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Objective Approximately 2.4 million people in the United States are living with hepatitis C virus (HCV) infection. The objective of our study was to describe demographic and socioeconomic characteristics, liver disease–related risk factors, and modifiable health behaviors associated with self-reported testing for HCV infection among adults. Methods Using data on adult respondents aged ≥18 from the 2013-2017 National Health Interview Survey, we summarized descriptive data on sociodemographic characteristics and liver disease–related risk factors and stratified data by educational attainment. We used weighted logistic regression to examine predictors of HCV testing. Results During the study period, 11.7% (95% CI, 11.5%-12.0%) of adults reported ever being tested for HCV infection. Testing was higher in 2017 than in 2013 (adjusted odds ratio [aOR] = 1.27; 95% CI, 1.18-1.36). Adults with ≥some college were significantly more likely to report being tested (aOR = 1.60; 95% CI, 1.52-1.69) than adults with ≤high school education. Among adults with ≤high school education (but not adults with ≥some college), those who did not have health insurance were less likely than those with private health insurance (aOR = 0.78; 95% CI, 0.68-0.89) to get tested, and non–US-born adults were less likely than US-born adults to get tested (aOR = 0.77; 95% CI, 0.68-0.87). Conclusions Rates of self-reported HCV testing increased from 2013 to 2017, but testing rates remained low. Demographic characteristics, health behaviors, and liver disease–related risk factors may affect HCV testing rates among adults. HCV testing must increase to achieve hepatitis C elimination targets.

Hepatitis C virus (HCV) infection is a public health threat. The electronic health record (EHR) can be used to monitor patients along the HCV cure cascade and highlight opportunities for interventions to improve cascade outcomes. We developed an HCV patient registry using data from Grady Health System's (GHS) EHR and performed a cross-sectional analysis of 72 745 GHS patients who received anti-HCV testing from 2004 to 2016. We created a testing cascade: (1) anti-HCV reactive, (2) HCV RNA tested and (3) HCV RNA detectable; and a cure cascade: (1) HCV RNA detectable, (2) engaged in care, (3) treatment prescribed, (4) sustained virologic response (SVR) tested and (5) SVR documented. A total of 9893 (14%) had reactive anti-HCV tests of 72 745 patients tested, 5109 (52%) of these had HCV RNA tested, and 4224 (43%) were HCV RNA detectable. A total of 2738 (65%) of 4224 with detectable RNA were engaged in care, 909 (22%) were prescribed antiviral therapy, and 354 (8%) achieved SVR. Factors associated with HCV treatment included cirrhosis, tobacco use, depression, diabetes, obesity, alcohol use, male gender, black race and Medicare insurance. Uninsured patients were significantly less likely to be prescribed HCV treatment. In conclusion, using EHR data, we identified high anti-HCV prevalence and noted gaps in HCV RNA testing, linkage to care and treatment. The EHR can be used to evaluate the effectiveness of targeted interventions to overcome these gaps.

To estimate the clinical effects and cost-effectiveness of universal prenatal hepatitis C screening, and to calculate potential life expectancy, quality of life, and health care costs associated with universal prenatal hepatitis C screening and linkage to treatment.Using a stochastic individual-level microsimulation model, we simulated the lifetimes of 250 million pregnant women matched at baseline with the U.S. childbearing population on age, injection drug use behaviors, and hepatitis C virus (HCV) infection status. Modeled outcomes included hepatitis C diagnosis, treatment and cure, lifetime health care costs, quality-adjusted life years (QALY) and incremental cost-effectiveness ratios comparing universal prenatal hepatitis C screening to current practice. We modeled whether neonates exposed to maternal HCV at birth were identified as such.Pregnant women with hepatitis C infection lived 1.21 years longer and had 16% lower HCV-attributable mortality with universal prenatal hepatitis C screening, which had an incremental cost-effectiveness ratio of $41,000 per QALY gained compared with current practice. Incremental cost-effectiveness ratios remained below $100,000 per QALY gained in most sensitivity analyses; notable exceptions included incremental cost-effectiveness ratios above $100,000 when assuming mean time to cirrhosis of 70 years, a cost greater than $500,000 per false positive diagnosis, or population HCV infection prevalence below 0.16%. Universal prenatal hepatitis C screening increased identification of neonates exposed to HCV at birth from 44% to 92%.In our model, universal prenatal hepatitis C screening improves health outcomes in women with HCV infection, improves identification of HCV exposure in neonates born at risk, and is cost-effective.

AIM To investigate hepatitis C virus (HCV) testing recommendations from the United States and other high-income countries. METHODS A comprehensive search for current HCV testing recommendations from the top quartile of United Nations Human Development Index (HDI) countries (very high HDI) was performed using Google and reviewed from May 1 - October 30, 2014 and re-reviewed April 1 - October 2, 2017. RESULTS Of the 51 countries identified, 16 had HCV testing recommendations from a government body or recommendations issued collaboratively between a government and a medical organization. Of these 16 countries, 15 had HCV testing recommendations that were primarily risk-based and highlight behaviors, exposures, and conditions that are associated with HCV transmission in that region. In addition to risk-based testing, the HCV Guidance Panel (United States) incorporates recommendations for a one-time test for individuals born during 1945-1965 (the birth cohort) without prior ascertainment of risk into their guidance. In addition to the United States, six other countries either have an age-based testing recommendation or recommend one-time testing for all adults independent of risk factors typical of the region. CONCLUSION This review affirmed the similarities of the HCV Guidance Panel’s guidance with those of recommendations from very high HDI countries.

Summary Hepatitis B virus (HBV) is transmitted via blood or sexual contact. Persons with chronic HBV infection are at increased risk for cirrhosis and liver cancer and require medical care. This report updates and summarizes previously published recommendations from the Advisory Committee on Immunization Practices (ACIP) and CDC regarding the prevention of HBV infection in the United States. ACIP recommends testing all pregnant women for hepatitis B surface antigen (HBsAg), and testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA); administration of HepB vaccine and hepatitis B immune globulin (HBIG) for infants born to HBV-infected women within 12 hours of birth, followed by completion of the vaccine series and postvaccination serologic testing; universal hepatitis B vaccination within 24 hours of birth, followed by completion of the vaccine series; and vaccination of children and adolescents aged

Background and aims Effective strategies are needed to address dramatic increases in hepatitis C virus (HCV) infection among people who inject drugs (PWID) in rural settings of the United States. We determined the required scale-up of HCV treatment with or without scale-up of HCV prevention interventions to achieve a 90% reduction in HCV chronic prevalence or incidence by 2025 and 2030 in a rural US setting. Design An ordinary differential equation model of HCV transmission calibrated to HCV epidemiological data obtained primarily from an HIV outbreak investigation in Indiana. Setting Scott County, Indiana (population 24 181), USA, a rural setting with negligible baseline interventions, increasing HCV epidemic since 2010, and 55.3% chronic HCV prevalence among PWID in 2015. Participants PWID. Measurements Required annual HCV treatments per 1000 PWID (and initial annual percentage of infections treated) to achieve a 90% reduction in HCV chronic prevalence or incidence by 2025/30, either with or without scaling-up syringe service programmes (SSPs) and medication-assisted treatment (MAT) to 50% coverage. Sensitivity analyses considered whether this impact could be achieved without re-treatment of re-infections, and whether greater intervention scale-up was required due to the increasing epidemic in this setting. Findings To achieve a 90% reduction in incidence and prevalence by 2030, without MAT and SSP scale-up, 159 per 1000 PWID (initially 24.9% of infected PWID) need to be HCV-treated annually. However, with MAT and SSP scaled-up, treatment rates are halved (89 per 1000 annually or 14.5%). To reach the same target by 2025 with MAT and SSP scaled-up, 121 per 1000 PWID (19.9%) need treatment annually. These treatment requirements are threefold higher than if the epidemic was stable, and the impact targets are unattainable without retreatment. Conclusions Combined scale-up of hepatitis C virus treatment and prevention interventions is needed to decrease the increasing burden of hepatitis C virus incidence and prevalence in rural Indiana, USA, by 90% by 2025/30.

Using commercial laboratory data, we found 80% of 29382 young persons currently infected with hepatitis C virus lived >10 miles from a syringe services program. The median distance was 37 miles, with greater distances in rural areas and Southern and Midwestern states. Strategies to improve access to preventive services are warranted.

