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Increases in Acute Hepatitis C Virus Infection Related to a Growing Opioid Epidemic and Associated Injection Drug Use, United States, 2004 to 2014
 
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"National surveillance data show a substantial increase in the incidence of acute HCV infection throughout the United States from 2004 to 2014. This increase was significant for persons aged 18 to 39 years, women and men, and non-Hispanic Whites and Hispanics, with rates of acute HCV infection increasing almost 4-fold among women and more than 2-fold among men over the 11-year period. IDU was the most frequently cited risk factor, and in the current analysis more than 80% of acute case reports with an identified HCV-related risk indicated IDU in 2014......
 
........Parallel increases in acute HCV infections and treatment admissions attributed to POA injection occurred among women and men alike, yet both increased at a higher rate for women than for men, with the largest percentage change for both genders occurring among those aged 18 to 39 years. The increase in the number of women of childbearing age with acute HCV infection is consistent with reports showing increases in the number of infants born to HCV-infected mothers (68% increase from 2011 to 2014)21 and a 4-fold increase in overall incident cases of neonatal abstinence syndrome from 1999 to 2013.22 The upward trends in infants born to HCV-infected mothers and infants diagnosed with neonatal abstinence syndrome correspond with the time period and risk profiles associated with increases in both acute HCV infections and SUD treatment admissions for persons injecting any opioid. These trends illustrate the extraordinary burden of the opioid epidemic on the health of women and children in the United States.
 
........Although our findings further corroborate those of previous studies identifying a demographic shift in persons affected by acute HCV infection in the United States,11,19 of particular concern and not previously identified at the national level is the significant increase in both acute HCV infections and treatment admissions attributed to POA injection among Hispanics from 2004 to 2014. Although admissions for POA injection account for less than 1% of total SUD admissions among Hispanics, and heroin admissions comprise the majority of admissions attributed to the injection of any opioid for this population, the increase in the percentage of admissions for POA injection (429%) was significant and substantially higher over time than that for heroin injection (4%). Consistent with these findings are those of studies showing increases in the number of Hispanics dying from opioid-involved overdoses in certain regions of the country23,24 and IDU prevalence estimates increasing more than 20% in a substantial proportion of metropolitan statistical areas with large Hispanic populations (Las Vegas, NV; New Orleans, LA; Atlanta, GA; St. Louis, MO; Tacoma, WA; Jacksonville, FL; and Detroit, MI, among others).25"

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Increases in Acute Hepatitis C Virus Infection Related to a Growing Opioid Epidemic and Associated Injection Drug Use, United States, 2004 to 2014
 
Amer Jnl of Public Health Feb 2018
 
"A total of 12 953 cases of acute HCV infection were reported in the United States from 2004 to 2014. The annual incidence rate of acute HCV infection increased significantly from 0.3 cases per 100 000 in 2004 to 0.7 cases per 100 000 in 2014 (P < .001), representing an overall rate increase of 133% (Figure 1; Table A, available as a supplement to the online version of this article at http://www.ajph.org). Annual increases in incidence over the 11-year period were also observed among persons in all age, gender, and race/ethnicity categories. The largest increases (> 100%) were among persons aged 18 to 29 and 30 to 39 years (400% and 325%, respectively), non-Hispanic Whites, and Hispanics. Increases were statistically significant among persons aged 18 to 29 years (P < .001) and 30 to 39 years (P < .001), for both women and men (P < .001) and among non-Hispanic Whites (P < .001) and Hispanics (P < .001). In almost every year from 2004 to 2014, IDU was reported in 60% or more of cases that included risk factor data, with more than 75% of cases reporting IDU each year from 2011 to 2014 (Table A). Of the 68% (836) of cases that included risk factor data in 2014, 84% (702) indicated IDU. The demographic characteristics and behavioral risk factors associated with the increase in cases of acute HCV infection correspond to the populations and behaviors that characterize the nation's opioid epidemic.
 
