RESUMO
Age-stratified path analyses modeled associations between enteric pathogen reservoirs, transmission pathways and height-for-age z-scores (HAZ) to identify determinants of childhood growth in the Kolkata, India site of the Global Enteric Multicenter Study (GEMS). Models tested direct associations of potential pathogen reservoirs with HAZ at 60-day follow-up in separate moderate and severe diarrhea (MSD) case and control cohorts or indirectly when mediated by enteric infections. In the MSD cohort, rotavirus and typical EPEC (tEPEC) infections among children 0-11 months of age and ST-ETEC infections among children 12-23 months of age were associated with lower HAZ. Handwashing after defecating and before cooking reduced impaired growth through reductions in rotavirus and tEPEC infections. Water storage increased rotavirus and ST-ETEC infection risks, resulting in increased impaired growth, but was reduced with reported child feces disposal. The GII norovirus variant was inversely associated with HAZ among children 12-59 months of age in the control cohort. Reported handwashing before the handling of children reduced GII infections and impaired growth. Boiling water and the disposal of children's feces mediated by stored water were positively associated with HAZ. The targeting of pathogen-specific reservoirs and transmission pathways may more effectively improve childhood linear growth in South Asian urban communities.
Assuntos
Diarreia , Humanos , Índia/epidemiologia , Lactente , Masculino , Pré-Escolar , Feminino , Diarreia/virologia , Diarreia/epidemiologia , Recém-Nascido , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/virologia , Estatura , Estudos de Casos e Controles , Infecções por Rotavirus/transmissão , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/epidemiologia , Fezes/virologia , Fezes/microbiologia , Desinfecção das Mãos , Rotavirus/isolamento & purificação , Reservatórios de Doenças/virologiaRESUMO
OBJECTIVES: This study aimed to describe growth and pubertal development of adolescents with HIV infection under highly active antiretroviral therapy (HAART) in Cameroon. DESIGN: Through an observational study, we included 74 adolescents aged 9-17 years who were taking HAART and had attended two care units in Cameroon for at least 6 months. Weight and height were measured and transferred to 2007 WHO curves for 5- to 19-year-olds. Stunting was defined by a height for age z-score less than -2 standard deviations. Wasting was defined by a BMI z-score for age less than -2 standard deviations. Pubertal development was assessed using Tanner stages. We looked into the association between HIV infection characteristics, HAART regimen, and growth/puberty abnormalities with multivariate analysis. The Mann-Whitney U-test was used to compare median values with a p-value ≤0.05. RESULTS: The median age was 13 (11.2-14.7) years. Stunting affected 44% of the children. Wasting affected 9.7% of the adolescents. The age at onset of puberty was in the normal range in both boys and girls. Adolescents aged 12-14 years (OR 3.4 [95% CI, 1.3-8.8], p=0.012) with a past history of opportunistic infection and taking HAART with protease inhibitors were more likely to have stunting. CONCLUSION: In the Cameroonian setting, growth was mainly affected by stunting, but pubertal development was normal in all patients. This may reflect the benefits of HAART in children with HIV infection.
Assuntos
Transtornos do Crescimento/virologia , Infecções por HIV/complicações , Puberdade/fisiologia , Adolescente , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Camarões , Criança , Estudos Transversais , Feminino , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/fisiopatologia , Síndrome de Emaciação por Infecção pelo HIV/diagnóstico , Síndrome de Emaciação por Infecção pelo HIV/epidemiologia , Humanos , Masculino , Fatores de RiscoRESUMO
Environmental enteric dysfunction (EED) is characterized by diffuse villous atrophy of the small bowel. EED is strongly associated with stunting, a major public health problem linked to increased childhood morbidity and mortality. EED and subsequent stunting of linear growth are surmised to have microbial origins. To interrogate this relationship, we defined the comprehensive virome (eukaryotic virus and bacteriophage) and bacterial microbiome of a longitudinal cohort of rural Malawian children with extensive metadata and intestinal permeability testing at each time point. We found thirty bacterial taxa differentially associated with linear growth. We detected many eukaryotic viruses. Neither the total number of eukaryotic families nor a specific viral family was statistically associated with improved linear growth. We identified 3 differentially abundant bacteriophage among growth velocities. Interestingly, there was a positive correlation between bacteria and bacteriophage richness in children with subsequent adequate/moderate growth which children with subsequent poor growth lacked. This suggests that a disruption in the equilibrium between bacteria and bacteriophage communities might be associated with subsequent poor growth. Future studies of EED and stunting should include the evaluation of viral communities in addition to bacterial microbiota to understand the complete microbial ecology of these poorly understood entities.
