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1.
Cell Host Microbe ; 30(5): 617-626, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35550665

RESUMO

Forty-five percent of deaths among children under 5 years of age are associated with undernutrition. Globally, almost 200 million children exhibit the two major forms of undernutrition-wasting (low weight-for-height) or stunting (low height-for-age), with many affected by both. Undernutrition is not due to food insecurity alone. Growing evidence indicates that perturbed postnatal gut microbiome development contributes to its pathogenesis. This perspective focuses on defining and repairing these defects in gut microbiome development. We describe an approach that involves the analysis of well-phenotyped human cohorts, followed by preclinical studies using gnotobiotic animals colonized with microbiota from these cohorts. Additionally, these models can be used to identify therapeutic targets and candidates that can then be tested clinically. Furthermore, introducing pretreatment microbiota from trial participants into gnotobiotic animals and re-enacting trial conditions allow mechanisms to be dissected. We highlight these recent advances as well as gaps in existing knowledge that present opportunities for future research.

2.
PLoS One ; 17(5): e0268093, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35604947

RESUMO

BACKGROUND: Seroprevalence studies have been carried out in many developed and developing countries to evaluate ongoing and past infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data on this infection in marginalized populations in urban slums are limited, which may offer crucial information to update prevention and mitigation policies and strategies. We aimed to determine the seroprevalence of SARS-CoV-2 infection and factors associated with seropositivity in slum and non-slum communities in two large cities in Bangladesh. METHODS: A cross-sectional study was carried out among the target population in Dhaka and Chattogram cities between October 2020 and February 2021. Questionnaire-based data, anthropometric and blood pressure measurements and blood were obtained. SARS-CoV-2 serology was assessed by Roche Elecsys® Anti-SARS-CoV-2 immunoassay. RESULTS: Among the 3220 participants (2444 adults, ≥18 years; 776 children, 10-17 years), the overall weighted seroprevalence was 67.3% (95% confidence intervals (CI) = 65.2, 69.3) with 71.0% in slum (95% CI = 68.7, 72.2) and 62.2% in non-slum (95% CI = 58.5, 65.8). The weighted seroprevalence was 72.9% in Dhaka and 54.2% in Chattogram. Seroprevalence was positively associated with limited years of formal education (adjusted odds ratio [aOR] = 1.61; 95% CI = 1.43, 1.82), lower income (aOR = 1.23; 95% CI = 1.03, 1.46), overweight (aOR = 1.2835; 95% CI = 1.26, 1.97), diabetes (aOR = 1.67; 95% CI = 1.21, 2.32) and heart disease (aOR = 1.38; 95% CI = 1.03, 1.86). Contrarily, negative associations were found between seropositivity and regular wearing of masks and washing hands, and prior BCG vaccination. About 63% of the population had asymptomatic infection; only 33% slum and 49% non-slum population showed symptomatic infection. CONCLUSION: The estimated seroprevalence of SARS-CoV-2 was more prominent in impoverished informal settlements than in the adjacent middle-income non-slum areas. Additional factors associated with seropositivity included limited education, low income, overweight and pre-existing chronic conditions. Behavioral factors such as regular wearing of masks and washing hands were associated with lower probability of seropositivity.

3.
Nutrients ; 14(9)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35565678

RESUMO

Infections and persistent immunological activation are linked to increased kynurenine (KYN) and the KYN-to-Tryptophan (TRP) or KT ratio and may be critical factors in undernutrition. We sought to determine the association between the KT ratio and adult malnutrition, as well as investigate if nutritional supplementation had any influence on the decrease of the KT ratio. A total of 525 undernourished adults aged 18-45 years were recruited and provided a nutrition intervention for 60 feeding days. TRP and KYN concentrations were determined from plasma samples using LC-MS/MS. At baseline, the median (interquartile range (IQR)) TRP, KYN and KT ratios were 24.1 (17.6, 34.3) µmol/L, 0.76 (0.53, 1.18) µmol/L and 30.9 (24.5, 41.7), respectively. Following intervention, the median (IQR) KYN and KT ratios were significantly reduced to 0.713 (0.46, 1.12) µmol/L and 27.5 (21.3, 35.8). The KT ratio was found to be inversely linked with adult BMI (coefficient: -0.09; 95% CI: -0.18, 0.004; p-value = 0.06) but not statistically significant. Additionally, Plasma CRP was correlated positively, while LRP1 was inversely correlated with the KT ratio. Our data suggest that in Bangladeshi adults, the KT ratio is not related to the pathophysiology of malnutrition but correlated with inflammatory and anti-inflammatory biomarkers, and the ratio can be reduced by a nutrition intervention.