Hepatitis C (HCV) and HIV have common modes of transmission but information about HCV transmission risk, prevention, and treatment among persons with coinfection is lacking. The Medical Monitoring Project produces nationally representative estimates describing adults with diagnosed HIV in the United States. Using medical record data recorded during 6/2013-5/2017, we identified persons with detectable HCV RNA documented during the past 24 months. Among persons with coinfection, we described HCV transmission risk factors and receipt of HCV prevention services during the past 12 months and prescription of HCV treatment during the past 24 months. Overall, 4.9% had documented active HCV coinfection, among whom 30.2% were men who have sex with men (MSM), 6.7% reported injection drug use, and 62.1% were prescribed HCV treatment. Among MSM, 45.5% reported condomless anal sex and 42.3% received free condoms. Among persons who used drugs, 30.8% received drug or alcohol counseling, and among persons who injected drugs, 79.2% received sterile syringes. Among persons with HIV/HCV coinfection, recent drug injection was uncommon and most received sterile syringes. However, 1 in 3 were MSM, of whom half reported recent HCV sexual transmission risk behaviors. More than one-third of those with coinfection were not prescribed curative HCV treatment.

Aims To examine the cost-effectiveness of hepatitis C virus (HCV) treatment of people who inject drugs (PWID), combined with medication-assisted treatment (MAT) and syringe-service programs (SSP), to tackle the increasing HCV epidemic in the United States. DesignHCV transmission and disease progression models with cost-effectiveness analysis using a health-care perspective. Setting Rural Perry County, KY (PC) and urban San Francisco, CA (SF), USA. Compared with PC, SF has a greater proportion of PWID with access to MAT or SSP. HCV treatment of PWID is negligible in both settings. Participants PWID data were collected between 1998 and 2015 from Social Networks Among Appalachian People, U Find Out, Urban Health Study and National HIV Behavioral Surveillance System studies. Interventions and comparator Three intervention scenarios modeled: baseline—existing SSP and MAT coverage with HCV screening and treatment with direct-acting antiviral for ex-injectors only as per standard of care; intervention 1—scale-up of SSP and MAT without changes to treatment; and intervention 2—scale-up as intervention 1 combined with HCV screening and treatment for current PWID. Measurements Incremental cost-effectiveness ratios (ICERs) and uncertainty using cost-effectiveness acceptability curves. Benefits were measured in quality-adjusted life-years (QALYs). Findings For both settings, intervention 2 is preferred to intervention 1 and the appropriate comparator for intervention 2 is the baseline scenario. Relative to baseline, for PC intervention 2 averts 1852 more HCV infections, increases QALYS by 3095, costs $21.6 million more and has an ICER of $6975/QALY. For SF, intervention 2 averts 36 473 more HCV infections, increases QALYs by 7893, costs $872 million more and has an ICER of $11 044/QALY. The cost-effectiveness of intervention 2 was robust to several sensitivity analysis. Conclusions Hepatitis C screening and treatment for people who inject drugs, combined with medication-assisted treatment and syringe-service programs, is a cost-effective strategy for reducing hepatitis C burden in the United States.

Objective Using a large nationally representative dataset, we estimated the prevalence of self-reported hepatitis C testing among individuals who were recommended to be tested (i.e., baby boomer cohort born between 1945 and 1965) by the CDC and United States Preventive Services Task Force. Introduction Hepatitis C virus (HCV) infection is the most common blood-borne disease in the US and the leading cause of liver-related morbidity and mortality. Approximately 3.5 million individuals in the US were estimated to have been living with hepatitis C in 2010 and approximately half of them were unaware that they were infected. Among HCV infected individuals, those born between 1945 and 1965 (usually referred to as the baby boomer cohort) represents approximately 75% of current cases. Because of the substantial burden of disease among this age group, CDC expanded its existing hepatitis C risk-based testing recommendations to include a one-time HCV antibody test for all persons born between 1945 and 1965. The United States Preventive Services Task Force (USPSTF) subsequently made the same recommendation in June 2013. Description Methods The following question "Have you ever had a blood test for hepatitis C?" has been administered annually from 2013 through 2017 on the National Health Interview Survey (NHIS). The NHIS is a nationally representative cross-sectional face-to-face household interview of civilian noninstitutionalized individuals in the U.S. The NHIS survey uses a complex multistage probability design that includes stratification, clustering, and oversampling. We estimated the prevalence of hepatitis C testing for adults in the US during the study period from 2013 to 2017. In addition, we carried out stratified analyses comparing those with private insurance to those who did not have private insurance. We reported weighted estimates taking into account the NHIS survey design. The R statistical software (R Core Team, 2018) was used to estimate weighted prevalence estimates for hepatitis C testing. Results During the study period from 2013-2017, there were 148,674 adults who responded to the ever tested for hepatitis C question. In addition, 33.56% of these individuals were born between 1945 and 1965; among all adults, the weighted percentage of individuals that responded yes they had received a hepatitis C screening test was 12.82% (95% CI: 12.54-13.10%) while for baby boomers the estimate was 13.93% (95% CI: 13.51-14.35%). Figure 1 presents the annual trend in the hepatitis C test prevalence over the study period by birth cohorts. For both cohorts, there were significant increases over time in hepatitis C testing prevalence. The two trend lines began to diverge in 2015 with the baby boomer cohort reporting higher rates of hepatitis C testing. For the baby boomer cohort, there was also a substantial increase in reported hepatitis C testing in 2017 relative to 2016. Similar trends were found for the samples when we restricted the sample to only those with private insurance. Compared to the people with private insurance, the baby boomers with 'Non-private’ insurance, including Medicaid, Medicare, or military- government sponsored insurances, reported higher rates of testing. Conclusion Across the five-year period from 2013 through 2017, we found increasing rates of self-reported hepatitis C testing among non-institutionalized U.S. adults. For the baby boomer cohort, we saw a substantial increase in testing in 2017, which was likely due in part, to increased awareness among both physicians and patients of the CDC and USPSTF recommendation to have all baby boomers tested. Efforts to increase the awareness of these recommendations should continue. Additional targeted promotions among hard to reach populations should also be considered. How the Moderator Intends to Engage the Audience in Discussions on the Topic This panel will discuss strengths and weaknesses for monitoring hepatitis C testing using alternative data sources including self-reported data, insurance claims data, and laboratory testing data.

To better understand hepatitis C virus (HCV) epidemiology in Punjab state, India, we estimated the distribution of HCV antibody positivity (anti-HCV+) using a 2013–2014 HCV household seroprevalence survey. Household anti-HCV+ clustering was investigated (a) by individual-level multivariable logistic regression, and (b) comparing the observed frequency of households with multiple anti-HCV+ persons against the expected, simulated frequency assuming anti-HCV+ persons are randomly distributed. Village/ward-level clustering was investigated similarly. We estimated household-level associations between exposures and the number of anti-HCV+ members in a household (N= 1593 households) using multivariable ordered logistic regression. Anti-HCV+ prevalence was 3.6% (95% confidence interval 3.0–4.2%). Individual-level regression (N= 5543 participants) found an odds ratio of 3.19 (2.25–4.50) for someone being anti-HCV+ if another household member was anti-HCV+. Thirty households surveyed had ⩾2 anti-HCV+ members, whereas 0/1000 (P< 0.001) simulations had ⩾30 such households. Excess village-level clustering was evident: 10 villages had ⩾6 anti-HCV+ members, occurring in 31/1000 simulations (P= 0.031). The household-level model indicated the number of household members, living in southern Punjab, lower socio-economic score, and a higher proportion having ever used opium/bhuki were associated with a household's number of anti-HCV+ members. Anti-HCV+ clusters within households and villages in Punjab, India. These data should be used to inform screening efforts.

