Search

In 1972, Nobel laureate Youyou Tu's research team conducted clinical trials on the dried material of

The incidence of hepatitis A virus (HAV) infection has been low in developed countries for decades; however, many adults in these countries are susceptible to HAV infection. In recent years, the global trade of food products originating from HAV-endemic countries resulted in HAV outbreaks associated with imported foods in developed countries. This article aims to review the characteristics of selected HAV outbreaks associated with imported food in developed countries during 2012-2018, and discusses improvements in global public health capabilities and new tools for effective detection, control, and prevention of HAV outbreaks.

Tenofovir disoproxil fumarate (TDF) is a prodrug of tenofovir, and after being administered orally, it converts to tenofovir in the blood. With the increasing use of TDF in women for treatment and prevention of mother-to-child transmission (MTCT) of both human immunodeficiency virus (HIV) and hepatitis B virus (HBV), or the pre-exposure prophylaxis (PrEP) for HIV, many nursing mothers have to understand the risk of exposure to tenofovir via breastmilk and make the decision about breastfeeding while on TDF treatment. Despite the safety record of TDF in pregnancy, some guidelines recommend against its use during breastfeeding. In this paper, we compared the dosage levels of tenofovir exposure in fetuses, breastfed infants, and children receiving tenofovir treatment. We found that breastfed infants were exposed to only 0.5%–16% of the tenofovir dosage that fetuses experienced via placental transfer, and 0.01–0.04% of the recommended weight-adjusted therapeutic dose. The assessment of toxicity risk from the dose perspective is an important and natural way of addressing safety concerns about exposure to tenofovir via breastfeeding. Based on the safety data from fetuses and children with tenofovir exposure, and the comparatively negligible exposure dosage from breastfeeding, our study supports mothers on TDF treatment should be encouraged to breastfeed. Keywords: Human Immunodeficiency virus, Hepatitis B virus, Breastfeeding, Tenofovir disoproxil fumarate, Antiviral therapy

Background The emergence of SARS-Cov2 variants has highlighted the need to implement sequencing-based surveillance in developing countries for early response to mutant viruses of concern. However, limited information on how to implement sequencing-based surveillance is available, and the feasibility and performance of this new type of surveillance are still in question. Methods To understand the challenges with the implementation and to promote sequencing-based surveillance, we reported findings from a pilot for hepatitis A (HepA) in five sentinel provinces in China as an example of sequencing-based surveillance implementation. The performance of the surveillance system was evaluated by indicators related to acceptability, data quality, simplicity, utility, and timeliness. We use a scale from 1 to 3 was used to provide a score for each aspect. Results During the pilot, 306 cases of HepA were reported, and 49.79% of samples were available for sequencing. Eleven genomic clusters were found, of which seven clusters were potentially related to a foodborne outbreak oyster based on identical viral sequence and epidemiologic investigations. The greatest strength of the system was its simplicity (Score: 2.63). The acceptability (Score: 2.0) and utility (Score: 2.33) were modest, but data quality (Score: 1.75) and timeliness (Score: 1.75) were the main challenges. Conclusions Overall, the system performed satisfactorily and proved to be useful for virological characterization of cases and early outbreak detection, with a great potential for scale-up. Further efforts are required to address financial and human resource constraints and inadequate support among physicians. Education should be given to health care professionals to improve the data quality. The establishment of decentralized surveillance networks can be an approach to improve timeliness for emerging infections.

What is already known about this topic? The Co-Administration of Multiple Vaccines were implemented in many countries and have been shown to significantly reduce many times of visiting the vaccination clinic. What is added by this report? It is the first time to calculate the cost of visiting vaccination clinic from transportation and work-absence for children’s families in Guangdong. What are the implications for public health practice? We demonstrated the importance of Co-Administration of Multiple Vaccines that reduce the vaccination cost of children’s families. The policy should be promoted as soon as possible.

Background Treating high-risk women with antivirals in their third trimester is a promising intervention to further reduce perinatal transmission in neonates born to hepatitis B surface antigen positive [HBsAg(+)] mothers. Methods We estimated the number of perinatal infections based on coverage and effectiveness of hepatitis B immunization. We compared cost-effectiveness of different approaches to identify high-risk women for antiviral treatment, by region and urban/rural residence. Results Of the 16.59 million live births in 2015, 1.04 million infants (6.3%) were born to HBsAg(+) mothers and 268 201 infants (1.6%) to HBsAg(+) and HBeAg(+) dual-positive mothers. Despite immunoprophylaxis, 51 478 perinatal hepatitis B virus (HBV) transmissions were estimated to have occurred from HBsAg and HBeAg dual-positive mothers in 2015. Using HBeAg or HBV viral load testing to identify high-risk pregnant women and to treat them with Tenofovir, the incremental cost ranged from US$68.2 million to US$90.3 million. Assuming HBV viral load testing is available and used to guide treatment and all women with HBV viral loads >200 000 IU/ml are treated, 25 912 infections would be averted at a projected cost of US$3500 per infection averted. Conclusions Identifying high-risk pregnant women and providing them with antiviral treatment is feasible and cost-effective to interrupt perinatal HBV transmissions. Policy options should be urgently explored in order for China to reach the HBV elimination goal of 0.1% prevalence among children by 2030.

