RESUMO
BACKGROUND: Entamoeba histolytica, Giardia, and Cryptosporidium are common intestinal protozoan parasites that contribute to a high burden of childhood morbidity and mortality. Our study quantified the association between intestinal protozoan parasites and child anthropometric outcomes among children under-5. METHODS: We analyzed data from 7,800 children enrolled in the Global Enteric Multicenter Study (GEMS) across seven study sites that were positive for intestinal protozoan parasites between December 2007 and March 2011. Parasites were assessed using stool immunoassays (ELISA). We applied multiple linear regression to test the association between any or concurrent parasite and child anthropometric outcomes: length/height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length/height (WHZ) z-score after 60 days of enrollment. Models were stratified by diarrheal symptoms, driven by the study design, and adjusted for potential covariates. FINDINGS: During the follow-up at day 60 after enrollment, child anthropometric outcomes, among the asymptomatic children showed, negative associations between Giardia with HAZ [ß: -0.13; 95% CI: -0.17, -0.09; p<0.001] and WAZ [ß -0.07; 95% CI: -0.11, -0.04; p<0.001], but not WHZ [ß: -0.02; 95% CI:-0.06, 0.02; p = 0.36]; Cryptosporidium with WAZ [ß: -0.15; 95% CI: -0.22, -0.09; p<0.001] and WHZ [ß: -0.18; 95%CI: -0.25, -0.12; p<0.001], but not with HAZ [ß: -0.03; 95% CI: -0.09, 0.04; p = 0.40]. For symptomatic children, no associations were found between Giardia and anthropometry; negative associations were found between Cryptosporidium with HAZ [ß: -0.17; 95% CI: -0.23, -0.11; p<0.001], WAZ [ß: -0.25; 95% CI: -0.31, -0.19; p<0.001] and WHZ [ß: -0.23; 95% CI: -0.30, -0.17; p<0.001]. Among the asymptomatic 24-59 months children, Giardia had a negative association with HAZ [ß: -0.09; 95% CI: -0.15, -0.04; p = 0.001]. No significant associations were found between E. histolytica with child growth. CONCLUSIONS: While some studies have found that Giardia is not associated with (or protective against) acute diarrhea, our findings suggest that it is associated with growth shortfall. This observation underscores the need for preventive strategies targeting enteric protozoan parasites among young children, to reduce the burden of childhood malnutrition.
Assuntos
Criptosporidiose , Cryptosporidium , Giardíase , Parasitos , Animais , Pré-Escolar , Humanos , Lactente , África Subsaariana , Ásia Meridional , Infecções Assintomáticas , Criptosporidiose/epidemiologia , Diarreia/epidemiologia , Diarreia/parasitologia , Giardíase/complicações , Giardíase/epidemiologiaRESUMO
Campylobacter is a major cause of food-borne gastrointestinal illnesses worldwide, predominantly affecting children under 5 years of age. This study examined potential associations of symptomatic (with diarrhea) and asymptomatic (without diarrhea) Campylobacter infections with child growth among children under 5 years of age in South Asia. The Global Enteric Multicenter Study was conducted from 2007 to 2011 with a case-control design. Children were followed for 60 days after enrollment. Stool culture was performed to isolate Campylobacter spp. Among the 22,567 enrolled children, 9,439 were symptomatic, with 786 (8.28%) testing positive for Campylobacter. Conversely, 13,128 asymptomatic healthy controls were included, with 1,057 (8.05%) testing positive for Campylobacter. Growth faltering was observed in the symptomatic group, particularly among children aged 0-11 months (-0.19 height-for-age z score [HAZ]; 95% CI: -0.36, -0.03; P = 0.018) and 24-59 months (-0.16 HAZ; 95% CI: -0.28, -0.04; P = 0.010). However, in the asymptomatic group, growth faltering was observed only in the 24- to 59-month age group, in terms of HAZ (-0.15 HAZ; 95% CI: -0.24, -0.05; P = 0.002) and weight-for-height z score (-0.16; 95% CI: -0.26, -0.06; P = 0.001). These findings underscore the importance of immediate and enhanced introduction of preventive modalities to reduce the burden of Campylobacter infections and reduce their long-term sequelae.