Assuntos
Bactérias/classificação , Bacteriófagos/classificação , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/virologia , Transtornos do Crescimento/microbiologia , Transtornos do Crescimento/virologia , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/virologia , Bacteriófagos/genética , Bacteriófagos/crescimento & desenvolvimento , Bacteriófagos/isolamento & purificação , Pré-Escolar , Feminino , Gastroenteropatias/microbiologia , Gastroenteropatias/virologia , Humanos , Lactente , Intestino Delgado/microbiologia , Intestino Delgado/virologia , Malaui , Masculino , Viabilidade Microbiana , Permeabilidade , RNA Ribossômico 16SRESUMO
BACKGROUND AND AIMS: Runting-stunting syndrome (RSS) in chickens, also known as malabsorption syndrome, which is characterized by mild to severe enteritis and diagnosed through typical histopathologic examination as well as clinical signs, results in considerable economic losses. Despite the many studies carried out over decades to determine the etiologic agents of RSS involved in the disease, several outbreaks remained without the elucidation of, potentially multiple, etiologies involved. METHODS: We performed comparative analysis of viral metagenomes from four chicken flocks affected with RSS using next-generation sequencing. Primers for the detection of chicken enteric viruses were designed from the sequencing data obtained with metagenomics. Multiplex reverse transcription-polymerase chain reaction (PCR) and PCR were performed to detect a variety of etiological agents previously described in natural cases of RSS. RESULTS: The most abundant viral families identified in this study were Astroviridae, Picornaviridae, Parvoviridae, Caliciviridae, Reoviridae and Picobirnaviridae. Chicken astrovirus sequences were present in all four samples, suggesting an association between chicken astrovirus and RSS and chicken astrovirus as a candidate pathogen responsible for RSS. Picobirnavirus and the newly identified chapparvovirus were found in chickens in the Republic of Korea for the first time, and the genetic diversity of enteric viruses and viral communities was showed. CONCLUSIONS: Chicken astrovirus was consistently detected in broilers affected with RSS and the result of this study may contribute to knowledge of enteric diseases and viruses in chickens.
Assuntos
Galinhas/virologia , Enterite/veterinária , Enterite/virologia , Transtornos do Crescimento/veterinária , Infecções por Vírus de RNA/veterinária , Vírus de RNA/classificação , Animais , Variação Genética , Transtornos do Crescimento/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Metagenoma , Filogenia , Doenças das Aves Domésticas/virologia , Infecções por Vírus de RNA/virologia , Vírus de RNA/patogenicidade , RNA Viral/genética , República da CoreiaRESUMO
Stunting, a severe and multigenerational growth impairment, globally affects 22% of children under the age of 5 years. Stunted children have altered gut bacterial communities with higher proportions of Proteobacteria, a phylum with several known human pathogens. Despite the links between an altered gut microbiota and stunting, the role of bacteriophages, highly abundant bacterial viruses, is unknown. Here, we describe the gut bacterial and bacteriophage communities of Bangladeshi stunted children younger than 38 months. We show that these children harbor distinct gut bacteriophages relative to their non-stunted counterparts. In vitro, these gut bacteriophages are infectious and can regulate bacterial abundance and composition in an age-specific manner, highlighting their possible role in the pathophysiology of child stunting. Specifically, Proteobacteria from non-stunted children increased in the presence of phages from younger stunted children, suggesting that phages could contribute to the bacterial community changes observed in child stunting.
Assuntos
Bacteriófagos/isolamento & purificação , Microbioma Gastrointestinal , Transtornos do Crescimento/microbiologia , Transtornos do Crescimento/virologia , Fatores Etários , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/virologia , Bacteriófagos/classificação , Bacteriófagos/genética , Pré-Escolar , Feminino , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Genes Bacterianos , Genes Virais , Interações entre Hospedeiro e Microrganismos , Humanos , Lactente , Masculino , Metagenômica , Proteobactérias/classificação , Proteobactérias/genética , Proteobactérias/isolamento & purificação , Proteobactérias/virologia , RNA Ribossômico 16SRESUMO
Importance: Studies suggest that postnatal cytomegalovirus (CMV) infection can lead to long-term morbidity in infants with very low birth weight (VLBW; <1500 g), including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and neurodevelopmental impairment. However, to date, the association of postnatal CMV with hearing, growth, and length of stay among VLBW infants is unknown. Objectives: To determine the risk for failed hearing screen, increased postnatal age at discharge, or decreased growth at discharge in VLBW infants with postnatal CMV infection compared with CMV-uninfected infants and to compare the risk for other major outcomes of prematurity, including BPD and NEC, in infants with and without postnatal CMV infection. Participants: This multicenter retrospective cohort study included VLBW infants from 302 neonatal intensive care units managed by the Pediatrix Medical Group from January 1, 2002, through December 31, 2016. Infants hospitalized on postnatal day 21 with a diagnosis of postnatal CMV and hearing screen results after a postmenstrual age of 34 weeks were included in the study population. Data were analyzed from December 11, 2017, to June 14, 2019. Main Outcomes and Measures: Infants with and without postnatal CMV infection were matched using propensity scores. Poisson and linear regression were used to examine the association between postnatal CMV and the risk of failed hearing screen, postnatal age at discharge, growth, BPD, and NEC. Results: A total of 304 infants with postnatal CMV were identified, and 273 of these infants (89.8%; 155 boys [56.8%]) were matched with 273 infants without postnatal CMV (148 boys [54.2%]). Hearing screen failure occurred in 45 of 273 infants (16.5%) with postnatal CMV compared with 25 of 273 infants (9.2%) without postnatal CMV (risk ratio [RR], 1.80; 95% CI, 1.14 to 2.85; P = .01). Postnatal CMV was also associated with an increased postnatal age at discharge of 11.89 days (95% CI, 6.72 to 17.06 days; P < .001) and lower weight-for-age z score (-0.23; 95% CI, -0.39 to -0.07; P = .005). Analysis confirmed an increased risk of BPD (RR, 1.30; 95% CI, 1.17 to 1.44; P < .001), previously reported on infants from this cohort from 1997 to 2012, but not an increased risk of NEC after postnatal day 21 (RR, 2.00; 95% CI, 0.18 to 22.06; P = .57). Conclusions and Relevance: These data suggest that postnatal CMV infection is associated with lasting sequelae in the hearing and growth status of VLBW infants and with prolonged hospitalization. Prospective studies are needed to determine the full effects of postnatal CMV infection and whether antiviral treatment reduces the associated morbidity.
