Bangladeshi Infants Research Articles

SEPSIS Observational Cohort Study in Young Infants in Bangladesh

SEPSIS Observational Cohort Study in Young Infants in Bangladesh

Neonatal Vitamin A Supplementation and Vitamin A Status Are Associated with Gut Microbiome Composition in Bangladeshi Infants in Early Infancy and at 2 Years of Age

Infancy is a crucial period for establishing the intestinal microbiome. This process may be influenced by vitamin A (VA) status because VA affects intestinal immunity and epithelial integrity, factors that can, in turn, modulate microbiome development. The aim of this study was to determine if neonatal VA supplementation (VAS) affected the abundance of Bifidobacterium, a beneficial commensal, or of Proteobacteria, a phylum containing enteric pathogens, in early (6-15 wk) or late (2 y) infancy. Secondary objectives were to determine if VAS affected the abundance of other bacterial taxa, and to determine if VA status assessed by measuring plasma retinol was associated with bacterial abundance. Three hundred and six Bangladeshi infants were randomized by sex and birthweight status (above/below median) to receive 1 VA dose (50,000 IU) or placebo within 48 h of birth. Relative abundance at the genus level and above was assessed by 16S rRNA gene sequencing. A terminal restriction fragment-length polymorphism assay was used to identify Bifidobacterium species and subspecies at 6 wk. Linear regression showed that Bifidobacterium abundance in early infancy was lower in boys (median, 1st/3rd quartiles; 0.67, 0.52/0.78) than girls (0.73, 0.60/0.80; P=0.003) but that boys receiving VAS (0.69, 0.55/0.78) had higher abundance than boys receiving placebo (0.65, 0.44/0.77; P=0.039). However this difference was not seen in girls (VAS 0.71, 0.54/0.80; placebo 0.75, 0.63/0.81; P=0.25). VAS did not affect Proteobacteria abundance. Sex-specific associations were also seen for VA status, including positive associations of plasma retinol with Actinobacteria (the phylum containing Bifidobacterium) and Akkermansia, another commensal with possible health benefits, for girls in late infancy. Better VA status in infancy may influence health both in infancy and later in life by promoting the establishment of a healthy microbiota. This postulated effect of VA may differ between boys and girls. This trial was registered at clinicaltrials.gov as NCT02027610.

The relationship between biological and psychosocial risk factors and resting-state functional connectivity in 2-month-old Bangladeshi infants: A feasibility and pilot study.

Childhood poverty has been associated with structural and functional alterations in the developing brain. However, poverty does not alter brain development directly, but acts through associated biological or psychosocial risk factors (e.g. malnutrition, family conflict). Yet few studies have investigated risk factors in the context of infant neurodevelopment, and none have done so in low‐resource settings such as Bangladesh, where children are exposed to multiple, severe biological and psychosocial hazards. In this feasibility and pilot study, usable resting‐state fMRI data were acquired in infants from extremely poor (n = 16) and (relatively) more affluent (n = 16) families in Dhaka, Bangladesh. Whole‐brain intrinsic functional connectivity (iFC) was estimated using bilateral seeds in the amygdala, where iFC has shown susceptibility to early life stress, and in sensory areas, which have exhibited less susceptibility to early life hazards. Biological and psychosocial risk factors were examined for associations with iFC. Three resting‐state networks were identified in within‐group brain maps: medial temporal/striatal, visual, and auditory networks. Infants from extremely poor families compared with those from more affluent families exhibited greater (i.e. less negative) iFC in precuneus for amygdala seeds; however, no group differences in iFC were observed for sensory area seeds. Height‐for‐age, a proxy for malnutrition/infection, was not associated with amygdala/precuneus iFC, whereas prenatal family conflict was positively correlated. Findings suggest that it is feasible to conduct infant fMRI studies in low‐resource settings. Challenges and practical steps for successful implementations are discussed.

Using functional near-infrared spectroscopy to assess social information processing in poor urban Bangladeshi infants and toddlers.