Of the 40 states with data reported to NNDSS for all years (2004-2014), an increase over time of 500% or higher in the number of cases of acute HCV infection was found in 15 states, with 6 states (Kansas, Maine, New Jersey, Wisconsin, Ohio, and Massachusetts) showing increases of 1000% or higher (Table C, available as a supplement to the online version of this article at http://www.ajph.org). Only 7 states (Delaware, North Dakota, Nevada, Texas, Vermont, South Carolina, and Michigan) saw decreases in reported cases of acute HCV infection over the 11-year period.....Among persons aged 12 to 17 years, admissions for any opioid injection, heroin injection, and POA injection increased 103% (P = .005), 97% (P = .008), and 194% (P = .020), respectively (Table B; Figure 2). Over this same time period, the percentage of admissions attributed to heroin injection significantly increased for both women and men (89% and 83%, respectively), as did those for POA injection (263% and 249%, respectively). We observed no significant changes over time for nonopioid injection admissions for either women or men.....Of the 50 states and the District of Columbia with reported TEDS data each year from 2004 to 2014, we found an increase over time of 500% or higher in the number of admissions for POA injection in 8 states, with 5 states (Arizona, Florida, New Hampshire, New Mexico, and West Virginia) showing increases of 1000% or higher (Table D, available as a supplement to the online version of this article at http://www.ajph.org)."
 
Jon E. Zibbell, PhD, Alice K. Asher, PhD, Rajiv C. Patel, MPH, Ben Kupronis, MPH, Kashif Iqbal, MPH, John W. Ward, MD, and Deborah Holtzman, PhD Jon E. Zibbell is with the Behavioral and Urban Health Program, RTI International, Atlanta, GA. Alice K. Asher is with the Epidemiology, Surveillance and Prevention among Substance users Unit, Epidemiology and Surveillance Branch, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention, Atlanta, GA. Rajiv C. Patel is a second year Medical Student with Virginia Commonwealth University, Richmond, VA. Ben Kupronis is with the Epidemiology and Surveillance Branch, Division of Viral Hepatitis, NCHHSTP, Centers for Disease Control and Prevention. Kashif Iqbal is with the Epidemiology Branch, Division of HIV/ AIDS Prevention,NCHHSTP, Centers for Disease Control and Prevention. John W.Ward and Deborah Holtzman are with the Division of Viral Hepatitis, NCHHSTP, Centers for Disease Control and Prevention.
 
Abstract
 
Objectives. To compare US trends in rates of injection drug use (IDU), specifically opioid injection, with national trends in the incidence of acute HCV infection to assess whether these events correlated over time.
 
Methods. We calculated the annual incidence rate and demographic and risk characteristics of reported cases of acute HCV infection using surveillance data from 2004 to 2014 and the annual percentage of admissions to substance use disorder treatment facilities reporting IDU for the same time period by type of drug injected and demographic characteristics. We then tested for trends.
 
Results. The annual incidence rate of acute HCV infection increased more than 2-fold (from 0.3 to 0.7 cases/100 000) from 2004 to 2014, with significant increases among select demographic subgroups. Admissions for substance use disorder attributed to injection of heroin and prescription opioid analgesics increased significantly, with an almost 4-fold increase in prescription opioid analgesic injection. Significant increases in opioid injection mirrored those for reported cases of acute HCV infection among demographic subgroups.
 
