Hepatitis B virus (HBV) causes acute and chronic infection of the liver leading to substantial morbidity and mortality. In the United States, since 1996, a total of 29 outbreaks of HBV infection in one or multiple long-term-care (LTC) facilities, including nursing homes and assisted-living facilities, were reported to CDC; of these, 25 involved adults with diabetes receiving assisted blood glucose monitoring. These outbreaks prompted the Hepatitis Vaccines Work Group of the Advisory Committee on Immunization Practices (ACIP) to evaluate the risk for HBV infection among all adults with diagnosed diabetes. The Work Group reviewed HBV infection-related morbidity and mortality and the effectiveness of implementing infection prevention and control measures. The strength of scientific evidence regarding protection was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology,* and safety, values, and cost-effectiveness were incorporated into a recommendation using the GRADE system. Based on the Work Group findings, on October 25, 2011, ACIP recommended that all previously unvaccinated adults aged 19 through 59 years with diabetes mellitus (type 1 and type 2) be vaccinated against hepatitis B as soon as possible after a diagnosis of diabetes is made (recommendation category A). Data on the risk for hepatitis B among adults aged ≥60 years are less robust. Therefore, ACIP recommended that unvaccinated adults aged ≥60 years with diabetes may be vaccinated at the discretion of the treating clinician after assessing their risk and the likelihood of an adequate immune response to vaccination (recommendation category B). This report summarizes these recommendations and provides the rationale used by ACIP to inform their decision making.

Importance: Although COVID-19 vaccines protect against infection and severe disease, the role of vaccination in preventing prolonged symptoms in those with subsequent infection is unclear. Objective(s): To determine differences in symptoms stratified by prior vaccination reported by healthcare personnel (HCP) 6 weeks after onset of COVID-19, and whether there were differences in timing of return to work. Design(s): Nested cohort study within a multicenter vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. Setting(s): Health systems in 12 U.S. states. Participant(s): HCP participating in a vaccine effectiveness study were eligible for inclusion if they had confirmed COVID-19 with either verified mRNA vaccination (symptom onset =14 days after two doses) or no prior COVID-19 vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey approximately 6 weeks after illness onset. Exposures: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. Main Outcomes and Measures: Presence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work after COVID-19 illness. Result(s): Among 419 HCP with confirmed COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants (60.6%) compared with unvaccinated participants (60.6% vs. 79.1%; aRR 0.70, 95% CI 0.58-0.84). Vaccinated HCP returned to work a median 2.0 days (95% CI 1.0-3.0) sooner than unvaccinated HCP (aHR 1.37; 95% CI, 1.04-1.79). Conclusion(s): A history of two doses of COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased risk of COVID-like symptoms at 6 weeks and earlier to return to work. Vaccination is associated with improved recovery from COVID-19, in addition to preventing symptomatic infection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

BACKGROUND: Although use of the 13-valent pneumococcal conjugate vaccine (PCV13) among children has reduced incidence of pneumococcal disease, a considerable burden of disease remains. PCV15 is a new vaccine that contains pneumococcal serotypes 22F and 33F in addition to serotypes contained in PCV13. To inform deliberations by the Advisory Committee on Immunization Practices on recommendations for PCV15 use among U.S. children, we estimated the health impact and cost-effectiveness of replacing PCV13 with PCV15 within the routine infant immunization program in the United States. We also assessed the impact and cost-effectiveness of a supplementary PCV15 dose among children aged 2-5 years who have already received a full PCV13 series. METHODS: We estimated the incremental number of pneumococcal disease events and deaths averted, costs per quality adjusted life-year (QALY) gained, and costs per life-year gained under different vaccination strategies using a probabilistic model following a single birth cohort of 3.9 million individuals (based on 2020 U.S. birth cohort). We assumed that vaccine effectiveness (VE) of PCV15 against the two additional serotypes was the same as the VE of PCV13. The cost of PCV15 use among children was informed from costs of PCV15 use among adults and from discussions with the manufacturer. RESULTS: Our base case results found that replacing PCV13 with PCV15 prevented 92,290 additional pneumococcal disease events and 22 associated deaths, while also saving $147 million in costs. A supplementary PCV15 dose among children aged 2-5 years who were fully vaccinated with PCV13 prevented further pneumococcal disease events and associated deaths but at a cost of more than $2.5 million per QALY gained. CONCLUSIONS: A further decrease in pneumococcal disease in conjunction with considerable societal cost savings could be expected from replacing PCV13 with PCV15 within the routine infant immunization program in the United States.