Children living in low‐resource settings are at risk for failing to reach their developmental potential. While the behavioral outcomes of growing up in such settings are well‐known, the neural mechanisms underpinning poor outcomes have not been well elucidated, particularly in the context of low‐ and middle‐income countries. In this study, we measure brain metabolic responses to social and nonsocial stimuli in a cohort of 6‐ and 36‐month‐old Bangladeshi children. Study participants in both cohorts lived in an urban slum and were exposed to a broad range of adversity early in life including extreme poverty, malnutrition, recurrent infections, and low maternal education. We observed brain regions that responded selectively to social stimuli in both ages indicating that these specialized brain responses are online from an early age. We additionally show that the magnitude of the socially selective response is related to maternal education, maternal stress, and the caregiving environment. Ultimately our results suggest that a variety of psychosocial hazards have a measurable relationship with the developing social brain.

Neural correlates of early adversity among Bangladeshi infants

In this paper we explore the relationship between the Visual Evoked Potential (VEP), a component of the electroencephalogram elicited by visual stimuli, and cognitive functions in children growing up in an urban slum in Bangladesh. VEPs in response to pattern-reversing checkerboards were collected in 6 month-old-infants (n = 91) and 36-month-old children (n = 112). We examine variation in the amplitude and latency of the first positive component, the P1, of the VEP in relation to cognitive scores on the Mullen Scales of Early Learning and the Wechsler Preschool and Primary Scale of Intelligence. We also examine whether children’s caregiving experiences prior to the neuro-cognitive assessment explain variation in the P1 of the VEP. We find that the P1 amplitude of the VEP is related to concurrent cognitive performance in each respective cohort. We also find that the P1 amplitude at 6 months is prospectively associated with cognitive outcomes at 27 months, and the P1 amplitude at 36 months is prospectively associated with children’s IQ at 60 months. We find no associations between caregiving experiences and variation in the P1 of the VEP at 6 months, yet caregiving experience do explain variation in the P1 amplitude at 36 months. Caregiving experiences also explain variation in children’s concurrent and prospective cognitive functioning. The VEP may be used as a biomarker to index the neurobiological embedding of early adversity, which in turn may impact children’s cognitive functions.

The Evasive Enemy: Insights into the Virulence and Epidemiology of the Emerging Attaching and Effacing Pathogen Escherichia albertii.

The diarrheic attaching and effacing (A/E) pathogen Escherichia albertii was first isolated from infants in Bangladesh in 1991, although the bacterium was initially classified as Hafnia alvei Subsequent genetic and biochemical interrogation of these isolates raised concerns about their initial taxonomic placement. It was not until 2003 that these isolates were reassigned to the novel taxon Escherichia albertii because they were genetically more closely related to E. coli, although they had diverged sufficiently to warrant a novel species name. Unfortunately, new isolates continue to be mistyped as enteropathogenic E. coli (EPEC) or enterohemorrhagic E. coli (EHEC) owing to shared traits, most notably the ability to form A/E lesions. Consequently, E. albertii remains an underappreciated A/E pathogen, despite multiple reports demonstrating that many provisional EPEC and EHEC isolates incriminated in disease outbreaks are actually E. albertii Metagenomic studies on dozens of E. albertii isolates reveal a genetic architecture that boasts an arsenal of candidate virulence factors to rival that of its better-characterized cousins, EPEC and EHEC. Beyond these computational comparisons, studies addressing the regulation, structure, function, and mechanism of action of its repertoire of virulence factors are lacking. Thus, the paucity of knowledge about the epidemiology, virulence, and antibiotic resistance of E. albertii, coupled with its misclassification and its ability to develop multidrug resistance in a single step, highlights the challenges in combating this emerging pathogen. This review seeks to synthesize our current but incomplete understanding of the biology of E. albertii.