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Infecções por Campylobacter , Campylobacter , Doenças Transmitidas por Alimentos , Humanos , Criança , Lactente , Pré-Escolar , Infecções por Campylobacter/epidemiologia , Ásia Meridional , Diarreia/epidemiologia , Diarreia/complicações , Trato Gastrointestinal , FezesRESUMO
With more than 100,000 cases estimated each year, Bangladesh is one of the countries with the highest number of people at risk for cholera. Moreover, Bangladesh is formulating a countrywide cholera-control plan to satisfy the GTFCC (The Global Task Force on Cholera Control) Roadmap's goals. With a particular focus on cholera trends, variance in baseline and clinical characteristics of cholera cases, and trends in antibiotic susceptibility among clinical isolates of Vibrio cholerae, we used data from facility-based surveillance systems from icddr,b's Dhaka, and Matlab Hospitals from years 2000 to 2021. Female patients comprised 3,553 (43%) in urban and 1,099 (51.6%) in rural sites. Of the cases and most patients 5,236 (63.7%) in urban and 1,208 (56.7%) in the rural site were aged 15 years and more. More than 50% of the families belonged to the poor and lower-middle-class; in 2009 (24.4%) were in urban and in 1,791 (84.2%) were in rural sites. In the urban site, 2,446 (30%) of households used untreated drinking water, and 702 (9%) of families disposed of waste in their courtyard. In the multiple logistic regression analysis, the risk of cholera has significantly increased due to waste disposal in the courtyard and the boiling of water has a protective effect against cholera. Rotavirus (9.7%) was the most prevalent co-pathogen among the under-5 children in both sites. In urban sites, the percentage of V. cholerae along with co-existing ETEC and Campylobacter is changing in the last 20 years; Campylobacter (8.36%) and Enterotoxigenic Escherichia coli (ETEC) (7.15%) were the second and third most prevalent co-pathogens. Shigella (1.64%) was the second most common co-pathogen in the rural site. Azithromycin susceptibility increased slowly from 265 (8%) in 2006-2010 to 1485 (47.8%) in 2016-2021, and erythromycin susceptibility dropped substantially over 20 years period from 2,155 (98.4%) to 21 (0.9%). Tetracycline susceptibility decreased in the urban site from 2051 (45.9%) to 186 (4.2%) and ciprofloxacin susceptibility decreased from 2,581 (31.6%) to 1,360 (16.6%) until 2015, then increased 1,009 (22.6%) and 1,490 (18.2%) in 2016-2021, respectively. Since 2016, doxycycline showed 902 (100%) susceptibility. Clinicians need access to up-to-date information on antimicrobial susceptibility for treating hospitalized patients. To achieve the WHO-backed objective of eliminating cholera by 2030, the health systems need to be put under a proper surveillance system that may help to improve water and sanitation practices and deploy oral cholera vaccines strategically.
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Cólera , Escherichia coli Enterotoxigênica , Vibrio cholerae , Criança , Humanos , Feminino , Cólera/epidemiologia , Cólera/tratamento farmacológico , Bangladesh/epidemiologia , Hospitais , ÁguaRESUMO
Asymptomatic infection by fecal enteropathogens is a major contributor to childhood malnutrition. Here, we investigated the incidence rate of asymptomatic infection by enterotoxigenic Escherichia coli (ETEC) and assessed its association with childhood stunting, wasting, and being underweight among children under 2 years of age. The Malnutrition and Enteric Disease birth cohort study included 1,715 children who were followed from birth to 24 months of age from eight distinct geographic locations including Bangladesh, Brazil, India, Peru, Tanzania, Pakistan, Nepal, and South Africa. The TaqMan array card assay was used to determine the presence of ETEC in the nondiarrheal stool samples collected from these children. Poisson regression was used to estimate the incidence rate, and multiple generalized estimating equations with binomial family, logit link function, and exchangeable correlation were used to analyze the association between asymptomatic ETEC infection and anthropometric indicators such as stunting, wasting, and being underweight. The site-specific incidence rates of asymptomatic ETEC infections per 100 child-months were also higher at the study locations in Tanzania (54.81 [95% CI: 52.64, 57.07]) and Bangladesh (46.75 [95% CI: 44.75, 48.83]). In the Bangladesh, India, and Tanzania sites, the composite indicator of anthropometric failure was significantly associated with asymptomatic ETEC infection. Furthermore, a significant association between asymptomatic heat-stable toxin ETEC infections and childhood stunting, wasting, and being underweight was found in only the Bangladesh and Tanzania sites.
