are needed to inform prevention and control measures, including the use of newly available typhoid vaccines. We established the Surveillance for Enteric Fever in Asia Project (SEAP) to inform these strategies.

Methods: From September, 2016, to September, 2019, we conducted prospective clinical surveillance for Salmonella enterica serotype Typhi (S Typhi) and Paratyphi (S Paratyphi) A, B, and C at health facilities in predetermined catchment areas in Dhaka, Bangladesh; Kathmandu and Kavrepalanchok, Nepal; and Karachi, Pakistan.

Influences on catch-up growth using relative versus absolute metrics: evidence from the MAL-ED cohort study.

Background: Poor growth in early childhood has been considered irreversible after 2-3 years of age and has been associated with morbidity and mortality over the short-term and with poor economic and cognitive outcomes over the long-term. The MAL-ED cohort study was performed in eight low-income settings with the goal of evaluating relationships between the child's environment and experience (dietary, illness, and pathogen exposure, among others) and their growth and development. The goal of this analysis is to determine whether there are differences in the factors associated with growth from 24 to 60 months using two different metrics.

Early Life Experiences and Trajectories of Cognitive Development.

Background: Multiple factors constrain the trajectories of child cognitive development, but the drivers that differentiate the trajectories are unknown. We examine how multiple early life experiences differentiate patterns of cognitive development over the first 5 years of life in low-and middle-income settings.

Methods: Cognitive development of 835 children from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite observational cohort study was assessed at 6, 15, 24 (Bayley Scales of Infant and Toddler Development), and 60 months (Wechsler Preschool and Primary Scale of Intelligence).

Correction: Impact of early-onset persistent stunting on cognitive development at 5 years of age: Results from a multi-country cohort study.

[This corrects the article DOI: 10.1371/journal.pone.

Impact of early-onset persistent stunting on cognitive development at 5 years of age: Results from a multi-country cohort study.

Background: Globally more than 150 million children under age 5 years were stunted in 2018, primarily in low- and middle-income countries (LMICs), and the impact of early-onset, persistent stunting has not been well explored. To explore the association between early-onset persistent stunting in children and cognitive development at 5 years of age, and to identify the factors associated with early-onset stunting.

Methods And Findings: Children from the MAL-ED cohort study were followed from birth to 5 years of age in six LMICs.

Intestinal permeability and inflammation mediate the association between nutrient density of complementary foods and biochemical measures of micronutrient status in young children: results from the MAL-ED study.

Background: Environmental enteric dysfunction (EED) is thought to increase the risk of micronutrient deficiencies, but few studies adjust for dietary intakes and systemic inflammation.

Objective: We tested whether EED is associated with micronutrient deficiency risk independent of diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status.

Methods: Using data from 1283 children in the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort we evaluated the risk of anemia, low retinol, zinc, and ferritin, and high transferrin receptor (TfR) at 15 mo.

Early childhood development and stunting: Findings from the MAL-ED birth cohort study in Bangladesh.

Information on the association between stunting and child development is limited from low-income settings including Bangladesh where 36% of children under- 5 are stunted. This study aimed to explore differences in early childhood development (ECD) between stunted (length-for-age z-score [LAZ] < -2) and nonstunted (LAZ ≥ -2) children in Bangladesh. Children (n = 265) aged 6-24 months who participated in the MAL-ED birth cohort study were evaluated by trained psychologists at 6, 15, and 24 months of age using the Bayley Scales of Infant and Toddler Development-III; child length and weight were measured using standard procedures.

Early Life Child Micronutrient Status, Maternal Reasoning, and a Nurturing Household Environment have Persistent Influences on Child Cognitive Development at Age 5 years: Results from MAL-ED.

Background: Child cognitive development is influenced by early-life insults and protective factors. To what extent these factors have a long-term legacy on child development and hence fulfillment of cognitive potential is unknown.

Objective: The aim of this study was to examine the relation between early-life factors (birth to 2 y) and cognitive development at 5 y.

Enteric dysfunction and other factors associated with attained size at 5 years: MAL-ED birth cohort study findings.