4.
Nutrients ; 14(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35565901

RESUMO

Malnutrition in women has been a long-standing public health concern, with serious effects on child survival and development. Maternal body mass index (BMI) is an important maternal nutritional indicator. There are few published studies although child anthropometric failures do not occur in isolation and identifying children with single versus several co-occurring failures can better capture cases of growth failure in combination: stunting, wasting, and underweight. In the context of multiple anthropometric failures, traditional markers used to assess children's nutritional status tend to underestimate overall undernutrition. Using the composite index of anthropometric failure (CIAF), we aimed to assess the association between maternal undernutrition and child undernutrition among children with diarrhea under the age of two and to investigate the correlates. Using 1431 mother-child dyads from the Antibiotic for Children with Diarrhea (ABCD) trial, we extracted children's data at enrollment and on day 90 and day 180 follow-ups. ABCD was a randomized, multi-country, multi-site, double-blind, placebo-controlled clinical trial. The Bangladesh site collected data from July 2017 to July 2019. The outcome variable, CIAF, allows combinations of height-for-age, height-for-weight, and weight-for-age to determine the overall prevalence of undernutrition. The generalized estimating equation was used to explore the correlates of CIAF. After adjusting all the potential covariates, maternal undernutrition status was found to be strongly associated with child undernutrition using the CIAF [aOR: 1.4 (95% CI: 1.0, 1.9), p-value = 0.043] among the children with diarrhea under 2 years old. Maternal higher education had a protective effect on CIAF [aOR: 0.7 (95% CI: 0.5, 0.9), p-value = 0.033]. Our study findings highlight the importance of an integrated approach focusing on maternal nutrition and maternal education could affect a reduction in child undernutrition based on CIAF.

5.
Front Pediatr ; 10: 841628, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601439

RESUMO

Background: Pneumonia has been the leading infectious cause of morbidity and mortality in children under 5 years of age for the last several decades. Although most of these deaths occur due to respiratory failure, published data are limited regarding predicting factors and outcomes of respiratory failure in children hospitalized with pneumonia or severe pneumonia. Objective: This study aimed to explore the prevalence, predicting factors, and outcomes of respiratory failure in children under-five with pneumonia or severe pneumonia. Methods: In this retrospective chart analysis, we enrolled children under 5 years of age hospitalized with pneumonia or severe pneumonia in the Dhaka Hospital of International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) between August 2013 and December 2017. Comparisons were made between children with respiratory failure (n = 212) and those without respiratory failure (n = 4,412). Respiratory failure was defined when the oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) was <315. Results: A total of 4,625 children with pneumonia or severe pneumonia were admitted during this study period. Among them, 212 (4.6%) children developed respiratory failure and formed the case group. A total of 4,412 (95.3%) children did not develop respiratory failure and formed the comparison group. In logistic regression analysis, after adjusting with potential confounders, severe sepsis [adjusted odds ratio (aOR): 12.68, 95% CI: 8.74-18.40], convulsion (aOR: 4.52, 95% CI: 3.06-6.68), anemia (aOR: 1.76, 95% CI: 1.20-2.57), and severe underweight (aOR: 1.97, 95% CI: 1.34-2.89) were found to be independently associated with respiratory failure. As expected, children with respiratory failure more often had fatal outcome than without respiratory failure (74, 1%, p < 0.001). Conclusion: The results of our analyses revealed that prevalence of respiratory failure was 4.6% among under-five children hospitalized for pneumonia or severe pneumonia. Severe sepsis, convulsion, anemia, and severe underweight were the independent predictors for respiratory failure in such children and their case-fatality rate was significantly higher than those without respiratory failure. Early recognition of these predicting factors of respiratory failure may help clinicians imitating prompt treatment that may further help to reduce deaths in such children, especially in resource-limited settings.