Based on example investigation, this research categorised the failure modes of the column into three typical types, which are one plastic hinge, two plastic hinges and three plastic hinges models, respectively. The first two modes would appear when the sliding body impacted the RC column, while the last mode would occur when the structures are subjected to huge rockfall. Subsequently, the relationship between the critical velocity of sliding body and the properties of the RC column were obtained. To investigate the interaction between a sliding body and a structure, a typical type of RC column was selected for the analysis. The dependence of the critical velocity and the impact angle of the sliding body on the density of the sliding body and the height of the column are determined. It also took the width of the cross section, the ultimate bending moment of the column and the horizontal displacement at the top of the column into consideration. In order to validate the applicability of present model...

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. 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. 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). 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.

Guidelines for the treatment of HCV-infected persons were updated in August 2015 with new recommendations for patients with renal impairment. Treatment is imperative for patients with severe, renal-associated extrahepatic manifestations of HCV infection.We sought to describe the prevalence of these conditions among current HCV-infected patients in a population-based prospective, observational cohort study at four large US health systems.Data from cohort patients with chronic HCV infection during 2012 were analyzed for the period from 2006 to 2013. We determined the prevalence of mild to moderately impaired renal function defined as having the most recent estimated glomerular filtration rate [eGFR] ≤ 80 ml/min/1.73 m(2), with severe impairment defined as eGFR 30 ml/min/1.73 m(2), based on the treatment guidelines. Prevalence of extrahepatic conditions was ascertained using ICD9-codes.Among 5772 persons, the prevalence of eGFR ≤ 80 was 33 % and eGFR 30 was 2 %, including among patients with hepatic fibrosis. Diagnosed extrahepatic renal manifestations were rare: vasculitis- 0.2 %, nephrotic syndrome- 0.3 %, and cryoglobulinemia- 0.9 %.While the prevalence of severe renal impairment and diagnosed extrahepatic manifestations was low, mild-to-moderate renal impairment was common in HCV patients, including those with advanced liver fibrosis for whom the need for treatment is urgent.

BACKGROUNDIn November and December 2012, 6 patients at a hemodialysis clinic were given a diagnosis of new hepatitis C virus (HCV) infection.OBJECTIVETo investigate the outbreak to identify risk factors for transmission.METHODSA case patient was defined as a patient who was HCV-antibody negative on clinic admission but subsequently was found to be HCV-antibody positive from January 1, 2008, through April 30, 2013. Patient charts were reviewed to identify and describe case patients. The hypervariable region 1 of HCV from infected patients was tested to assess viral genetic relatedness. Infection control practices were evaluated via observations. A forensic chemiluminescent agent was used to identify blood contamination on environmental surfaces after cleaning.RESULTSEighteen case patients were identified at the clinic from January 1, 2008, through April 30, 2013, resulting in an estimated 16.7% attack rate. Analysis of HCV quasispecies identified 4 separate clusters of transmission involving 11 case patients. The case patients and previously infected patients in each cluster were treated in neighboring dialysis stations during the same shift, or at the same dialysis station on 2 consecutive shifts. Lapses in infection control were identified. Visible and invisible blood was identified on multiple surfaces at the clinic.CONCLUSIONSEpidemiologic and laboratory data confirmed transmission of HCV among numerous patients at the dialysis clinic over 6 years. Infection control breaches were likely responsible. This outbreak highlights the importance of rigorous adherence to recommended infection control practices in dialysis settings.Infect. Control Hosp. Epidemiol. 2016;37(2):125–133

The severity of liver disease in the hepatitis C virus (HCV)-infected population in the United States remains uncertain. We estimated the prevalence of cirrhosis in adults with chronic hepatitis C (CHC) using multiple parameters including liver biopsy, diagnosis/procedure codes, and a biomarker.Patients enrolled in the Chronic Hepatitis Cohort Study (CHeCS) who received health services during 2006-2010 were included. Cirrhosis was identified through liver biopsy reports, diagnosis/procedure codes for cirrhosis or hepatic decompensation, and Fibrosis-4 (FIB-4) scores ≥5.88. Demographic and clinical characteristics associated with cirrhosis were identified through multivariable logistic modeling.Among 9,783 patients, 2,788 (28.5%) were cirrhotic by at least one method. Biopsy identified cirrhosis in only 661 (7%) patients, whereas FIB-4 scores and diagnosis/procedure codes for cirrhosis and hepatic decompensation identified cirrhosis in 2,194 (22%), 557 (6%), and 482 (5%) patients, respectively. Among 661 patients with biopsy-confirmed cirrhosis, only 356 (54%) had an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for cirrhosis. Older age, male gender, Asian race, Hispanic ethnicity, genotype 3 infection, HIV coinfection, diabetes, history of antiviral therapy, and history of alcohol abuse were independently associated with higher odds of cirrhosis (all, P0.05). Conversely, private health insurance coverage, black race, and HCV genotype 2 were associated with lower odds of cirrhosis.A high proportion of patients with biopsy-confirmed cirrhosis are not assigned ICD-9 codes for cirrhosis. Consequently, ICD-9 codes may not be reliable as the sole indicator of the prevalence of cirrhosis in cohort studies. Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed.

