Akdag D, Knudsen A, Thudium R, et al.

AbstractBackgroundPrior to the introduction of combination antiretroviral therapy (cART), cytopenias were common in people with HIV (PWH), but it is unknown if well-controlled HIV infection is a risk factor for cytopenia. In this study we aimed to determine if HIV infection is an independent risk factor for anemia, neutropenia, lymphocytopenia, and thrombocytopenia.MethodsPWH with undetectable viral replication and absence of chronic hepatitis infection (n=796) were recruited from the Copenhagen Comorbidity in HIV infection (COCOMO) study and matched uninfected controls from the Copenhagen General Population Study (n=2388). Hematology was analyzed in venous blood samples. Logistic regression analyses adjusted for age, sex, ethnicity, smoking status, alcohol, and hs-CRP were performed to determine possible associations between HIV and cytopenias.ResultsPWH had a higher prevalence of anemia (6.9% vs. 3.4%, P

Peak C, Stous S, Healy J, et al.

AbstractBackgroundHepatitis A is a vaccine-preventable viral disease transmitted by the fecal-oral route. During 2016–2018, the County of San Diego investigated an outbreak of hepatitis A infections primarily among people experiencing homelessness (PEH) to identify risk factors and support control measures. At the time of the outbreak, homelessness was not recognized as an independent risk factor for the disease.MethodsWe tested the association between homelessness and infection with hepatitis A virus (HAV) using a test-negative study design comparing patients with laboratory-confirmed hepatitis A with control subjects who tested negative for HAV infection. We assessed risk factors for severe hepatitis A disease outcomes, including hospitalization and death, using multivariable logistic regression. We measured the frequency of indications for hepatitis A vaccination according to Advisory Committee on Immunization Practice (ACIP) guidelines.ResultsAmong 589 outbreak-associated cases reported, 291 (49%) occurred among PEH. Compared with those who were not homeless, PEH were at 3.3 (95% CI: 1.5–7.9) times higher odds of HAV infection, 2.5 (95% CI: 1.7–3.9) times higher odds of hospitalization, and 3.9 (95% CI: 1.1–16.9) times higher odds of death associated with hepatitis A. Among PEH, 212 (73%) patients recorded other ACIP indications for hepatitis A vaccination.ConclusionsPEH were at higher risk for infection with HAV and higher risk for severe hepatitis A disease outcomes compared with those not experiencing homelessness. Approximately one-fourth of PEH had no other ACIP indication for hepatitis A vaccination. These findings support the recent ACIP recommendation to add homelessness as an indication for hepatitis A vaccination.

Abstract Background Female sex workers (FSWs) at substantial risk of HIV are potentially a suitable group for HIV prevention trials including vaccine trials. Few HIV vaccine preparatory studies have been conducted among FSWs in Sub-Saharan Africa (SSA); data are therefore limited on acceptability of vaccine trial procedures. We determined vaccination completion and one-year retention among FSWs in Kampala, Uganda. Methods We conducted a prospective study that simulated a vaccine efficacy trial among HIV negative FSWs (18–49 years). Hepatitis B vaccine (Engerix B) was used to mimic an HIV vaccine product. Volunteers received 1 ml intramuscular injection at 0, 1 and 6 months, and made additional visits (3 days post-vaccination and months 3, 9 and 12). They were censored at that visit if diagnosed as HIV positive or pregnant. We collected socio-demographic, behavioral and clinical data at baseline, 6 and 12 months and fitted Poisson regression models with robust standard error to find factors associated with vaccination completion and retention. Results We enrolled 290 volunteers (median age 27 years) of whom 230 reached a study end-point as follows: 7 became HIV infected, 11 became pregnant and 212 completed both the vaccination schedule and 12-month visit giving a retention of 77.9% (212/272). Vaccination completion was 82.4%. Non-retention at 1 year was more likely among those reporting symptoms of genital ulcer disease (GUD) in the past 3 months (IRR 1.90; 95% CI 1.09–3.32) and those

Abstract Background Hepatitis C virus (HCV) is a leading cause of chronic liver disease. As yet there is no approved vaccine protects against contracting hepatitis C. HCV seriously affects many people’s health in the world. Methods In this article, an epidemiological model is proposed and discussed to understand the transmission and prevalence of hepatitis C in mainland China. This research concentrates on hepatitis C data from Chinese Center for Disease Control and Prevention (China’s CDC). The optimal parameters of the model are obtained by calculating the minimum chi-square value. Sensitivity analyses of the basic reproduction number and the endemic equilibrium are conducted to evaluate the effectiveness of control measures. Results Vertical infection is not the most important factor that causes hepatitis C epidemic, but contact transmission is. The proportion of acute patients who are transformed into chronic patients is about 82.62%. The possibility of the hospitalized patients who are restored to health is about 76.24%. There are about 92.32% of acute infected are not treated. The reproduction number of hepatitis C in mainland China is estimated as approximately 1.6592. Conclusion We find that small changes of transmission infection rate of acutely infected population, transmission infection rate of exposed population, transition rate for the acutely infected, and rate of progression to acute stage from the exposed can achieve the purpose of controlling HCV through sensitivity analysis. Finally, based on the results of sensitivity analysis, we find out several preventions and control strategies to control the Hepatitis C.…

Choi Y, Perez-Cuevas M, Kodani M, et al.