Background: Poor growth in early childhood has been associated with increased risk of mortality and morbidity, as well as long-term deficits in cognitive development and economic productivity.

Objectives: Data from the MAL-ED cohort study were used to identify factors in the first 2 y of life that are associated with height-for-age, weight-for-age, and body mass index z-scores (HAZ, WAZ, BMIZ) at 5 y of age.

Methods: A total of 1017 children were followed from near birth until 5 y of age at sites in Bangladesh, Brazil, India, Nepal, Peru, South Africa, and Tanzania.

Assessing development across cultures: Invariance of the Bayley-III Scales Across Seven International MAL-ED sites.

The Bayley's Scales of Infant and Toddler Development-Third Edition (Bayley-III) were used to measure the development of 24-month-old children (N = 1,452) in the Interactions of Malnutrition and Enteric Infections: Consequences for Child Health and Development (MAL-ED) study (an international, multisite study on many aspects of child development). This study examined the factor structure and measurement equivalence/invariance of Bayley-III scores across 7 international research sites located in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, and South Africa. Exploratory and confirmatory factor analyses were used to identify the factor structure of Bayley-III scores.

Oral polio vaccine response in the MAL-ED birth cohort study: Considerations for polio eradication strategies.

Background: Immunization programs have leveraged decades of research to maximize oral polio vaccine (OPV) response. Moving toward global poliovirus eradication, the WHO recommended phased OPV-to-IPV replacement on schedules in 2012. Using the MAL-ED prospective birth cohort data, we evaluated the influence of early life exposures impacting OPV immunization by measuring OPV response for serotypes 1 and 3.

Temporal Variability of Diversity in the Gastrointestinal Tracts of Tanzanian Children with and without Exposure to Antibiotics.

The stability of the populations in the human gastrointestinal tract is not fully appreciated, and represents a significant knowledge gap regarding gastrointestinal community structure, as well as resistance to incoming pathogenic bacterial species and antibiotic treatment. The current study examines the genomic content of 240 isolates from 30 children, aged 2 to 35 months old, in Tanzania. The strains were isolated from three time points spanning a six-month time period, with and without antibiotic treatment.

Use of quantitative molecular diagnostic methods to assess the aetiology, burden, and clinical characteristics of diarrhoea in children in low-resource settings: a reanalysis of the MAL-ED cohort study.

Background: Optimum management of childhood diarrhoea in low-resource settings has been hampered by insufficient data on aetiology, burden, and associated clinical characteristics. We used quantitative diagnostic methods to reassess and refine estimates of diarrhoea aetiology from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study.

Methods: We re-analysed stool specimens from the multisite MAL-ED cohort study of children aged 0-2 years done at eight locations (Dhaka, Bangladesh; Vellore, India; Bhaktapur, Nepal; Naushero Feroze, Pakistan; Venda, South Africa; Haydom, Tanzania; Fortaleza, Brazil; and Loreto, Peru), which included active surveillance for diarrhoea and routine non-diarrhoeal stool collection.

Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study.

Background: Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We used molecular diagnostics to assess whether particular enteropathogens were associated with linear growth across seven low-resource settings.

Methods: We used quantitative PCR to detect 29 enteropathogens in diarrhoeal and non-diarrhoeal stools collected from children in the first 2 years of life obtained during the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite cohort study.

Genetic Diversity of Noroviruses Circulating in a Pediatric Cohort in Bangladesh.

Noroviruses are a leading cause of diarrhea in children aged <5 years worldwide. We genotyped 88 viruses collected by active surveillance in a birth cohort of children <2 years of age in Dhaka, Bangladesh, during 2010-2013. Twenty-five of 31 (81%) established GI and GII genotypes were detected, with GII.

Relationships among Common Illness Symptoms and the Protective Effect of Breastfeeding in Early Childhood in MAL-ED: An Eight-Country Cohort Study.

Children in low-income countries experience multiple illness symptoms in early childhood. Breastfeeding is protective against diarrhea and respiratory infections, and these illnesses are thought to be risk factors of one another, but these relationships have not been explored simultaneously. In the eight-site MAL-ED study, 1,731 infants were enrolled near birth and followed for 2 years.