Daily Maternal Lipid-Based Nutrient Supplementation with 20 mg Iron, Compared with Iron and Folic Acid with 60 mg Iron, Resulted in Lower Iron Status in Late Pregnancy but Not at 6 Months Postpartum in Either the Mothers or Their Infants in Bangladesh

Maternal anemia and iron deficiency are prevalent in low- and middle-income countries. We aimed to determine the effects of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on hemoglobin (Hb), anemia, and iron status (nonprimary outcomes) at 36 weeks of gestation (women) and 6 mo postpartum (women and infants). The Rang-Din Nutrition Study, a cluster-randomized effectiveness trial, enrolled 4011 Bangladeshi pregnant women at ≤20 weeks of gestation to receive either daily LNS-PL (20 mg Fe) during pregnancy and the first 6 mo postpartum, or iron and folic acid (IFA, 60 mg Fe+400 µg folic acid) daily during pregnancy and every other day during the first 3 mo postpartum. Biochemical measurements from a subsample of women (n=1128) and their infants (n=1117) included Hb (g/L), serum ferritin (µg/L), and soluble transferrin receptor (sTfR; mg/L). Anemia was defined as maternal Hb <110 g/L at 36 weeks of gestation, <120 g/L at 6 mo postpartum, or infant Hb <105 g/L; iron deficiency (ID) was defined as ferritin <12 µg/L or elevated sTfR (>8.3 mg/L for women and >11 mg/L for infants). Compared with the IFA group, women in the LNS-PL group had lower ferritin (-6.2 µg/L; P<0.001) and higher sTfR concentrations (+0.5 mg/L; P<0.001), and higher risk of ID (OR=1.93; P<0.05) at 36 weeks of gestation but not at 6 mo postpartum, whereas no consistent differences were observed for Hb or anemia. Among infants at 6 mo, there were no group differences except for a lower risk of elevated sTfR (OR=0.61; P<0.05) in the LNS-PL group than in the IFA group. Provision of LNS-PL including a lower dose of iron than what is recommended during pregnancy resulted in differences in maternal iron status in late pregnancy that disappeared by 6 mo postpartum, and caused no undesirable effects regarding anemia or iron status of infants. This trial was registered at clinicaltrials.gov as NCT01715038.

Bifidobacterial Dominance of the Gut in Early Life and Acquisition of Antimicrobial Resistance.

Bifidobacterium species are important commensals capable of dominating the infant gut microbiome, in part by producing acids that suppress growth of other taxa. Bifidobacterium species are less prone to possessing antimicrobial resistance (AMR) genes (ARGs) than other taxa that may colonize infants. Given that AMR is a growing public health crisis and ARGs are present in the gut microbiome of humans from early life, this study examines the correlation between a Bifidobacterium-dominated infant gut microbiome and AMR levels, measured by a culture-independent metagenomic approach both in early life and as infants become toddlers. In general, Bifidobacterium dominance is associated with a significant reduction in AMR in a Bangladeshi cohort, both in the number of acquired AMR genes present and in the abundance of AMR genes. However, by year 2, Bangladeshi infants had no significant differences in AMR related to their early-life Bifidobacterium levels. A generalized linear model including all infants in a previously published Swedish cohort found a significant negative association between log-transformed total AMR and Bifidobacterium levels, thus confirming the relationship between Bifidobacterium levels and AMR. In both cohorts, there was no change between early-life and later-life AMR abundance in high-Bifidobacterium infants but a significant reduction in AMR abundance in low-Bifidobacterium infants. These results support the hypothesis that early Bifidobacterium dominance of the infant gut microbiome may help reduce colonization by taxa containing ARGs.IMPORTANCE Infants are vulnerable to an array of infectious diseases, and as the gut microbiome may serve as a reservoir of AMR for pathogens, reducing the levels of AMR in infants is important to infant health. This study demonstrates that high levels of Bifidobacterium are associated with reduced levels of AMR in early life and suggests that probiotic interventions to increase infant Bifidobacterium levels have the potential to reduce AMR in infants. However, this effect is not sustained at year 2 of age in Bangladeshi infants, underscoring the need for more detailed studies of the biogeography and timing of infant AMR acquisition.