6.
Nutrients ; 14(7)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35406021

RESUMO

Children living in resource-limited settings often suffer from multiple micronutrient deficiencies (MMD). However, there lacks evidence on the correlates of MMD in young children. We investigated the role of diets, water, sanitation and hygiene practice, enteric infections, and impaired gut health on MMD in children at 24 months of age using data from the multi-country MAL-ED birth cohort study. Co-existence of more than one micronutrient deficiency (e.g., anemia, iron, zinc, or retinol deficiency) was considered as MMD. We characterized intestinal inflammation by fecal concentrations of myeloperoxidase (MPO) and neopterin (NEO) measured in the non-diarrheal stool samples. Bayesian network analysis was applied to investigate the factors associated with MMD. A total of 1093 children were included in this analysis. Overall, 47.6% of the children had MMD, with the highest prevalence in Pakistan (90.1%) and lowest in Brazil (6.3%). MMD was inversely associated with the female sex [OR: 0.72, 95% CI: 0.54, 0.92]. A greater risk of MMD was associated with lower vitamin C intake [OR: 0.70, 95% CI: 0.48, 0.94] and increased fecal concentrations of MPO [OR: 1.31, 95% CI: 1.08, 1.51]. The study results imply the importance of effective strategies to ameliorate gut health and improve nutrient intake during the early years of life.


Assuntos
Anemia Ferropriva , Desnutrição , Deficiência de Vitamina A , Ácido Ascórbico , Teorema de Bayes , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Inflamação/epidemiologia , Micronutrientes , Prevalência
7.
Nutrients ; 14(7)2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35406127

RESUMO

The association between mother's education and the World Health Organization's (WHO's) eight Infant and Young Child Feeding (IYCF) core indicators has yet to be explored in South Asia (SA). This study aimed to explore the association between mother's education and the WHO's eight IYCF core indicators in SA. We analyzed data from the most recent nationally representative Demographic and Health Surveys of six South Asian Countries (SACs)-Afghanistan, Bangladesh, India, Maldives, Nepal, and Pakistan. We found significantly higher odds (adjusted odds ratio, AOR, 1.13 to 1.47) among mothers who completed secondary or higher education than among mothers with education levels below secondary for the following seven IYCF indicators: early initiation of breastfeeding (EIBF), exclusive breastfeeding under 6 months (EBF), the introduction of solid, semisolid or soft foods (ISSSF), minimum dietary diversity (MDD), minimum meal frequency (MMF), minimum acceptable diet (MAD), and consumption of iron-rich or iron-fortified foods (CIRF); the exception was for the indicator of continued breastfeeding at one year. Country-specific analyses revealed significantly higher odds in EIBF (AOR 1.14; 95% CI: 1.11, 1.18) and EBF (AOR 1.27; 95% CI: 1.19, 1.34) among mothers with secondary or higher education levels in India. In contrast, the odds were lower for EIBF in Bangladesh and for EBF in Pakistan among mothers with secondary or higher education levels. For country-specific analyses for complementary feeding indicators such as ISSSF, MDD, MMF, MAD, and CIRF, significantly higher odds (AOR, 1.15 to 2.34) were also observed among mothers with secondary or higher education levels. These findings demonstrate a strong positive association between mother's education and IYCF indicators. Strengthening national policies to educate women at least to the secondary level in SACs might be a cost-effective intervention for improving IYCF practices.


Assuntos
Comportamento Alimentar , Mães , Aleitamento Materno , Criança , Feminino , Humanos , Índia , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Ferro
8.
Nutrients ; 14(8)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35458174

RESUMO

Dysregulations in the mammalian target of rapamycin (mTOR) pathway are associated with several human anomalies. We aimed to elucidate possible implications for potential aberrations in the mTOR pathway with childhood malnutrition. We analyzed the activity of phospho-mTORC1 and the expressions of several mTOR pathway genes, namely: MTOR, TSC1, LAMTOR2, RPS6K1 and RICTOR from peripheral blood mononuclear cells isolated from venous blood of children suffering from different forms of malnutrition and compared them with those from healthy children. Significant reduction in the phosphorylation of mTORC1 was noted, as well as a decrease in expression of LAMTOR2 gene and increase in TSC1 gene expression were observed between malnourished children in comparison to the healthy children. The deregulation in the activity of the TSC1 and LAMTOR2 gene was significantly associated with all forms of childhood malnutrition. Our findings provide key insights into possible down-modulation in the overall activity of the mTOR pathway in childhood malnutrition. Further studies focusing on the analysis of a multitude of components involved in the mTOR pathway both at the gene and protein expression levels are required for conclusive evidence for the aforementioned proposition.