Assuntos
Displasia Broncopulmonar/virologia , Infecções por Citomegalovirus/complicações , Enterocolite Necrosante/virologia , Transtornos do Crescimento/virologia , Transtornos da Audição/virologia , Tempo de Internação/estatística & dados numéricos , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Estudos RetrospectivosRESUMO
Mitochondrial impairment is reported in HIV-infected children receiving antiretroviral therapy (ART), as well as those naive to ART. Whether mitochondrial function recovers with early initiation of ART and sustained viral suppression on long-term ART is unclear. In this study, we evaluate mitochondrial markers in well-suppressed perinatally HIV-infected children initiated on ART early in life. We selected a cross-sectional sample of 120 HIV-infected children with viral load <400 copies/mL and 60 age-matched uninfected children (22 HIV-exposed uninfected) enrolled in a cohort study in Johannesburg, South Africa. Complex IV (CIV) and citrate synthase (CS) activity were measured by spectrophotometry. Mitochondrial DNA (mtDNA) content relative to nuclear DNA (nDNA) was measured by quantitative real-time polymerase chain reaction and expressed as copies/nDNA. Mitochondrial markers were impaired in HIV-infected children, including lower mean CIV activities [1.76 vs. 1.40 optical densities (OD)/min], higher risk of a CIV/CS ratio ≤0.22 (third quartile; odds ratio = 3.03, 95% confidence interval: 1.38-6.66), and lower mtDNA content. Children with shorter versus longer ART duration (<6.3 vs. ≥6.3 years) had lower means of CIV activity (1.22-1.58 OD/min) and mtDNA content (386-907 copies/nDNA). There were no differences in mitochondrial markers between children who started ART earlier (<6 months) or later (6-24 months). CIV activity was impaired in children with lower height-for-age Z-scores (HAZs). Despite early treatment and prolonged viral suppression, HIV-infected children had detectable mitochondrial impairment, particularly among those with stunted growth. Further study is required to determine if continued treatment will lead to full recovery of mitochondrial function in HIV-infected children.
Assuntos
Fármacos Anti-HIV/uso terapêutico , DNA Mitocondrial/análise , Infecções por HIV/tratamento farmacológico , Mitocôndrias/patologia , Resposta Viral Sustentada , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Feminino , Transtornos do Crescimento/virologia , Infecções por HIV/complicações , Humanos , Estudos Longitudinais , Masculino , Mitocôndrias/efeitos dos fármacos , África do Sul , Carga Viral/efeitos dos fármacosRESUMO
Diarrheal disease is a leading cause of childhood morbidity and mortality worldwide, but particularly in low-income countries in sub-Saharan Africa and South Asia. The Global Enteric Multicenter Study (GEMS) examined the infectious etiologies as well as associated demographics, socioeconomic markers, health-care-seeking behaviors, and handwashing practices of the households of children with diarrhea and their age- and gender-matched controls in seven countries over a 3-year period (December 2007-December 2010). Stool studies to determine diarrheal etiologies and anthropometry were performed at baseline and at 60-day follow-up visits, along with surveys to record demographics and living conditions of the children. We performed secondary analyses of the GEMS data derived from the Bangladesh portion of the study in children with diarrhea associated with viral enteropathogens and explored pathogen-specific features of disease burden. Rotavirus and norovirus were the most prevalent pathogens (39.3% and 35%, respectively). Disease due to rotavirus and adenovirus was more common in infants than in older children (P < 0.001 and P = 0.001, respectively). Height for age decreased from baseline to follow-up in children with diarrhea associated with rotavirus, norovirus, and adenovirus (P < 0.001). Based on these analyses, preventive measures targeted at rotavirus, norovirus, and adenovirus will be expected to have meaningful clinical impact. Cost of treatment was highest for rotavirus as well, making it an obvious target for intervention. Association of specific viruses with stunting is particularly notable, as stunting is an attributable risk factor for poor cognitive development and future productivity and economic potential.