Genome-Wide Association Study Reveals Genetic Link between Diarrhea-Associated Entamoeba histolytica Infection and Inflammatory Bowel Disease.

Entamoeba histolytica is the etiologic agent of amebic dysentery, though clinical manifestation of infection is highly variable ranging from subclinical colonization to invasive disease. We hypothesize that host genetics contribute to the variable outcomes of E. histolytica infection; thus, we conducted a genome-wide association study (GWAS) in two independent birth cohorts of Bangladeshi infants monitored for susceptibility to E. histolytica disease in the first year of life. Children with at least one diarrheal episode positive for E. histolytica (cases) were compared to children with no detectable E. histolytica infection in the same time frame (controls). Meta-analyses under a fixed-effect inverse variance weighting model identified multiple variants in a region of chromosome 10 containing loci associated with symptomatic E. histolytica infection. An intergenic insertion between CREM and CCNY (rs58000832) achieved genome-wide significance (P value from meta-analysis [Pmeta] = 6.05 × 10-9), and each additional risk allele of rs58000832 conferred 2.42 increased odds of a diarrhea-associated E. histolytica infection. The most strongly associated single nucleotide polymorphism (SNP) within a gene was in an intron of CREM (rs58468612; Pmeta = 8.94 × 10-8), which has been implicated as a susceptibility locus for inflammatory bowel disease (IBD). Gene expression resources suggest associated loci are related to the lower expression of CREM Increased CREM expression is also observed in early E. histolytica infection. Further, CREM-/- mice were more susceptible to E. histolytica amebic colitis. These genetic associations reinforce the pathological similarities observed in gut inflammation between E. histolytica infection and IBD.IMPORTANCE Diarrhea is the second leading cause of death for children globally, causing 760,000 deaths each year in children less than 5 years old. Amebic dysentery contributes significantly to this burden, especially in developing countries. The identification of host factors that control or enable enteric pathogens has the potential to transform our understanding of disease predisposition, outcomes, and treatments. Our discovery of the transcriptional regulator cAMP-responsive element modulator (CREM) as a genetic modifier of susceptibility to amebic disease has implications for understanding the pathogenesis of other diarrheal infections. Further, emerging evidence for CREM in IBD susceptibility suggests that CREM is a critical regulator of enteric inflammation and may have broad therapeutic potential as a drug target across intestinal inflammatory diseases.

Identification of Etiology-Specific Diarrhea Associated With Linear Growth Faltering in Bangladeshi Infants.

Childhood diarrhea in low-resource settings has been variably linked to linear growth shortfalls. However, the association between etiology-specific diarrhea and growth has not been comprehensively evaluated. We tested diarrheal stools collected from the Performance of Rotavirus and Oral Polio Vaccines in Developing Countries study from 2011 to 2013 in Dhaka, Bangladesh, by quantitative polymerase chain reaction for a broad range of enteropathogens to characterize diarrhea etiology and examine the association between etiology-specific diarrhea and linear growth and systemic inflammation. Pathogen-specific burdens of diarrhea were determined using attributable fractions. Linear regression was used to examine associations of pathogen-specific diarrhea with length-for-age z scores (LAZ) and serum C-reactive protein. There was no relationship between all-cause diarrhea and length at 12 months (change in 12-month LAZ per episode, −0.01, 95% confidence interval (CI): −0.06, 0.03). However, Cryptosporidium (change in 12-month LAZ per attributable episode, −0.23, 95% CI: −0.50, 0.03), Campylobacter jejuni/coli (change of −0.16, 95% CI: −0.32, −0.01), and Shigella/enteroinvasive Escherichia coli diarrhea (change of −0.12, 95% CI: −0.26, 0.03) were associated with linear growth deficits. Diarrhea attributable to C. jejuni/coli and Shigella/enteroinvasive E. coli were associated with elevated C-reactive protein. The association between diarrhea and linear growth appears to be pathogen-specific, reinforcing the need for pathogen-specific interventions.