Conclusions. These findings strongly suggest that the national increase in acute HCV infection is related to the country's opioid epidemic and associated increases in IDU. Hepatitis C virus infection is the most common chronic blood-borne infection in the United States and a substantial cause of morbidity and mortality.1 Injection drug use (IDU) is the primary risk factor for HCV transmission and the leading cause of incidence in the United States.2 HCV infection can occur rapidly after IDU initiation: A meta-analysis examining the time from onset of injection to incidence of HCV infection found a cumulative incidence of 28% (95% confidence interval = 17%, 42%) at 1 year of drug injection.3 Consequently, once the virus is introduced into a network of persons who inject drugs (PWID), it can circulate quickly through the reuse of contaminated drug injection equipment-specifically, needles, syringes, cookers, and filters.4,5 Other factors associated with increased risk for HCV infection include having a high injection frequency,6 using high dead-space syringes,7 and injecting prescription opioid analgesics (POAs).8,9
 
The demographic characteristics and behavioral risk factors associated with the increase in cases of acute HCV infection correspond to the populations and behaviors that characterize the nation's opioid epidemic. State surveillance data indicate a nationwide increase in reported cases of acute HCV infection since 2004, with the largest increases occurring east of the Mississippi River and exceptionally high concentrations in central Appalachia.10 Findings from an analysis of data of 4 central Appalachian states from 2006 to 2012 showed that 45% of the increases in acute cases of HCV infection were among young persons (aged ≤ 30 years), with nearly three-quarters (196/265) of persons who reported a risk factor citing IDU.11 Over the same time period, these 4 states also experienced a significant increase in the proportion of young persons admitted to substance use disorder (SUD) treatment who reported injecting opioids, including heroin and POAs. Similar increases in IDU and HCV infection have been documented in Massachusetts,12 Wisconsin,13 and New York,14 and most recently a major HIV outbreak in southeastern Indiana was facilitated by the injection of the prescription opioid oxymorphone, with 92% of persons newly identified with HIV coinfected with HCV.15 Overall, these reports suggest that national increases in acute HCV infections are being fueled by the nation's opioid epidemic.
 
To improve our understanding of the relationship between the epidemics of acute HCV infection and opioid use and misuse, we extend our previous 4-state analysis of central Appalachia11 to the country as a whole. In this work, we examine cases of acute HCV infection reported by US states from 2004 to 2014 in conjunction with analyzing national SUD admissions data from the Substance Abuse and Mental Health Services Administration's (SAMHSA's) Treatment Episode Data Set-Admissions (TEDS) for trends in any opioid injection, heroin injection, POA injection, and other (i.e., nonopioid drug) injection for the same time period. We expected to find concurrent increases in SUD treatment admissions among persons with opioid use disorders who inject drugs and acute HCV infections on a national scale, echoing the dual epidemics previously identified in Appalachia.
 
RESULTS
 
From 2004 to 2014, we found significant concurrent increases in reported cases of acute HCV infection and reported treatment admissions for injection of opioids. These increases were observed for the nation as a whole and among select demographic populations.
 
National Notifiable Disease Surveillance System
 
A total of 12 953 cases of acute HCV infection were reported in the United States from 2004 to 2014. The annual incidence rate of acute HCV infection increased significantly from 0.3 cases per 100 000 in 2004 to 0.7 cases per 100 000 in 2014 (P < .001), representing an overall rate increase of 133% (Figure 1; Table A, available as a supplement to the online version of this article at http://www.ajph.org). Annual increases in incidence over the 11-year period were also observed among persons in all age, gender, and race/ethnicity categories. The largest increases (> 100%) were among persons aged 18 to 29 and 30 to 39 years (400% and 325%, respectively), non-Hispanic Whites, and Hispanics. Increases were statistically significant among persons aged 18 to 29 years (P < .001) and 30 to 39 years (P < .001), for both women and men (P < .001) and among non-Hispanic Whites (P < .001) and Hispanics (P < .001). In almost every year from 2004 to 2014, IDU was reported in 60% or more of cases that included risk factor data, with more than 75% of cases reporting IDU each year from 2011 to 2014 (Table A). Of the 68% (836) of cases that included risk factor data in 2014, 84% (702) indicated IDU. Of the 40 states with data reported to NNDSS for all years (2004-2014), an increase over time of 500% or higher in the number of cases of acute HCV infection was found in 15 states, with 6 states (Kansas, Maine, New Jersey, Wisconsin, Ohio, and Massachusetts) showing increases of 1000% or higher (Table C, available as a supplement to the online version of this article at http://www.ajph.org. Only 7 states (Delaware, North Dakota, Nevada, Texas, Vermont, South Carolina, and Michigan) saw decreases in reported cases of acute HCV infection over the 11-year period.
 