Assuntos
Desnutrição , Sirolimo , Criança , Humanos , Leucócitos Mononucleares/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fosforilação , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
9.
Sci Transl Med ; 14(640): eabk1107, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35417188

RESUMO

Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. Bifidobacterium longum subspecies infantis is a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of Bifidobacterium infantis is lower in 3- to 24-month-old Bangladeshi infants with severe acute malnutrition (SAM) compared to their healthy age-matched counterparts. A single-blind, placebo-controlled trial (SYNERGIE) was conducted in 2- to 6-month-old Bangladeshi infants with SAM. A commercial U.S. donor-derived B. infantis strain (EVC001) was administered daily with or without the HMO lacto-N-neotetraose for 28 days. This intervention increased fecal B. infantis abundance in infants with SAM, although to levels still 10- to 100-fold lower than in untreated healthy controls. EVC001 treatment promoted weight gain that was associated with reduced intestinal inflammation markers in infants with SAM. We cultured fecal B. infantis strains from Bangladeshi infants and colonized gnotobiotic mice with these cultured strains. The gnotobiotic mice were fed a diet representative of that consumed by 6-month-old Bangladeshi infants, with or without HMO supplementation. One B. infantis strain, Bg_2D9, expressing two gene clusters involved in uptake and utilization of N-glycans and plant-derived polysaccharides, exhibited superior fitness over EVC001. The fitness advantage of Bg_2D9 was confirmed in a gnotobiotic mouse model of mother-to-infant gut microbiota transmission where dams received a pretreatment fecal community from a SAM infant in the SYNERGIE trial. Whether Bg_2D9 is superior to EVC001 for treating malnourished infants who consume a diet with limited breastmilk requires further clinical testing.


Assuntos
Bifidobacterium longum subspecies infantis , Desnutrição Aguda Grave , Animais , Bifidobacterium , Fezes/microbiologia , Humanos , Lactente , Camundongos , Leite Humano , Método Simples-Cego , Ganho de Peso
11.
Cell Rep ; 39(4): 110738, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35476981

RESUMO

Perturbed gut microbiome development has been linked to childhood malnutrition. Here, we characterize bacterial Toll/interleukin-1 receptor (TIR) protein domains that metabolize nicotinamide adenine dinucleotide (NAD), a co-enzyme with far-reaching effects on human physiology. A consortium of 26 human gut bacterial strains, representing the diversity of TIRs observed in the microbiome and the NAD hydrolase (NADase) activities of a subset of 152 bacterial TIRs assayed in vitro, was introduced into germ-free mice. Integrating mass spectrometry and microbial RNA sequencing (RNA-seq) with consortium membership manipulation disclosed that a variant of cyclic-ADPR (v-cADPR-x) is a specific product of TIR NADase activity and a prominent, colonization-discriminatory, taxon-specific metabolite. Guided by bioinformatic analyses of biochemically validated TIRs, we find that acute malnutrition is associated with decreased fecal levels of genes encoding TIRs known or predicted to generate v-cADPR-x, as well as decreased levels of the metabolite itself. These results underscore the need to consider microbiome TIR NADases when evaluating NAD metabolism in the human holobiont.


