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1.
Am J Epidemiol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31712804

RESUMO

Hepatitis C virus (HCV) is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic Type 1 MI (T1MI) and supply-demand mismatch Type 2 MI (T2MI). We examined the association between HCV and MI in the Centers for Acquired Immunodeficiency Syndrome Research Network of Integrated Clinical Systems, a multi-center clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Universal MI definition. We estimated the association between chronic HCV (RNA+) and time to MI adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics and history of injecting drug use. Among 23,407 PLWH aged ≥18, there were 336 T1MI and 330 T2MI during a median of 4.7 years of follow-up during 1998 through 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) 1.46, 95% CI: 1.09, 1.97) but not T1MI (aHR 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.

2.
Genome Biol ; 20(1): 219, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672155

RESUMO

BACKGROUND: Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. RESULTS: Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. CONCLUSIONS: Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

3.
Clin Infect Dis ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31748797

RESUMO

BACKGROUND: Alterations in gut microbiota (GMB) and host metabolites have been noted in HIV-infected individuals. However, it remains unclear whether alterations in GMB and related functional groups may contribute to disrupted host metabolite profiles in HIV-infected individuals. METHODS: This study included 185 women (128 with long-standing HIV infection, 88% under antiretroviral therapy; and 57 HIV-uninfected from the same geographic location with comparable characteristics). Stool samples were analyzed by 16S rRNA V4 region sequencing, and GMB function was inferred by PICRUSt. Plasma metabolomic profiling was performed using liquid chromatography tandem mass spectrometry, and133 metabolites (amino acids, biogenic amines, acylcarnitines and lipids) were analyzed. RESULTS: Four predominant bacterial genera were identified to be associated with HIV infection, with higher abundances of Ruminococcus and Oscillospira and lower abundances of Bifidobacterium and Collinsella in HIV-infected women compared to HIV-uninfected women. HIV-infected women showed a distinct plasma metabolite profile, featured with elevated glycerophospholipid levels, compared to HIV-uninfected women. Functional analyses also indicated that GMB lipid metabolism was enriched in HIV-infected women. Ruminococcus and Oscillospira were among the top bacterial genera that contribute to the GMB glycerophospholipid metabolism pathway and showed positive correlations with host plasma glycerophospholipid levels. One bacterial functional capacity in the acetate and propionate biosynthesis pathway was identified to be mainly contributed by Bifidobacterium, and this functional capacity was lower in HIV-infected women than that in HIV-uninfected women. CONCLUSION: Our integrative analyses identified altered gut microbiota with related functional capacities that might be associated with disrupted plasma metabolite profiles in HIV-infected women.

4.
Open Forum Infect Dis ; 6(4): ofz100, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30949539

RESUMO

Background: Direct-acting antiviral (DAA) therapy have been shown to be highly successful in clinical trials and observational studies, but less is known about treatment success in patients with a high burden of comorbid conditions, including mental health and substance use disorders. We evaluated DAA effectiveness across a broad spectrum of patients with human immunodeficiency virus (HIV)-hepatitis C virus (HCV) coinfection in routine clinical care, including those with psychosocial comorbid conditions. Methods: The primary end point was sustained virologic response (SVR), defined as HCV RNA not detected or <25 IU/mL ≥10 weeks after treatment. We calculated SVR rates and 95% confidence intervals (CIs) in a modified intent-to-treat analysis. We repeated this analysis after multiply imputing missing SVR values. Results: Among 642 DAA-treated patients, 536 had SVR assessments. The median age was 55 years; 79% were men, 59% black, and 32% white. Cirrhosis (fibrosis-4 index>3.25) was present in 24%, and 17% were interferon treatment experienced; 96% had genotype 1 infection and 432 (81%) had received ledipasvir-sofosbuvir. SVR occurred in 96.5% (95% CI, 94.5%-97.9%). Patients who were black, treatment experienced, or cirrhotic all had SVR rates >95%. Patients with depression and/or anxiety, psychotic disorder, illicit drug use, or alcohol use disorder also had high SVR rates, ranging from 95.4% to 96.8%. The only factor associated with lower SVR rate was early discontinuation (77.8%; 95% CI, 52.4%-93.6%). Similar results were seen in multiply imputed data sets. Conclusions: Our study represents a large multicenter examination of DAA therapy in HIV/HCV-coinfected patients. The broad treatment success we observed across this diverse group of patients with significant comorbid conditions is highly affirming and argues for widespread implementation of DAA therapy.