Assuntos
Efeitos Psicossociais da Doença , Diarreia/virologia , População Rural , Vírus/patogenicidade , Adenoviridae/patogenicidade , Bangladesh , Estudos de Casos e Controles , Pré-Escolar , Diarreia/economia , Características da Família , Fezes/virologia , Feminino , Transtornos do Crescimento/virologia , Humanos , Lactente , Recém-Nascido , Masculino , Norovirus/patogenicidade , Fatores de Risco , Rotavirus/patogenicidadeRESUMO
AIM: Despite high pathogen burden and malnutrition in low-income settings, knowledge on relationship between asymptomatic viral or parasitic infections, nutrition and growth is insufficient. We studied these relationships in a cohort of six-month-old Malawian infants. METHODS: As part of a nutrient supplementation trial for 12 months, we documented disease symptoms of 840 participant daily and anthropometric measurements every three months. Stool specimens were collected every six months and analysed for Giardia lamblia, Cryptosporidium species and enterovirus, rotavirus, norovirus, parechovirus and rhinovirus using polymerase chain reaction (PCR). The prevalence of the microbes was compared to the children's linear growth and the dietary. RESULTS: The prevalence of the microbes was similar in every intervention group. All age groups combined, children negative for G. lamblia had a mean standard deviation (SD) of -0.01 (0.49) change in length-for-age Z-score (LAZ), compared to -0.12 (0.045) among G. lamblia positive children (difference -0.10, 95% CI -0.21 to -0.00, p = 0.047). The LAZ change difference was also statistically significant (p = 0.042) at age of 18-21 months but not at the other time points. CONCLUSION: Asymptomatic G. lamblia infection was mainly associated with growth reduction in certain three-month periods. The result refers to the chronic nature of G. lamblia infection.
Assuntos
Fezes/parasitologia , Giardia lamblia/isolamento & purificação , Giardíase/complicações , Transtornos do Crescimento/parasitologia , Infecções Assintomáticas/epidemiologia , Suplementos Nutricionais , Fezes/virologia , Feminino , Giardíase/epidemiologia , Transtornos do Crescimento/dietoterapia , Transtornos do Crescimento/virologia , Humanos , Lactente , Malaui/epidemiologia , MasculinoRESUMO
BACKGROUND: HIV-exposed but uninfected (HEU) children may be at an increased risk of impaired growth when compared with their HIV-unexposed and uninfected (HUU) counterparts. We compared the growth patterns of HEU to HUU children in Nigeria. METHODS: Pregnant women with and without HIV infection were enrolled at the Plateau State Specialist Hospital, Jos, Nigeria. Infants born to these mothers were recruited at birth and the mother-infant pairs followed up for 18 months. Weight, length and head circumference of the infants were measured at each visit. Age- and sex-standardized Z scores were generated for each anthropometric measure using the World Health Organization Child Growth Standards. Children with length-for-age, weight-for-age and weight-for-length Z scores <-2 were classified as stunted, underweight and wasted, respectively. RESULTS: Of 415 children (307 HEU and 108 HUU) recruited for this study, 117 (28.4%), 9 (2.2%) and 32 (7.8%) infants were stunted, underweight and wasted, respectively, at birth. In a multivariable longitudinal analysis, the odds of stunting were higher among HEU as compared with HUU children [adjusted odds ratio: 2.4 (95% confidence interval: 1.4-4.1)]. Similarly, odds of being underweight were higher among the HEU children [adjusted odds ratio: 1.6 (95% confidence interval: 1.1-2.2)]. CONCLUSIONS: Linear and ponderal growth were more impaired among HEU as compared with HUU children in Nigeria during the first 18 months of life. Further studies are needed to explore the causal basis for these differences.
Assuntos
Desenvolvimento Infantil , Transtornos do Crescimento/epidemiologia , Infecções por HIV/complicações , Efeitos Tardios da Exposição Pré-Natal/virologia , Peso Corporal , Feminino , Transtornos do Crescimento/virologia , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Mães , Nigéria/epidemiologia , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Vertical transmission of Zika virus leads to infection of neuroprogenitor cells and destruction of brain parenchyma. Recent evidence suggests that the timing of infection as well as host factors may affect vertical transmission. As a result, congenital Zika virus infection may only become clinically apparent in the postnatal period. OBJECTIVE: We sought to develop an outbred mouse model of Zika virus vertical transmission to determine if the timing of gestational Zika virus exposure yields phenotypic differences at birth and through adolescence. We hypothesized that later gestational inoculations would only become apparent in adolescence. STUDY DESIGN: To better recapitulate human exposures, timed pregnant Swiss-Webster dams (n = 15) were subcutaneously inoculated with 1 × 104 plaque-forming units of first passage contemporary Zika virus HN16 strain or a mock injection on embryonic day 4, 8, or 12 with bioactive antiinterferon alpha receptor antibody administered in days preceding and proceeding inoculation. The antibody was given to prevent the robust type I interferon signaling cascade that make mice inherently resistant to Zika virus infection. At birth and adolescence (6 weeks of age) offspring were assessed for growth, brain weight, and biparietal head diameters, and Zika virus viral levels by reverse transcription-polymerase chain reaction or in situ hybridization. RESULTS: Pups of Zika virus-infected dams infected at embryonic days 4 and 8 but not 12 were growth restricted (P < .003). Brain weights were significantly smaller at birth (P = .01) for embryonic day 8 Zika virus-exposed offspring. At 6 weeks of age, biparietal diameters were smaller for all Zika virus-exposed males and females (P < .05), with embryonic day 8-exposed males smallest by biparietal diameter and growth-restriction measurements (weight >2 SD, P = .0007). All pups and adolescent mice were assessed for Zika virus infection by reverse transcription-polymerase chain reaction. Analysis of all underweight pups reveled 1 to be positive for neuronal Zika virus infection by in situ hybridization, while a second moribund animal was diffusely positive at 8 days of age by Zika virus infectivity throughout the brain, kidneys, and intestine. CONCLUSION: These findings demonstrate that postnatal effects of infection occurring at single time points continue to be detrimental to offspring in the postnatal period in a subset of littermates and subject to a window of gestational susceptibility coinciding with placentation. This model recapitulates frequently encountered clinical scenarios in nonendemic regions, including the majority of the United States, where travel-related exposure occurs in short and well-defined windows of gestation. Our low rate of infection and relatively rare evidence of congenital Zika syndrome parallels human population-based data.
