Prenatal nutrition supplementation and growth biomarkers in preadolescent Bangladeshi children: A birth cohort study.

Little is known about the usefulness of biomarkers to study the influence of prenatal nutrition supplementation in improving child growth. Anthropometry is not always straightforward to understand how nutrition might impact growth, especially in settings with high rates of malnutrition and infections. We examined the effects of prenatal supplementation on growth and growth biomarkers and the relationship between anthropometric measures and growth biomarkers of children at 4.5 and 9 years of age. Children were enrolled from a longitudinal cohort, where mothers were randomized into daily supplementation with either early-food (≤9 gestation week [GW]) or usual-food (~20 GW) (608 kcal 6 days/week); they were further randomized to receive 30-mg or 60-mg iron with 400-µg folic acid, or multiple micronutrients (MM) in rural Bangladesh. Anthropometric data were collected from mothers at GW8 and children at 4.5 (n = 640) and 9 years (n = 536). Fasting blood was collected from children at each age. Early-food supplementation showed reduced stunting and underweight at 4.5 and 9 years age respectively compared to usual-food. Prenatal supplementations did not have any effect on growth biomarkers except for STAT5b expression which was lower in the early-food compared to the usual-food group (ß = -0.21; 95 CI% = -0.36, -0.07). Plasma concentrations of 25-hydroxy vitamin D and calcium were both inversely associated with weight-for-age and body mass index-for-age Z-scores at 9 years, particularly in early-food and MM groups. Although there was minimal effect on child growth by prenatal supplementations, the associations of biomarkers with anthropometric indices were predominantly driven by timing of food or MM supplementations.

High-Dose Neonatal Vitamin A Supplementation to Bangladeshi Infants Increases the Percentage of CCR9-Positive Treg Cells in Infants with Lower Birthweight in Early Infancy, and Decreases Plasma sCD14 Concentration and the Prevalence of Vitamin A Deficiency at Two Years of Age.

BACKGROUND: Vitamin A (VA) stores are low in early infancy and may impair development of the immune system. OBJECTIVE: This study determined if neonatal VA supplementation (VAS) affects the following: 1) development of regulatory T (Treg) cells; 2) chemokine receptor 9 (CCR9) expression, which directs mucosal targeting of immune cells; and 3) systemic endotoxin exposure as indicated by changed plasma concentrations of soluble CD14 (sCD14). Secondarily, VA status, growth, and systemic inflammation were investigated. METHODS: In total, 306 Bangladeshi infants were randomly assigned to receive 50,000 IU VA or placebo (PL) within 48 h of birth, and immune function was assessed at 6 wk, 15 wk, and 2 y. Primary outcomes included the following: 1) peripheral blood Treg cells; 2) percentage of Treg, T, and B cells expressing CCR9; and 3) plasma sCD14. Secondary outcomes included the following: 4) VA status measured using the modified relative dose-response (MRDR) test and plasma retinol; 5) infant growth; and 6) plasma C-reactive protein (CRP). Statistical analysis identified group differences and interactions with sex and birthweight. RESULTS: VAS increased (P = 0.004) the percentage of CCR9+ Treg cells (13.2 ± 1.37%) relative to PL (9.17 ± 1.15%) in children below the median birthweight but had the opposite effect (P = 0.04) in those with higher birthweight (VA, 9.13 ± 0.89; PL, 12.1 ± 1.31%) at 6 and 15 wk (values are combined mean ± SE). VAS decreased (P = 0.003) plasma sCD14 (1.56 ± 0.025 mg/L) relative to PL (1.67 ± 0.032 mg/L) and decreased (P = 0.034) the prevalence of VA deficiency (2.3%) relative to PL (9.2%) at 2 y. CONCLUSIONS: Neonatal VAS enhanced mucosal targeting of Treg cells in low-birthweight infants. The decreased systemic exposure to endotoxin and improved VA status at 2 y may have been due to VA-mediated improvements in gut development resulting in improved barrier function and nutrient absorption. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.

Infant cortisol stress-response is associated with thymic function and vaccine response.

Stress can impair T cell-mediated immunity. To determine if infants with high stress responses had deficits in T-cell mediated immunity, we examined the association of pain-induced cortisol responsiveness with thymic function and vaccine responses in infants. This study was performed among 306 (male = 153 and female = 153) participants of a randomized, controlled trial examining the effect of neonatal vitamin A supplementation on immune function in Bangladesh (NCT01583972). Salivary cortisol was measured before and 20 min after a needle stick (vaccination) at 6 weeks of age. The thymic index (TI) was determined by ultrasonography at 1, 6, 10 and 15 weeks. T-cell receptor excision circle and blood T-cell concentrations were measured at 6 and 15 weeks. Responses to Bacillus Calmette-Guérin (BCG), tetanus toxoid, hepatitis B virus and oral poliovirus vaccination were assayed at 6 and 15 weeks. Cortisol responsiveness was negatively associated with TI at all ages (p < .01) in boys only, was negatively associated with naïve helper T-cell concentrations in both sexes at both 6 (p = .0035) and 15 weeks (p = .0083), and was negatively associated with the delayed-type hypersensitivity (DTH) skin test response to BCG vaccination at 15 weeks (p = .034) in both sexes. Infants with a higher cortisol response to pain have differences in the T-cell compartment and a lower DTH response to vaccination. Sex differences in the immune system were seen as early as 6 weeks of age in these healthy infants.

Risk factors for delay in starting age-appropriate vaccinations among infants in urban slums of Bangladesh.