We estimated the number of people infected with HCV in the United States who would qualify for immediate treatment according to the 2014 guidance. We based fibrosis stage on biopsy results, when available, or on FIB-4 scores. We used laboratory tests and International Classification of Diseases, Ninth Revision, Clinical Modification codes to determine if patients had any qualifying comorbidities. Of the 2.7 million people with HCV infection, we assumed that 1.35 million (50%) had been diagnosed. We estimated 457 000 met the highest and 356 000 the high-priority criteria for treatment, indicating that as many as 813 000 people could be treated immediately with new therapies. These estimates can inform planning efforts to address clinical capacity constraints and treatment costs.

New treatments for hepatitis C virus (HCV) may be highly effective but are associated with substantial costs that may compel clinicians and patients to consider delaying treatment. This study investigated the cost-effectiveness of these treatments with a focus on patients in early stages of liver disease. We developed a state-transition (or Markov) model to calculate costs incurred and quality-adjusted life-years (QALYs) gained following HCV treatment, and we computed incremental cost-effectiveness ratios (cost per QALY gained, in 2012 US dollars) for treatment at different stages of liver disease versus delaying treatment until the subsequent liver disease stage. Our analysis did not include the potential treatment benefits associated with reduced non–liver-related mortality or preventing HCV transmission. All parameter values, particularly treatment cost, were varied in sensitivity analyses. The base case scenario represented a 55-year-old patient with genotype 1 HCV infection with a treatment cost of $100,000 and treatment effectiveness of 90%. In this scenario, for a 55-year-old patient with moderate liver fibrosis (Metavir stage F2), the cost-effectiveness of immediately initiating treatment at F2 (versus delaying treatment until F3) was $37,300/QALY. For patients immediately treated at F0 (versus delaying treatment until F1), the threshold of treatment costs that yielded $50,000/QALY and $100,000/QALY cost-effectiveness ratios were $22,200 and $42,400, respectively. Conclusion: Immediate treatment of HCV-infected patients with moderate and advanced fibrosis appears to be cost-effective, and immediate treatment of patients with minimal or no fibrosis can be cost-effective as well, particularly when lower treatment costs are assumed. (Hepatology 2015;61:1860–1869)

Hepatitis A illness severity increases with age. One indicator of hepatitis A illness severity is whether persons are hospitalized. We describe changes in primary hepatitis A hospitalization rates in the United States from 2002-2011, including changes in demographics, secondary discharge diagnoses, and factors affecting hospitalization duration. We describe changes from 2002-2011 among U.S. residents hospitalized with a principal hepatitis A diagnosis and accompanying secondary diagnoses using ICD-9 codes from the National Inpatient Survey discharge data. We calculated rates of hospitalizations with hepatitis A as the principal discharge diagnosis and rates of secondary discharge diagnoses. Using multiple regression, we assessed the effect of secondary diagnoses on hospitalization length of stay for five time intervals: 2002-2003, 2004-2005, 2006-2007, 2008-2009, and 2010-2011. Rates of hospitalization for hepatitis A as a principal diagnosis decreased from 0.72/100,000 to 0.29/100,000 (P

Risk of hepatocellular carcinoma (HCC) may be difficult to determine in the clinical setting. Develop a scoring system to forecast HCC risk among patients with chronic hepatitis C. 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. 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). 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.

Disease burden models have predicted worsening morbidity of liver disease caused by hepatitis C in the United States. The aim of this study was to determine the trend in hospitalizations caused by hepatitis C and advanced liver disease. We analyzed data for the period 2004-11 from the Nationwide Inpatient Sample, the largest nationwide all-payer hospital inpatient care database. Hospitalization rates for hepatitis C per 100,000 people increased significantly from 4.76 in 2004-05 to 13.81 in 2010-11-an increase of 190 percent. Hospitalization rates for advanced liver disease also increased, particularly for hepatorenal syndrome (93 percent) and portal hypertension (62 percent). Hepatitis C was the principal diagnosis for 64,867 hospitalizations in 2010-11, resulting in a total charge of $3.5 billion. We found nationwide trends in increasing morbidity and medical costs for advanced liver disease associated with hepatitis C. Our findings suggest that hepatitis C is a public health problem and has been growing in magnitude in recent years. Stakeholders and policy makers should implement both recommended screenings for people born in the period 1945-65 and more effective treatment for hepatitis C, which have the potential to reverse the rising morbidity and costs of hepatitis C.