Assuntos
Transtornos do Crescimento/virologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/virologia , Zika virus/patogenicidade , Animais , Modelos Animais de Doenças , Feminino , Idade Gestacional , Masculino , Camundongos , Microcefalia/virologia , GravidezRESUMO
Despite descriptions of runting-stunting syndrome (RSS) in broiler chickens dating back over 40 years, the aetiology has not yet been described. A novel chicken astrovirus (CkAstV) was isolated in an LMH liver cell line from the intestines of chickens affected with RSS. Clinical RSS is characterized by retarded growth and cystic crypt lesions in the small intestine. In 1-day-old broiler chickens infected with the CkAstV isolate, virus was only detected in the intestinal epithelial cells during the first few days after infection. Notably, the preferred host cells are the crypt epithelial cells following initial replication in the villous epithelial cells, thus implying viral preference for immature intestinal cells. Nevertheless, the CkAstV isolate did not induce remarkable pathological changes, despite the presence of the virus in situ. Serial chicken-to-chicken passages of the virus induced increased virulence, as displayed by decreased weight gain and the presence of cystic lesions in the small intestine reproducing clinical RSS in chickens. The analysis of the full-length genome sequences from the isolated CkAstV and the CkAstV from the bird-to-bird passages showed >99â% similarity. The data obtained in this study suggest that the CkAstV isolate is capable of inducing RSS following serial bird-to-bird passages in broilers and is as an aetiological agent of the disease.
Assuntos
Infecções por Astroviridae/veterinária , Avastrovirus/fisiologia , Transtornos do Crescimento/veterinária , Doenças das Aves Domésticas/virologia , Animais , Infecções por Astroviridae/patologia , Infecções por Astroviridae/virologia , Avastrovirus/genética , Avastrovirus/isolamento & purificação , Galinhas , Transtornos do Crescimento/patologia , Transtornos do Crescimento/virologia , Intestinos/patologia , Intestinos/virologia , Doenças das Aves Domésticas/patologia , Replicação ViralRESUMO
BACKGROUND: Child development is negatively impacted by HIV with children that are infected and affected by HIV performing worse than their peers in cognitive assessments. METHODS: We conducted a descriptive follow-up comparison study (n=989) in South Africa and Malawi. We tracked child development in 135 HIV-positive children compared to 854 uninfected children aged 4-13 years attending community-based organizations at baseline and again 12-15 months later. RESULTS: Children with HIV were more often stunted (58.8% vs. 27.4%) and underweight (18.7% vs. 7.1%). They also had significantly poorer general physical functioning (M=93.37 vs. M=97.00). HIV-positive children scored significantly lower on digit span and the draw-a-person task. CONCLUSIONS: These data clearly show that HIV infection poses a serious risk for child development and that there is a need for scaled up interventions. Community-based services may be ideally placed to accommodate such provision and deliver urgently needed support to these children.
Assuntos
Serviços de Saúde da Criança , Disfunção Cognitiva/complicações , Disfunção Cognitiva/fisiopatologia , Deficiências do Desenvolvimento/complicações , Transtornos do Crescimento/complicações , Transtornos do Crescimento/fisiopatologia , Infecções por HIV/complicações , Fármacos Anti-HIV/uso terapêutico , Criança , Desenvolvimento Infantil , Serviços de Saúde da Criança/organização & administração , Pré-Escolar , Disfunção Cognitiva/reabilitação , Disfunção Cognitiva/virologia , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/fisiopatologia , Deficiências do Desenvolvimento/reabilitação , Feminino , Seguimentos , Transtornos do Crescimento/virologia , Infecções por HIV/epidemiologia , Infecções por HIV/fisiopatologia , Infecções por HIV/reabilitação , Necessidades e Demandas de Serviços de Saúde , Humanos , Malaui/epidemiologia , Masculino , Qualidade de Vida , Fatores Socioeconômicos , África do Sul/epidemiologia , Magreza/epidemiologia , Magreza/fisiopatologia , Magreza/virologiaRESUMO
BACKGROUND: Nutrition training can boost competence of health workers to improve children's feeding practices. In this way, child undernutrition can be ameliorated in general populations. However, evidence is lacking on efficacy of such interventions among Human Immunodeficiency Virus (HIV)-positive children. We aimed to examine the efficacy of a nutrition training intervention to improve midlevel providers' (MLPs) nutrition knowledge and feeding practices and the nutrition statuses of HIV-positive children in Tanga, Tanzania. METHODS: This cluster-randomized controlled trial was conducted in 16 out of 32 care and treatment centers (CTCs) in Tanga. Eight CTCs were assigned to the intervention arm and a total of 16 MLPs received nutrition training and provided nutrition counseling and care to caregivers of HIV-positive children. A total of 776 pairs of HIV-positive children and their caregivers were recruited, of whom 397 were in the intervention arm. Data were analyzed using instrumental variable random effects regression with panel data to examine the efficacy of the intervention on nutrition status through feeding practices. RESULTS: Mean nutrition knowledge scores were higher post-training compared to pre-training among MLPs (37.1 vs. 23.5, p < 0.001). A mean increment weight gain of 300 g was also observed at follow-up compared to baseline among children of the intervention arm. Feeding frequency and dietary diversity improved following the intervention and a 6 months follow-up (p < 0.001). An increase in each unit of feeding frequency and dietary diversity were associated with a 0.15-unit and a 0.16-unit respectively decrease in the child underweight (p < 0.001). CONCLUSIONS: Nutrition training improved nutrition knowledge among MLPs caring for HIV-positive children attending CTCs in Tanga, Tanzania. Caregivers' feeding practices also improved, which in turn led to a modest weight gain among HIV-positive children. To sustain weight gain, efforts should be made to also improve households' food security and caregivers' education in addition to inservice nutrition trainings. The protocol was registered on 15/02/2013, before the recruitment at ISRCTN trial registry with the trial registration number: ISRCTN65346364.
