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Aka P.V.,U.S. National Cancer Institute | Kuniholm M.H.,Yeshiva University | Pfeiffer R.M.,U.S. National Cancer Institute | Wang A.S.,U.S. National Cancer Institute | And 11 more authors.
Journal of Infectious Diseases | Year: 2014

Interferon lambda 4 protein can be generated in IFNL4-ΔG carriers but not IFNL4-TT homozygotes. We studied 890 anti-hepatitis C virus (HCV)-positive participants in the Women's Interagency HIV Study. Among blacks (n = 555), HCV was more often cleared for those with genotype IFNL4-TT/TT (32.6%; odds ratio [OR], 3.59; P = 3.3 × 10-5) than IFNL4-TT/ΔG (11.3%; OR, 0.95; P =. 86) or IFNL4-ΔG/ΔG (11.9%; referent). Pooling these data with published results in blacks (n = 1678), ORs were 3.84 (P = 8.6 × 10-14) for IFNL4-TT/TT and 1.44 (P =. 03) IFNL4-TT/ΔG, and the area under the curve was 0.64 for IFNL4-ΔG genotype and 0.61 for rs12979860 (IL28B). IFNL4-ΔG is strongly associated with impaired spontaneous HCV clearance. © 2013 The Author.

PubMed | University of Southern California, Institute for Infectious Disease Research, Georgetown University, U.S. National Cancer Institute and 5 more.
Type: Journal Article | Journal: PloS one | Year: 2015

IFNL4-G/TT (rs368234815) genotype is associated with hepatitis C virus clearance and may play a role in other infections. IFN-4 protein is generated only in individuals who carry the IFNL4-G allele. The IFNL4 rs12979860-T allele, which is in strong linkage disequilibrium with IFNL4-G, was recently reported to be associated with more frequent and severe oral herpes episodes. We investigated the association of IFNL4-G/TT with herpes simplex virus (HSV)-related outcomes among 2,192 African American and European American participants in the Womens Interagency HIV Study (WIHS). WIHS is a prospective cohort study of human immunodeficiency virus (HIV)-infected and at-risk women that began in 1994. This report includes follow-up through 2013. Available data included: HSV-1 and HSV-2 antibodies at study entry; bi-annually ascertained episodes of (self-reported) oral herpes, (self-reported) genital sores and (clinician-observed) genital ulcers; HSV-2 DNA in cervicovaginal lavage (CVL) specimens. IFNL4-G/TT genotyping was determined by TaqMan. We compared women with IFNL4-G/G or IFNL4-TT/G genotypes (i.e., IFNL4-G carriers) to those with the IFNL4-TT/TT genotype, adjusting for age, race and HIV status. For outcomes with repeated measurements, the adjusted odds ratio (aOR), 95% confidence interval [CI] and p-value were determined using a generalized estimating equations approach. Median participant age at enrollment was 36 years; 81% were African American, 74% were HIV-infected. Among 1,431 participants tested for antibodies, 72.8% were positive for HSV-1 and 79.0% were positive for HSV-2. We observed no association between IFNL4-G/TT genotype and any outcome: HSV-1 or HSV-2 antibody prevalence (p>0.1, all comparisons); oral herpes (aOR, 1.2; p = 0.35); genital sores (aOR, 1.0; p = 0.71); genital ulcers (aOR, 1.1; p = 0.53); detectable HSV-2 DNA in CVL (N = 322; aOR, 0.71; p = 0.49); HSV-2 DNA level (p = 0.68). In this large prospective study, IFNL4-G/TT genotype was not associated with HSV-related outcomes, including episodes of oral or genital herpes.

Edlin B.R.,New York Medical College | Edlin B.R.,Institute for Infectious Disease Research | Eckhardt B.J.,New York Medical College | Shu M.A.,Beth Israel Deaconess Medical Center | And 2 more authors.
Hepatology | Year: 2015