Background Hepatitis C virus (HCV) testing and treatment uptake in prisons remains low. We aimed to estimate clinical outcomes, cost-effectiveness (CE), and budgetary impact (BI) of HCV testing and treatment in United States (US) prisons or linkage to care at release. Methods We used individual-based simulation modeling with healthcare and Department of Corrections (DOC) perspectives for CE and BI analyses, respectively. We simulated a US prison cohort at entry using published data and Washington State DOC individual-level data. We considered permutations of testing (risk factor based, routine at entry or at release, no testing), treatment (if liver fibrosis stage ≥F3, for all HCV infected or no treatment), and linkage to care (at release or no linkage). Outcomes included quality-adjusted life-years (QALY); cases identified, treated, and cured; cirrhosis cases avoided; incremental cost-effectiveness ratios; DOC costs (2016 US dollars); and BI (healthcare cost/prison entrant) to generalize to other states. Results Compared to “no testing, no treatment, and no linkage to care,” the “test all, treat all, and linkage to care at release” model increased the lifetime sustained virologic response by 23%, reduced cirrhosis cases by 54% at a DOC annual additional cost of $1440 per prison entrant, and would be cost-effective. At current drug prices, targeted testing and liver fibrosis–based treatment provided worse outcomes at higher cost or worse outcomes at higher cost per QALY gained. In sensitivity analysis, fibrosis-based treatment restrictions were cost-effective at previous higher drug costs. Conclusions Although costly, widespread testing and treatment in prisons is considered to be of good value at current drug prices.

In the United States, hepatitis C virus (HCV) transmission is rising among people who inject drugs (PWID). Many regions have insufficient prevention intervention coverage. Using modeling, we investigated the impact of scaling up prevention and treatment interventions on HCV transmission among PWID in Perry County, Kentucky, and San Francisco, California, where HCV seroprevalence among PWID is >50%. A greater proportion of PWID access medication-assisted treatment (MAT) or syringe service programs (SSP) in urban San Francisco (established community) than in rural Perry County (young, expanding community). We modeled the proportion of HCV-infected PWID needing HCV treatment annually to reduce HCV incidence by 90% by 2030, with and without MAT scale-up (50% coverage, both settings) and SSP scale-up (Perry County only) from 2017. With current MAT and SSP coverage during 2017–2030, HCV incidence would increase in Perry County (from 21.3 to 22.6 per 100 person-years) and decrease in San Francisco (from 12.9 to 11.9 per 100 person-years). With concurrent MAT and SSP scale-up, 5% per year of HCV-infected PWID would need HCV treatment in Perry County to achieve incidence targets—13% per year without MAT and SSP scale-up. In San Francisco, a similar proportion would need HCV treatment (10% per year) irrespective of MAT scale-up. Reaching the same impact by 2025 would require increases in treatment rates of 45%–82%. Achievable provision of HCV treatment, alongside MAT and SSP scale-up (Perry County) and MAT scale-up (San Francisco), could reduce HCV incidence.

ObjectiveTo evaluate the use of commercial laboratory data for monitoring trends in HAV infections over time and identifying geographic and demographic characteristics of HAV case clusters for the purpose of targeting interventions.IntroductionHepatitis A virus (HAV) infections have persisted in the United States despite the availability of an effective vaccine. Recent outbreaks of HAV infections among unvaccinated adults attributed to consumption of HAV-contaminated food, or person-to-person contact in certain populations (e.g., men who have sex with men) or settings (e.g., homeless shelters) have emphasized the importance of targeted vaccination of at-risk adults.MethodsWe used commercial laboratory data from Quest Diagnostics (Quest) and Laboratory Corporation of America (LabCorp) to identify unique individuals within each database who tested positive for HAV IgM antibody (indicative of acute HAV infection) from January 2011 through June 2017. Though de-depulication across the two laboratories was not possible, comparison of case characteristics indicated limited possible overlap of cases (

Nurses are on the front lines of health care delivery, and many of them routinely administer immunizations. The authors describe the Centers for Disease Control and Prevention’s (CDC) vaccine safety monitoring systems, explaining how nurses can access inquiry channels and other immunization information resources. Examples of recent vaccine safety inquiries are also provided.

Some studies reported an increased risk of Guillain-Barré syndrome (GBS) within six weeks of influenza vaccination. It has also been suggested that this finding could have been confounded by influenza illnesses. We explored the complex relationship between influenza illness, influenza vaccination, and GBS, from an ecologic perspective using nationally representative data. We also studied seasonal patterns for GBS hospitalizations. Monthly hospitalization data (2000-2009) for GBS, and pneumonia and influenza (PI) in the Nationwide Inpatient Sample were included. Seasonal influenza vaccination coverage for 2004-2005 through the 2008-2009 influenza seasons (August-May) was estimated from the National Health Interview Survey data. GBS seasonality was determined using Poisson regression. GBS and PI temporal clusters were identified using scan statistics. The association between PI and GBS hospitalizations in the same month (concurrent) or in the following month (lagged) were determined using negative binomial regression. Vaccine coverage increased over the years (from 19.7% during 2004-2005 to 35.5% during 2008-2009 season) but GBS hospitalization did not follow a similar pattern. Overall, a significant correlation between monthly PI and GBS hospitalizations was observed (Spearman's correlation coefficient=0.7016, p0.0001). A significant (p=0.001) cluster of PI hospitalizations during December 2004-March 2005 overlapped a significant (p=0.001) cluster of GBS hospitalizations during January 2005-February 2005. After accounting for effects of monthly vaccine coverage and age, PI hospitalization was significantly associated (p0.0001) with GBS hospitalization in the concurrent month but not with GBS hospitalization in the following month. Monthly vaccine coverage was not associated with GBS hospitalization in adjusted models (both concurrent and lagged). GBS hospitalizations demonstrated a seasonal pattern with winter months having higher rates compared to the month of June. PI hospitalization rates were significantly correlated with hospitalization rates for GBS. Vaccine coverage did not significantly affect the rates of GBS hospitalization at the population level.

Hepatitis C virus (HCV) infection is a substantial and largely unrecognized public health problem. An estimated 3.5 million persons in the United States are currently living with HCV infection, at least half of whom are unaware of their infection (1-3). Persons born during 1945-1965 (the "baby boomer" birth cohort) have a sixfold higher prevalence (2.6%) than adults of other ages, and represent 81% of all persons chronically infected with HCV (4). Therefore, in addition to recommending testing for all persons at risk for HCV infection, CDC and the U.S. Preventive Services Task Force (USPSTF) recommend one-time HCV testing for the birth cohort (5,6). Compared with the national average, American Indian/Alaska Native (AI/AN) persons have approximately twofold the rate of acute HCV incidence and HCV associated mortality (2). In June 2012, the Indian Health Service (IHS) implemented HCV testing in the 1945-1965 birth cohort and created a nationally standardized performance measure to monitor implementation of the recommendation. As of June 2015, the proportion of the birth cohort screened for HCV increased from a baseline of 7.9% (14,402/182,503) to 32.5% (68,514/211,014) among the AI/AN population served by IHS nationwide; provider training and the use of clinical decision tools were associated with increases in HCV testing. With this fourfold increase in testing in just 3 years, IHS needs to prepare for the challenges associated with increased identification of persons living with HCV infection.

Objectives The US National Viral Hepatitis Action Plan calls for major efforts to expand hepatitis C virus (HCV) diagnosis and treatment; prenatal care settings are potential venues for expanding HCV testing. We aimed to characterize the HCV diagnostic cascade for women and infants and investigate factors associated with linkage and follow-up. Study design We used electronic health records for a 10-year cohort of 879 women with opioid use disorder from an obstetric clinic serving women with substance use disorders. Results Altogether, 744 women (85%) were screened for HCV; 510 (68%) were seropositive, of whom 369 (72%) had nucleic acid testing performed and of these 261 (71%) were viremic. Of 404 infants born to HCV-seropositive women, 273 (68%) were tested at least once for HCV, 180 (45%) completed the American Academy of Pediatrics-recommended perinatal HCV screening, and 5 (2.8%) were diagnosed with HCV infection and linked to care. More recent delivery date (2014-2015) was associated with maternal linkage to care (aOR, 2.5; 95% CI, 1.4-4.7). Maternal coinfection with HIV (aOR, 9.0; 95% CI, 1.1-72.8) and methadone maintenance therapy, compared with buprenorphine (aOR, 1.5; 95% CI, 0.9-2.5), were associated with higher rates of infant HCV testing. Conclusions HCV prevalence among pregnant women with opioid use is high and infant HCV screening is imperfect. Programmatic changes to improve both mother and infant follow-up may help to bridge identified gaps in the cascade to cure.