Summary Background In May, 2013, an outbreak of symptomatic hepatitis A virus infections occurred in the USA. Federal, state, and local public health officials investigated the cause of the outbreak and instituted actions to control its spread. We investigated the source of the outbreak and assessed the public health measures used. Methods We interviewed patients, obtained their shopping information, and did genetic analysis of hepatitis A virus recovered from patients' serum and stool samples. We tested products for the virus and traced supply chains. Findings Of 165 patients identified from ten states, 69 (42%) were admitted to hospital, two developed fulminant hepatitis, and one needed a liver transplant; none died. Illness onset occurred from March 31 to Aug 12, 2013. The median age of patients was 47 years (IQR 35–58) and 91 (55%) were women. 153 patients (93%) reported consuming product B from retailer A. 40 patients (24%) had product B in their freezers, and 113 (68%) bought it according to data from retailer A. Hepatitis A virus genotype IB, uncommon in the Americas, was recovered from specimens from 117 people with hepatitis A virus illness. Pomegranate arils that were imported from Turkey—where genotype IB is common—were identified in product B. No hepatitis A virus was detected in product B. Interpretation Imported frozen pomegranate arils were identified as the vehicle early in the investigation by combining epidemiology—with data from several sources—genetic analysis of patient samples, and product tracing. Product B was removed from store shelves, the public were warned not to eat product B, product recalls took place, and postexposure prophylaxis with both hepatitis A virus vaccine and immunoglobulin was provided. Our findings show that modern public health actions can help rapidly detect and control hepatitis A virus illness caused by imported food. Our findings show that postexposure prophylaxis can successfully prevent hepatitis A illness when a specific product is identified. Imported food products combined with waning immunity in some adult populations might make this type of intervention necessary in the future. Funding US Centers for Disease Control and Prevention, US Food and Drug Administration, and US state and local public health departments.

Post-exposure prophylaxis with hepatitis B vaccine (HepB) alone is highly effective in preventing perinatal hepatitis B virus (HBV) transmission and the World Health Organization recommends administering HepB to all infants within 24 h after delivery. Maternal screening for HBsAg and administration of hepatitis B immune globulin (HBIG) in addition to HepB for infants born to HBsAg-positive pregnant women can increase the effectiveness of post-exposure prophylaxis for perinatal HBV transmission. In Shangdong Province, China which has a high prevalence of chronic HBV infection, HepB birth dose and HBIG were integrated into the routine childhood immunization program in 2002 and July 2011 respectively. We assessed progress toward implementation of these measures. Hospital-based reporting demonstrated an increase in maternal screening from 70.7% to 96.9% from 2004–2012; HepB birth dose coverage (within 24 h) remained high (96.3–97.1%) during this period. For infants with known HBsAg-positive mothers, the coverage of HBIG increased from 85.0% (before July 2011) to 92.1% (after July 2011). However, HBIG coverage in western areas of Shandong Province remained at 81.1% among infants with known HBsAg-positive mothers. Preterm/low-birth-weight and illness after birth were the most commonly reported reasons for delay in the first dose of HepB to >24 h of birth. Additional education on the safety and immune protection from HepB and HBIG might help to correct delays in administering the HepB birth dose and low HBIG coverage in the western areas of the Shandong Province.

Background. The number of deaths in hepatitis C virus (HCV)–infected persons recorded on US death certificates has been increasing, but actual rates and causes of death in these individuals have not been well elucidated. Methods. Disease-specific, liver-related, and non-liver-related mortality data for HCV-infected patients in an observational cohort study, the Chronic Hepatitis Cohort Study (CHeCS) at 4 US healthcare systems, were compared with multiple cause of death (MCOD) data in 12 million death certificates in 2006–2010. Premortem diagnoses, liver biopsies, and FIB-4 scores (a noninvasive measure of liver damage) were examined. Results. Of 2 143 369 adult patients seen at CHeCS sites in 2006–2010, 11 703 (0.5%) had diagnosed chronic HCV infection, and 1590 (14%) died. The majority of CHeCS decedents were born from 1945 to 1965 (75%), white (50%), and male (68%); mean age of death was 59 years, 15 years younger than MCOD deaths. The ageadjusted mortality rate for liver disease in CHeCS was 12 times higher than the MCOD rate. Before death, 63% of decedents had medical record evidence of chronic liver disease, 76% had elevated FIB-4 scores, and, among those biopsied, 70% had moderate or worse liver fibrosis. However, only 19% of all CHeCS decedents and only 30% of those with recorded liver disease had HCV listed on their death certificates. Conclusions. HCV infection is greatly underdocumented on death certificates. The 16 622 persons with HCV listed in 2010 may represent only one-fifth of about 80 000 HCV-infected persons dying that year, at least two-thirds of whom (53 000 patients) would have had premortem indications of chronic liver disease.

Genital herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections in the United States. We sought to assess differences in HSV-2 seroprevalence among non-Hispanic blacks and non-Hispanic whites and describe trends over time from 1988 to 2010.Data from National Health and Nutrition Examination Surveys (NHANES) were used to determine national HSV-2 seroprevalence estimates from National Health and Nutrition Examination Surveys 1988 to 1994, 1999 to 2002, 2003 to 2006, and 2007 to 2010. Persons aged 14 to 49 years were included in the analyses. Race/Ethnicity was defined by self-report as non-Hispanic white or non-Hispanic black. Purified glycoprotein specific for HSV-2 was used to detect type-specific antibodies using an immunodot assay. The same assay was used in all surveys. History of diagnosed genital herpes was self-reported.Overall, HSV-2 seroprevalence decreased in the United States between 1988 to 1994 and 2007 to 2010, from 21.2% to 15.5%. Among non-Hispanic white females, HSV-2 seroprevalence decreased from 19.5% (1988-1994) to 15.3% (2007-2010; P0.001); HSV-2 seroprevalence remained stable among non-Hispanic black females, 52.5% (1988-1994) to 49.9% (2007-2010; P = 0.1). The female black/white prevalence ratio was 2.7 (95% confidence interval [CI], 2.4-3.0) in 1988 to 1994 increasing to 3.3 (95% CI, 2.9-3.7) in 2007 to 2010 (P = 0.01). Among males, the black/white prevalence ratio was 2.4 (95% CI, 1.9-2.9) in 1988 to 1994 increasing to 4.4 (95% CI, 3.3-5.8) in 2007 to 2010 (P = 0.001). The overall percentage of HSV-2-seropositive survey participants who reported never being told by a doctor or health care professional that they had genital herpes did not change significantly between 1988 to 1994 and 2007 to 2010 and remained high (90.7% and 87.4%, respectively).Although HSV-2 seroprevalence decreased overall, the decrease was most marked among non-Hispanic whites, and racial disparities significantly increased over time. These persistent disparities demonstrate the need for innovative prevention strategies among this at-risk population.