BACKGROUND: People with HIV (PWH) are at increased risk for invasive pneumococcal disease (IPD). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for use in US children in 2010 and for PWH aged 19 years or older in 2012. We evaluated the population-level impact of PCV13 on IPD among PWH and non-PWH aged 19 years or older. METHODS: We identified IPD cases from 2008 to 2018 through the Active Bacterial Core surveillance platform. We estimated IPD incidence using the National HIV Surveillance System and US Census Bureau data. We measured percent changes in IPD incidence from 2008 to 2009 to 2017-2018 by HIV status, age group, and vaccine serotype group, including serotypes in recently licensed 15-valent (PCV15) and 20-valent (PCV20) PCVs. RESULTS: In 2008-2009 and 2017-2018, 8.4% (552/6548) and 8.0% (416/5169) of adult IPD cases were among PWH, respectively. Compared with non-PWH, a larger proportion of IPD cases among PWH were in adults aged 19-64 years (94.7%-97.4% vs. 56.0%-60.1%) and non-Hispanic Black people (62.5%-73.0% vs. 16.7%-19.2%). Overall and PCV13-type IPD incidence in PWH declined by 40.3% (95% confidence interval: -47.7 to -32.3) and 72.5% (95% confidence interval: -78.8 to -65.6), respectively. In 2017-2018, IPD incidence was 16.8 (overall) and 12.6 (PCV13 type) times higher in PWH compared with non-PWH; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2%, and 16.5% of IPD in PWH, respectively. CONCLUSIONS: Despite reductions post-PCV13 introduction, IPD incidence among PWH remained substantially higher than among non-PWH. Higher-valent PCVs provide opportunities to reduce remaining IPD burden in PWH.

Hepatitis B virus (HBV) infection causes hepatocellular carcinoma but its association with other cancers is not well established. We compared age-adjusted incidence of primary cancers among 5,773 HBV-infected persons with US cancer registries during 2006-2018. Compared with the US population, substantially higher incidence among HBV-infected persons was observed for hepatocellular carcinoma (Standardized rate ratio [SRR] 30.79), gastric (SRR 7.95), neuroendocrine (SRR 5.88), cholangiocarcinoma (SRR 4.62), and ovarian (SRR 3.72) cancers, and non-Hodgkin lymphoma (SRR 2.52). Clinicians should be aware of a heightened potential for certain non-hepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival.

Persons with isolated antibody to HBV core antigen (IAHBc) may have occult HBV infection (OBI), which is associated with reactivation and potential risk for hepatocellular carcinoma and HBV transmission. We used National Health and Nutrition Examination Survey (NHANES) data to estimate US IAHBc prevalence and published studies of IAHBc-associated OBI prevalence to estimate OBI burden. During 2001-2018, IAHBc prevalence was 0.8% (approximately 2.1 million persons); OBI burden range was 35,500-83,600 persons. These data support the need for more robust estimates of IAHBc-associated OBI prevalence in the general US population.

BACKGROUND: The distribution of Clostridioides difficile strains and transmission dynamics in the United States are not well defined. Whole genome sequencing (WGS) across two CDC Emerging Infections Program C. difficile infection (CDI) surveillance regions (Minnesota and New York) was performed to identify predominant multilocus sequence types (MLSTs) in community and healthcare-associated disease and assess transmission. METHODS: C. difficile isolates from CDI cases over three months between 2016 and 2017 underwent WGS. Cases were residents of the catchment area without a positive C. difficile test in the preceding 8 weeks. Cases were epidemiologically classified as healthcare (HCA) or community (CA) associated. RESULTS: Of 422 isolates, 212 (50.2%) were HCA and 203 (48.1%) were CA. Predominant MLSTs were ST42 (9.3%), ST8 (7.8%), and ST2 (8.1%). MLSTs associated with HCA-CDI included ST1 (76%), ST53 (83.3%), ST43 (80.0%), while those associated with CA-CDI included ST3 (76.9%), and ST41 (77.8%). ST1 was more frequent in NY than MN (10.8% vs 3.1%). Thirty three pairs were closely related genomically, 14 of which had potential patient-patient transmission supported by chart review. DISCUSSION: The genomic epidemiology of C. difficile across two regions of the US indicates the presence of a diverse strain profile and limited direct transmission.

BACKGROUND: After decades of decline, US incidence of acute hepatitis B flattened since 2010. In persons aged ≥40 years and in jurisdictions affected by the opioid epidemic, there is an increase in new cases. Data suggest new infections are occurring among US-born persons. METHODS: We used National Health and Nutrition Examination Survey data during 2001-2018 to examine trends and differences in total antibody to hepatitis B virus core antigen (anti-HBc) prevalence in US-born persons. During 2013-2018, the distribution of characteristics was examined. Cochran-Mantel-Haenszel test was used to assess trends. RESULTS: During 2001-2006, 2007-2012, and 2013-2018, anti-HBc prevalence was 3.5%, 2.5%, and 2.6% among US-born persons, respectively. This corresponded to 5.7 (range, 4.8-6.6) million US-born persons with resolved or current HBV infection during 2013-2018, including 347,100 persons aged 6-29 years. The most pronounced increase and highest anti-HBc prevalence was among persons who reported injection drug use (IDU), which increased from 35.3% during 2001-2006 to 58.4% during 2013-2018 (P=.07). CONCLUSIONS: Anti-HBc prevalence among US-born persons remained flat during the most recent period, coinciding with a doubling of prevalence among persons reporting IDU. These data are consistent with acute hepatitis B surveillance trends, showing increasing incidence in sub-populations where prevention could be strengthened.