Assuntos
Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Enteropatias , Desnutrição , Criança , Humanos , Lactente , Magreza/epidemiologia , Incidência , Estudos de Coortes , Coorte de Nascimento , Infecções Assintomáticas , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/complicações , Desnutrição/complicações , Desnutrição/epidemiologia , Transtornos do Crescimento/etiologiaRESUMO
Severe acute malnutrition (SAM) is a major global public health problem. We aimed to assess the effects of probiotic and synbiotic supplementation on rate of weight gain and change in length in young SAM infants. This study was substudy of a single-blind randomized clinical trial (NCT0366657). During nutritional rehabilitation, 67 <6 months old SAM infants were enrolled and randomized to receive either probiotic (Bifidobacterium. infantis EVC001) or synbiotic (B. infantis EVC001 + Lacto-N-neotetraose [LNnT]) or placebo (Lactose) for four weeks and were followed for four more weeks after supplementation. In multivariable linear regression model, the mean rate of weight gain in the probiotic arm compared to placebo was higher by 2.03 unit (P < 0.001), and 1.13 unit (P = 0.030) in the synbiotic arm. In linear mixed-effects model, mean WAZ was higher by 0.57 unit (P = 0.018) in probiotic arm compared to placebo. Although not statistically significant, delta length for age z score (LAZ) trended to be higher among children in probiotc (ß = 0.25) and synbiotic (ß = 0.26) arms compared to placebo in multivariable linear regression model. Our study describes that young SAM infants had a higher rate of weight gain when supplemented with probiotic alone, compared to their counterparts with either synbiotic or placebo.
Assuntos
Probióticos , Simbióticos , Criança , Humanos , Lactente , Pré-Escolar , Método Simples-Cego , Probióticos/uso terapêutico , Aumento de Peso , Método Duplo-CegoRESUMO
Malnourished children are susceptible to an increased risk of mortality owing to impaired immune functions. However, the underlying mechanism of altered immune functions and its interaction with malnutrition is poorly understood. This study investigates the immune function and evaluates the effect of a particular nutritional intervention on the immune cells of undernourished children. Stunted (LAZ <-2) and at-risk of being stunted (length-for-age Z-scores, LAZ <-1 to -2) children aged between 12 and 18 months were enrolled and were provided with the daily nutritional intervention of one egg and 150 mL cow's milk for 90 days. Peripheral blood mononuclear cells (PBMCs) were isolated at enrolment and upon completion of the intervention. Phenotypic profiles for CD3+ cells, CD4+ cells, CD8+ cells, NKT cells, and B cells were similar in both cohorts, both before and after the intervention. However, activated B cells (CD25+) were increased after nutritional intervention in the at-risk of being stunted cohort. Several pro-inflammatory cytokines, IL-6, IFN-γ, and TNF-α, were elevated in the stunted children following the nutritional intervention. The results of the study indicate that nutritional intervention may have a role on activated B cells (CD25+) s in children who are at-risk of being stunted and may alter the capacity of PBMC to produce inflammatory cytokines in stunted children.