In 2009, an estimated 3590 new heterosexually acquired HIV infections occurred in males in the United States. Three randomized controlled trials demonstrated that male circumcision decreased a man's risk for HIV acquisition through heterosexual sex. We describe circumcision prevalence in US males and determine circumcision prevalence among males potentially at increased risk for heterosexually acquired HIV infection.We estimated circumcision prevalence among men and boys aged 14 to 59 years using data from the National Health and Nutrition Examination Surveys 2005-2010. We defined men and boys with 2 or more female partners in the last year as potentially at increased risk for heterosexually acquired HIV infection.Estimated circumcision prevalence was 80.5%. Prevalence varied significantly by year of birth, race/ethnicity, health insurance type, and family income. Circumcision prevalence among men and boys reporting 2 or more female partners in the last year was 80.4%, which corresponded to an estimated 3.5 million uncircumcised men and boys potentially at increased risk for heterosexually acquired HIV infection. Of these men and boys, 48.3% lacked health insurance.Circumcision prevalence in the United States differs by demographic group, and half of uncircumcised men and boys potentially at increased risk for heterosexually acquired HIV are uninsured. These data could inform recommendations and cost analyses concerning circumcision in the United States.

Most sexually active people will be infected with a sexually transmitted infection (STI) at some point in their lives. The number of STIs in the United States was previously estimated in 2000. We updated previous estimates to reflect the number of STIs for calendar year 2008.We reviewed available data and literature and conservatively estimated incident and prevalent infections nationally for 8 common STIs: chlamydia, gonorrhea, syphilis, herpes, human papillomavirus, hepatitis B, HIV, and trichomoniasis. Where available, data from nationally representative surveys such as the National Health and Nutrition Examination Survey were used to provide national estimates of STI prevalence or incidence. The strength of each estimate was rated good, fair, or poor, according to the quality of the evidence.In 2008, there were an estimated 110 million prevalent STIs among women and men in the United States. Of these, more than 20% of infections (22.1 million) were among women and men aged 15 to 24 years. Approximately 19.7 million incident infections occurred in the United States in 2008; nearly 50% (9.8 million) were acquired by young women and men aged 15 to 24 years. Human papillomavirus infections, many of which are asymptomatic and do not cause disease, accounted for most of both prevalent and incident infections.Sexually transmitted infections are common in the United States, with a disproportionate burden among young adolescents and adults. Public health efforts to address STIs should focus on prevention among at-risk populations to reduce the number and impact of STIs.

BACKGROUND After the first monovalent 2009 pandemic influenza A (H1N1) vaccine became available in September 2009, Chinese officials conducted a mass vaccination program in Beijing. We evaluated the safety and effectiveness of the vaccine. METHODS During a 5-day period in September 2009, a total of 95,244 children and adults received the PANFLU.1 vaccine (Sinovac Biotech), a monovalent split-virion vaccine of 15 μg of hemagglutinin antigen without adjuvant. We assessed adverse events after immunization through an enhanced passive-surveillance system and through active surveillance, using diary cards and telephone interviews. Active surveillance for neurologic diseases was implemented in hospitals citywide. To assess vaccine effectiveness, we compared the rates of reported laboratory-confirmed cases of 2009 H1N1 virus infection in students who received the vaccine with the rates in those who did not receive the vaccine, starting 2 weeks after the mass vaccination. RESULTS As of December 31, 2009, adverse events were reported by 193 vaccine recipients. Through hospital-based active surveillance, 362 cases of incident neurologic diseases were identified within 10 weeks after the mass vaccination, including 27 cases of the Guillain-Barre syndrome. None of the neurologic conditions occurred among vaccine recipients. From 245 schools, 25,037 students participated in the mass vaccination and 244,091 did not. During the period from October 9 through November 15, 2009, the incidence of confirmed cases of 2009 H1N1 virus infection per 100,000 students was 35.9 (9 of 25,037) among vaccinated students and 281.4 (687 of 244,091) among unvaccinated students. Thus, the estimated vaccine effectiveness was 87.3% (95% confidence interval, 75.4 to 93.4). CONCLUSIONS Among 95,244 children and adults in Beijing, the PANFLU.1 vaccine had a safety profile similar to those of seasonal influenza vaccines and appeared to be effective against confirmed H1N1 virus infection in school-age children. (Funded by the Beijing Municipal Health Bureau.).