The contribution of gestational age, area deprivation and mother's country of birth to ethnic variations in infant mortality in England and Wales: A national cohort study using routinely collected data.

ObjectivesWe aimed to describe ethnic variations in infant mortality and explore the contribution of area deprivation, mother’s country of birth, and prematurity to these variations.MethodsWe analyzed routine birth and death data on singleton live births (gestational age≥22 weeks) in England and Wales, 2006–2012. Infant mortality by ethnic group was analyzed using logistic regression with adjustment for sociodemographic characteristics and gestational age.ResultsIn the 4,634,932 births analyzed, crude infant mortality rates were higher in Pakistani, Black Caribbean, Black African, and Bangladeshi infants (6.92, 6.00, 5.17 and 4.40 per 1,000 live births, respectively vs. 2.87 in White British infants). Adjustment for maternal sociodemographic characteristics changed the results little. Further adjustment for gestational age strongly attenuated the risk in Black Caribbean (OR 1.02, 95% CI 0.89–1.17) and Black African infants (1.17, 1.06–1.29) but not in Pakistani (2.32, 2.15–2.50), Bangladeshi (1.47, 1.28–1.69), and Indian infants (1.24, 1.11–1.38). Ethnic variations in infant mortality differed significantly between term and preterm infants. At term, South Asian groups had higher risks which cannot be explained by sociodemographic characteristics. In preterm infants, adjustment for degree of prematurity (<28, 28–31, 32–33, 34–36 weeks) fully explained increased risks in Black but not Pakistani and Bangladeshi infants. Sensitivity analyses with further adjustment for small for gestational age, or excluding deaths due to congenital anomalies did not fully explain the excess risk in South Asian groups.ConclusionsHigher infant mortality in South Asian and Black infants does not appear to be explained by sociodemographic characteristics. Higher proportions of very premature infants appear to explain increased risks in Black infants but not in South Asian groups. Strategies targeting the prevention and management of preterm birth in Black groups and suboptimal birthweight and modifiable risk factors for congenital anomalies in South Asian groups might help reduce ethnic inequalities in infant mortality.

Rotavirus-Specific Immunoglobulin A Responses Are Impaired and Serve as a Suboptimal Correlate of Protection Among Infants in Bangladesh.

BackgroundRotavirus (RV)–specific immunoglobulin A (IgA) responses following oral RV vaccination are impaired in low-income countries, where the utility of RV-IgA as a correlate of protection (CoP) remains unclear. In a monovalent oral RV vaccine (Rotarix) efficacy trial among infants in Dhaka, Bangladesh, we identified factors associated with poor RV-IgA responses and explored the utility of RV-IgA as a CoP.MethodsInfants were randomized to receive Rotarix or no Rotarix at 10 and 17 weeks of life and followed with active diarrheal surveillance. RV-IgA concentration, seroconversion, and seropositivity were determined at 18 weeks of life and analyzed for correlation(s) with rotavirus diarrhea (RVD) and for contribution to Rotarix vaccine effect.ResultsAmong vaccinated infants, overall RV-IgA geometric mean concentration was 21 U/mL; only 27% seroconverted and 32% were seropositive after vaccination. Increased RV-specific maternal antibodies significantly impaired immunogenicity. Seroconversion was associated with reduced risk of RVD through 1 year of life, but RV-IgA seropositivity only explained 7.8% of the vaccine effect demonstrated by the clinical endpoint (RVD).ConclusionsRV-IgA responses were low among infants in Bangladesh and were significantly impaired by maternal antibodies. RV-IgA is a suboptimal CoP in this setting; an improved CoP for RV in low-income countries is needed.Clinical Trials RegistrationNCT01375647.

Differences in the pregnancy gestation period and mean birth weights in infants born to Indian, Pakistani, Bangladeshi and white British mothers in Luton, UK: a retrospective analysis of routinely collected data

ObjectiveTo compare mean birth weights and gestational age at delivery of infants born to Indian, Pakistani, Bangladeshi and white British mothers in Luton, UK.DesignRetrospective analysis using routinely recorded secondary data...