Assuntos
Linfócitos B , Células T Matadoras Naturais , Criança , Animais , Bovinos , Feminino , Humanos , Recém-Nascido , Linfócitos T CD4-Positivos , Citocinas , ImunidadeRESUMO
Antimicrobial resistance against shigellosis is increasingly alarming. However, evidence-based knowledge gaps regarding the changing trends of shigellosis in Bangladesh exist due to the scarcity of longitudinal data on antimicrobial resistance. Our study evaluated the last 20 years antimicrobial resistance patterns against shigellosis among under-5 children in the urban and rural sites of Bangladesh. Data were extracted from the Diarrheal Disease Surveillance System (DDSS) of Dhaka Hospital (urban site) and Matlab Hospital (rural site) of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) between January 2001 and December 2020. We studied culture-confirmed shigellosis cases from urban Dhaka Hospital (n = 883) and rural Matlab Hospital (n = 1263). Since 2001, a declining percentage of shigellosis in children observed in urban and rural sites. Moreover, higher isolation rates of Shigella were found in the rural site [1263/15684 (8.1%)] compared to the urban site [883/26804 (3.3%)] in the last 20 years. In both areas, S. flexneri was the predominant species. The upward trend of S. sonnei in both the study sites was statistically significant after adjusting for age and sex. WHO-recommended 1st line antibiotic ciprofloxacin resistance gradually reached more than 70% in both the urban and rural site by 2020. In multiple logistic regression after adjusting for age and sex, ciprofloxacin, azithromycin, mecillinam, ceftriaxone, and multidrug resistance (resistance to any two of these four drugs) among under-5 children were found to be increasing significantly (p<0.01) in the last 20 years in both sites. The study results underscore the importance of therapeutic interventions for shigellosis by appropriate drugs based on their current antibiogram for under-5 children. These observations may help policymakers in formulating better case management strategies for shigellosis.
Assuntos
Disenteria Bacilar , Criança , Humanos , Disenteria Bacilar/tratamento farmacológico , Disenteria Bacilar/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bangladesh/epidemiologia , Farmacorresistência Bacteriana , Diarreia/epidemiologia , Hospitais Rurais , Ciprofloxacina/uso terapêuticoRESUMO
There is a lack of information highlighting associations between different pathogenic variants of diarrheagenic Escherichia coli and childhood growth. Pathogenic variants of E. coli from stool samples, collected from 22,567 children enrolled in the Global Enteric Multicenter Study from December 2007 to March 2011, were detected by real-time polymerase chain reaction. We estimated the associations of different pathogenic variants of diarrheagenic E. coli with child growth. The association between an explanatory variable and the outcome variable was assessed using multiple linear regression, where the dependent variables were height-for-age, weight-for-age, and weight-for-height z-scores, and the independent variable was the presence of different pathogenic variants of diarrheagenic E. coli. After adjusting for potential covariates, such as age, gender, diarrhea, breastfeeding status, mother's education, number of under-5 children, handwashing practice, handwashing material, source of drinking water, wealth index, available toilet facility, copathogens, comorbidity, time, and study site, the multivariable model identified a negative association between different pathogenic variants of diarrheagenic E. coli and child growth. Our analyses may provide the cornerstone for prospective epidemiologic investigation for the development of preventive measures for diarrheagenic E. coli and combat childhood undernutrition.
Assuntos
Desenvolvimento Infantil , Diarreia/microbiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/patogenicidade , Pré-Escolar , Diarreia/epidemiologia , Diarreia/prevenção & controle , Escherichia coli/genética , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/prevenção & controle , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Secretor status refers to the ability of an individual to secrete blood group antigens into body fluids and onto the different epithelial surfaces. Concurrent findings have demonstrated an association of the secretor status of children with susceptibility to a plethora of enteropathogens. We aimed to determine a possible association of secretor status of children with childhood enteropathy, an important causal factor for childhood growth failure. Participants of the Malnutrition and Enteric Disease (MAL-ED) birth cohort study from the Bangladesh site were enrolled along with their mothers. Saliva was analyzed for determining blood groups and secretor status of the children and their mothers by using an in-house ELISA. Approximately 59% of children and 65% of mothers were found to be secretor positive. Secretor-positive children were found to have a significantly positive association with alpha-1-antitrypsin (ß-coefficient: 0.11, 95% CI: 0.07, 0.21, P < 0.01) and with environmental enteric dysfunction score (ß-coefficient: 0.32, 95% CI: 0.29, 0.65, P = 0.05). However, despite a negative effect size, secretor-positive children did not show any statistical significance with length-for-age and weight-for-age z scores (LAZ and WAZ), respectively. Our findings indicate toward the genetic factor of secretor status of children being associated with childhood growth faltering, through increased susceptibility to distinct enteropathogens and the consequent development of enteric inflammation and enteropathy among children. However, these findings are only applicable in Bangladeshi settings and thus need to be validated in several other similar settings, to establish a possible relationship between the secretor status of children with enteropathy and resulting childhood growth failure.