Data from the 2003-2010 National Health and Nutrition Examination Survey (NHANES) indicate that about 3.6 million people in the United States have antibodies to the hepatitis C virus, of whom 2.7 million are currently infected. NHANES, however, excludes several high-risk populations from its sampling frame, including people who are incarcerated, homeless, or hospitalized; nursing home residents; active-duty military personnel; and people living on Indian reservations. We undertook a systematic review of peer-reviewed literature and sought out unpublished presentations and data to estimate the prevalence of hepatitis C in these excluded populations and in turn improve the estimate of the number of people with hepatitis C in the United States. The available data do not support a precise result, but we estimated that 1.0 million (range 0.4 million-1.8 million) persons excluded from the NHANES sampling frame have hepatitis C virus antibody, including 500,000 incarcerated people, 220,000 homeless people, 120,000 people living on Indian reservations, and 75,000 people in hospitals. Most are men. An estimated 0.8 million (range 0.3 million-1.5 million) are currently infected. Several additional sources of underestimation, including nonresponse bias and the underrepresentation of other groups at increased risk of hepatitis C that are not excluded from the NHANES sampling frame, were not addressed in this study. Conclusion: The number of US residents who have been infected with hepatitis C is unknown but is probably at least 4.6 million (range 3.4 million-6.0 million), and of these, at least 3.5 million (range 2.5 million-4.7 million) are currently infected; additional sources of potential underestimation suggest that the true prevalence could well be higher. © 2015 by the American Association for the Study of Liver Diseases.

PubMed | Centers for Disease Control and Prevention, ZevRoss Spatial Analysis, Rothschild, Institute for Infectious Disease Research and Emory University
Type: Journal Article | Journal: Annals of epidemiology | Year: 2016

Investigate whether characteristics of geographic areas are associated with condomless sex and injection-related risk behavior among racial/ethnic groups of people who inject drugs (PWID) in the United States.PWID were recruited from 19 metropolitan statistical areas for 2009 National HIV Behavioral Surveillance. Administrative data described ZIP codes, counties, and metropolitan statistical areas where PWID lived. Multilevel models, stratified by racial/ethnic groups, were used to assess relationships of place-based characteristics to condomless sex and injection-related risk behavior (sharing injection equipment).Among black PWID, living in the South (vs. Northeast) was associated with injection-related risk behavior (adjusted odds ratio [AOR]= 2.24, 95% confidence interval [CI]= 1.21-4.17; P= .011), and living in counties with higher percentages of unaffordable rental housing was associated with condomless sex (AOR= 1.02, 95% CI= 1.00-1.04; P= .046). Among white PWID, living in ZIP codes with greateraccessto drug treatment was negatively associated with condomless sex (AOR= 0.93, 95% CI=0.88-1.00; P= .038).Policies that increase access to affordable housing and drug treatment may make environments more conducive to safe sexual behaviors among black and white PWID. Future research designed to longitudinally explore the association between residence in the south and injection-related risk behavior might identify specific place-based features that sustain patterns of injection-related risk behavior.

PubMed | Centers for Disease Control and Prevention, Rothschild, ZevRoss SpatialAnalysis, Emory University and Institute for Infectious Disease Research
Type: | Journal: The International journal on drug policy | Year: 2016

Substantial racial/ethnic disparities exist in HIV infection among people who inject drugs (PWID) in many countries. To strengthen efforts to understand the causes of disparities in HIV-related outcomes and eliminate them, we expand the Risk Environment Model to encompass the construct racialized risk environments, and investigate whether PWID risk environments in the United States are racialized. Specifically, we investigate whether black and Latino PWID are more likely than white PWID to live in places that create vulnerability to adverse HIV-related outcomes.As part of the Centers for Disease Control and Preventions National HIV Behavioral Surveillance, 9170 PWID were sampled from 19 metropolitan statistical areas (MSAs) in 2009. Self-reported data were used to ascertain PWID race/ethnicity. Using Census data and other administrative sources, we characterized features of PWID risk environments at four geographic scales (i.e., ZIP codes, counties, MSAs, and states). Means for each feature of the risk environment were computed for each racial/ethnic group of PWID, and were compared across racial/ethnic groups.Almost universally across measures, black PWID were more likely than white PWID to live in environments associated with vulnerability to adverse HIV-related outcomes. Compared to white PWID, black PWID lived in ZIP codes with higher poverty rates and worse spatial access to substance abuse treatment and in counties with higher violent crime rates. Black PWID were less likely to live in states with laws facilitating sterile syringe access (e.g., laws permitting over-the-counter syringe sales). Latino/white differences in risk environments emerged at the MSA level (e.g., Latino PWID lived in MSAs with higher drug-related arrest rates).PWID risk environments in the US are racialized. Future research should explore the implications of this racialization for racial/ethnic disparities in HIV-related outcomes, using appropriate methods.