Age-appropriate vaccination is crucial for infants, protecting them from vaccine-preventable diseases. Delaying in starting initial immunization may result in incomplete or non-vaccination in early life. However, limited vaccine coverage data are available regarding the starting age of vaccination. In this study, we determined the factors associated with the delay in infant immunization. We carried out a cross-sectional study at three maternal-child health clinics in Dhaka city. Mothers visited these clinics for their infant immunization were surveyed with structured questionnaires. A multivariate logistic regression model was used to estimate the significant influencing factors on untimely vaccination. A total of 548 mother-infant pairs were surveyed. 46.5% of mothers did not receive Tetanus (TT) vaccines, and mothers who had a previous pregnancy were less likely to receive TT-vaccine (p < .01). 41.2% of infants did not receive BCG vaccines within 1-week of birth. Mothers working outside the home showed a negative impact on BCG vaccination (p < .05). Among the infants' born in-clinic facilities, 39% were BCG unvaccinated, and 69% had c-section delivery. The median age of infants for starting vaccination was 6.57 wks (95% CI: 6.43-7.14); however, 17.3% infants received vaccination at ≥8 wks of age. Mother's schooling-years and infant normal body-weight positively associated with vaccination at <8 wks, whereas sickness after birth increased the age to start vaccination program recommended at 6 wks. Our analysis suggests the need for specific interventions based on potential maternal determinants, such as educating mothers about the timing and the importance of infant immunization, and addressing programmatic barriers to timely vaccination among infants in Bangladesh.

Guillain-Barré syndrome associated with SARS-CoV-2 infection: A case report with long term follow up.

A 50-years old male presented with quadriplegia and paresthesia and was diagnosed as Guillain-Barré syndrome (GBS). He was found positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) six weeks prior to the onset of weakness. GBS disability score was 4. Electrophysiology showed acute inflammatory demyelinating polyradiculopathy. Anti-SARS-CoV-2 IgG was found positive. Immunological tests for Campylobacter jejuni, Zika virus, Hepatitis E virus, Herpes Simplex virus, Haemophilus influanzae and Mycoplasma pneumoniae were negative. Patient received standard dose of intravenous immunoglobulin and after six months had almost complete recovery of muscle power. This case represents possible association of SARS-CoV-2 infection and GBS with good clinical outcome.

Helicobacter pylori infection and micronutrient deficiency in pregnant women: a systematic review and meta-analysis.

BACKGROUND: Over the last few years, epidemiological studies have shown that infection with Helicobacter pylori has a major effect on micronutrient deficiency as well as on adverse pregnancy outcomes. Importantly, there are gaps in understanding the linkage of H. pylori infection with micronutrients deficiency in pregnant women. OBJECTIVE: We conducted a systematic review and meta-analysis to estimate the association between H. pylori infection and micronutrient deficiencies in pregnant women. METHODS: A systematic literature search was conducted for relevant articles using PubMed, Web of Science, and Scopus database from inception to March 2020. The OR with 95% CIs was determined by meta-analysis of data extracted from the selected studies. RESULTS: From 2384 primary articles, 6 studies were selected for systematic reviews and 4 studies distinctively (with 1274 participants: 553 cases and 721 controls) were selected for meta-analysis. The meta-analysed fixed effect model estimated the odds of having H. pylori infection was not significantly higher among pregnant women with micronutrient deficiencies than those without deficiencies (OR=1.12, 95% CI 0.88 to 1.42, p=0.37). In the subgroup analysis, no correlation was found between H. pylori infection and vitamin B12 (OR=0.74, 95% CI 0.45 to 1.21, p=0.22), folate (OR=1.07, 95% CI 0.73 to 1.58, p=0.73), and ferritin (OR=0.81, 95% CI 0.51 to 1.31, p=0.4). However, a positive correlation was found between iron-deficiency anaemia (IDA) and H. pylori infection (OR=16.23, 95% CI 4.19 to 62.93, p<0.0001) during pregnancy. CONCLUSION: H. pylori infection is associated with increased risk of IDA but not with deficiency of other micronutrients in pregnancy. PROSPERO REGISTRATION NUMBER: CRD42019135683.

Functional, structural and epitopic prediction of hypothetical proteins of Mycobacterium tuberculosis H37Rv: An in silico approach for prioritizing the targets.

The global control of tuberculosis (TB) remains a great challenge from the standpoint of diagnosis, detection of drug resistance, and treatment. Major serodiagnostic limitations include low sensitivity and high cost in detecting TB. On the other hand, treatment measures are often hindered by low efficacies of commonly used drugs and resistance developed by the bacteria. Hence, there is a need to look into newer diagnostic and therapeutic targets. The proteome information available suggests that among the 3906 proteins in Mycobacterium tuberculosis H37Rv, about quarter remain classified as hypothetical uncharacterized set. This study involves a combination of a number of bioinformatics tools to analyze those hypothetical proteins (HPs). An entire set of 999 proteins was primarily screened for protein sequences having conserved domains with high confidence using a combination of the latest versions of protein family databases. Subsequently, 98 of such potential target proteins were extensively analyzed by means of physicochemical characteristics, protein-protein interaction, sub-cellular localization, structural similarity and functional classification. Next, we predicted antigenic proteins from the entire set and identified B and T cell epitopes of these proteins in M. tuberculosis H37Rv. We predicted the function of these HPs belong to various classes of proteins such as enzymes, transporters, receptors, structural proteins, transcription regulators and other proteins. However, the structural similarity prediction of the annotated proteins substantiated the functional classification of those proteins. Consequently, based on higher antigenicity score and sub-cellular localization, we choose two (NP_216420.1, NP_216903.1) of the antigenic proteins to exemplify B and T cell epitope prediction approach. Finally we found 15 epitopes those located partially or fully in the linear epitope region. We found 21 conformational epitopes by using Ellipro server as well. In silico methodology used in this study and the data thus generated for HPs of M. tuberculosis H37Rv may facilitate swift experimental identification of potential serodiagnostic and therapeutic targets for treatment and control.