5.
Epidemiology ; 30(1): 69-74, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30273188

RESUMO

BACKGROUND: People living with HIV are at risk of increased myocardial infarction (MI). Cumulative HIV viral load (VL) has been proposed as a better measure of HIV inflammation than other measures of VL, like baseline VL, but its associations with MI are not known. METHODS: The multisite Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort includes clinical data and centrally adjudicated MI with distinction between atheroembolic MI (type 1) and MI related to supply-demand mismatch (type 2). We examined CNICS participants who were not on antiretroviral therapy (ART) at enrollment. Cumulative VL (copy-days of virus) from 6 months after enrollment was estimated with a time-weighted sum using the trapezoidal rule. We modeled associations of cumulative and baseline VL with MI by type using marginal structural Cox models. We contrasted the 75% percentile of the VL distribution with the 25% percentile. RESULTS: Among 11,324 participants, 218 MIs occurred between 1996 and 2016. Higher cumulative VL was associated with risk of all MI (hazard ratio [HR] = 1.72; 95% confidence interval [CI] = 1.26, 2.36), type 1 MI (HR = 1.23; 95% CI = 0.78, 1.96), and type 2 MI (HR = 2.52; 95% CI = 1.74, 3.66). While off ART, cumulative VL had a stronger association with type 1 MI (HR = 2.13; 95% CI = 1.15, 3.94) than type 2 MI (HR = 1.25; 95% CI = 0.70, 2.25). Baseline VL was associated with all MI (HR = 1.60; 95% CI = 1.28, 2.01), type 1 MI (HR = 1.73; 95% CI = 1.26, 2.38), and type 2 MI (HR = 1.51; 95% CI = 1.10, 2.08). CONCLUSIONS: Higher cumulative and baseline VL is associated with all MI, with a particularly strong association between cumulative VL and type 2 MI.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infarto do Miocárdio/epidemiologia , Viremia/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estados Unidos/epidemiologia , Carga Viral
6.
Anim Health Res Rev ; 18(2): 112-127, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29231804

RESUMO

There is a growing concern about the role of the environment in the dissemination of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In this systematic review, we summarize evidence for increases of ARG in the natural environment associated with potential sources of ARB and ARG such as agricultural facilities and wastewater treatment plants. A total of 5247 citations were identified, including studies that ascertained both ARG and ARB outcomes. All studies were screened for relevance to the question and methodology. This paper summarizes the evidence only for those studies with ARG outcomes (n = 24). Sixteen studies were at high (n = 3) or at unclear (n = 13) risk of bias in the estimation of source effects due to lack of information or failure to control for confounders. Statistical methods were used in nine studies; three studies assessed the effect of multiple sources using modeling approaches, and none reported effect measures. Most studies reported higher ARG concentration downstream/near the source, but heterogeneous findings hindered making any sound conclusions. To quantify increases of ARG in the environment due to specific point sources, there is a need for studies that emphasize analytic or design control of confounding, and that provide effect measure estimates.


Assuntos
Farmacorresistência Bacteriana , Resistência Microbiana a Medicamentos/genética , Microbiologia Ambiental , Agricultura , Animais , Águas Residuárias/microbiologia
7.
Anim Health Res Rev ; 17(1): 9-15, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27427189

RESUMO

Herein we describe a protocol for a systematic review of the evidence on whether point sources of anthropogenic effluent are associated with an increase in antibiotic resistance in the adjacent environment. The review question was based on the Population, Exposure, Comparator, Outcome, Study Design (PECOS) framework as follows: Is the prevalence or concentration of antibiotic resistant bacteria or resistance genes (O) in soil, water, air or free-living wildlife (P) higher in close proximity to, or downstream from, known or suspected sources of anthropogenic effluent (E) compared to areas more distant from or upstream from these sources (C)? A comprehensive search strategy was created to capture all relevant, published literature. Criteria for two stages of eligibility screening were developed to exclude publications that were not relevant to the question, and determine if the study used a design that permitted estimation of an association between a source and levels of resistance. A decision matrix was created for assessment of risk of bias to internal validity due to sample selection bias, information bias, and confounding. The goal of this protocol is to provide a method for determining the state of knowledge about the effect of point sources on antibiotic resistance in the environment.