Treatment Episode Data Set-Admissions
 
Among all admissions reported to TEDS from 2004 to 2014, admissions attributed to any IDU increased 76%, and admissions attributed to heroin injection and POA injection both increased significantly by 85% and 258%, respectively (Figure 2; Table B, available as a supplement to the online version of this article at http://www.ajph.org). In 2004, 13% of all admissions reported IDU compared with 22% reporting IDU in 2014. Among all reported admissions, the percentage of those reporting injection of any opioid increased 93% (P < .001) from 2004 to 2014 (10% in 2004 to 19% in 2014), whereas admissions for other nonopioid injection showed no significant change over time.
 
Among persons aged 12 to 17 years, admissions for any opioid injection, heroin injection, and POA injection increased 103% (P = .005), 97% (P = .008), and 194% (P = .020), respectively (Table B; Figure 2). Among persons aged 18 to 29 years, admissions significantly increased for any opioid injection (622%), heroin injection (603%), and POA injection (817%). Among persons aged 30 to 39 years, admissions significantly increased for any opioid injection (83%), heroin injection (77%), and POA injection (169%). We observed no significant increases among persons aged 40 to 49 years for all categories except POA injection. Among persons aged 50 years or older, all injection categories significantly decreased, except POA injection, which showed no significant change over time.
 
From 2004 to 2014, the percentage of admissions attributed to any opioid injection increased significantly for both women and men (99% and 89%, respectively; Table B; Figure 3). Over this same time period, the percentage of admissions attributed to heroin injection significantly increased for both women and men (89% and 83%, respectively), as did those for POA injection (263% and 249%, respectively). We observed no significant changes over time for nonopioid injection admissions for either women or men. Among non-Hispanic Whites, admissions attributed to any opioid injection significantly increased 134% over the 11-year period, with heroin injection increasing 126% and POA injection increasing 248% (Table B). Among non-Hispanic Blacks and Hispanics, only admissions attributed to POA injection increased significantly (167% and 429%, respectively).
 
Of the 50 states and the District of Columbia with reported TEDS data each year from 2004 to 2014, we found an increase over time of 500% or higher in the number of admissions for POA injection in 8 states, with 5 states (Arizona, Florida, New Hampshire, New Mexico, and West Virginia) showing increases of 1000% or higher (Table D, available as a supplement to the online version of this article at http://www.ajph.org). For heroin injection admissions, 5 states and the District of Columbia saw increases of 500% or higher, and 2 states (Kentucky and West Virginia) and the District of Columbia saw increases of 1000% or higher. No state reported a decrease in admissions for POA injection, although Hawaii reported a decrease in admissions for heroin injection over the 11-year period. Results from the scatterplot showed a positive correlation, which increased in strength over time, between state rates of acute HCV infection and the corresponding state percentage of treatment admissions reporting any opioid IDU (Figure 3).
 
METHODS
 
We obtained confirmed cases of acute HCV infection and associated demographic and risk characteristics from the National Notifiable Disease Surveillance System (NNDSS) for 2004 to 2014.16 The surveillance case definition for confirmed acute HCV infection requires satisfying clinical and laboratory criteria as defined by the Council of State and Territorial Epidemiologists. From 2004 to 2014, all cases of acute HCV infection had laboratory-confirmed infection with acute illness of discreet onset. Acute illness was considered as the presence of any sign or symptom of acute viral hepatitis plus either jaundice or elevated liver enzyme levels. In 2012, the surveillance case definition was modified to include cases with a documented negative HCV antibody test result followed by a positive result within 6 months. Demographic characteristics included age, gender, race/ethnicity, and state of residence. Of cases that included risk factor data from 2004 to 2014, we report the proportion indicating IDU.
 