In June 2019, the Advisory Committee on Immunization Practices (ACIP) changed the recommendation for routine 13-valent pneumococcal conjugate vaccine (PCV13) use in immunocompetent adults aged ≥65 years, including those with select chronic medical conditions (CMC). ACIP now recommends PCV13 for this group of adults based on shared clinical decision-making. Because adults with CMC continue to be at increased risk for pneumococcal disease, we assessed the cost-effectiveness of administering PCV13 in series with the recommended 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥19 years with CMC. We used a probabilistic model following a cohort of 19-year-old adults. We used Monte Carlo simulation to estimate the impact on program, medical, and non-medical costs (in 2017 U.S. dollars [$], societal perspective), and pneumococcal disease burden when administering PCV13 in series with PPSV23. We used PCV13 efficacy and post-licensure vaccine effectiveness (VE) data to estimate VE against PCV13 type disease (separately for disease by serotype 3 [ST3], the most common PCV13 type, and all other PCV13 serotypes). We considered a range of estimates for sensitivity analyses. Analyses were performed in 2019. In the base case, assuming no PCV13 effectiveness against ST3 disease, adding a dose of PCV13 upon CMC diagnosis cost $689,299 per QALY gained. This declined to $79,416 per QALY if VE against ST3 was estimated to be equivalent to other PCV13-types. Administering PCV13 in series with the recommended PPSV23 for adults with CMC was not cost saving. Results were sensitive to estimated PCV13 VE against ST3 disease.

BACKGROUND & AIMS: During 2016-2020, the United States experienced person-to-person hepatitis A outbreaks that are unprecedented in the vaccine era, during which case-fatality ratios reported by some jurisdictions exceeded those historically associated with hepatitis A. APPROACH & RESULTS: To identify factors associated with hepatitis A-related mortality, we performed a matched case-control study (matched on age [±5 years] and county of residence in a 1:4 ratio) using data collected from health department and hospital medical records of outbreak-associated patients in Kentucky, Michigan, and West Virginia. Controls were hepatitis A outbreak-associated patients who did not die. There were 110 cases (mean age 53.6 years) and 414 matched controls (mean age 51.9 years); most cases (68.2%) and controls (63.8%) were male. Significantly (p<0.05) higher odds of mortality were associated with pre-existing non-viral liver disease (adjusted odds ratio [aOR] 5.2), history of hepatitis B (aOR 2.4), diabetes (aOR 2.2), and cardiovascular disease (aOR 2.2), as well as initial MELD score ≥30 (aOR 10.0), AST/ALT ratio >2 (aOR 10.3), and platelet count <150,000/uL (aOR 3.7) among hepatitis A outbreak-associated patients in the independent multivariable conditional logistic regression analyses (each model adjusted for sex). CONCLUSIONS: Pre-existing liver disease, diabetes, cardiovascular disease, and initial MELD score ≥30, AST/ALT ratio ≥1, or platelet count <150,000/uL among hepatitis A patients were independently associated with higher odds of mortality. Providers should be vigilant for such features and have a low threshold to escalate care and consider consultation for liver transplantation. Our findings support the Advisory Committee on Immunization Practices recommendation to vaccinate persons with chronic liver disease, though future recommendations to include adults with diabetes and cardiovascular disease should be considered.

BACKGROUND: Since 2016, the US has experienced person-to-person hepatitis A outbreaks unprecedented in the vaccine era. The proportion of cases hospitalized in these outbreaks exceeds historical national surveillance data. METHODS: We described the epidemiology, characterized the reported increased morbidity, and identified factors associated with hospitalization during the outbreaks by reviewing a 10% random sample of outbreak-associated hepatitis A cases in Kentucky, Michigan, and West Virginia-three heavily affected states. We calculated descriptive statistics and conducted age-adjusted log-binomial regression analyses to identify factors associated with hospitalization. RESULTS: Participants in the random sample (n=817) were primarily male (62.5%) with mean age of 39.0 years; 51.8% were hospitalized. Among those with available information, 73.2% reported drug use, 14.0% were experiencing homelessness, 29.7% were currently or recently incarcerated, and 61.6% were epidemiologically linked to a known outbreak-associated case. Residence in Michigan (adjusted risk ratio [aRR] 1.8), being a man who has sex with men (aRR 1.5), non-injection drug use (aRR 1.3), and homelessness (aRR 1.3) were significantly (p<0.05) associated with hepatitis A-related hospitalization. CONCLUSIONS: Our findings support current Advisory Committee on Immunization Practices recommendations to vaccinate all persons who use drugs, men who have sex with men, and persons experiencing homelessness against hepatitis A.