Assuntos
Microbioma Gastrointestinal , Desnutrição , Animais , Bactérias/metabolismo , Criança , ADP-Ribose Cíclica , Vida Livre de Germes , Humanos , Camundongos , NAD/metabolismo , NAD+ Nucleosidase/metabolismo , Receptores de Interleucina-1
12.
Am J Trop Med Hyg ; 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35405659

RESUMO

We identified the determinants of positive (children who had a birth weight < 2.5 kg and/or maternal height < 145 cm but were nonstunted at 24 months of age) and negative (children who had a birth weight ≥ 2.5 kg and maternal height ≥ 145 cm but were stunted at 24 months of age) deviance in childhood linear growth. We found that socioeconomic status (ß = 1.54, P < 0.01), serum retinol (ß = 0.05, P < 0.01), hemoglobin (ß = 0.36, P < 0.01), length-for-age Z-score (LAZ) at birth (ß = 0.47, P < 0.01), and tetanus vaccine titer (ß = 0.182, P < 0.05) were positively and maternal depressive symptom (ß = -0.05, P < 0.01), serum ferritin (ß = -0.03, P < 0.01), male sex (ß = -1.08, P < 0.01), and α1-antitrypsin (ß = -0.81, P < 0.01) were negatively associated with positive deviance. Further, diarrhea episodes (ß = 0.02, P < 0.01), male sex (ß = 0.72, P < 0.01), and α1-antitrypsin (ß = 0.67, P < 0.01) were positively and hemoglobin (ß= -0.28, P < 0.01), soluble transferrin receptor level (ß = -0.15, P < 0.01), and LAZ score at birth (ß = -0.90, P < 0.01) were negatively associated with negative deviance. To summarize, enteric protein loss, micronutrient deficiency, vaccine responses and maternal depressive symptoms were associated with linear growth deviance in early childhood. In such a background, public health approaches aimed at reducing the risk of intestinal inflammation and altered gut permeability could prove fruitful in ensuring desired linear growth in children. In addition, maternal mental health issue should also be considered, especially for promoting better nutritional status in children in the context of linear growth deviance.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35457563

RESUMO

The objective of this study was to explore the socioeconomic inequalities in undernutrition among ever-married women of reproductive age. We used nationally representative cross-sectional data from the Bangladesh Demographic and Health Survey, 2017-2018. Undernutrition was defined as a body mass index (BMI) of <18.5 kg/m2. The concentration index (C) was used to measure the socioeconomic inequality in the prevalence of women's undernutrition. A multiple binary logistic regression model was carried out to find out the factors associated with women's undernutrition. The prevalence of undernutrition among women of 15-49 years was 12%. Among them, 8.5% of women were from urban and 12.7% of women were from rural areas. The prevalence of undernutrition was highest (21.9%) among women who belonged to the adolescent age group (15-19 years). The C showed that undernutrition was more prevalent among the socioeconomically worst-off (poorest) group in Bangladesh (C = -0.26). An adjusted multiple logistic regression model indicated that women less than 19 years of age had higher odds (adjusted odds ratio, AOR: 2.81; 95% confidence interval, CI: 2.23, 3.55) of being undernourished. Women from the poorest wealth quintile (AOR: 3.93, 95% CI: 3.21, 4.81) had higher odds of being undernourished. On the other hand, women who had completed secondary or higher education (AOR: 0.55; 95% CI: 0.49, 0.61), married women who were living with their husbands (AOR: 0.72, 95% CI: 0.61, 0.86), and women exposed to mass media (AOR: 0.87, 95% CI: 0.79, 0.97) were less likely to be undernourished. Intervention strategies should be developed targeting the poorest to combat undernutrition in women of reproductive age in Bangladesh.


Assuntos
Desnutrição , Adolescente , Adulto , Bangladesh/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Desnutrição/epidemiologia , Casamento , Prevalência , Fatores Socioeconômicos , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-35410032