Background. Some screening and treatment programs implemented to control Chlamydia trachomatis genital infections and their complications have shown initial reductions in infection prevalence, followed by increases to preprogram levels or higher. One hypothesis is that treatment shortens duration of infection, attenuates development of protective immunity, and thereby, increases risk of reinfection. Methods. A literature review was undertaken to assess evidence supporting the concept of protective immunity,its characteristics, and its laboratory correlates in human chlamydial infection. The discussion is organized around key questions formulated in preparation for the Chlamydia Immunology and Control Expert Advisory Meeting held by the Centers for Disease Control and Prevention in April 2008. Results. Definitive human studies are not available, but cross-sectional studies show that chlamydia prevalence,organism load, and concordance rates in couples decrease with age, and organism load is lower in those with repeat infections, supporting the concept of protective immunity. The protection appears partial and can be overcome after reexposure, similar to what has been found in rodent models of genital infection. No data are available to define the duration of infection required to confer a degree of immunity or the time course of immunity after resolution of untreated infection. In longitudinal studies involving African sex workers, a group presumed to have frequent and ongoing exposure to chlamydial infection, interferon-g production by peripheral blood mononuclear cells in response to chlamydial heat-shock protein 60 was associated with low risk of incident infection.In cross-sectional studies, relevant T helper 1-type responses were found in infected persons, paralleling the studies in animal models. Conclusions. The data support the concept that some degree of protective immunity against reinfection develops after human genital infection, although it appears, at best, to be partial. It is likely that factors besides population levels of immunity contribute to trends in prevalence observed in screening and treatment programs.Future studies of protective immunity in humans will require longitudinal follow-up of individuals and populations,frequent biological and behavioral sampling, and special cohorts to help control for exposure.

OBJECTIVES To describe demographic and behavioral characteristics and the prevalence of HIV and herpes simplex virus type 2 (HSV-2) infections in men who had sex with men identified through a nationally representative, population-based survey. METHODS As part of National Health and Nutrition Examination Surveys in 2001-2006, men 18 to 59 years of age were interviewed about sexual behavior using audio computer assisted self-interview and were tested for antibodies to HIV and HSV-2. RESULTS Of the 4319 men interviewed, 5.2% reported having ever had sex with men (MSM). MSM were more likely than non-MSM (those reporting female partners only) to have first sex at or =10 lifetime sex partners (73.6% vs. 40.8%), and have ever used cocaine (46.1% vs. 26.6%) (all P < 0.004). Among MSM, the prevalence of HIV and HSV-2 was 9.1% and 18.4%, respectively. Only 44.5% of MSM reported their sexual orientation as homosexual or gay. Comparing with bisexual and heterosexual MSM, homosexual MSM reported the highest number of lifetime male partners and had the highest HIV prevalence (16.5%). CONCLUSIONS In this population-based sample of men in the United States, self-reported same-sex behavior and homosexual orientation are strong markers for high risk of HIV infection.

OBJECTIVE: Most young women initiate sexual activity during adolescence; risk for sexually transmitted infections (STIs) accompanies this initiation. In this study we estimated the prevalence of the most common STIs among a representative sample of female adolescents in the United States. METHODS: Data were analyzed from 838 females who were aged 14 to 19 and participating in the nationally representative National Health and Nutrition Examination Survey 2003–2004. After interview and examination, survey participants provided biological specimens for laboratory testing. The main outcome was weighted prevalence of at least 1 of 5 STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, herpes simplex virus type 2, and human papillomavirus (HPV) (any of 23 high-risk types or type 6 or 11). RESULTS: Prevalence of any of the 5 STIs was 24.1% among all and 37.7% among sexually experienced female adolescents. HPV (23 high-risk types or type 6 or 11) was the most common STI among all female adolescents (prevalence: 18.3%), followed by C trachomatis infection (prevalence: 3.9%). Prevalence of any of the STIs was 25.6% among those whose age was the same or 1 year greater than their age at sexual initiation and 19.7% among those who reported only 1 lifetime sex partner. CONCLUSIONS: The prevalence of STIs among female adolescents is substantial, and STIs begin to be acquired soon after sexual initiation and with few sex partners. These findings support early and comprehensive sex education, routine HPV vaccination at the age of 11 to 12 years, and C trachomatis screening of sexually active female adolescents.

Objectives To describe HSV-1 seroprevalence in children in the United States and to examine factors associated with herpes simplex virus type 1 (HSV-1) infection in children. Study design Sera samples available from 2989 children age 6 to 13 years who participated in the National Health and Nutrition Examination Surveys (NHANES) 1999-2002 were tested for HSV-1 antibodies using a type-specific immunodot assay. HSV-1 seroprevalence in children age 12 to 13 years was compared with that reported in an earlier survey (NHANES 1988-1994). Results Overall, HSV-1 seroprevalence in children age 6 to 13 years was 31.1% (95% confidence interval [CI], 28.6% to 33.9%). Seroprevalence increased with age, from 26.3% in 6- to 7-year-olds to 36.1% in 12-to 13-year-olds, and varied by race/ethnicity, birthplace, and poverty level. Among US-born children age 12 to 13 years, the point estimate of HSV-1 seroprevalence was lower in NHANES 1999-2002 than in NHANES 1988-1994 (34.3% vs 38.1%), but the differences were not statistically significant. Conclusions HSV-1 is a common infection in US children, with more than 25% infected by age 7. Race/ethnicity, birthplace, and poverty level are predictors for HSV-1 infection in children.