OBJECTIVES: To evaluate the impact of International Classification of Disease, 10th revision, Clinical Modification (ICD-10-CM) implementation on pneumonia hospitalizations rates, which had declined following pneumococcal conjugate vaccine introduction for infants in 2000. METHODS: We randomly selected records from a single hospital 1 year before (n = 500) and after (n = 500) October 2015 implementation of ICD-10-CM coding. We used a validated ICD-9-CM algorithm and translation of that algorithm to ICD-10-CM to identify pneumonia hospitalizations pre- and post-implementation, respectively. We recoded ICD-10-CM records to ICD-9-CM and vice versa. We calculated sensitivity and positive predictive value (PPV) of the ICD-10-CM algorithm using ICD-9-CM coding as the reference. We used sensitivity and PPV values to calculate an adjustment factor to apply to ICD-10 era rates to enable comparison with ICD-9-CM rates. We reviewed primary diagnoses of charts not meeting the pneumonia definition when recoded. RESULTS: Sensitivity and PPV of the ICD-10-CM algorithm were 94% and 92%, respectively, for young children and 74% and 79% for older adults. The estimated adjustment factor for ICD-10-CM period rates was -2.09% (95% credible region [CR], -7.71% to +3.0%) for children and +6.76% (95% CR, -3.06% to +16.7%) for older adults. We identified a change in coding adult charts that met the ICD-9-CM pneumonia definition that led to recoding in ICD-10-CM as chronic obstructive pulmonary disease (COPD) exacerbation. CONCLUSIONS: The ICD-10-CM algorithm derived from a validated ICD-9-CM algorithm should not introduce substantial bias for evaluating pneumonia trends in children. However, changes in coding of pneumonia associated with COPD in adults warrant further study.

GOALS: To determine the proportion and characteristics of adults with hepatitis C at health care organizations in 4 US states who initiated direct-acting antivirals (DAAs). BACKGROUND: There are almost no data to assess the penetrance of treatment of the hepatitis C population in general US health care settings. STUDY: We conducted a prospective observational study using electronic clinical, pharmacy, and mortality data to determine the fraction of patients who initiated DAAs between January 2014 and December 2017, by start date and regimen. We used stepwise multivariate logistic regression analysis to identify sociodemographic and clinical characteristics associated with receipt of DAAs. RESULTS: Of 8823 patients, 2887 (32.7%) received DAAs. Quarterly (Q) uptake ranged from 1.1% in Q3 2014 to a high of 5.6% in Q2 2015. Characteristics associated with receipt of DAAs included age 51 to 70 years, higher income, pre-2014 treatment failure, and higher noninvasive fibrosis score (FIB4); however, over one half of patients with FIB4 scores >3.25, consistent with severe liver disease, were not treated. A lower likelihood of initiation was associated with Medicaid coverage. Of 5936 patients who did not initiate treatment, 911 (15.3%) had died and 2774 (46.7%) had not had a clinical encounter in >/=12 months by the end of the study. Fewer than 1% of DAA prescriptions originated from nonspecialty providers. CONCLUSIONS: During 4 calendar years of follow-up, one third of patients initiated DAAs. Large fractions of untreated patients had advanced liver disease, died, or were lost to follow-up. Even among patients in integrated health care systems, receipt of DAAs was limited.

OBJECTIVES: Chronic hepatitis C virus (HCV) infection is typically asymptomatic until severe liver disease occurs and even then can remain undiagnosed for some time; thus, screening and treatment of asymptomatic persons are needed to prevent poor outcomes. In a previous analysis of data from between 2006 and 2011, we found that 17% of newly diagnosed HCV infections in 4 large health systems were among persons with cirrhosis and/or end-stage liver disease, termed "late diagnosis." We sought to determine the proportion with late diagnosis during 2014-2016, after release of CDC baby boomer (1945-1965 birth cohort) testing guidelines in 2012. STUDY DESIGN: The cohort was based on analysis of electronic health records and administrative data of about 2.7 million patients visiting the same healthcare systems during 2014-2016. METHODS: Among persons with newly diagnosed chronic HCV infection during 2014-2016, we analyzed data collected up to January 1, 2017. RESULTS: Among 2695 patients with newly diagnosed HCV infection, 576 (21.4%) had late diagnosis. Most were born between 1945 and 1965 (n = 1613 [59.9%]), and among these, 27.6% had late diagnosis. Patients with versus without late diagnosis had equally lengthy prediagnosis observation in the health systems (mean and median, 9.1 and 9.1 vs 8.3 and 7.8 years, respectively) but were more likely to have a postdiagnosis hospitalization (32.5% vs 12.5%; P <.001) with greater number of hospital days (358.8 vs 78.5 per 100 person-years; P <.001). CONCLUSIONS: More than one-fifth of patients with newly diagnosed HCV infection during 2014-2016-and more than a quarter of those born between 1945 and 1965-had late diagnosis despite many years of in-system care, an increase of 5 percentage points since 2006-2011, after the interim initiation of age-based screening recommendations. Our data highlight missed opportunities for diagnosis and therapeutic intervention before the onset of severe liver disease, which is associated with high cost and diminished outcomes.

