Causal Pathways from Enteropathogens to Environmental Enteropathy: Findings from the MAL-ED Birth Cohort Study

Background Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Methods Non-diarrheal stool samples (N = 22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N = 6363) and plasma alpha-1-acid glycoprotein (AGP) (N = 2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0–2 years of age. Findings Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. Interpretation The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation

Perfil epidemiológico de pacientes adultos com tuberculose e AIDS no estado do Espírito Santo, Brasil: relacionamento dos bancos de dados de tuberculose e AIDS Epidemiological profile of adult patients with tuberculosis and AIDS in the state of Espírito Santo, Brazil: cross-referencing tuberculosis and AIDS databases

OBJETIVO: Avaliar o perfil epidemiológico de pacientes com tuberculose (TB) e daqueles com TB e HIV no estado do Espírito Santo entre 2000 e 2006. MÉTODOS: Coletamos dados demográficos e clínicos dos pacientes de interesse do Centro de Vigilância Epidemiológica do Estado do Espírito Santo (banco de dados para TB), do Sistema de Informação de Agravos de Notificação, do Sistema de Informação sobre Mortalidade, do Sistema de Controle de Exames Laboratoriais da Rede Nacional de Contagem de Linfócitos CD4+/CD8+ e Carga Viral e do Sistema de Controle Logístico de Medicamentos (bancos de dados para HIV/AIDS). Todos os dados compilados foram cruzados. RESULTADOS: Durante o período do estudo, 9.543 pacientes com TB > 15 anos de idade foram identificados, dos quais 437 (4,6%) tinham HIV. A mediana de idade não diferiu entre os pacientes com TB/AIDS e somente com TB (35 anos vs. 38 anos). Dos 437 pacientes com TB/AIDS, 298 (68,2%) eram homens, e 156 (35,8%) estavam na faixa etária de 30-39 anos. Quanto ao desfecho do tratamento da TB, 79,0% foram curados, 9,7% foram transferidos para outros locais, 6,0% foram a óbito, 5,2% abandonaram o tratamento, e 0,2% desenvolveram TB multirresistente. O óbito foi 4,75 vezes mais comum nos pacientes com TB/AIDS do que naqueles somente com TB. A TB pulmonar representou 82,4% dos casos. A combinação de TB pulmonar e extrapulmonar foi 8,2 vezes mais frequente nos pacientes com TB/AIDS do que naqueles somente com TB (IC95%: 6,2-10,8). CONCLUSÕES: Nossos resultados enfatizam a significância da AIDS em pacientes com TB no Brasil, assim como a importância de se avaliar dados secundários a fim de melhorar a sua qualidade e desenvolver intervenções de saúde pública<br>OBJECTIVE: To evaluate the epidemiological profile of patients with tuberculosis (TB) only and that of patients with TB/AIDS in the state of Espírito Santo, Brazil, between 2000 and 2006. METHODS: For the patients of interest, we collected demographic and clinical data from the Epidemiological Surveillance Center (TB database), Brazilian Case Registry Database, and Brazilian National Mortality Database, as well as the Brazilian National CD4+/CD8+ T Lymphocyte Count and Viral Load Network Laboratory Test Control System and the Logistic Medication Monitoring System (HIV/AIDS databases). All of the compiled data were cross-referenced. RESULTS: During the study period, we identified 9,543 TB patients > 15 years of age, 437 of whom (4.6%) had AIDS. The median age did not differ between TB/AIDS and TB-only patients (35 years vs. 38 years). Of the 437 TB/AIDS patients, 298 (68.2%) were male, and 156 (35.8%) were in the 30-39 age bracket. In terms of TB treatment outcome, 79.0% were cured, 9.7% were referred to other facilities, 6.0% died, 5.2% abandoned treatment, and 0.2% developed multidrug-resistant TB. Death was 4.75 times more common in patients with TB/AIDS than in those with TB only. Pulmonary TB accounted for 82.4% of the cases. The combination of pulmonary and extrapulmonary TB was 8.2 times more common in the TB/AIDS patients than in the TB-only patients (95% CI: 6.2-10.8). CONCLUSIONS: Our results emphasize the significance of AIDS among TB patients in Brazil, as well as the importance of evaluating secondary data in order to improve their quality and develop public health intervention