Associations between Histo-Blood Group Antigen Status in Mother-Infant Dyads and Infant Oral Rotavirus Vaccine Immunogenicity in rural Zimbabwe.

Introduction: Histo-blood group antigen (HBGA) phenotypes may contribute to poor oral rotavirus vaccine (RVV) immunogenicity, since rotavirus binds intestinal epithelial HBGA glycans, while maternal HBGA status shapes breastmilk composition, which influences the composition of the infant microbiome. We investigated associations between maternal/infant HBGA phenotypes and RVV immunogenicity in rural Zimbabwe.

Methods: We undertook salivary FUT2/FUT3 phenotyping in mother-infant pairs.

Inflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants.

Children who are HIV-exposed but uninfected have increased infectious mortality compared to HIV-unexposed children, raising the possibility of immune abnormalities following exposure to maternal viraemia, immune dysfunction, and co-infections during pregnancy. In a secondary analysis of the SHINE trial in rural Zimbabwe we explored biological pathways underlying infant mortality, and maternal factors shaping immune development in HIV-exposed uninfected infants. Maternal inflammation and cytomegalovirus viraemia were independently associated with infant deaths: mortality doubled for each log rise in maternal C-reactive protein (adjusted hazard ratio (aHR) 2.

Stunting Status and Exposure to Infection and Inflammation in Early Life Shape Antibacterial Immune Cell Function Among Zimbabwean Children.

Background: Children who are stunted (length-for-age Z-score<-2) are at greater risk of infectious morbidity and mortality. Previous studies suggest that stunted children have elevated inflammatory biomarkers, but no studies have characterised their capacity to respond to new infections (i.e.

Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants.

Background: Oral rotavirus vaccines (RVV) are poorly immunogenic in low-income countries. Environmental enteric dysfunction (EED) resulting from poor water, sanitation and hygiene (WASH) may contribute. We therefore tested associations between EED and RVV immunogenicity, and evaluated the effect of improved WASH on EED.

Biomarkers of environmental enteric dysfunction are not consistently associated with linear growth velocity in rural Zimbabwean infants.

Background: Child stunting remains a poorly understood, prevalent public health problem. Environmental enteric dysfunction (EED) is hypothesized to be an important underlying cause.

Objectives: Within a subgroup of 1169 children enrolled in the SHINE (Sanitation Hygiene Infant Nutrition Efficacy) trial in rural Zimbabwe, followed longitudinally from birth to 18 mo of age, we evaluated associations between the concentration of 11 EED biomarkers and linear growth velocity.

Inflammation, cytomegalovirus and the growth hormone axis in HIV-exposed uninfected Zimbabwean infants.

Objectives: Despite avoiding HIV infection, HIV-exposed uninfected (HEU) infants have poorer clinical outcomes than HIV-unexposed infants, including impaired growth. The growth hormone (GH) axis is an important regulator of infant growth through hepatic synthesis of insulin-like growth-factor-1 (IGF-1), and may be disrupted by chronic inflammation and acute infections, including cytomegalovirus (CMV). We tested the hypothesis that these factors lead to disruption of the GH axis in HEU infants, which might contribute to their impaired growth.

Predictors of oral rotavirus vaccine immunogenicity in rural Zimbabwean infants.

Background: Oral rotavirus vaccines (RVV) have poor immunogenicity in low-income countries, for reasons that remain unclear. This study identified the determinants of RVV immunogenicity among infants in rural Zimbabwe.

Methods: Anti-rotavirus IgA titres were measured among a sub-group of infants enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (NCT01824940).

Enteropathogens and Rotavirus Vaccine Immunogenicity in a Cluster Randomized Trial of Improved Water, Sanitation and Hygiene in Rural Zimbabwe.

Background: Oral rotavirus vaccines (RVVs) are less efficacious in low-income versus high-income settings, plausibly due to more enteropathogen exposure through poor water, sanitation and hygiene (WASH). We explored associations between enteropathogens and RVV immunogenicity and evaluated the effect of improved WASH on enteropathogen carriage.