Introduction. Pregnant women should receive hepatitis B virus (HBV) testing with hepatitis B surface antigen (HBsAg), but it is unclear whether HBV-infected pregnant women are linked to care. Methods. We analyzed MarketScan™ commercial insurance claims. We included pregnant women, aged 10–50 years, with 42 weeks of continuous enrollment before (predelivery) and 6 months after (postdelivery) the first delivery claim for each unique pregnancy between 1/1/2011 and 6/30/2014. We identified claims for HBsAg testing by CPT code and described the care continuum among pregnancies with an associated ICD-9 HBV diagnosis code by demographic and clinical characteristics, including HBV-directed care ([HBV DNA or hepatitis B e antigen] and ALT test codes) and antiviral treatment (claims for tenofovir, entecavir, lamivudine, adefovir, or telbivudine) pre- and postdelivery. Results. There were 870,888 unique pregnancies (819,752 women) included. Before delivery, 714,830 (82%) pregnancies had HBsAg test claims, but this proportion decreased with subsequent pregnancies (p<0.0001): second (80%), third (71%), and fourth (61%). We identified 1,190 (0.14%) pregnancies with an associated HBV diagnosis code: most were among women aged ≥ 30 years (76%) residing in the Pacific (34%) or Middle Atlantic (18%) regions. Forty-two percent of pregnancies with an HBV diagnosis received HBV-directed care (42% predelivery and 39% postdelivery). Antiviral treatment was initiated before delivery in 128 (13%) of 975 pregnancies and postdelivery in 16 (1.6%) pregnancies. Conclusions. While most of these commercially insured pregnant women received predelivery HBV screening, we identified gaps in HBV testing and the HBV care continuum which highlight potential targets for public health interventions.

Introduction Perinatal transmission is an increasingly important mode of hepatitis C virus transmission. The authors characterized U.S. births among hepatitis C virus–infected women and evaluated trends in hepatitis C virus testing and positivity in women of childbearing age, pregnant women, and children aged less than 5years. Methods In 2017, National Center for Health Statistics birth certificate data (48 states and District of Columbia) were analyzed to assess the number of hepatitis C virus–infected women delivering live births in 2015, and commercial laboratory data were analyzed to assess hepatitis C virus testing and positivity among women of childbearing age, pregnant women, and children aged Results In 2015, a total of 0.38% (n=14,417) of live births were delivered by hepatitis C virus–infected women. Births delivered by hepatitis C virus–infected women, compared with births overall, occurred more often in women who were aged 20–29years (60.7% vs 50.9%); white, non-Hispanic (80.2% vs 52.8%); covered by Medicaid or other government insurance (79.2% vs 43.9%); and had rural residence (26.0% vs 14.0%). From 2011 to 2016 laboratory data, among women of childbearing age, hepatitis C virus testing increased by 39%, from 6.1% to 8.4%, and positivity increased by 36%, from 4.4% to 6.0%. Among pregnant women, hepatitis C virus testing increased by 135%, from 5.7% to 13.4%, and positivity increased by 39%, from 2.6% to 3.6%. Among children, hepatitis C virus testing increased by 25%, from 0.47% to 0.59%, and positivity increased by 13%, from 3.6% to 4.0%. Conclusions The potential for perinatal hepatitis C virus transmission exists. Expanded hepatitis C virus testing guidelines may address the burden of disease in this population.

Background The US Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force recommend one-time hepatitis C virus (HCV) testing for persons born 1945-1965 and targeted testing for high-risk persons. This strategy targets HCV testing to a prevalent population at high risk for HCV morbidity and mortality, but does not include younger populations with high incidence. To address this gap and improve access to HCV testing, age-based strategies should be considered. Methods We used a simulation of HCV to estimate the effectiveness and cost-effectiveness of HCV testing strategies: 1) standard of care (SOC) - recommendation for one-time testing for all persons born 1945-1965, 2) recommendation for one-time testing for adults ≥40 years (≥40 strategy), 3) ≥30 years (≥30 strategy), and 4) ≥18 years (≥18 strategy). All strategies assumed targeted testing of high-risk persons. Inputs were derived from national databases, observational cohorts and clinical trials. Outcomes included quality-adjusted life expectancy, costs, and cost-effectiveness. Results Expanded age-based testing strategies increased US population lifetime case identification and cure rates. Greatest increases were observed in the ≥18 strategy. Compared to the SOC, this strategy resulted in an estimated 256,000 additional infected persons identified and 280,000 additional cures at the lowest cost per QALY gained (ICER = $28,000/QALY). Conclusions In addition to risk-based testing, one-time HCV testing of persons 18 and older appears to be cost-effective, leads to improved clinical outcomes and identifies more persons with HCV than the current birth cohort recommendations. These findings could be considered for future recommendation revisions.

This review highlights key studies and recently published data, policies, and recommendations related to hepatitis C virus (HCV) epidemiology, transmission, and treatment.HCV is a leading cause of liver-related deaths, cirrhosis, and hepatocellular carcinoma. Since 2011 and accelerating since 2013, new, safe, tolerable, and curative therapies have considerably altered clinical and public health frameworks related to the prevention, control and clinical management of HCV. Nevertheless, there are several populations in the United States that are important to consider because of disparities in HCV prevalence and transmission risk. Adults born during 1945-1965 have an estimated anti-HCV antibody prevalence of ~3%, which is six times higher than among other adults, are often unaware of their infections, and are at increased risk of having HCV-associated morbidity and mortality from decades of chronic infection. Since the early 2000s, increasing incidence of acute HCV infections among young, white, non-urban people who inject drugs have been reported. Despite promising therapeutic advances, significant challenges remain for reducing HCV-associated morbidity and mortality.The high burden of HCV and significant health consequences associated with chronic infection make HCV a critical public health priority. Advances in HCV treatment have created new opportunities for reducing HCV-associated morbidity and mortality. These treatments are safe, well-tolerated, and highly effective; however, benefits cannot be realized without a significant increase in the number of persons tested for HCV so that all chronically infected individuals can be aware of their diagnosis and linked to appropriate clinical care.

Objective In response to widespread pertussis outbreaks and infant deaths, in 2010, the California Department of Health (CDPH) and in 2011 the Advisory Committee on Immunization Practices (ACIP) advised that the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine be administered during pregnancy. The goals of this study were to describe Tdap coverage among pregnant women following these recommendations. Methods In this observational cohort study, we utilized electronic medical record and claims data from seven Vaccine Safety Datalink sites to identify pregnancies and Tdap administrations. All Tdap doses were classified as pre-pregnancy, during pregnancy or post-pregnancy/postpartum. For pregnancies ending in a live birth, we evaluated factors associated with Tdap vaccination. Results Among 289,141 live births at the California VSD sites, receipt of Tdap during pregnancy increased substantially in the years 2010, 2011, and 2012, when coverage was 15.9, 30.0 and 19.5%, respectively. Among 82,398 women with live births at the Oregon, Washington, Colorado, Wisconsin and Minnesota VSD sites, receipt of Tdap during pregnancy first increased in 2012, at 16.0%. Women receiving early prenatal care and other vaccine(s) during pregnancy had higher Tdap coverage. Conclusion We observed substantial increases in Tdap coverage during pregnancy following CDPH and ACIP recommendations.