RESUMO

This study aimed to explore variations in Infant and Young Child Feeding (IYCF) practices between different South Asian Countries (SACs) and within their sociodemographic characteristics including place of residence, mother age, mother education, child sex, and wealth quintiles within the SACs. We extracted 0-23 months age children's data from the nationally representative survey of Afghanistan, Bangladesh, India, Maldives, Nepal, and Pakistan. Among all SACs, the early initiation of breastfeeding (EIBF) practice was 45.4% with the highest prevalence in the Maldives (68.2%) and the lowest prevalence in Pakistan (20.8%). Exclusive breastfeeding (EBF) practice was 53.9% with the highest prevalence in Nepal (67%) and the lowest prevalence in Afghanistan (42%). Only 13% of children had a minimum acceptable diet (MAD), with the highest prevalence in the Maldives (52%) and the lowest prevalence in India (11%). We found higher IYCF practices among the mothers with secondary or higher levels of education (EIBF: 47.0% vs. 43.6%; EBF: 55.5% vs. 52.0%; MAD: 15.3% vs. 10.0%), urban mothers (MAD: 15.6% vs. 11.8%), and mothers from the richest households (MAD: 17.6% vs. 8.6%) compared to the mothers with no formal education or below secondary level education, rural mothers and mothers from the poorest households, respectively. Mothers from the poorest households had better EIBF, EBF, and continued breastfeeding at 1-year (CBF) practices compared to the mothers from the richest households (EIBF: 44.2% vs. 40.7%; EBF: 54.8% vs. 53.0%; CBF: 86.3% vs. 77.8%). Poor IYCF practices were most prevalent in Afghanistan, Pakistan, and India.


Assuntos
Aleitamento Materno , Comportamento Alimentar , Bangladesh/epidemiologia , Criança , Dieta , Feminino , Humanos , Lactente , Mães
15.
Sci Rep ; 12(1): 5724, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388098

RESUMO

There is a lack of information highlighting the possible association between the genomic subtypes of enteropathogenic Escherichia coli (EPEC) on environmental enteric dysfunction (EED) and on linear growth during childhood. Genomic subtypes of EPEC from stool samples collected from 1705 children enrolled in the MAL-ED birth cohort were detected by TaqMan Array Cards. We measured site-specific incidence rate by using Poisson regression models, identified the risk factors and estimated the association of genomic subtypes of EPEC with the composite EED score and linear growth at 24 months of age. In general, the highest incidence rate (39%) was found among children having aEPEC infection, which was the greatest in Tanzania (54%). Exclusive breastfeeding and having an improved sanitation facility were found to be protective factors against EPEC infection. In the multivariate models, in overall effect after adjusting for the potential covariates aEPEC showed strong positive associations with the EED scores and tEPEC showed a positive association with poor linear growth at 24 months of age. Our analyses may lay the cornerstone for a prospective epidemiologic investigation for a potential vaccine development aimed at reducing the burden of EPEC infections and combat childhood malnutrition.


Assuntos
Escherichia coli Enteropatogênica , Infecções por Escherichia coli , Proteínas de Escherichia coli , Criança , Diarreia/epidemiologia , Escherichia coli Enteropatogênica/genética , Infecções por Escherichia coli/epidemiologia , Proteínas de Escherichia coli/genética , Feminino , Humanos , Incidência , Inflamação , Estudos Prospectivos
16.
Microbiol Spectr ; 10(2): e0039122, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35315699

RESUMO

Comparative genomic analysis of Vibrio cholerae El Tor associated with endemic cholera in Asia revealed two distinct lineages, one dominant in Bangladesh and the other in India. An in-depth whole-genome study of V. cholerae El Tor strains isolated during endemic cholera in Bangladesh (1991 to 2017) included reference genome sequence data obtained online. Core genome phylogeny established using single nucleotide polymorphisms (SNPs) showed V. cholerae El Tor strains comprised two lineages, BD-1 and BD-2, which, according to Bayesian phylodynamic analysis, originated from paraphyletic group BD-0 around 1981. BD-1 and BD-2 lineages overlapped temporally but were negatively associated as causative agents of cholera during 2004 to 2017. Genome-wide association study (GWAS) revealed 140 SNPs and 31 indels, resulting in gene alleles unique to BD-1 and BD-2. Regression analysis of root to tip distance and year of isolation indicated early BD-0 strains at the base, whereas BD-1 and BD-2 subsequently emerged and progressed by accumulating SNPs. Pangenome analysis provided evidence of gene acquisition by both BD-1 and BD-2, of which six crucial proteins of known function were predominant in BD-2. BD-1 and BD-2 diverged and have distinctively different genomic traits, namely, heterogeneity in VSP-2, VPI-1, mobile elements, toxin encoding elements, and total gene abundance. In addition, the observed phage-inducible chromosomal island-like element (PLE1), and SXT ICE elements (ICETET) in BD-2 presumably provided a fitness advantage for the lineage to outcompete BD-1 as the etiological agent of endemic cholera in Bangladesh, with implications for global cholera epidemiology. IMPORTANCE Cholera is a global disease with specific reference to the Bay of Bengal Ganges Delta where Vibrio cholerae O1 El Tor, the causative agent of the disease showed two circulating lineages, one dominant in Bangladesh and the other in India. Results of an in-depth genomic study of V. cholerae associated with endemic cholera during the past 27 years (1991 to 2017) indicate emergence and succession of the two lineages, BD-1 and BD-2, arising from a common ancestral paraphyletic group, BD-0, comprising the early strains and short-term evolution of the bacterium in Bangladesh. Among the two V. cholerae lineages, BD-2 supersedes BD-1 and is predominant in the most recent endemic cholera in Bangladesh. The BD-2 lineage contained significantly more SNPs and indels, and showed richness in gene abundance, including antimicrobial resistance genes, gene cassettes, and PLE to fight against bacteriophage infection, acquired over time. These findings have important epidemic implications on a global scale.