BACKGROUND: The 13-valent pneumococcal vaccine (PCV13) was introduced for U.S. children in 2010, and for immunocompromised adults >/=19 years old in series with the 23-valent polysaccharide vaccine (PPSV23) in 2012. To quantify indirect effects before the 2014 introduction of PCV13 for all adults >/=65 years old, we evaluated PCV13 impact on invasive pneumococcal disease (IPD) among adults with and without PCV13 indications. METHODS: We estimated IPD incidence using Active Bacterial Core surveillance and National Health Interview Survey. We compared incidence in 2013-2014 and 2007-2008, by age and serotype group (PCV13, PPSV23-unique, or types in neither vaccine [NVT]), among adults with and without PCV13 indications. RESULTS: IPD incidence declined among all adults. Among adults 19-64 years, PCV13-type IPD declined 57% (95%CI:-68,-43) in adults with immunocompromising conditions (IC, indication for PCV13 use), 57% (95%CI:-62, -52) in immunocompetent adults with chronic medical conditions (CMC, indications for PPSV23 use alone), and 74% (95%CI:-78,-70) in adults with neither vaccine indication. Among adults >/=65 years, PCV13-type IPD decreased 68% (95%CI:-76,-60) in those with IC, 68% (95%CI:-72,-63) in those with CMC, and 71% (95%CI:-77,-64) in healthy adults. PPSV23-unique types increased in adults 1964 years with CMC, and NVT did not change among adults with or without PCV13 indications. From 2013-2014, non-PCV13 serotypes accounted for nearly 80% of IPD. CONCLUSION: IPD incidence among U.S. adults declined after PCV13 introduction in children. Similar reductions in PCV13-type IPD in those with and without PCV13 indications suggest observed benefits are largely due to indirect effects from pediatric PCV13 use rather than direct use among adults.

BACKGROUND: Hepatitis B virus (HBV) can transmit through needle sharing. National HBV infection prevalence in persons who inject drugs remains ill-defined. We estimated the prevalence of total HBV core antibody (anti-HBc) positivity, indicating previous or ongoing HBV infection, among adults aged 20-59 years with injection drug use (IDU) history. We compared select characteristics by anti-HBc status. METHODS: Using 2001-2016 National Health and Nutrition Examination Survey data, we calculated anti-HBc+ prevalence among adults with IDU history and among the general US population. For adults with IDU history, we compared sex, age group, birth cohort, race/ethnicity, health insurance coverage, and hepatitis A immunity by anti-HBc status. Using marginal structural models, we calculated model-adjusted prevalence rates and ratios to determine characteristics associated with anti-HBc positivity among adults with IDU history. RESULTS: From 2001-2016, anti-HBc+ prevalence was 19.7% (95% CI, 16.0%-24.0%) among those with IDU history compared with 4.6% (95% CI, 4.3%-5.0%) in the general population. HBsAg+ prevalence was 0.4% (95% CI, 0.3%-0.5%) in the general population. Among adults with IDU history, 19.8% reported past year IDU and 28.5% had hepatitis A immunity. CONCLUSION: One-fifth of adults with IDU history had previous or ongoing HBV infection, which was over four times higher than the prevalence in the general population. One-fifth of adults with IDU history reported past year use. Programs promoting safe IDU practices, drug treatment, and hepatitis A and B vaccination should be key components of viral hepatitis prevention.

BACKGROUND: Hepatitis B virus (HBV) infection can be prevented through vaccination; however previous data show that only about 24%-45% of U.S. adults at high risk of HBV infection are protected. Our aims were to assess prevalence and trends in protective levels of hepatitis B surface antibody from 2003-2014 and explore factors associated with protection among U.S. adults at high risk. METHODS: Data were from the 2003-2014 National Health and Nutrition Examination Surveys. Our sample included adults, aged 18-49 years, who were tested for HBV and reported at least one of the following infection risks: history of STD, sex with men (for male respondents), infection with HIV, and injection drug use. We calculated the prevalence of hepatitis B surface antibody (anti-HBs, >/=10mIU/mL), indicative of immunity from vaccination among respondents for three 4-year time intervals (2003-2006, 2007-2010, and 2011-2014) and applied the Cochran-Mantel-Haenszel test to assess trends. Using multivariable logistic regression, we examined factors associated with positive anti-HBs serology. RESULTS: From 2003-2014, the prevalence of positive anti-HBs serology was 23.4%. Prevalence increased from 2003-2006 (16.3%) to 2007-2010 (27.3%), but no change occurred from 2007-2010 (27.3%) to 2011-2014 (28.1%). Among factors predicting positive anti-HBs serology were young age, female sex, and higher education. CONCLUSIONS: By 2014, less than one-third of adults, aged 18-49 years, at risk of infection exhibited anti-HBs >/=10 mIU/mL indicative of protection. Because these adults account for a substantial proportion of unprotected adults, targeted intervention strategies are essential to achieve the goal of hepatitis B elimination.