Assuntos
Agentes Comunitários de Saúde/educação , Transtornos do Crescimento/prevenção & controle , Infecções por HIV/terapia , Promoção da Saúde/métodos , Desnutrição/prevenção & controle , Terapia Nutricional/métodos , Adolescente , Criança , Cuidado da Criança/métodos , Fenômenos Fisiológicos da Nutrição Infantil , Pré-Escolar , Competência Clínica , Feminino , Seguimentos , Transtornos do Crescimento/virologia , Infecções por HIV/complicações , Humanos , Lactente , Modelos Logísticos , Masculino , Desnutrição/virologia , Tanzânia , Resultado do Tratamento , Aumento de PesoRESUMO
OBJECTIVE: Diarrheal diseases are a leading cause of morbidity and mortality worldwide, but the etiology of diarrhea and its relation to nutritional outcomes in resource-limited settings is poorly defined. We sought to determine the etiology of community-acquired diarrhea in Tanzanian infants and to assess the association with anthropometrics and novel intestinal biomarkers. METHODS: A convenience sample of infants in a trial of zinc and/or multivitamin supplementation in Tanzania was selected. Subjects were enrolled at age 6 weeks and studied for 18 months. Stool samples were obtained from children with acute diarrhea. A novel, polymerase chain reaction-based TaqMan array was used to screen stool for 15 enteropathogens. A subset of subjects had serum gastrointestinal biomarkers measured. RESULTS: One hundred twenty-three subjects with diarrhea were enrolled. The mean ± SD age at stool sample collection was 12.4â±â3.9 months. Thirty-five enteropathogens were identified in 34 (27.6%) subjects: 11 rotavirus, 9 Cryptosporidium spp, 7 Shigella spp, 3 Campylobacter jejuni/coli, 3 heat stable-enterotoxigenic Escherichia coli, and 2 enteropathogenic E coli. Subjects with any identified enteropathogen had significantly lower weight-for-length z scores (-0.55â±â1.10 vs 0.03â±â1.30, Pâ=â0.03) at the final clinic visit than those without an identified pathogen. Fifty of the 123 subjects (40.7%) had serum analyzed for antibodies to lipopolysaccharide (LPS) and flagellin. Subjects with any identified enteropathogen had lower immunoglobulin (IgA) antibodies to LPS (0.75â±â0.27 vs 1.13â±â0.77, Pâ=â0.01) and flagellin (0.52â±â0.16 vs 0.73â±â0.47, Pâ=â0.02) than those without an identified pathogen. CONCLUSIONS: This quantitative polymerase chain reaction method may allow identification of enteropathogens that place children at higher risk for suboptimal growth. IgA anti-LPS and flagellin antibodies hold promise as emerging intestinal biomarkers.