Purpose We conducted weekly surveillance for pre-specified adverse events following receipt of the 2012–2013 influenza vaccines in the Vaccine Safety Datalink (VSD). Methods For each outcome, risk intervals (i.e., period after vaccination with a potentially increased risk) were defined on the basis of biologic plausibility and prior literature. Seizures following inactivated influenza vaccine (IIV) were monitored in children in three age groups (6–23 months, 24–59 months, and 5–17 years) using a self-controlled risk interval design. We also monitored for Guillain–Barre syndrome, encephalitis, and anaphylaxis following IIV in patients ≥6 months of age using a cohort design with historical controls. In the risk intervals following live attenuated influenza vaccine (LAIV), we collected weekly counts of Guillain–Barre syndrome, encephalitis, and anaphylaxis in patients ages 2–49. Among LAIV vaccinees, numbers of expected events based on rates in historical controls were calculated, adjusted for age and site. Results At the end of surveillance, approximately 3.6 million first doses of IIV and 250 000 first doses of LAIV had been administered in the VSD. No elevated risks were identified in risk intervals following 2012–2013 IIV, as compared with a self-matched control interval or to historical controls. For each outcome, fewer than three events occurred in the risk interval following 2012–2013 LAIV, and we thus were unable to estimate measures of relative risks. Conclusions No increased risk was identified for any of the pre-specified outcomes following 2012–2013 influenza vaccinations in the VSD. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Background Hypersensitivity disorders following vaccinations are a cause for concern. Objective To determine the type and rate by age, gender, and vaccine received for reported hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines. Design A systematic review of reports to the Vaccine Adverse Event Reporting System (VAERS) following monovalent 2009 pandemic influenza A (H1N1) vaccines. Setting/patients US Civilian reports following vaccine received from October 1, 2009 through May 31, 2010. Measurements Age, gender, vaccines received, diagnoses, clinical signs, and treatment were reviewed by nurses and physicians with expertise in vaccine adverse events. A panel of experts, including seven allergists reviewed complex illnesses and those with conflicting evidence for classification of the event. Results Of 1984 reports, 1286 were consistent with immediate hypersensitivity disorders and 698 were attributed to anxiety reactions, syncope, or other illnesses. The female-to-male ratio was ≥4:1 for persons 20-to-59 years of age, but approximately equal for children under 10. One hundred eleven reports met Brighton Collaboration criteria for anaphylaxis; only one-half received epinephrine for initial therapy. The overall rate of reported hypersensitivity reactions was 10.7 per million vaccine doses distributed, with a 2-fold higher rate for live vaccine. Limitations Underreporting, especially of mild events, would result in an underestimate of the true rate of immediate hypersensitivity reactions. Selective reporting of events in adult females could have resulted in higher rates than reported for males. Conclusions Adult females may be at higher risk of hypersensitivity reactions after influenza vaccination than men. Although the risk of hypersensitivity reactions following 2009 pandemic influenza A (H1N1) vaccines was low, all clinics administering vaccines should be familiar with treatment guidelines for these adverse events, including the use of intramuscular epinephrine early in the course of serious hypersensitivity reactions.

OBJECTIVE: To characterize maternal and infant outcomes for pregnant women who received live H1N1 influenza vaccine and had no reported adverse events. METHODS: We identified Vaccine Adverse Event Reporting System reports, which described receipt of live H1N1 vaccine during pregnancy without an indication of an adverse event at the time of the report during October 2009 to June 2010. We reviewed the initial reports and obtained pregnancy outcome and infant data through 6 months of age from medical records. We reviewed the numbers and characteristics of pregnancy complications and infant outcomes including major birth defects and medically important infant conditions. Rates of spontaneous abortion, preterm birth, and major birth defects and their 95% confidence intervals were calculated. RESULTS: The Vaccine Adverse Event Reporting System received 113 reports stating receipt of live H1N1 vaccine during pregnancy with no adverse events reported. We obtained follow-up maternal records on 95 of the 113 (84%) live H1N1 reports (40.2% were vaccinated in the first trimester) and found: 87 live births (two twin pregnancies) and no maternal deaths occurred. Number and rates of pregnancy-specific adverse events included: 10 (10.5%, 5.8–18.3) spontaneous abortions; four (4.7%, 1.8–11.4) preterm deliveries at 35–36 weeks of gestation; three (3.4%, 1.2–9.7) infants had one or more major birth defects noted at birth: one cleft palate, one cleft lip, and one microtia (underdeveloped or absent external ear). Seven neonates and infants were hospitalized for medically important conditions. One infant death occurred in a 2.5-month-old boy as a result of pertussis. CONCLUSION: Rates of spontaneous abortion, preterm birth, and major birth defects in pregnant women who received live H1N1 vaccine were similar to or lower than published background rates. No concerning patterns of medical conditions in infants were identified. LEVEL OF EVIDENCE: III

Background. Guillain-Barre syndrome (GBS) is an acute polyradiculoneuropathy, thought to be an autoimmune process. Although cases of GBS have been reported following a wide range of vaccines, a clear association has only been established with the 1976 H1N1 inactivated influenza vaccine. Methods. We identified hospitalized GBS cases from Kaiser Permanente Northern California (KPNC) from 1995 through 2006. The medical record of each suspected case was neurologist-reviewed according to the Brighton Collaboration GBS case definition; only confirmed cases were included in the analyses, and cases of Miller Fisher syndrome were excluded. Using a case-centered design, we compared the odds of vaccination in the 6 and 10 weeks prior to onset of GBS to the odds of vaccination during the same time intervals in all vaccinated individuals in the entire KPNC population. Results. We confirmed 415 incident cases of GBS (including Brighton levels 1, 2, and 3) during the study period (>30 million person-years). Incidence peaked during the winter months. The odds ratio of influenza vaccination within a 6-week interval prior to GBS, compared with the prior 9 months, was 1.1 (95% confidence interval [CI], .4–3.1). The risk in the 6-week interval compared to the prior 12 months for tetanus diphtheria combination, 23-valent pneumococcal polysaccharide, and for all vaccines combined was 1.4 (95% CI, .3–4.5), 0.7 (95% CI, .1– 2.9), and 1.3 (95% CI, .8–2.3), respectively. Conclusions. In this large retrospective study, we did not find evidence of an increased risk of GBS following vaccinations of any kind, including influenza vaccination.

Background Certain sociodemographic subgroups of HIV-infected patients may experience more chronic disease than others due to behavioural risk factors, advanced HIV disease or complications from extended use of combination antiretroviral therapy (cART), but recent comparative data are limited. Methods We studied HIV-infected adult patients in care during 2006–2010 who had been prescribed ≥6 months of cART. We analysed the prevalence of selected key chronic conditions and polymorbidity (having 2 or more out of 10 key conditions) by gender and race/ethnicity. Results Of the 3,166 HIV-infected patients (median age 47 years, CD4+ T-cell count 496 cells/mm3, duration of cART use 6.8 years), 21% were female, 57% were non-Hispanic White and over half were current or former tobacco smokers. The five most frequent conditions among women (median age 45 years) were dyslipidaemia (67.3%), hypertension (57.4%), obesity (31.7%), viral hepatitis B or C coinfection (29.0%) and low high-density lipoprotein cholesterol (HDLc; 27.3%). The five most frequent conditions in men (median age 47 years) were dyslipidaemia (81.2%), hypertension (54.4%), low HDLc (41.1%), elevated triglycerides (32.3%) and elevated non-HDLc (26.8%). In multivariable analyses, Hispanic patients had higher prevalence of obesity and diabetes than White patients; Black patients had higher prevalence of obesity and hypertension but lower rates of lipid abnormalities. Of all patients, 73.7% of women and 66.8% of men had polymorbidity, with no evidence of disparities by race/ethnicity. Conclusions Among contemporary cART-treated HIV-infected adults, chronic conditions and polymorbidity were common, underscoring the importance of chronic disease prevention and management among ageing HIV-infected patients.

Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality (1). Transmission of HCV is primarily via parenteral blood exposure, and HCV can be transmitted vertically from mother to child. Vertical transmission occurs in 5.8% (95% confidence interval = 4.2%-7.8%) of infants born to women who are infected only with HCV and in up to twice as many infants born to women who are also infected with human immunodeficiency virus (HIV) (2) or who have high HCV viral loads (3,4); there is currently no recommended intervention to prevent transmission of infection from mother to child (3). Increased reported incidence of HCV infection among persons aged ≤30 years (5,6) with similar increases among women and men in this age group (6), raises concern about increases in the number of pregnant women with HCV infection, and in the number of infants who could be exposed to HCV at birth. Data from one large commercial laboratory and birth certificate data were used to investigate trends in HCV detection among women of childbearing age,* HCV testing among children aged ≤2 years, and the proportions of infants born to HCV-infected women nationally and in Kentucky, the state with the highest incidence of acute HCV infection during 2011-2014 (6). During 2011-2014, commercial laboratory data indicated that national rates of HCV detection (antibody or RNA positivity(†)) among women of childbearing age increased 22%, and HCV testing (antibody or RNA) among children aged ≤2 years increased 14%; birth certificate data indicated that the proportion of infants born to HCV-infected mothers increased 68%, from 0.19% to 0.32%. During the same time in Kentucky, the HCV detection rate among women of childbearing age increased >200%, HCV testing among children aged ≤2 years increased 151%, and the proportion of infants born to HCV-infected women increased 124%, from 0.71% to 1.59%. Increases in the rate of HCV detection among women of childbearing age suggest a potential risk for vertical transmission of HCV. These findings highlight the importance of following current CDC recommendations to identify, counsel, and test persons at risk for HCV infection (1,7), including pregnant women, as well as consider developing public health policies for routine HCV testing of pregnant women, and expanding current policies for testing and monitoring children born to HCV-infected women. Expansion of HCV reporting and surveillance requirements will enhance case identification and prevention strategies.