Assuntos
Enteropatias , Desnutrição , Feminino , Humanos , Criança , Lactente , Estudos de Coortes , Bangladesh/epidemiologia , Enteropatias/genética , Intestino Delgado , Desnutrição/complicaçõesRESUMO
Human milk oligosaccharides (HMOs) support the development of a healthy gut microbiome and the growth of infants. We aimed to determine the association of different HMOs with severe acute malnutrition (SAM) among Bangladeshi young infants. This study was nested within a single-blind, randomized, pilot clinical trial (NCT0366657). A total of 45 breastmilk samples from mothers of < 6 months old infants who had SAM (n = 26) or were non-malnourished (n = 19) and were analyzed for constituent HMOs. Of the infants with SAM, 14 (53.85%) had secretor mothers, and 11 (57.89%) of the non-malnourished infants had secretor mothers. A one-unit increase in the relative abundance of sialylated HMOs was associated with higher odds of SAM in age and sex adjusted model (aOR = 2.00, 90% CI 1.30, 3.06), in age, sex, and secretor status adjusted model (aOR = 1.96, 90% CI 1.29, 2.98), and also in age and sex adjusted model among non-secretor mothers (aOR = 2.86, 90% CI 1.07, 7.62). In adjusted models, there was no evidence of a statistically significant association between SAM and fucosylated or undecorated HMOs. Our study demonstrates that a higher relative abundance of sialylated HMOs in mothers' breastmilk may have a negative impact on young infants' nutritional status.
Assuntos
Leite Humano , Mães , Feminino , Humanos , Lactente , Estado Nutricional , Oligossacarídeos , Método Simples-CegoRESUMO
Asymptomatic or subclinical infection by diarrheal enteropathogens during childhood has been linked to poor health and nutritional outcomes. In this study, we aimed to assess the impact of asymptomatic Shigella infection on different forms of childhood malnutrition including the composite index of anthropometric failure (CIAF). We used data from 1715 children enrolled in the multi-country birth cohort study, MAL-ED, from November 2009 to February 2012. Monthly non-diarrheal stools were collected and assessed using TaqMan Array Cards (TAC). Poisson regression was used to calculate incidence rates of asymptomatic Shigella infection. Generalized estimating equations (GEE) were used to assess the association between asymptomatic Shigella infection and nutritional indicators after adjusting for relevant covariates. Incidence rates per 100 child-months were higher in Tanzania, Bangladesh and Peru. Overall, after adjusting for relevant covariates, asymptomatic Shigella infection was significantly associated with stunting (aOR 1.60; 95% CI: 1.50, 1.70), wasting (aOR 1.26; 95% CI: 1.09, 1.46), underweight (aOR 1.45; 95% CI: 1.35, 1.56), and CIAF (aOR 1.55; 95% CI: 1.46, 1.65) in all the study sites except for Brazil. The high incidence rates of asymptomatic Shigella infection underscore the immediate need for Shigella vaccines to avert the long-term sequelae involving childhood growth.
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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 ProspectivosRESUMO
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/metabolismoRESUMO
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.