Assuntos
Cólera , Vibrio cholerae O1 , Bangladesh/epidemiologia , Teorema de Bayes , Cólera/epidemiologia , Cólera/microbiologia , Toxina da Cólera/genética , Toxina da Cólera/metabolismo , Estudo de Associação Genômica Ampla , Genômica/métodos , Humanos , Vibrio cholerae O1/genética
17.
Viruses ; 14(3)2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35337054

RESUMO

The prevalence of norovirus infections in different geographical locations and their attribution to childhood diarrhea is well established. However, there are no reports showing possible relationships of different norovirus genogroups with subsequent childhood malnutrition. In this study, we attempted to establish a potential association between asymptomatic norovirus infections with childhood growth faltering during. Non-diarrheal stools were collected from 1715 children enrolled in locations in a multi-county birth cohort study across eight different geographical locations and were assessed for norovirus genogroup I (GI) and norovirus genogroup II (GII). Asymptomatic norovirus GI infections were negatively associated with monthly length-for-age Z score/LAZ (ß = -0.53, 95% CI: -0.73, -0.50) and weight-for-age Z score/WAZ (ß = -0.39, 95% CI: -0.49, -0.28), respectively. The burden of asymptomatic norovirus GI infections was negatively associated with LAZ (ß = -0.46, 95% CI: -0.67, -0.41) and WAZ (ß = -0.66, 95% CI: -0.86, -0.53) at 2 years of age, whilst the burden of asymptomatic norovirus GII infections was negatively associated with WAZ (ß = -0.27, 95% CI: -0.45, -0.25) at 2 years of age. Our findings warrant acceleration in attempts to develop vaccines against norovirus GI and norovirus GII, with the aim of minimizing the long-term sequelae on childhood growth.


Assuntos
Infecções por Caliciviridae , Norovirus , Infecções Assintomáticas , Infecções por Caliciviridae/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Diarreia/epidemiologia , Fezes , Genótipo , Humanos , Norovirus/genética , Fatores de Risco
18.
Sci Rep ; 12(1): 3623, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35256680

RESUMO

We conducted an observational study to assess the prevalence and risk factors of vitamin D deficiency in 12-24 months old children living in urban and rural Bangladesh. Serum 25-hydroxyvitamin D (free 25(OH)D) level, socio-demographic status, anthropometric status, dietary intake, exposure to sunlight and single nucleotide polymorphisms in vitamin-D pathway genes were measured in 208 children. Vitamin D deficiency (free 25(OH)D < 50 nmol/l) was reported in 47% of the children. Multivariable logistic regression model identified duration to sunlight exposure (regression coefficient, ß = - 0.01; 95% CI 0.00, - 0.02; p-value < 0.05), UV index (ß = - 0.36; 95% CI 0.00, - 0.02; p-value < 0.05) and breast-feeding (ß = - 1.15; 95% CI - 0.43, - 1.86; p-value < 0.05) to be negatively associated with vitamin D deficiency. We measured the role of single nucleotide polymorphisms in pathway genes (GC-rs7041 T > G, rs4588 C > A, CYP2R1-rs206793 A > G, CYP27B1-rs10877012 A > C and DHCR7-rs12785878 G > T) and found statistically significant differences in serum vitamin D levels between various genotypes. SNPs for CYP27B1 (CA & CC genotype) had statistically significant positive association (ß = 1.61; 95% CI 2.79, 0.42; p-value < 0.05) and TT genotype of GC-rs7041 had negative association (ß = - 1.33; 95% CI - 0.02, - 2.64; p-value < 0.05) with vitamin-D deficiency in the surveyed children.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase , Deficiência de Vitamina D , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Bangladesh/epidemiologia , Criança , Pré-Escolar , Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Comportamento Alimentar , Genótipo , Humanos , Lactente , Polimorfismo de Nucleotídeo Único , Luz Solar , Vitamina D , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/genética , Proteína de Ligação a Vitamina D/genética , Vitaminas
19.
PLoS One ; 17(3): e0265871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35320317