National Estimates of Acute Hepatitis C Virus Infection
 
We used NNDSS data from 2004 to 2014 to assess the annual incidence rate (per 100 000 persons) and demographic and risk characteristics of reported cases of acute HCV infection among persons of all ages. To calculate annual incidence, we stratified cases reported through NNDSS by year, age, gender, and race/ethnicity categories as numerators and midyear (July) population estimates from the US Census Bureau17 as denominators. Statistical significance of a linear trend in annual incidence of acute HCV infection by year, age, gender, and race/ethnicity was assessed using the Spearman correlation trend test. Changes in incidence over time were considered statistically significant at P < .05. We conducted analyses using SAS version 9.4 (SAS Institute Inc., Cary, NC).
 
Treatment Episode Data Set-Admissions
 
TEDS is a national data system administered by SAMHSA. It collects information on annual admissions to SUD treatment facilities in the United States. TEDS contains data on admissions to publicly funded and state-certified SUD treatment facilities by year and by state of treatment facility for all persons aged 12 years or older. By state law, treatment facilities provide data to TEDS. TEDS is estimated to include 67% of all SUD treatment admissions and 83% of TEDS-eligible admissions in the United States. For each admission, up to 3 substances of abuse with a corresponding route of administration and demographic characteristics may be reported. Reportable substances of abuse, data collection methods, and limitations of TEDS have previously been listed.18 TEDS classifies opioids into 3 categories: heroin, nonprescription methadone, and opiates and synthetics. For this analysis, 3 types of opioid drug injection were defined: any opioid injection (includes heroin, nonprescription methadone, and opiates and synthetics), heroin injection, and POA injection (includes nonprescription methadone and opiates and synthetics). We compare the percentages of the 3 categories of opioid injection with that of a fourth category, nonopioid injection (includes injection of drugs not classified as opioids, e.g., cocaine and methamphetamine).
 
National Estimates
 
We calculated the national annual percentage of admissions reporting any IDU and any opioid injection, heroin injection, POA injection, and nonopioid injection among all admissions in TEDS for 2004 to 2014. Additionally, we calculated the annual percentage of admissions reporting any opioid injection, heroin injection, POA injection, and other injection by age group (12-17, 18-29, 30-39, 40-49, and ≥ 50 years), gender (female, male), and race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic). We report the percentage difference and percentage change from 2004 to 2014 for each indicator. Denominators for all annual percentages are the total number of reported treatment admissions in that year for each respective demographic group. Statistical significance of a linear trend from 2004 to 2014 was assessed using the Mann-Kendall test for trend and was considered significant at P < .05. We generated all TEDS analyses using R version 3.3.2 (R Foundation for Statistical Learning, Vienna, Austria).
 
State-Level Estimates
 
We also calculated the annual percentage of cases of acute HCV infection by state from 2004 to 2014. Denominators for each year were calculated using midyear (July) population estimates for each state. In addition, we calculated the annual percentage of admissions for any IDU, heroin injection, and POA injection and report the percentage change for these 3 indicators over the 11-year period by state. Some states did not have admissions data available for 2004, 2014, or both years. When 2004 data were missing, we used the next available year (i.e., 2005) to calculate percentage differences and percentage change. When 2014 data were missing, we used the latest year for which data were available (i.e., 2013) to calculate percentage difference and percentage change. Denominators for all annual percentages are the total number of reported treatment admissions within each state in that year. Last, we examined scatterplots to further gauge the relationship between state-level rates of acute HCV infection and the percentage of treatment admissions reporting the injection of any opioid. Rates of acute HCV infection were plotted on the y-axis and percentage of treatment admissions for any opioid IDU was plotted on the x-axis for 2004, 2009, and 2014. We fit a linear trend line and calculated the R2.

 
 
 
 
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