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Bifidobacterium longum subspecies infantis , Desnutrição Aguda Grave , Animais , Bifidobacterium , Fezes/microbiologia , Humanos , Lactente , Camundongos , Leite Humano , Método Simples-Cego , Aumento de PesoRESUMO
Shigella species account for the second-leading cause of deaths due to diarrheal diseases among children of less than 5 years of age. The emergence of multi-drug-resistant Shigella isolates and the lack of availability of Shigella vaccines have led to the pertinence in the efforts made for the development of new therapeutic strategies against shigellosis. Consequently, designing small-interfering RNA (siRNA) candidates against such infectious agents represents a novel approach to propose new therapeutic candidates to curb the rampant rise of anti-microbial resistance in such pathogens. In this study, we analyzed 264 conserved sequences from 15 different conserved virulence genes of Shigella sp., through extensive rational validation using a plethora of first-generation and second-generation computational algorithms for siRNA designing. Fifty-eight siRNA candidates were obtained by using the first-generation algorithms, out of which only 38 siRNA candidates complied with the second-generation rules of siRNA designing. Further computational validation showed that 16 siRNA candidates were found to have a substantial functional efficiency, out of which 11 siRNA candidates were found to be non-immunogenic. Finally, three siRNA candidates exhibited a sterically feasible three-dimensional structure as exhibited by parameters of nucleic acid geometry such as: the probability of wrong sugar puckers, bad backbone confirmations, bad bonds, and bad angles being within the accepted threshold for stable tertiary structure. Although the findings of our study require further wet-lab validation and optimization for therapeutic use in the treatment of shigellosis, the computationally validated siRNA candidates are expected to suppress the expression of the virulence genes, namely: IpgD (siRNA 9) and OspB (siRNA 15 and siRNA 17) and thus act as a prospective tool in the RNA interference (RNAi) pathway. However, the findings of our study require further wet-lab validation and optimization for regular therapeutic use for treatment of shigellosis.
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Disenteria Bacilar , Shigella , Criança , Diarreia/tratamento farmacológico , Disenteria Bacilar/tratamento farmacológico , Disenteria Bacilar/genética , Humanos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Shigella/genéticaRESUMO
Gestational Toxoplasma gondii (T. gondii) infection may cause substantial adverse effects on developing fetuses, newborns and also mothers. This study aims to estimate the seroprevalence of T. gondii among rural Bangladeshi pregnant women and determine the risk of a low birth weight (LBW). We followed a longitudinal design where 208 pregnant women were followed until the birth of their infants. Levels of IgG and IgM of T. gondii were assessed using chemiluminescent immunoassay. Modified Poisson regression was used to estimate crude and adjusted associations and multiple regression analysis was performed to understand the confounding and modifying effects of the variables. Thirty-nine (19%) children were born with LBW, among whom 15 (39%) mothers were positive for T. gondii IgG during pregnancy. After adjusting for several confounders and modifiers, pregnant women with T. gondii IgG or IgM seropositivity were significantly associated with LBW of infants (aRR: 2.00, 95% CI: 1.17-3.42). The strength of this association increased after adjusting for maternal education (aRR: 4.88, 95% CI: 1.74-13.69). The final model had an AROC of 0.84 with a sensitivity of 36% and specificity of 97%. Although causality is yet to be established, the study observed an association between T. gondii infection during pregnancy among rural Bangladeshi women and LBW of newborns.
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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.
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Infecções por Caliciviridae , Norovirus , Infecções Assintomáticas , Coorte de Nascimento , Infecções por Caliciviridae/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Diarreia/epidemiologia , Fezes , Genótipo , Humanos , Norovirus/genética , Fatores de RiscoRESUMO
OBJECTIVE: To compare the health and nutrition of children younger than 5 years admitted to hospital during and before the coronavirus disease 2019 (COVID-19) pandemic in Bangladesh. METHODS: We collected data from hospital records of children 0-59 months admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh in March 2020-February 2021 (COVID-19 period; n = 2552) and March 2019-February 2020 (pre-COVID-19 period; n = 6738). Data collected included sociodemographic, anthropometric, clinical and biochemical characteristics. We compared these data for child admissions in the COVID-19 and pre-COVID-19 periods, including infants 0-11 months born during and before the pandemic and admitted to hospital. FINDINGS: Admissions of children as a percentage of total admissions were lower in March 2020 (2.47%; 63/2552) than March 2019 (8.30%; 559/6738), but increased to 20.61% (526/2552) in February 2021, three times greater than in the pre-COVID-19 period (6.69%; 451/6738). Children admitted during the COVID-19 period were significantly more likely to have dehydration, severe sepsis or septic shock, convulsions, hypernatraemia and raised creatinine than children admitted before the pandemic (P < 0.05). In infants < 6 months and those born during the pandemic, stunting and wasting were significantly higher than in infants in the pre-COVID-19 period (P < 0.05). The risk of death was higher in infants < 6 months during the pandemic (odds ratio: 1.66; 95% confidence interval: 0.95-2.92). CONCLUSION: During the pandemic, children presented with more severe illness and poorer nutrition. Efforts are needed to reduce the adverse effects of the pandemic on the health and well-being of children.