OBJECTIVES: To describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China. DESIGN: This was a multicentre, retrospective, observational study. SETTING: 13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014 PARTICIPANTS: Information on hospitalised patients aged >/=14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms. PRIMARY AND SECONDARY OUTCOME MEASURES: Resource use for CAP management. RESULTS: Of 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0-1 and Pneumonia Severity Index risk class I-II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%. CONCLUSIONS: These data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China. TRIAL REGISTRATION NUMBER: NCT02489578; Results.

BACKGROUND: Streptococcus pneumoniae (Sp) is a leading cause of bacterial pneumonia, meningitis, and sepsis and a major source of morbidity and mortality worldwide. Invasive pneumococcal disease (IPD) is defined as isolation of Sp from a normally sterile site, including blood or cerebrospinal fluid. The aim of this study is to describe outcomes as well as clinical and epidemiological characteristics of hospitalized IPD case patients in central China. METHODS: We conducted surveillance for IPD among children and adults from April 5, 2010 to September 30, 2012, in four major hospitals in Jingzhou City, Hubei Province. We collected demographic, clinical, and outcome data for all enrolled hospitalized patients with severe acute respiratory infection (SARI) or meningitis, and collected blood, urine, and cerebrospinal fluid (CSF) for laboratory testing for Sp infections. Collected data were entered into Epidata software and imported into SPSS for analysis. RESULTS: We enrolled 22,375 patients, including 22,202 (99%) with SARI and 173 (1%) with meningitis. One hundred and eighteen (118, 3%) with either SARI or meningitis were Sp positive, 32 (0.8%) from blood/CSF culture, and 87 (5%) from urine antigen testing. Of those 118 patients, 57% were aged >/=65 years and nearly 100% received antibiotics during hospitalization. None were previously vaccinated with 7-valent pneumococcal conjugate vaccine (PCV 7), 23-valent pneumococcal polysaccharide vaccine, or seasonal influenza vaccine. The main serotypes identified were 14, 12, 3, 1, 19F, 4, 5, 9V, 15 and 18C, corresponding to serotype coverage rates of 42%, 63%, and 77% for PCV7, PCV10, and PCV13, respectively. CONCLUSIONS: Further work is needed to expand access to pneumococcal vaccination in China, both among children and potentially among the elderly, and inappropriate use of antibiotics is a widespread and serious problem in China.

Chronic Hepatitis Cohort Study (CHeCS) publications using data from "real-world" patients with hepatitis C virus (HCV) have described demographic disparities in access to care; rates of advanced liver disease, morbidity, and mortality (2.5%-3.5% per year during 2006-10, although only 19% of all CHeCS decedents, and just 30% of those with deaths attributed to liver disease, had HCV listed on death certificate); substantial comorbidities, such as diabetes, advanced liver fibrosis (29% prevalence), renal disease, and depression, and partial reversal of all these with successful antiviral therapy; patient risk behaviors; and use of noninvasive markers to assess liver disease.

Severe morbidity can result from viral hepatitis co-infection, particularly in persons with existing chronic liver disease. Vaccination is the most effective way of preventing infection with the hepatitis A virus (HAV) and hepatitis B virus (HBV). Persons with chronic liver disease are currently recommended by the Advisory Committee on Immunization Practices to receive the hepatitis A (HepA) and hepatitis B (HepB) vaccines if they have not previously been vaccinated. Recently, the Advisory Committee on Immunization Practices approved language clarifying that all patients with hepatitis C virus (HCV) infection are recommended for HepB vaccination1 and that persons with HBV and HCV infections should also be specifically considered for vaccination against HAV.2,3

The rare emergence of hepatitis B virus (HBV) reactivation among hepatitis C virus (HCV)-infected patients receiving direct-acting antiviral (DAA) therapy raises questions about how many HCV-infected patients have active, past, or latent/occult HBV co-infection, and their DAA treatment experience1–3 We sought to characterize these factors, including possible post-DAA reactivation, among HCV patients in the Chronic Hepatitis Cohort Study (CHeCS), a “dynamic” observational study conducted at 4 large integrated U.S. health care systems. Study methods have been described elsewhere.4