Objectives: To study the prevalence of circumcision in the United States and to examine the association between circumcision and herpes simplex virus Type 2 (HSV-2) infection. Methods: As part of National Health and Nutrition Examination Surveys from 1999 to 2004, 6174 men were interviewed about circumcision status and sexual behaviors, and were tested for HSV-2 antibodies. Medical artwork was used to aid the reporting of circumcision status. Results: The overall prevalence of circumcision was 79% and varied by race/ethnicity (88% in non-Hispanic whites, 73% in non-Hispanic blacks, 42% in Mexican Americans, and 50% in others). For men born in the United States from 1940 through 1979, the prevalence of circumcision increased, with larger increases in non-Hispanic blacks and Mexican Americans than in non-Hispanic whites; the prevalence of circumcision decreased significantly in those born in the 1980s (84%) compared to those born in 1970s (91%) (P

Sustained virological response (SVR) to antiviral therapy for hepatitis C virus (HCV) correlates with changes in biochemical measures of liver function. However, little is known about the long-term effects of SVR on liver fibrosis. We investigated the effects of HCV therapy on fibrosis, based on the Fibrosis-4 (FIB4) score, over a 10-year period.We collected data from participants in the Chronic Hepatitis Cohort Study-a large observational multicenter study of patients with hepatitis at 4 US health systems-from January 1, 2006, through December 31, 2013. We calculated patients' FIB4 score and the aminotransferase-to-platelet ratio index (APRI) score over a 10-year period. Of 4731 patients with HCV infection, 1657 (35%) were treated and 755 (46%) of these patients achieved SVR.In propensity score-adjusted analyses, we observed significant longitudinal changes in FIB4 score that varied with treatment and response to treatment. In patients achieving SVR, FIB4 scores decreased sharply, remaining significantly lower over the 10-year period than in untreated patients or patients with treatment failure (P.001). In independent analyses, men and patients with HCV genotype 1 or 3 infections had higher FIB4 scores than women or patients with HCV genotype 2 infections (P.01 for both). Findings were similar in a sensitivity analysis that substituted the APRI as the marker of fibrosis instead of the FIB4 score.SVR to HCV treatment appears to induce long-term regression of fibrosis based on FIB4 scores collected over 10 years from a large observational study of US hepatitis patients. Patients receiving no treatment or with treatment failure had progressive increases in FIB4 scores.

Background A key question in care of patients with chronic hepatitis C virus (HCV) infection is beginning treatment immediately vs delaying treatment. Risks of mortality and disease progression in "real world" settings are important to assess the implications of delaying HCV treatment. Methods This was a cohort study of HCV patients identified from 4 integrated health systems in the United States who had liver biopsies during 2001-2012. The probabilities of death and progression to hepatocellular carcinoma, hepatic decompensation (hepatic encephalopathy, esophageal varices, ascites, or portal hypertension) or liver transplant were estimated over 1, 2, or 5 years by fibrosis stage (Metavir F0-F4) determined by biopsy at beginning of observation. Results Among 2799 HCV-monoinfected patients who had a qualifying liver biopsy, the mean age at the time of biopsy was 50.7 years. The majority were male (58.9%) and non-Hispanic white (66.9%). Over a mean observation of 5.0 years, 261 (9.3%) patients died and 34 (1.2%) received liver transplants. At 5 years after biopsy, the estimated risk of progression to hepatic decompensation or hepatocellular carcinoma was 37.2% in stage F4, 19.6% in F3, 4.7% in F2, and 2.3% in F0-F1 patients. Baseline biopsy stage F3 or F4 and platelet count below normal were the strongest predictors of progression to hepatic decompensation or hepatocellular carcinoma. Conclusions The risks of death and progression to liver failure varied greatly by fibrosis stage. Clinicians and policy makers could use these progression risk data in prioritization and in determining the timing of treatment for patients in early stages of liver disease.

Persons chronically infected with hepatitis C (HCV) may be at higher risk for developing and dying from non-liver as well as liver cancers than the general population. We therefore assessed cancer incidence and mortality among HCV-infected patients in four large health systems in the United States serving over 1.6 million adults, and compared with rates for the general population during the five-year period from 2006 to 2010. 12,126 chronic HCV-infected persons in the Chronic Hepatitis Cohort Study (CHeCS) contributed 39,984 person-years of follow-up from 2006 to 2010, and were compared to 133,795,010 records from 13 Surveillance, Epidemiology and End Results Program (SEER) cancer registries, and approximately 12 million US death certificates from Multiple Cause of Death (MCOD) data. Standardized rate ratios (SRR) and relative risk (RR) were calculated for incidence and mortality, respectively. The incidence of the following cancers was significantly higher among patients with chronic HCV infection: liver (SRR, 48.6 [95% CI, 44.4–52.7]), pancreas (2.5 [1.7–3.2]), rectum (2.1 [1.3–2.8]), kidney (1.7 [1.1–2.2]), non-Hodgkin lymphoma (1.6 [1.2–2.1]), and lung (1.6 [1.3–1.9]). Age-adjusted mortality was significantly higher among patients with: liver (RR, 29.6 [95% CI, 29.1–30.1]), oral (5.2 [5.1–5.4]), rectum (2.6 [2.5–2.7]), non-Hodgkin lymphoma (2.3 [2.2–2.31]), and pancreatic (1.63 [1.6–1.7]) cancers. The mean age of cancer diagnosis and cancer-related death was significantly younger in CHeCS HCV cohort patients compared to the general population for many cancers.