Assuntos
Diarreia/etiologia , Flagelina/imunologia , Microbioma Gastrointestinal , Transtornos do Crescimento/etiologia , Imunoglobulina A/sangue , Intestinos , Lipopolissacarídeos/imunologia , Biomarcadores/sangue , Peso Corporal , Campylobacter/crescimento & desenvolvimento , Cryptosporidium/crescimento & desenvolvimento , Diarreia/microbiologia , Diarreia/parasitologia , Diarreia/virologia , Escherichia coli Enteropatogênica/crescimento & desenvolvimento , Fezes/microbiologia , Fezes/parasitologia , Fezes/virologia , Feminino , Transtornos do Crescimento/microbiologia , Transtornos do Crescimento/parasitologia , Transtornos do Crescimento/virologia , Humanos , Lactente , Infecções/complicações , Enteropatias/complicações , Intestinos/microbiologia , Intestinos/parasitologia , Intestinos/virologia , Masculino , Estado Nutricional , Reação em Cadeia da Polimerase , Rotavirus/crescimento & desenvolvimento , Shigella/crescimento & desenvolvimento , TanzâniaRESUMO
Malnutrition and human immunodeficiency virus (HIV)-related complications are commonly seen in HIV-infected children, and these have been shown in high-prevalent areas such as Africa. Antiviral therapy (ART) has notably controlled disease progression, whereas it effectively reverses underweight and growth retardation in HIV-infected children. This study was conducted to evaluate the growth status after initiation of ART in HIV-infected children in China. A retrospective cohort study was conducted based on the National Science and Technology Major Project. HIV-infected children who initiated antiretroviral treatment between January 1st, 2012 and December 31st, 2012 were followed up to December 31st, 2014. Z-scores of height and weight were calculated by WHO Anthro (plus). Linear mixed-effects models were used to model trajectories of weight- and height-for-age Z-scores. Seven hundred forty-four participants enrolled in the study, with 585 participants and 712 participants who had WAZ (weight-for-age Z-score) and HAZ (height-for-age Z-score), respectively, before initiation of ART. Among them, 125 (21.4%) were underweight and 301 (42.3%) were stunted. After treatment, among the 125 underweight children, WAZ improved in 69 patients, regained more than -2 on average. Among the 301 stunted children, HAZ improved in 123 patients, regained more than -2 on average. WAZ improved for the first 6 months by 0.052 units each month and then stabilized, whereas HAZ consistently improved by 0.014 units each month over time. Antiretroviral treatment reversed the adverse effects of HIV to some degree. Early diagnosis and treatment, with an effective nutrition program, is necessary to improve malnutrition further.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Crescimento/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Criança , Pré-Escolar , China/epidemiologia , Feminino , Transtornos do Crescimento/fisiopatologia , Transtornos do Crescimento/virologia , Infecções por HIV/complicações , Infecções por HIV/etnologia , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Runting stunting syndrome (RSS) is a disease condition that affects broilers and causes impaired growth and poor feed conversion because of enteritis characterized by pale and distended small intestines with watery contents. The etiology of the disease is multifactorial, and a large variety of viral agents have been implicated. Here we describe the detection and isolation of an infectious bronchitis virus (IBV) -like coronavirus from the intestines of a flock of 60,000 14-day-old brown/red broiler chicks. The birds showed typical clinical signs of RSS including stunting and uneven growth. At necropsy, the small intestines were pale and distended with watery contents. Histopathology of the intestines revealed increased cellularity of the lamina propria, blunting of villi, and cystic changes in the crypts. Negative stain electron microscopy of the intestinal contents revealed coronavirus particles. Transmission electron microscopy of the intestine confirmed coronavirus in the cytoplasm of enterocytes. Using immunohistochemistry (IHC), IBV antigen was detected in the intestinal epithelial cells as well as in the proventriculus and pancreas. There were no lesions in the respiratory system, and no IBV antigen was detected in trachea, lung, air sac, conjunctiva, and cecal tonsils. A coronavirus was isolated from the intestine of chicken embryos but not from the allantoic sac inoculated with the intestinal contents of the broiler chicks. Sequencing of the S1 gene showed nucleic acid sequence identities of 93.8% to the corresponding region of IBV California 99 and of 85.7% to IBV Arkansas. Nucleic acid sequence identities to other IBV genotypes were lower. The histopathologic lesions in the intestines were reproduced after experimental infection of specific-pathogen-free chickens inoculated in the conjunctiva and nares. Five days after infection, six of nine investigated birds showed enteritis associated with IBV antigen as detected by IHC. In contrast to the field infection, birds in the experimental group showed clear respiratory signs and lesions in the upper respiratory tract. The results suggest a broader tissue tropism of this isolate, which might be related to the mutations in the S1 gene.
Assuntos
Galinhas , Infecções por Coronavirus/veterinária , Transtornos do Crescimento/veterinária , Vírus da Bronquite Infecciosa/fisiologia , Doenças das Aves Domésticas/diagnóstico , Animais , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/virologia , Intestinos/virologia , Doenças das Aves Domésticas/virologia , Organismos Livres de Patógenos EspecíficosRESUMO
Runting-stunting syndrome (RSS) in broiler chickens is an enteric disease that causes significant economic losses to poultry producers worldwide due to elevated feed conversion ratios, decreased body weight during growth, and excessive culling. Of specific interest are the viral agents associated with RSS which have been difficult to fully characterize to date. Past research into the aetiology of RSS has implicated a wide variety of RNA and DNA viruses however, to date, no individual virus has been identified as the main agent of RSS and the current opinion is that it may be caused by a community of viruses, collectively known as the virome. This paper attempts to characterize the viral pathogens associated with 2-3-week-old RSS-affected and unaffected broiler chickens using next-generation sequencing and comparative metagenomics. Analysis of the viromes identified a total of 20 DNA and RNA viral families, along with 2 unidentified categories, comprised of 31 distinct viral genera and 7 unclassified genera. The most abundant viral families identified in this study were the Astroviridae, Caliciviridae, Picornaviridae, Parvoviridae, Coronaviridae, Siphoviridae, and Myoviridae. This study has identified historically significant viruses associated with the disease such as chicken astrovirus, avian nephritis virus, chicken parvovirus, and chicken calicivirus along with relatively novel viruses such as chicken megrivirus and sicinivirus 1 and will help expand the knowledge related to enteric disease in broiler chickens, provide insights into the viral constituents of a healthy avian gut, and identify a variety of enteric viruses and viral communities appropriate for further study.