Background: From December 2012-March 2014, three randomized trials, each implementing a unique intervention in primary care settings (mail recruitment [repeated-mailing], an electronic health record best practice alert [BPA], and patient-solicitation [patient-solicitation]), evaluated HCV antibody testing, diagnosis, and costs for each of the interventions compared to standard-of-care testing. Multilevel multivariable models were used to estimate the adjusted risk ratio (aRR) for receiving an HCV antibody test, and costs were estimated using activity-based costing. Rationale: To estimate the effects of interventions conducted as part of the Birth-cohort Evaluation to Advance Screening and Testing for Hepatitis C study on hepatitis C virus (HCV) testing and costs among persons of the 1945-1965 birth-cohort (BC). Main Results: Intervention resulted in substantially higher HCV testing rates compared to standard-of-care (26.9% vs. 1.4% for repeated-mailing, 30.9% vs. 3.6% for BPA, and 63.5% vs. 2.0% for patient-solicitation), and significantly higher aRR for testing after controlling for sex, birth year, race, insurance type, and median household income (19.2 [95% Confidence Interval (CI) 9.7-38.2] for repeated-mailing, 13.2 [95% CI 3.6-48.6] for BPA, and 32.9 [95% CI 19.3-56.1] for patient-solicitation). The BPA intervention had the lowest incremental cost per completed test ($24 with fixed startup costs, $3 without) and also the lowest incremental cost per new case identified after omitting fixed startup costs ($1,691). Conclusion: HCV testing interventions resulted in an increase in BC testing compared to standard-of-care but also increased costs. The effect size and incremental costs of BPA intervention (excluding startup costs) support more widespread adoption compared to the other interventions. This article is protected by copyright. All rights reserved.

An estimated 3.5 million persons in the United States are living with hepatitis C virus (HCV) infection, resulting in approximately 20,000 deaths each year, primarily from cirrhosis or hepatocellular carcinoma (1,2). American Indian/Alaska Native (AI/AN) populations have the highest incidence of acute HCV infection among all U.S. racial/ethnic groups and are at greater risk for HCV-related mortality compared with the general population (3). In 2013, new antiviral drugs became available that make possible 8-12 week treatment regimens with fewer adverse events and are able to achieve sustained virologic response (SVR) in >90% of treated patients (4), equivalent to a cure of HCV infection. Also of note, HCV testing recommendations were expanded in 2012 by CDC and in 2013 by the U.S. Preventive Services Task Force to include one-time testing of persons born during 1945-1965 (the "baby boomer" cohort) in addition to anyone at increased risk for HCV infection (5,6). Given the availability of new HCV drugs, expanded testing recommendations, and high incidence of HCV infection in AI/AN populations, in October 2012, Cherokee Nation Health Services (CNHS) implemented a tribal HCV testing policy.* As part of the policy, CNHS added a reminder in the electronic health record (EHR) for clinical decision support and provided HCV education to primary care clinicians. From October 2012 to July 2015, among 92,012 persons with at least one CNHS clinic encounter, the cumulative number who received HCV screening for the first time increased from 3,337 (3.6%) to 16,772 (18.2%). The largest percentage of HCV screening was among persons born during 1945-1965. Of 715 persons who tested positive for HCV antibodies, 488 (68.3%) were tested for HCV RNA; among those 488 persons, 388 (79.5%) were RNA positive and were thus confirmed to have chronic HCV infection. Treatment was initiated for 223 (57.5%) of the 388 with chronic infection; 201 (90.1%) completed treatment, of whom 180 (89.6%) achieved SVR. CNHS has successfully increased HCV testing and treatment and is now collaborating with CDC and other external partners to develop an HCV elimination program for the Cherokee Nation that might serve as a model for similar settings.

Inactivated influenza vaccines have been given to pregnant women since 1964. Since 2004, the Advisory Committee on Immunization Practices has recommended that pregnant women receive trivalent inactivated influenza vaccine at any time during pregnancy. Studies conducted before 2009 did not identify any safety concerns after trivalent inactivated influenza vaccine in mothers or their infants. During the 2009-2010 influenza A (H1N1) influenza vaccination program, several monitoring systems were established or enhanced to assess whether adverse events were associated with H1N1 2009 monovalent vaccines (2009 H1N1 influenza vaccines). Data from these systems did not identify any safety concerns in pregnant women who received 2009 H1N1 influenza vaccines or their infants. Although live attenuated influenza vaccines are not recommended in pregnant women, a small number of studies have not shown any safety concern among pregnant women or their infants who were inadvertently exposed to these vaccines. This review summarizes US and international safety data for influenza vaccines in pregnant women with an emphasis on 2009 H1N1 influenza vaccines.

Because of widespread distribution of the influenza A (H1N1) 2009 monovalent vaccine (pH1N1 vaccine) and the prior association between Guillain-Barré syndrome (GBS) and the 1976 H1N1 influenza vaccine, enhanced surveillance was implemented to estimate the magnitude of any increased GBS risk following administration of pH1N1 vaccine. The authors conducted active, population-based surveillance for incident cases of GBS among 45 million persons residing at 10 Emerging Infections Program sites during October 2009–May 2010; GBS was defined according to published criteria. The authors determined medical and vaccine history for GBS cases through medical record review and patient interviews. The authors used vaccine coverage data to estimate person-time exposed and unexposed to pH1N1 vaccine and calculated age- and sex-adjusted rate ratios comparing GBS incidence in these groups, as well as age- and sex-adjusted numbers of excess GBS cases. The authors received 411 reports of confirmed or probable GBS. The rate of GBS immediately following pH1N1 vaccination was 57% higher than in person-time unexposed to vaccine (adjusted rate ratio = 1.57, 95% confidence interval: 1.02, 2.21), corresponding to 0.74 excess GBS cases per million pH1N1 vaccine doses (95% confidence interval: 0.04, 1.56). This excess risk was much smaller than that observed during the 1976 vaccine campaign and was comparable to some previous seasonal influenza vaccine risk assessments.

Purpose The Centers for Disease Control and Prevention Emerging Infections Program implemented active, population-based surveillance for Guillain–Barre syndrome (GBS) following H1N1 vaccines in 10 states/metropolitan areas. We report additional analyses of these data using self-controlled methods, which avoid potential confounding from person-level factors and co-morbidities. Methods Surveillance officers identified GBS cases with symptom onset during October 2009–April 2010 and ascertained receipt of H1N1 vaccines. We calculated self-controlled relative risks by comparing the number of cases with onset during a risk interval 1–42 days after vaccination with cases with onset during fixed (days 43–84) or variable (days 43–end of study period) control intervals. We calculated attributable risks by applying statistically significant relative risks to an independent estimate of GBS incidence. Results Fifty-nine GBS cases received H1N1 vaccine with or without seasonal vaccine. The relative risk was 2.1 (95%CI 1.2, 3.5) by the variable-window and 3.0 (95%CI 1.4, 6.4) by the fixed-window analyses. The corresponding attributable risks per million doses administered were 1.5 (95%CI 0.3, 3.4) and 2.8 (95%CI 0.6, 7.4). Conclusions These attributable risks are similar to those of some previous formulations of seasonal influenza vaccine (about one to two cases per million doses administered), suggesting a low risk of GBS following the H1N1 vaccine that is not clearly higher than that of seasonal influenza vaccines. Published 2012. This article is a US Government work and is in the public domain in the USA.