Assuntos
Resistência Microbiana a Medicamentos , Poluição Ambiental/efeitos adversos , Animais , Viés , Protocolos Clínicos , Estudos Transversais , Resistência Microbiana a Medicamentos/genética , Atividades Humanas , Humanos , Estudos Observacionais como Assunto/normas , Reprodutibilidade dos Testes , Fatores de Risco , Viés de Seleção , Revisão Sistemática como Assunto
8.
J Environ Qual ; 45(2): 394-406, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27065386

RESUMO

We propose a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of natural ecosystems, and agricultural productivity. Available evidence for each causal link is briefly summarized, and key knowledge gaps are highlighted. A lack of quantitative estimates of human exposure to environmental bacteria, in general, and antibiotic-resistant bacteria, specifically, is a significant data gap hindering the assessment of effects on human health. The contribution of horizontal gene transfer to resistance in the environment and conditions that might foster the horizontal transfer of antibiotic resistance genes into human pathogens also need further research. Existing research has focused heavily on human health effects, with relatively little known about the effects of antibiotics and antibiotic resistance on natural and agricultural ecosystems. The proposed causal model is used to elucidate gaps in knowledge that must be addressed by the research community and may provide a useful starting point for the design and analysis of future research efforts.


Assuntos
Antibacterianos , Resistência Microbiana a Medicamentos , Ecossistema , Agricultura , Bactérias , Humanos
9.
Curr Opin Microbiol ; 19: 1-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24945599

RESUMO

Resistant bacterial infections in humans continue to pose a significant challenge globally. Antibiotic use in agriculture contributes to this problem, but failing to appreciate the relative importance of diverse potential causes represents a significant barrier to effective intervention. Standard epidemiologic methods alone are often insufficient to accurately describe the relationships between agricultural antibiotic use and resistance. The integration of diverse methodologies from multiple disciplines will be essential, including causal network modeling and population dynamics approaches. Because intuition can be a poor guide in directing investigative efforts of these non-linear and interconnected systems, integration of modeling efforts with empirical epidemiology and microbiology in an iterative process may result in more valuable information than either in isolation.


Assuntos
Agricultura , Antibacterianos , Farmacorresistência Bacteriana , Humanos
10.
BMC Public Health ; 13: 837, 2013 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-24025220

RESUMO

BACKGROUND: Toxoplasmosis is among the most widespread and prevalent zoonosis in the world. People can become infected through ingestion of oocysts shed by felids or of tissue cysts contained in meat from infected animals. Acute infection can result in a wide spectrum of consequences, including flu-like illness and retinitis, as well as congenital infection in pregnant women. Severe disease can occur, especially if people are immunocompromised. Frequency of human infection varies substantially by region due to ecological, social, and cultural factors. The most recent nationwide prevalence estimates in children from United States were 3.6% in 6-11 year olds and 5.8% in 12-19 year olds. Because of the limited knowledge of the occurrence of common zoonotic pathogens in children in the United States, the objective of this study was to estimate the sero-prevalence of T. gondii-specific antibodies in children from the Marshfield area in Wisconsin and to examine the association between sero-positivity and farm living. METHODS: Banked sera from 342 Wisconsin children collected in 1997-1999, aged 2 to 18 years, were tested for Toxoplasma gondii-specific IgG antibodies using ELISA. Recorded information included age, sex, and whether the child resided on a farm. Impact of assay accuracy, sensitivity and specificity, on sero-prevalence was examined using Bayesian methods. RESULTS: Observed prevalence of T. gondii-specific antibodies was 10.8% (37/347). Adjusting for sensitivity and specificity of the assays yielded a prevalence estimate of 8.0% (95% probability interval: 4%-12.4%). Children living on a farm had a 5 times higher odds of T. gondii-specific antibodies than children not living on a farm (OR=5.08, 95% CI: 2.2-11.6). CONCLUSION: Results suggest that even in apparently low-risk populations, the true extent of the infection in children is significant. In this study population, children living on farms were differentially exposed, with earlier and higher infection risk than children not living on farms. Findings highlight the need to increase awareness about toxoplasmosis acquired early in life and to improve our understanding of the ecology of T. gondii in rural environments from developed and developing countries.


Assuntos
Agricultura , Anticorpos Antiprotozoários/sangue , Toxoplasma/imunologia , Toxoplasmose/sangue , Toxoplasmose/epidemiologia , Adolescente , Animais , Criança , Pré-Escolar , Estudos Transversais , Meio Ambiente , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Prevalência , Estudos Retrospectivos , Medição de Risco , População Rural , Estudos Soroepidemiológicos , Toxoplasmose/diagnóstico , População Urbana , Wisconsin/epidemiologia
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