Assuntos
Avastrovirus/genética , Galinhas/virologia , Transtornos do Crescimento/veterinária , Metagenômica , Parvovirus/genética , Doenças das Aves Domésticas/virologia , Animais , Avastrovirus/classificação , Galinhas/crescimento & desenvolvimento , Análise por Conglomerados , DNA Viral/química , DNA Viral/genética , Biblioteca Gênica , Genoma Viral/genética , Transtornos do Crescimento/patologia , Transtornos do Crescimento/virologia , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , Parvovirus/classificação , Doenças das Aves Domésticas/patologia , RNA Viral/genética , Análise de Sequência de DNA/veterináriaRESUMO
BACKGROUND: HIV-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa especially with the increasing coverage of more effective prevention of mother-to-child transmission (PMTCT) antiretroviral therapy regimens. This study describes the characteristics of South African HEU infants, investigates factors impacting birth weight and assesses their growth within the first 28 weeks of life. METHODS: This is a retrospective cohort based on routine clinical data from two South African PMTCT programmes. Data were collected between 2007 and 2013. Linear regression assessed factors affecting birth weight-for-age z-scores (WAZ) while growth (longitudinal WAZ) was assessed using mixed effects models. RESULTS: We assessed the growth of 2621 HEU infants (median birth WAZ was -0.65 (IQR -1.46; 0.0) and 51% were male). The feeding modalities practised were as follows: 0.5% exclusive breastfeeding, 7.9% breastfeeding with unknown exclusivity, 0.08% mixed breastfeeding and 89.2% formula feeding. Mothers with CD4 <200 cells/µl delivered infants with a lower birth WAZ (adjusted ß -0.253 [95% CI -0.043; -0.072], p = 0.006) compared to mothers with aCD4 ≥500 cells/µl. Similarly, mothers who did not receive antiretroviral drugs delivered infants with a lower birth WAZ (adjusted ß -0.39 [95% CI -0.67; -0.11], p = 0.007) compared to mothers who received antenatal antiretrovirals. Infants with a birth weight <2 500g (ß 0.070 [95% CI 0.061; 0.078], p <0.0001) experienced faster growth within the first 28 weeks of life compared to infants with a birth weight ≥2 500g. Infants with any breastfeeding exposure experienced slower longitudinal growth compared to formula fed infants (adjusted ß -0.012 [95% CI 0.021; -0.003], p = 0.011). CONCLUSION: Less severe maternal disease and the use of antiretrovirals positively impacts birth weight in this cohort of South African HEU infants. Formula feeding was common with breastfed infants experiencing marginally slower longitudinal growth.
Assuntos
Transtornos do Crescimento/virologia , Infecções por HIV/complicações , HIV-1/fisiologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Feminino , Seguimentos , Transtornos do Crescimento/fisiopatologia , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Lactente , Fórmulas Infantis , Recém-Nascido , Masculino , Mães , Gravidez , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
UNLABELLED: Expression of the cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly reduced in the brain prefrontal cortex of HIV-positive individuals with HIV-associated neurocognitive disorders (HAND). Furthermore, this HO-1 deficiency correlates with brain viral load, markers of macrophage activation, and type I interferon responses. In vitro, HIV replication in monocyte-derived macrophages (MDM) selectively reduces HO-1 protein and RNA expression and induces production of neurotoxic levels of glutamate; correction of this HO-1 deficiency reduces neurotoxic glutamate production without an effect on HIV replication. We now demonstrate that macrophage HO-1 deficiency, and the associated neurotoxin production, is a conserved feature of infection with macrophage-tropic HIV-1 strains that correlates closely with the extent of replication, and this feature extends to HIV-2 infection. We further demonstrate that this HO-1 deficiency does not depend specifically upon the HIV-1 accessory genes nef, vpr, or vpu but rather on HIV replication, even when markedly limited. Finally, antiretroviral therapy (ART) applied to MDM after HIV infection is established does not prevent HO-1 loss or the associated neurotoxin production. This work defines a predictable relationship between HIV replication, HO-1 loss, and neurotoxin production in MDM that likely reflects processes in place in the HIV-infected brains of individuals receiving ART. It further suggests that correcting this HO-1 deficiency in HIV-infected MDM could provide neuroprotection above that provided by current ART or proposed antiviral therapies directed at limiting Nef, Vpr, or Vpu functions. The ability of HIV-2 to reduce HO-1 expression suggests that this is a conserved phenotype among macrophage-tropic human immunodeficiency viruses that could contribute to neuropathogenesis. IMPORTANCE: The continued prevalence of HIV-associated neurocognitive disorders (HAND) underscores the need for adjunctive therapy that targets the neuropathological processes that persist in antiretroviral therapy (ART)-treated HIV-infected individuals. To this end, we previously identified one such possible process, a deficiency of the antioxidative and anti-inflammatory enzyme heme oxygenase-1 (HO-1) in the brains of individuals with HAND. In the present study, our findings suggest that the HO-1 deficiency associated with excess glutamate production and neurotoxicity in HIV-infected macrophages is a highly conserved phenotype of macrophage-tropic HIV strains and that this phenotype can persist in the macrophage compartment in the presence of ART. This suggests a plausible mechanism by which HIV infection of brain macrophages in ART-treated individuals could exacerbate oxidative stress and glutamate-induced neuronal injury, each of which is associated with neurocognitive dysfunction in infected individuals. Thus, therapies that rescue the HO-1 deficiency in HIV-infected individuals could provide additional neuroprotection to ART.