In fall 2010 in the southern hemisphere, an increased risk of febrile seizures was noted in young children in Australia in the 24 h after receipt of trivalent inactivated influenza vaccine (TIV) manufactured by CSL Biotherapies. Although the CSL TIV vaccine was not recommended for use in young children in the US, during the 2010-2011 influenza season near real-time surveillance was conducted for febrile seizures in the 0-1 days following first dose TIV in a cohort of 206,174 vaccinated children ages 6 through 59 months in the Vaccine Safety Datalink Project. On a weekly basis, surveillance was conducted with the primary approach of a self-controlled risk interval design and the secondary approach of a current vs. historical vaccinee design. Sequential statistical methods were employed to account for repeated analyses of accumulating data. Signals for seizures based on computerized data were identified in mid November 2010 using a current vs. historical design and in late December 2010 using a self-controlled risk interval design. Further signal evaluation was conducted with chart-confirmed febrile seizure cases using only data from the primary approach (i.e. self-controlled risk interval design). The magnitude of the incidence rate ratio and risk difference comparing risk of seizures in the 0-1 days vs. 14-20 days following TIV differed by receipt of concomitant 13-valent pneumococcal conjugate vaccine (PCV13). Among children 6-59 months of age, the incidence rate ratio (IRR) for TIV adjusted for concomitant PCV13 was 2.4 (95% CI 1.2, 4.7) while the IRR for PCV13 adjusted for concomitant TIV was 2.5 (95% CI 1.3, 4.7). The IRR for concomitant TIV and PCV13 was 5.9 (95% CI 3.1, 11.3). Risk difference estimates varied by age due to the varying baseline risk for seizures in young children, with the highest estimates occurring at 16 months (12.5 per 100,000 doses for TIV without concomitant PCV13, 13.7 per 100,000 doses for PCV13 without concomitant TIV, and 44.9 per 100,000 doses for concomitant TIV and PCV13) and the lowest estimates occurring at 59 months (1.1 per 100,000 doses for TIV without concomitant PCV13, 1.2 per 100,000 doses for PCV13 without concomitant TIV, and 4.0 per 100,000 doses for concomitant TIV and PCV13). Incidence rate ratio and risk difference estimates were lower for children receiving TIV without concomitant PCV13 or PCV13 without concomitant TIV. Because of the importance of preventing influenza and pneumococcal infections and associated complications, our findings should be placed in a benefit-risk framework to ensure that population health benefits are maximized.

Liver disease due to hepatitis C virus (HCV) infection is a leading cause of non-AIDS-related morbidity and mortality in patients infected with HIV. We assessed the frequency of and predictors for initiation of treatment for HCV infection among patients coinfected with HCV/HIV enrolled in the HIV Outpatient Study (HOPS) during 1999-2007. We included patients with confirmed HCV infection, at least 1 year of subsequent follow-up, and no evidence of prior HCV treatment. We assessed predictors of HCV treatment initiation using Cox proportional hazards analyses. During 1999-2007, 103 (20%) HOPS patients coinfected with HCV/HIV initiated HCV treatment during a median of 4.3 years of follow-up (interquartile range: 2.7, 6.7). In multivariable analysis, non-Hispanic black race/ethnicity (hazard ratio HR] 0.3; 95% confidence interval [CI] = 0.2, 0.6) was independently associated with a lower likelihood of HCV treatment. Elevated alanine aminotransferase (ALT; HR 3.5; 95% CI = 2.2, 5.6) and CD4+ cell count ≥500 cells/mm(3) (HR 1.8; 95% CI = 1.2, 2.8) at the start of observation were independently associated with higher likelihood of HCV treatment. For patients starting observation in 1999-2001, 2002-2004 and 2005-2007, 5%, 11% and 21% of patients initiated treatment during the first year of follow-up, respectively. Between 1999 and 2007, despite a stable low fraction of patients coinfected with HCV/HIV initiating treatment for HCV infection, an increasing proportion initiated treatment within the first year after the infection was confirmed. Treatment of HCV infection in patients coinfected with HCV/HIV should be considered a priority, given the increased risk of accelerated end-stage liver disease.

Background Human papillomavirus (HPV) infection of the cervix and related abnormal cervical cytology in HIV-infected women has been well described. Little is known about anal HPV infection in HIV-infected women. Methods The SUN Study is a prospective cohort study of 700 HIV-infected patients including 167 women. At baseline, patients completed a behavioral questionnaire and provided, among other samples, cervical and anal swabs for HPV detection and genotyping and for cytologic examination. Here, we present the available baseline data on the 167 women in the SUN study. Results Baseline results were available for 120 women (median age: 38 years, 57% non-Hispanic black, median CD4 cell count 444.5 cells/mm3), of whom, 77% were taking antiretroviral therapy. The prevalences in the anus and cervix of any HPV were 90% and 83%, respectively (P = 0.039), and of high-risk (HR) types 85% and 70%, respectively, (P = 0.001). There was no significant difference in the prevalences of abnormal cytology between the anus and cervix: 38% and 33%, respectively (P = 0.217). Although the presence of abnormal cervical cytology was associated with the presence of abnormal anal cytology (relative risk: 1.7, P = 0.024), its sensitivity (52.5%) and positive predictive value positive (45.6%) for identifying women with abnormal anal cytology were poor. A history of anal sex was not associated with anal HPV infection or abnormal anal cytology. Conclusions In this cohort of HIV-infected women, anal HPV infection was more prevalent and diverse than cervical HPV infection. Anal cytologic abnormalities were as prevalent as cervical cytologic abnormalities, and although abnormal cervical cytology was predictive of abnormal anal cytology, results were not highly concordant. These data support the need for studies of anal cytologic screening of HIV-infected women.

Treatment of human immunodeficiency virus (HIV) infection with highly active combination antiretroviral therapy has increased survival and shifted the spectrum of HIV-associated morbidity and mortality from opportunistic infections toward a variety of other medical conditions. The prospective cohort Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study) monitors the clinical course of HIV-infected individuals treated with combination antiretroviral therapy in 4 US cities. Every 6 months, clinical assessments, medical record abstraction, audio computer-assisted self-interview, and neurocognitive measurements are completed and blood and urine specimens are banked centrally. At enrollment and periodically thereafter, additional techniques such as anal cytology, dual energy x-ray absorptiometry, carotid ultrasonography, echocardiography, and abdominal and cardiac computed tomography are performed. From March 2004 through June 2006, 700 participants were enrolled; median age was 41 years, 76% were men, 58% were non-Hispanic white, 62% were men who have sex with men, 78% were taking combination antiretroviral therapy (of whom 86% had an HIV viral load of

As many as 2.2 million persons in the United States are chronically infected with hepatitis B virus (HBV) (1), and approximately 15%-25% of persons with chronic HBV infection will die prematurely from cirrhosis or liver cancer (2). Since 2006, the overall U.S. incidence of acute HBV infection has remained stable; the rate in 2013 was 1.0 case per 100,000 persons (3). Hepatitis B vaccination is highly effective in preventing HBV infection and is recommended for all infants (beginning at birth), all adolescents, and adults at risk for HBV infection (e.g., persons who inject drugs, men who have sexual contact with men, persons infected with human immunodeficiency virus [HIV], and others). Hepatitis B vaccination coverage is low among adults: 2013 National Health Interview Survey data indicated that coverage with ≥3 doses of hepatitis B vaccine was 32.6% for adults aged 19-49 years (4). Injection drug use is a risk factor for both hepatitis C virus (HCV) and HBV. Among young adults in some rural U.S. communities, an increased incidence of HCV infection has been associated with a concurrent increase of injection drug use (5); and recent data indicate an increase of acute HCV infection in the Appalachian region associated with injection drug use (6). Using data from the National Notifiable Diseases Surveillance System (NNDSS) during 2006-2013, CDC assessed the incidence of acute HBV infection in three of the four Appalachian states (Kentucky, Tennessee, and West Virginia) included in the HCV infection study (6). Similar to the increase of HCV infections recently reported, an increase in incident cases of acute HBV infection in these three states has occurred among non-Hispanic whites (whites) aged 30-39 years who reported injection drug use as a common risk factor. Since 2009, cases of acute HBV infection have been reported from more non-urban than urban regions. Evidence-based services to prevent HBV infection are needed.