Early Life Inflammation and Neurodevelopmental Outcome in Bangladeshi Infants Growing Up in Adversity.

.Exposure to profound adversity can negatively affect the neurodevelopment of children, but biologic mechanisms that underlie this association remain unknown. We sought to determine whether elevated levels of the inflammatory markers C-reactive protein (CRP) and soluble CD14 (sCD14) are associated with neurodevelopmental outcomes in Bangladeshi children. A total of 422 infant–mother pairs from an urban slum in Dhaka, Bangladesh were enrolled at birth and followed prospectively. Inflammation was measured with sCD14, interleukin (IL)-1β, and IL-6 at 18 weeks, and CRP at 6, 18, 40, and 53 weeks. Psychologists assessed cognitive, language, motor, and social emotional development using the Bayley Scales of Infant and Toddler Development at 78 and 104 weeks of age. We tested for the association of inflammatory markers with developmental outcomes, independent of previously identified associations such as malnutrition, family income, and maternal education. Every 10 pg/mL increase in sCD14 was associated with a 1.1–2.0 decrement in cognitive and motor scores at 78 weeks and in all domains at 104 weeks. The cumulative number of CRP elevations that a child experienced in the first year of life, as well as IL-1β and IL-6 at 18 weeks of age, were also negatively associated with Bayley Scales results. CRP, sCD14, IL-1β, and IL-6 were associated with lower neurodevelopmental outcomes. Our findings implicate a role of inflammation in the neurodevelopment of children growing up in adversity.

Nonspecific Effects of Oral Polio Vaccine on Diarrheal Burden and Etiology Among Bangladeshi Infants

As the global polio eradication initiative prepares to cease use of oral polio vaccine (OPV) in 2020, there is increasing interest in understanding if oral vaccination provides non-specific immunity to other infections so that the consequences of this transition can be effectively planned for and mitigated. Data were collected from infants in an urban slum in Bangladesh (Mirpur, Dhaka) as part of the performance of rotavirus and oral polio vaccines in developing countries (PROVIDE) study. Following vaccination with trivalent oral polio vaccine (tOPV) at 6, 10, and 14 weeks, infants were randomly assigned to receive tOPV (n = 315) or inactivated polio vaccine (IPV) (n = 299) at 39 weeks. Episodes of diarrhea were documented through clinic visits and twice-weekly house visits through 52 weeks. In sum, 14 pathogens associated with diarrhea were analyzed with TaqMan Array Cards. Although the proportion of children experiencing diarrhea was not different between the tOPV and IPV groups (P = .18), the number of days with diarrhea (P = .0037) and the number of separate diarrheal episodes (P = .054) trended lower in the OPV arm. Etiological analysis revealed that male tOPV recipients were less likely to have diarrhea of bacterial etiology (P = .0099) compared to male IPV recipients but equally likely to experience diarrhea due to viruses (P = .57) or protozoa (P = .14). Among the 6 bacterial enteric pathogens tested, only Campylobacter jejuni/coli detection was significantly reduced in the OPV arm (P = .0048). Our results suggest that OPV may cause nonspecific reductions in mortality, as has been studied elsewhere, by reducing etiology-specific diarrheal burden. This is likely driven by reductions in bacterial diarrhea. Further study of nonspecific OPV effects before global cessation is supported. NCT01375647.

What Pertussis Mortality Rates Make Maternal Acellular Pertussis Immunization Cost-Effective in Low- and Middle-Income Countries? A Decision Analysis.