Methods: We detected stool enteropathogens using quantitative molecular methods and measured anti-rotavirus immunoglobulin A by enzyme-linked immunosorbent assay in infants enrolled to a cluster randomized 2 × 2 factorial trial of improved WASH and improved infant feeding in Zimbabwe (NCT01824940).

The Impact of Improved Water, Sanitation, and Hygiene on Oral Rotavirus Vaccine Immunogenicity in Zimbabwean Infants: Substudy of a Cluster-randomized Trial.

Background: Oral vaccines have lower efficacy in developing compared to developed countries. Poor water, sanitation, and hygiene (WASH) may contribute to reduced oral vaccine immunogenicity.

Methods: We conducted a cluster-randomized 2 × 2 factorial trial in rural Zimbabwe.

Neonatal vitamin A supplementation and immune responses to oral polio vaccine in Zimbabwean infants.

Background: Micronutrient deficiencies may contribute to reduced oral vaccine immunogenicity in developing countries. We hypothesised that neonatal vitamin A supplementation (NVAS) would improve oral vaccine responses.

Methods: We performed a cross-sectional study of infants recruited at birth to the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial, a randomised controlled trial of single, high-dose NVAS vs placebo conducted in Zimbabwe between 1997-2001.

Intestinal Damage and Inflammatory Biomarkers in Human Immunodeficiency Virus (HIV)-Exposed and HIV-Infected Zimbabwean Infants.

Background: Disease progression is rapid in human immunodeficiency virus (HIV)-infected infants. Whether intestinal damage and inflammation underlie mortality is unknown.

Methods: We measured plasma intestinal fatty acid binding protein (I-FABP), soluble CD14 (sCD14), interleukin 6 (IL-6), and C-reactive protein (CRP) at 6 weeks and 6 months of age in 272 HIV-infected infants who either died (cases) or survived (controls), and in 194 HIV-exposed uninfected (HEU) and 197 HIV-unexposed infants.

Immune responses to oral poliovirus vaccine in HIV-exposed uninfected Zimbabwean infants.

It remains uncertain whether HIV-exposed uninfected (HEU) infants have impaired responses to oral vaccines. We performed a cross-sectional study of 6-month-old infants recruited at birth to the ZVITAMBO trial in Zimbabwe between 1997-2001, before introduction of prevention of mother-to-child transmission interventions. We measured poliovirus-specific IgA to type 1-3 polio strains by semi-quantitative capture ELISA in cryopreserved serum samples collected from 85 HEU and 101 HIV-unexposed infants at 6 months of age, one month after their last immunisation with trivalent OPV.

Cytomegalovirus Acquisition and Inflammation in Human Immunodeficiency Virus-Exposed Uninfected Zimbabwean Infants.

Cytomegalovirus (CMV) acquisition and inflammation were evaluated in 231 human immunodeficiency virus (HIV)-exposed uninfected (HEU) and 100 HIV-unexposed Zimbabwean infants aged 6 weeks. The HEU and HIV-unexposed infants had a similarly high prevalence of CMV (81.4% vs 74.

Assessment of Environmental Enteric Dysfunction in the SHINE Trial: Methods and Challenges.

Environmental enteric dysfunction (EED) is a virtually ubiquitous, but poorly defined, disorder of the small intestine among people living in conditions of poverty, which begins early in infancy and persists. EED is characterized by altered gut structure and function, leading to reduced absorptive surface area and impaired intestinal barrier function. It is hypothesized that recurrent exposure to fecal pathogens and changes in the composition of the intestinal microbiota initiate this process, which leads to a self-perpetuating cycle of pathology.

Formative research on hygiene behaviors and geophagy among infants and young children and implications of exposure to fecal bacteria.

We conducted direct observation of 23 caregiver-infant pairs for 130 hours and recorded wash-related behaviors to identify pathways of fecal-oral transmission of bacteria among infants. In addition to testing fingers, food, and drinking water of infants, three infants actively ingested 11.3 ± 9.