Assuntos
COVID-19 , Bangladesh/epidemiologia , Criança , Humanos , Lactente , Estado Nutricional , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination has recently been found to have beneficial effects among children infected other than Mycobacterium tuberculosis. Due to the paucity of data on the outcomes of children who had successful BCG vaccination following Expanded Programme on Immunization (EPI) schedule, we aimed to investigate the characteristics of such children and their outcomes who were hospitalized for severe malnutrition. METHODS: A prospective observational study was conducted to determine the viral etiology of pneumonia in severely malnourished children those were admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) between April 2015 and December 2017, constituted the study population. Using a case-control design for the analysis, children having BCG vaccination prior hospital admission were treated as cases (n = 611) and those without vaccination, constituted as controls (n = 83). Bi-variate analysis was conducted using socio-demographic, clinical, laboratory, and treatment characteristics on admission and outcomes during hospitalization. Finally, log-linear binomial regression analysis was done to identify independent impact of BCG vaccination. RESULTS: The cases more often presented with older age, have had lower proportion of maternal illiteracy, higher rate of breastfeeding, severe wasting and lower rate of hypoglycemia, compared to the controls. The cases were also found to have lower risk of severe sepsis and deaths, compared to the controls (for all, p<0.05). However, in log-linear binomial regression analysis, after adjusting for potential confounders, BCG vaccination following EPI schedule (RR:0.54; 95%CI = 0.33-0.89; p = 0.015) and breastfeeding (RR:0.53; 95%CI = 0.35-0.81; p = 0.003) were found to be protective for the development of severe sepsis. CONCLUSION: BCG vaccination and breastfeeding were found to be protective for the development of severe sepsis in hospitalized severely malnourished under-five children which underscores the importance of continuation of BCG vaccination at birth and breastfeeding up to two years of age.
Assuntos
Vacina BCG/uso terapêutico , Transtornos da Nutrição Infantil/epidemiologia , Tuberculose/prevenção & controle , Bangladesh/epidemiologia , Estudos de Casos e Controles , Transtornos da Nutrição Infantil/diagnóstico , Pré-Escolar , Feminino , Hospitalização , Humanos , Programas de Imunização , Esquemas de Imunização , Lactente , Masculino , Estudos ProspectivosRESUMO
Despite reports of enterotoxigenic Bacteroides fragilis (ETBF) isolation from asymptomatic children, no reports exist regarding the possible association of ETBF with long-term complications such as development of environmental enteric dysfunction (EED) and subsequent linear growth faltering in childhood. We aimed to establish a potential association between the burden of asymptomatic ETBF infection and EED and linear growth at 24 months of age using the data collected from 1,715 children enrolled in the multi-country birth cohort study, known as the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health study. Using Poisson regression models, we evaluated the site-specific incidence rate and, subsequently, identified the risk factors and assessed the association between the burden of ETBF infection and EED score and linear growth at 24 months of age. The overall incidence rate of ETBF infections per 100 child-months across all study sites was 10.6%, with the highest and lowest incidence of ETBF infections being reported in Tanzania (19.6%) and Peru (3.6%), respectively. Female gender, longer duration of breastfeeding, and improved water access, sanitation, and hygiene practices, such as improved drinking water source, improved sanitation, and improved floor material in households, along with enhanced maternal education and less crowding in the households were found to be protective against incidences of ETBF infection. The burden of ETBF infections was found to have significant associations with EED and linear growth faltering at 24 months of age across all the study sites. Our findings warrant regular clinical monitoring to reduce the burden of ETBF infections and diminish the burden of enteropathy and linear growth faltering in childhood.