Objective. In 2012, CDC's Division of Viral Hepatitis launched a public health initiative to increase hepatitis B virus (HBV) and hepatitis C virus (HCV) infection testing for those at risk and to improve linkage to medical care for those infected. We describe testing outcomes of previously unidentified people at risk for HBV and HCV infection and the lessons learned while linking patients to care. Methods. CDC's Hepatitis Testing and Linkage to Care (HepTLC) initiative provided 34 financial awards to U.S. organizations that serve people at risk for viral hepatitis, 25 of which focused on HCV and nine of which focused on HBV. Grantees offered testing and test result notification to people at risk for HBV and/or HCV infection, as well as counseling, referral, and verification or notification of linkage to care for people with positive test results. We entered demographic data, self-reported risk factors, country of origin (for HBV), and testing outcomes into a confidential database. Results. The 34 grantees tested 87,860 people at more than 260 sites in 17 states. Of the 23,144 people tested for HBV, 1,317 (6%) were positive. Of the 64,716 people tested for HCV, 57,570 (89%) received an HCV antibody (anti-HCV) test, of whom 7,580 (13%) tested anti-HCV positive. Of the 4,765 people who received an HCV RNA test, 3,449 (72%) tested positive. Of the 4,766 people who tested positive for either HBV or HCV infection, 2,116 (44%) were linked to care. Conclusion. Interventions targeting people at risk for HBV and HCV infection reached a substantial number of people for whom testing is recommended and identified a large proportion of those who had previously unrecognized infection. Patient navigation was critical for follow-up and linkage to care.

During 1996 through 2004, 29 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) have been reported worldwide; 17 were fatal. Stress-dose corticosteroid (SDS) therapy has recently been found to improve survival among patients with septic shock but benefit for the treatment of YEL-AVD patients in septic shock is unknown. We retrospectively reviewed medical records of 11 U.S. YEL-AVD cases reported to the Vaccine Adverse Event Reporting System (VAERS) from 1996 through 2004. Four of 11 case-patients received SDS; 3 of these 4 (75%) survived. Seven patients did not receive SDS and 2 (29%) survived. Altered mental status was documented on admission for 5 of the 11 patients; 4 of these 5 did not receive SDS and died, whereas one received SDS and survived. The use of stress-dose steroids might be a factor that influenced the survival of these YEL-AVD patients and should be further evaluated in the management of both YEL-AVD and wild-type yellow fever septic shock.

Objective: To assess the occurrence of narcolepsy after influenza vaccines used in the United States that contained the influenza A(H1N1)pdm09 virus strain. Methods: A population-based cohort study in the Vaccine Safety Datalink with an annual population of more than 8.5 million people. All persons younger than 30 years who received a 2009 pandemic or a 2010–2011 seasonal influenza vaccine were identified. Their medical visit history was searched for a first-ever occurrence of an ICD-9 narcolepsy diagnosis code through the end of 2011. Chart review was done to confirm the diagnosis and determine the date of symptom onset. Cases were patients who met the International Classification of Sleep Disorders, 2nd edition, narcolepsy diagnostic criteria. We compared the observed number of cases after vaccination to the number expected to occur by chance alone. Results: The number vaccinated with 2009 pandemic vaccine was 650,995 and with 2010–2011 seasonal vaccine was 870,530. Among these patients, 70 had a first-ever narcolepsy diagnosis code after vaccination, of which 16 had a chart-confirmed incident diagnosis of narcolepsy. None had their symptom onset during the 180 days after receipt of a 2009 pandemic vaccine compared with 6.52 expected, and 2 had onset after a 2010–2011 seasonal vaccine compared with 8.83 expected. Conclusions: Influenza vaccines containing the A(H1N1)pdm09 virus strain used in the United States were not associated with an increased risk of narcolepsy. Vaccination with the influenza A(H1N1)pdm09 vaccine viral antigens does not appear to be sufficient by itself to increase the incidence of narcolepsy in a population.

Objectives. We sought to assess risk of Guillain–Barré syndrome (GBS) among influenza A (H1N1) 2009 monovalent (pH1N1) vaccinated and unvaccinated populations at the end of the 2009 pandemic. Methods. We applied GBS surveillance data from a US population catchment area of 45 million from October 15, 2009, through May 31, 2010. GBS cases meeting Brighton Collaboration criteria were included. We calculated the incidence density ratio (IDR) among pH1N1 vaccinated and unvaccinated populations. We also estimated cumulative GBS risk using life table analysis. Additionally, we used vaccine coverage data and census population estimates to calculate denominators. Results. There were 392 GBS cases; 64 (16%) occurred after pH1N1vaccination. The vaccinated population had lower average risk (IDR = 0.83, 95% confidence interval = 0.63, 1.08) and lower cumulative risk (6.6 vs 9.2 cases per million persons, P = .012) of GBS. Conclusions. Our findings suggest that at the end of the influenza season cumulative GBS risk was less among the pH1N1vaccinated than the unvaccinated population, suggesting the benefit of vaccination as it relates to GBS. The observed potential protective effect on GBS attributed to vaccination warrants further study.

Although current rotavirus vaccines were not associated with an increased risk of intussusception in large trials before licensure, recent postlicensure data from international settings suggest the possibility of a small increase in risk of intussusception after monovalent rotavirus vaccination. We examined this risk in a population in the United States.Participants were infants between the ages of 4 and 34 weeks who were enrolled in six integrated health care organizations in the Vaccine Safety Datalink (VSD) project. We reviewed medical records and visits for intussusception within 7 days after monovalent rotavirus vaccination from April 2008 through March 2013. Using sequential analyses, we then compared the risk of intussusception among children receiving monovalent rotavirus vaccine with historical background rates. We further compared the risk after monovalent rotavirus vaccination with the risk in a concurrent cohort of infants who received the pentavalent rotavirus vaccine.During the study period, 207,955 doses of monovalent rotavirus vaccine (including 115,908 first doses and 92,047 second doses) were administered in the VSD population. We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine. For the two doses combined, the expected number of intussusception cases was 0.72, resulting in a significant relative risk of 8.4. For the pentavalent rotavirus vaccine, 1,301,810 doses were administered during the study period, with 8 observed intussusception cases (7.11 expected), for a nonsignificant relative risk of 1.1. The relative risk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination, as compared with the risk after pentavalent rotavirus vaccination, was 9.4 (95% confidence interval, 1.4 to 103.8). The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 5.3 per 100,000 infants vaccinated.In this prospective postlicensure study of more than 200,000 doses of monovalent rotavirus vaccine, we observed a significant increase in the rate of intussusception after vaccination, a risk that must be weighed against the benefits of preventing rotavirus-associated illness. (Funded by the Centers for Disease Control and Prevention.).

Guillain-Barre syndrome (GBS) is the most common cause of acute flaccid paralysis worldwide, and is thought to be immune-mediated. It is preceded by upper respiratory or gastrointestinal infection in about two-thirds of cases and is associated with some viral infections, including influenza. GBS has also been associated with the 1976 swine-influenza vaccine. Thereafter, some studies have shown a small increased risk of GBS following receipt of seasonal and 2009 H1N1 monovalent influenza vaccines. Studies over the years have also shown an increased risk of GBS following influenza infection, and the magnitude of risk is several times greater than that following influenza vaccination. Because GBS is rare, and even rarer following vaccination, it is difficult to estimate precise risk. We try to shed light on the complex relationship of GBS and its association with influenza and influenza vaccines over the past 35 years.

To study the impact of influenza vaccine administered to pregnant women during all trimesters on the rates of preterm and small for gestational age (SGA) births, evaluating both increased and decreased risk.This retrospective observational matched cohort study involved 7 Vaccine Safety Datalink sites across the US for the 2004-05 through 2008-09 influenza seasons. Cohort eligibility and outcomes were determined from administrative, claims, medical records, and birth data. In propensity score- and vaccine exposure time-matched analyses, ORs for preterm and SGA births were calculated.Among 57 554 matched vaccinated and unvaccinated pregnant women, including 16 240 women in the first trimester, maternal vaccination was not associated with increased or decreased risk for preterm birth (OR for delivery at37 weeks gestation, 0.97 [95% CI, 0.93-1.02]; for delivery at ≤32 weeks gestation, 0.98 [95% CI, 0.86-1.12]; and for delivery at ≤34 weeks gestation, 0.96 [95% CI, 0.88-1.04]) or SGA birth (OR for5th percentile weight for gestational age, 1.02 [95% CI, 0.96-1.09], and for10th percentile weight for gestational age, 1.00 [95% CI, 0.96-1.04]). Similarly, first trimester vaccination was not associated with increased or decreased risk for preterm or SGA birth.Receipt of trivalent inactivated influenza vaccine during pregnancy was not associated with increased or decreased risk of preterm or SGA birth. These findings support the safety of vaccinating pregnant women against influenza during the first, second, and third trimesters, and suggest that a nonspecific protective effect of the influenza vaccine for these outcomes does not exist.