PubMed | University of Oxford, Institute for Infectious Disease Research and National and Kapodistrian University of Athens
Type: | Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases | Year: 2016

The number of public health applications for molecular epidemiology and social network analysis has increased rapidly since the improvement in computational capacities and the development of new sequencing techniques. Currently, molecular epidemiology methods are used in a variety of settings: from infectious disease surveillance systems to the description of disease transmission pathways. The latter are of great epidemiological importance as they let us describe how a virus spreads in a community, make predictions for the further epidemic developments, and plan preventive interventions. Social network methods are used to understand how infections spread through communities and what the risk factors for this are, as well as in improved contact tracing and message-dissemination interventions. Research is needed on how to combine molecular and social network data as both include essential, but not fully sufficient information on infection transmission pathways. The main differences between the two data sources are that, firstly, social network data include uninfected individuals unlike the molecular data sampled only from infected network members. Thus, social network data include more detailed picture of a network and can improve inferences made from molecular data. Secondly, network data refer to the current state and interactions within the social network, while molecular data refer to the time points when transmissions happened, which might have happened years before the sampling date. As of today, there have been attempts to combine and compare the data obtained from the two sources. Even though there is no consensus on whether and how social and genetic data complement each other, this research might significantly improve our understanding of how viruses spread through communities.

Moroz E.,Cornell College | Moroz E.,Sloan Kettering Cancer Center | Albrecht R.A.,Mount Sinai School of Medicine | Aden B.,Cornell College | And 6 more authors.
Vaccine | Year: 2016

Background: Influenza vaccination is recommended for vulnerable individuals, including active drug users, to prevent influenza complications and decrease influenza spread. Recent studies suggest that opioids negatively regulate immune responses in experimental models, but the extent to which opioid use will affect the humoral responses to influenza vaccine in humans is unknown. This information is critical in maximizing vaccination efforts. Objective: To determine whether there is a difference in antibody response after influenza vaccination in heroin or methadone users compared to control subjects. Methods: We studied active heroin users, subjects on methadone maintenance treatment (MMT) and subjects that did not use any drugs before and 1 and 4 weeks after vaccination with trivalent influenza vaccine (TIV). We measured hemagglutination inhibition and microneutralization titers, and we compared geometric mean titers (GMT), and rates of seroprotection and seroconversion for each of the vaccine strains among the 3 groups of subjects. Results: Heroin users, subjects on MMT and non-user controls mount a similarly robust serologic response to TIV. GMT and rates of seroprotection and seroconversion were not significantly different among groups. Conclusion: Our results suggest that opioid use do not significantly alter antibody responses to influenza vaccine supporting the vaccination effort in these populations. © 2016 Elsevier Ltd.

Swiercz J.P.,Institute for Infectious Disease Research | Nanji T.,McMaster University | Gloyd M.,McMaster University | Guarne A.,McMaster University | Elliot M.A.,Institute for Infectious Disease Research
Nucleic Acids Research | Year: 2013

Effective chromosome organization is central to the functioning of any cell. In bacteria, this organization is achieved through the concerted activity of multiple nucleoid-associated proteins. These proteins are not, however, universally conserved, and different groups of bacteria have distinct subsets that contribute to chromosome architecture. Here, we describe the characterization of a novel actinobacterial-specific protein in Streptomyces coelicolor. We show that sIHF (SCO1480) associates with the nucleoid and makes important contributions to chromosome condensation and chromosome segregation during Streptomyces sporulation. It also affects antibiotic production, suggesting an additional role in gene regulation. In vitro, sIHF binds DNA in a length-dependent but sequence-independent manner, without any obvious structural preferences. It does, however, impact the activity of topoisomerase, significantly altering DNA topology. The sIHF-DNA co-crystal structure reveals sIHF to be composed of two domains: a long N-terminal helix and a C-terminal helix-two turns-helix domain with two separate DNA interaction sites, suggesting a potential role in bridging DNA molecules. © 2013 The Author(s).

PubMed | Institute for Infectious Disease Research and New York University
Type: | Journal: AIDS and behavior | Year: 2017

Nonmedical prescription opioid use has become widespread. It can lead to heroin use, drug injection and HIV infection. We describe young adult opioid users sexual risk behavior, partnerships and settings. 464 youth aged 18-29 who reported opioid use in the past 30days were recruited using Respondent-Driven Sampling. Eligible participants completed a computer-assisted, interviewer-administered risk questionnaire and were tested for STIs and HIV. Participants (33% female; 66% white non-Hispanic) almost all had sex in the prior 90days; 42% reported more than one partner. Same-sex sex was reported by 3% of men and 10% of women. Consistent condom use was rare. Seven percent reported group sex participation in the last 90days but lifetime group sex was common among men and women. Young opioid users unprotected sex, multiple partners and group sex puts them and others at high HIV and STI risk.

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