RESUMO

BACKGROUND: Pneumonia is the leading cause of death in children globally with the majority of these deaths observed in resource-limited settings. Globally, the annual incidence of clinical pneumonia in under-five children is approximately 152 million, mostly in the low- and middle-income countries. Of these, 8.7% progressed to severe pneumonia requiring hospitalization. However, data to predict children at the greatest risk to develop severe pneumonia from pneumonia are limited. METHOD: Secondary data analysis was performed after extracting relevant data from a prospective cluster randomized controlled clinical trial; children of either sex, aged two months to five years with pneumonia or severe pneumonia acquired in the community were enrolled over a period of three years in 16 clusters in urban Dhaka city. RESULTS: The analysis comprised of 2,597 children aged 2-59 months. Of these, 904 and 1693 were categorized as pneumonia (controls) and severe pneumonia (cases), respectively based on WHO criteria. The median age of children was 9.2 months (inter quartile range, 5.1-17.1) and 1,576 (60%) were male. After adjustment for covariates, children with temperature ≥38°C, duration of illness ≥3 days, male sex, received prior medical care and severe stunting showed a significantly increased likelihood of developing severe pneumonia compared to those with pneumonia. Severe pneumonia in children occurred more often in older children who presented commonly from wealthy quintile families, and who often sought care from private facilities in urban settings. CONCLUSION AND RECOMMENDATION: Male sex, longer duration of illness, fever, received prior medical care, and severe stunting were significantly associated with development of WHO-defined severe childhood pneumonia in our population. The results of this study may help to develop interventions target to reduce childhood morbidity and mortality of children suffering from severe pneumonia.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Bangladesh/epidemiologia , Estudos de Casos e Controles , Criança , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/epidemiologia , Feminino , Transtornos do Crescimento/complicações , Humanos , Lactente , Masculino , Pneumonia/complicações , Estudos Prospectivos
20.
Nutrients ; 14(3)2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35276840

RESUMO

A sensitive and reliable biomarker of zinc status has yet to be identified, but observational research suggests that the exchangeable zinc pool (EZP) size may be a possible biomarker. This randomized, placebo-controlled trial aimed to compare the change in EZP size from baseline to endline in 174 children who were preventatively supplemented with 10 mg of zinc as part of a multiple micronutrient power (MNP) or as a standalone dispersible tablet for 24 weeks versus a placebo powder. The effects of systemic inflammation on EZP size were also evaluated. Zinc stable isotopes were administered intravenously to children at baseline and endline, and the EZP was measured by the urine extrapolation method. A total of 156 children completed the study with the zinc dispersible tablet group having the greatest increase in EZP (14.1 mg) over 24 weeks when compared with the MNP group (6.8 mg) (p < 0.01) or placebo group (2.0 mg) (p < 0.001). Median EZP size was not different between children with normal or elevated serum inflammatory markers. EZP size was responsive to longitudinal zinc supplementation and reflected the expected difference in bioavailability for two forms of supplementation. The apparent absence of an effect of inflammation on EZP size may offer an advantage for use as a biomarker for group comparisons between different interventions.


Assuntos
Suplementos Nutricionais , Zinco , Biomarcadores , Criança , Pré-Escolar , Humanos , Inflamação , Pós
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