OBJECTIVES: To describe how select Social Determinants of Health (SDH) are associated with the burden of hepatitis B virus (HBV) infection among foreign-born persons residing in the United States. METHODS: Multivariate logistic regression was used to examine the Racial and Ethnic Approaches to Community Health (REACH) 2010 Risk Factor Survey data to investigate the independent relationship between SDH and HBV testing and access to care. RESULTS: HBV infected persons with insurance were more likely to see a physician than those without. Respondents worried about money to pay rent or mortgage were more likely to report HBV infection than individuals who reported they never worry. Compared to English speakers, Spanish-speakers were less likely to report HBV infection, Vietnamese-speakers were more likely to see a physician for HBV infection, and Khmer-speakers were less likely to be tested. CONCLUSIONS: Health insurance coverage, worries about paying rent, and language of interview all differentially affect HBV testing and linkages to care among foreign-born persons. Multi-sectorial stakeholder collaborative efforts should integrate resources to provide culturally sensitive health promotion campaigns which may improve HBV related outcomes.

BACKGROUND: Risk of hepatocellular carcinoma (HCC) may be difficult to determine in the clinical setting. AIM: Develop a scoring system to forecast HCC risk among patients with chronic hepatitis C. METHODS: Using data from the Chronic Hepatitis Cohort Study collected during 2005-2014, we derived HCC risk scores for males and females using an extended Cox model with aspartate aminotransferase-to-platelet ratio index (APRI) as a time-dependent variables and mean Kaplan-Meier survival functions from patient data at two study sites, and used data collected at two separate sites for external validation. For model calibration, we used the Greenwood-Nam-D'Agostino goodness-of-fit statistic to examine differences between predicted and observed risk. RESULTS: Of 12,469 patients (1628 with a history of sustained viral response [SVR]), 504 developed HCC; median follow-up was 6 years. Final predictors in the model included age, alcohol abuse, interferon-based treatment response, and APRI. Point values, ranging from -3 to 14 (males) and -3 to 12 (females), were established using hazard ratios of the predictors aligned with 1-, 3-, and 5-year Kaplan-Meier survival probabilities of HCC. Discriminatory capacity was high (c-index 0.82 males and 0.84 females) and external calibration demonstrated no differences between predicted and observed HCC risk for 1-, 3-, and 5-year forecasts among males (all p values >0.97) and for 3- and 5-year risk among females (all p values >0.87). CONCLUSION: This scoring system, based on age, alcohol abuse history, treatment response, and APRI, can be used to forecast up to a 5-year risk of HCC among hepatitis C patients before and after SVR.

Lack of a consistent and reliable genotyping system can critically impede HIV genomic research on pathogenesis, fitness, virulence, drug resistance, and genomic-based healthcare and treatment. At present, mis-genotyping, i.e., background noises in molecular genotyping, and its impact on epidemic surveillance is unknown. For the first time, we present a comprehensive assessment of HIV genotyping quality. HIV sequence data were retrieved from worldwide published records, and subjected to a systematic genotyping assessment pipeline. Results showed that mis-genotyped cases occurred at 4.6% globally, with some regional and high-risk population heterogeneities. Results also revealed a consistent mis-genotyping pattern in gp120 in all studied populations except the group of men who have sex with men. Our study also suggests novel virus diversities in the mis-genotyped cases. Finally, this study reemphasizes the importance of implementing a standardized genotyping pipeline to avoid genotyping disparity and to advance our understanding of virus evolution in various epidemiological settings.

BACKGROUND: Limited information is available describing the uptake of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection among patients in general US health care settings. We determined the proportion of HCV-infected patients in the Chronic Hepatitis Cohort Study prescribed DAAs in 2014, who initiated treatment and identified characteristics associated with treatment initiation. METHODS: Uptake was defined as the proportion of HCV-infected patients with at least 1 clinical encounter in 2013 who were prescribed a DAA regimen during 2014 and initiated the regimen by August 2015. Using multivariable analysis, we examined demographic and clinical characteristics associated with receipt of DAAs. RESULTS: The cohort comprised 9508 patients; 544 (5.7%) started a DAA regimen. Higher annual income [adjusted odds ratios (aOR) 2.3 for income>$50K vs. <$30K], higher Fibrosis-4 score (aORs, 2.1, 2.0, and 1.4 for Fibrosis-4, >5.88, 3.25 to 5.88, 2.0 to 3.25, respectively, vs. <2.0), genotype 2 infection (aOR 2.2 vs. genotype 1), pre-2014 treatment failure (aOR 2.0 vs. treatment-naive), and human immunodeficiency virus (HIV) coinfection (aOR 1.8 vs. HCV monoinfection) were associated with DAA initiation. Black race/ethnicity (aOR 0.7 vs. whites) and Medicaid coverage (aOR 0.5 vs. private insurance) were associated with noninitiation. Sex, age, comorbidity, previous liver transplant, and duration of follow-up were not associated with receipt of DAAs. CONCLUSIONS: Among patients in these general US health care settings, uptake of DAA therapy was low in 2014, and especially so among minority and Medicaid patients. Systemic efforts to improve access to DAAs for all patients are essential to reduce morbidity and mortality from HCV infection.