To determine the stage of liver disease at initial diagnosis of hepatitis C virus (HCV) infection, we analyzed data from the Chronic Hepatitis Cohort Study (CHeCS), a large U.S. observational study. We examined the temporal relationships of initial HCV infection diagnosis with cirrhosis—defined by liver biopsy or mean FIB-4 score >5.88—and time to onset of cirrhotic decompensation in electronic medical records. We determined time in the health system prior to HCV diagnosis and rates of hospitalization and death following HCV diagnosis. Of 14,717 patients with chronic HCV seen during 2006-2011, 6,166 (42%) had a definable time of initial HCV diagnosis. Of these, 1,056 (17%) patients met our definition for “late diagnosis” with either cirrhosis concurrent with initial HCV diagnosis (n = 550), a first diagnosis of hepatic decompensation before or within 12 months after initial HCV diagnosis (n = 506), or both (n = 314). Patients with late diagnosis had an average of 6 years in the health system before their HCV diagnosis. In a comparison with patients without late diagnosis, hospitalization (59% versus 35%) and death (33% versus 9%) were more frequent among patients with late diagnosis. Among all who died, mean (median) time from initial HCV diagnosis to death was 4.8 (4.2) years. Conclusion: Many CHeCS patients had advanced liver disease concurrent with their initial HCV diagnosis despite many years of engagement with the healthcare system, and these patients had high rates of hospitalization and mortality. (Hepatology 2015;61:1479–1484)

Most cases of severe acute respiratory syndrome (SARS) have occurred in close contacts of SARS patients. However, in Beijing, a large proportion of SARS cases occurred in persons without such contact. We conducted a case-control study in Beijing that compared exposures of 94 unlinked, probable SARS patients with those of 281 community-based controls matched for age group and sex. Case-patients were more likely than controls to have chronic medical conditions or to have visited fever clinics (clinics at which possible SARS patients were separated from other patients), eaten outside the home, or taken taxis frequently. The use of masks was strongly protective. Among 31 case-patients for whom convalescent-phase (>21 days) sera were available, 26% had immunoglobulin G to SARS-associated coronavirus. Our finding that clinical SARS was associated with visits to fever clinics supports Beijing's strategy of closing clinics with poor infection-control measures. Our finding that mask use lowered the risk for disease supports the community's use of this strategy.

Hepatitis E virus (HEV) is a common cause of acute viral hepatitis in developing countries; however, its contribution to acute jaundice syndrome is not well-described. A large outbreak of hepatitis E occurred in northern Uganda from 2007 to 2009. In response to this outbreak, acute jaundice syndrome surveillance was established in 10 district healthcare facilities to determine the proportion of cases attributable to hepatitis E. Of 347 acute jaundice syndrome cases reported, the majority (42%) had hepatitis E followed by hepatitis B (14%), malaria (10%), hepatitis C (5%), and other/unknown (29%). Of hepatitis E cases, 72% occurred in Kaboong district, and 68% of these cases occurred between May and August of 2011. Residence in Kaabong district was independently associated with hepatitis E (adjusted odds ratio = 13; 95% confidence interval = 7-24). The findings from this surveillance show that an outbreak and sporadic transmission of hepatitis E occur in northern Uganda.

Background Reports of acute hepatitis C in young persons in the United States have increased. We examined data from national surveillance and supplemental case follow-up at selected jurisdictions to describe the US epidemiology of hepatitis C virus (HCV) infection among young persons (aged ≤30 years). Methods We examined trends in incidence of acute hepatitis C among young persons reported to the Centers for Disease Control and Prevention (CDC) during 2006-2012 by state, county, and urbanicity. Sociodemographic and behavioral characteristics of HCV-infected young persons newly reported from 2011 to 2012 were analyzed from case interviews and provider follow-up at 6 jurisdictions. Results From 2006 to 2012, reported incidence of acute hepatitis C increased significantly in young persons-13% annually in nonurban counties (P = .003) vs 5% annually in urban counties (P = .028). Thirty (88%) of 34 reporting states observed higher incidence in 2012 than 2006, most noticeably in nonurban counties east of the Mississippi River. Of 1202 newly reported HCV-infected young persons, 52% were female and 85% were white. In 635 interviews, 75% of respondents reported injection drug use. Of respondents reporting drug use, 75% had abused prescription opioids, with first use on average 2.0 years before heroin. Conclusions These data indicate an emerging US epidemic of HCV infection among young nonurban persons of predominantly white race. Reported incidence was higher in 2012 than 2006 in at least 30 states, with largest increases in nonurban counties east of the Mississippi River. Prescription opioid abuse at an early age was commonly reported and should be a focus for medical and public health intervention.