Background. Despite longstanding infant vaccination programs in low- and middle-income countries (LMICs), pertussis continues to cause deaths in the youngest infants. A maternal monovalent acellular pertussis (aP) vaccine, in development, could prevent many of these deaths. We estimated infant pertussis mortality rates at which maternal vaccination would be a cost-effective use of public health resources in LMICs.Methods. We developed a decision model to evaluate the cost-effectiveness of maternal aP immunization plus routine infant vaccination vs routine infant vaccination alone in Bangladesh, Nigeria, and Brazil. For a range of maternal aP vaccine prices, one-way sensitivity analyses identified the infant pertussis mortality rates required to make maternal immunization cost-effective by alternative benchmarks ($100, 0.5 gross domestic product [GDP] per capita, and GDP per capita per disability-adjusted life-year [DALY]). Probabilistic sensitivity analysis provided uncertainty intervals for these mortality rates.Results. Infant pertussis mortality rates necessary to make maternal aP immunization cost-effective exceed the rates suggested by current evidence except at low vaccine prices and/or cost-effectiveness benchmarks at the high end of those considered in this report. For example, at a vaccine price of $0.50/dose, pertussis mortality would need to be 0.051 per 1000 infants in Bangladesh, and 0.018 per 1000 in Nigeria, to cost 0.5 per capita GDP per DALY. In Brazil, a middle-income country, at a vaccine price of $4/dose, infant pertussis mortality would need to be 0.043 per 1000 to cost 0.5 per capita GDP per DALY.Conclusions. For commonly used cost-effectiveness benchmarks, maternal aP immunization would be cost-effective in many LMICs only if the vaccine were offered at less than $1–$2/dose.

Colonization of Probiotics in Bangladeshi Infants After Different Administration Regimens

Colonization of Probiotics in Bangladeshi Infants After Different Administration Regimens

Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants

BackgroundOral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated. MethodsIn urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea. ResultsCampylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (−0.08 change in log titer per tenfold increase in quantity; P=0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64–0.96; P=0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05–1.71; P=0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity. ConclusionIn this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses.ClinicalTrials.gov Identifier: NCT01375647.

Infection Surveillance Protocol for a Multicountry Population-based Study in South Asia to Determine the Incidence, Etiology and Risk Factors for Infections Among Young Infants of 0 to 59 Days Old.

Insufficient knowledge of the etiology and risk factors for community-acquired neonatal infection in low-income countries is a barrier to designing appropriate intervention strategies for these settings to reduce the burden and treatment of young infant infection. To address these gaps, we are conducting the Aetiology of Neonatal Infection in South Asia (ANISA) study among young infants in Bangladesh, India and Pakistan. The objectives of ANISA are to establish a comprehensive surveillance system for registering newborns in study catchment areas and collecting data on bacterial and viral etiology and associated risk factors for infections among young infants aged 0-59 days. We are conducting active surveillance in 1 peri-urban and 4 rural communities. During 2 years of surveillance, we expect to enroll an estimated 66,000 newborns within 7 days of their birth and to follow-up them until 59 days of age. Community health workers visit each young infant in the study area 3 times in the first week of life and once a week thereafter. During these visits, community health workers assess the newborns using a clinical algorithm and refer young infants with signs of suspected infection to health care facilities where study physicians reassess them and provide care if needed. On physician confirmation of suspected infection, blood and respiratory specimens are collected and tested to identify the etiologic agent. ANISA is one of the largest initiatives ever undertaken to understand the etiology of young infant infection in low-income countries. The data generated from this surveillance will help guide evidence-based decision making to improve health care in similar settings.

Effect of Probiotics on Markers of Gut Health in Bangladeshi Infants

Yana Emmy Hoy-Schulz1, Kaniz Jannat2, Thomas Roberts3, Saira H. Zaidi4, Md. Mostafizur Rahman2, Mohammad Alauddin5, Leanne Unicomb2, Stephen Luby1, and Julie Parsonnet1 1Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford School of Medicine, Stanford, CA 94305; 2Center for Communicable Diseases, International Center for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh 1212; 3Department of Medicine, Stanford School of Medicine, Stanford, CA 94305; 4School of Public Health, University of California Berkeley, Berkeley, CA, 94720; 5Department of Chemistry, Wagner College, New York, NY