Taenia saginata, Taenia solium and Taenia asiatica (beef, pork and Asian tapeworms, respectively) are parasitic flatworms of major public health and food safety importance. Among them, T. asiatica is a newly recognized species that split from T. saginata via an intermediate host switch approximately 1.14 Myr ago. Here we report the 169- and 168-Mb draft genomes of T. saginata and T. asiatica. Comparative analysis reveals that high rates of gene duplications and functional diversifications might have partially driven the divergence between T. asiatica and T. saginata. We observe accelerated evolutionary rates, adaptive evolutions in homeostasis regulation, tegument maintenance and lipid uptakes, and differential/specialized gene family expansions in T. asiatica that may favour its hepatotropism in the new intermediate host. We also identify potential targets for developing diagnostic or intervention tools against human tapeworms. These data provide new insights into the evolution of Taenia parasites, particularly the recent speciation of T. asiatica.

BACKGROUND: Limited information exists regarding the distribution of disease phases, treatment prescription and severe liver disease among patients with chronic hepatitis B (CHB) in US general healthcare settings. AIM: To determine the distribution of disease phases, treatment prescription and severe liver disease among patients with CHB in general US healthcare settings. METHODS: We analysed demographic and clinical data collected during 2006-2013 from patients with confirmed CHB in the Chronic Hepatitis Cohort Study, an observational cohort study involving patients from healthcare organisations in Michigan, Pennsylvania, Oregon and Hawaii. CHB phases were classified according to American Association for the Study of Liver Disease guidelines. RESULTS: Of 1598 CHB patients with ≥12 months of follow-up (median 6.3 years), 457 (29%) were immune active during follow-up [11% hepatitis B e antigen (HBeAg)-positive, 16% HBeAg-negative, and 2% HBeAg status unknown], 10 (0.6%) were immune tolerant, 112 (7%) were inactive through the duration of follow-up and 886 (55%) were phase indeterminate. Patients with cirrhosis were identified within each group (among 21% of immune active, 3% of inactive and 9% of indeterminate phase patients) except among those with immune-tolerant CHB. Prescription of treatment was 59% among immune active patients and 84% among patients with cirrhosis and hepatitis B virus (HBV) DNA >2000 IU/mL. CONCLUSIONS: Approximately, one-third of the cohort had active disease during follow-up; 60% of eligible patients were prescribed treatment. Our findings underscore the importance of ascertainment of fibrosis status in addition to regular assessment of ALT and HBV DNA levels.

BACKGROUND: Linking persons with hepatitis C virus (HCV) to care and treatment is critical to reduction in disease burden; typically, this entailed referral to a specialist. However, data regarding the frequency and factors associated with referral among patients in healthcare organizations (HCOs) are lacking. METHODS: Among persons in four US HCOs with newly diagnosed HCV during 2006-2011, we determined the frequency of liver-related specialist care after diagnosis. We also identified sociodemographic and clinical characteristics associated with such care by multivariate analysis, adjusted for all variables. RESULTS: Among 3592 patients with newly diagnosed HCV, 57 % (range among sites 45-90 %) received specialist care; of these, 57 % received care within 90 days of diagnosis. Patient characteristics associated with receipt of specialist care included: affiliation with one of the study sites [adjusted odds ratio (aOR) 4.8 vs. the referent site); having Medicare plus private insurance (aOR 1.6 vs. Medicaid); and having elevated alanine aminotransferase (ALT) (aOR 1.6 vs. normal ALT) or lower platelet values (aOR 1.4 vs. normal platelet level). Specialist care within 90 days of diagnosis was associated with private insurance (aOR 1.5 vs. Medicaid), elevated ALT levels (aOR 1.3-2.3 vs. normal), and having ≥2 comorbid conditions (aOR 1.4 vs. no comorbid conditions). Compared to patients not referred, those referred were more likely to be treated (aOR 3.5). CONCLUSIONS: Receipt of specialist care among persons with newly diagnosed HCV varied among HCOs. Clinical evidence of liver disease and having private insurance were associated with prompt receipt of specialist care and HCV treatment.

Among 2,338 chronic hepatitis B patients followed during 2006-2013 in the Chronic Hepatitis Cohort Study, 78% had ≥1 alanine aminotransferase and 37% had ≥1 HBV DNA level assessed annually. Among cirrhotic patients, 46% never had hepatic imaging. Patients in this cohort were insufficiently monitored for disease activity and hepatocellular carcinoma.