AbstractBackgroundDissolvable microneedle patches (dMNPs) provide ease of deployment and eliminate need for hypodermic needle disposal after conventional vaccinations. In this study, immunogenicity of dMNP delivery of adjuvant-free monovalent hepatitis B surface antigen (HBsAg) vaccine (AFV) to standard intramuscular (IM) injection of monovalent aluminum-adjuvanted monovalent hepatitis B vaccine (AAV) were compared in rhesus macaques.MethodsSixteen macaques were immunized twice in 4 groups: dMNP delivery of 24 ± 8µg (n=4) or 48 ± 14µg (n=4) AFV; IM injection of 10µg AFV (IM AFV, n=4); and IM injection of 10µg AAV (IM AAV, n=4). Levels of hepatitis B surface antibody and HBsAg-specific T-cell responses were analyzed.ResultsSix of 8 animals with dMNP delivery of AFV had anti-HBs levels ≥10 mIU/ml after the first vaccine dose. After dMNP delivery of AFV, IFN-γ, IL-2, and IL-4 production by HBsAg-specific T-cells were detected. A statistically significant positive correlation was detected between anti-HBs levels and HBsAg-specific IFN-γ and IL-2 (Th1-type cytokine) and IL-4 (Th2-type cytokine) producing cells in all anti-HBs positive animals.ConclusionsdMNP delivery of AFV can elicit seroprotective anti-HBs levels in rhesus macaques that correlate in human seroprotection, and could be particularly promising for hepatitis B vaccine birth dose delivery in resource-constrained regions.

Stevens E, Nucifora K, Hagan H, et al.

AbstractBackgroundThere are too many plausible permutations and scale-up scenarios of combination hepatitis C (HCV) interventions for exhaustive testing in experimental trials. Therefore, we used computer simulation to project the health and economic impact of alternative combination intervention scenarios for people who inject drugs (PWID), focusing on direct anti-viral agents (DAA) and medication-assisted treatment combined with syringe access programs (MAT+).MethodsWe performed an allocative efficiency study using a mathematical model simulating the progression of HCV in PWID and its related consequences. Two previously validated simulations were combined to estimate the cost-effectiveness of intervention strategies that included a range of coverage levels. Analyses were performed from a health sector and societal perspective with a 15-year time horizon and a discount rate of 3%.ResultsFrom a health-sector perspective (excluding criminal justice system-related costs), four potential strategies fell on the cost-efficiency frontier. DAA at 20% coverage had an ICER of $27,251/QALY. Combinations of DAA 20% with MAT+ at 20%, 40%, and 80% coverage had ICERs of $165,985/QALY, $325,860/QALY, and $399,189/QALY, respectively. When analyzed from a societal perspective (including criminal justice system-related costs), DAA 20% with MAT+ 80% was most effective and was cost saving. While DAA 20% with MAT+ 80% was more expensive (e.g., less cost-saving) than MAT+ 80% alone without DAA, it offered favorable value compared to MAT+ 80% alone ($23,932/QALY).ConclusionWhen considering health sector costs alone, DAA alone was the most cost-effective intervention. However, with criminal justice system-related costs, DAA and MAT+ implemented together become the most cost-effective interventions.

Abstract Background In recent times, emerging and re-emerging infectious diseases are posing a public health threat in developing countries, and vigilant surveillance is necessary to prepare against these threats. Analyses of multi-year comprehensive infectious disease syndrome data are required in Mongolia, but have not been conducted till date. This study aimed to describe the trends in the incidence of infectious disease syndromes in Mongolia during 2009–2017 using a nationwide syndrome surveillance system for infectious diseases established in 2009. Methods We analyzed time trends using monthly data on the incidence of infectious disease syndromes such as acute fever with rash (AFR), acute fever with vesicular rash (AFVR), acute jaundice (AJ), acute watery diarrhea (AWD), acute bloody diarrhea (ABD), foodborne disease (FD) and nosocomial infection (NI) reported from January 1, 2009 to December 31, 2017. Time series forecasting models based on the data up to 2017 estimated the future trends in the incidence of syndromes up to December 2020. Results During the study, the overall prevalence of infectious disease syndromes was 71.8/10,000 population nationwide. The average number of reported infectious disease syndromes was 14,519 (5229-55,132) per year. The major types were AFR (38.7%), AFVR (31.7%), AJ (13.9%), ABD (10.2%), and AWD (1.8%), accounting for 96.4% of all reported syndromes. The most prevalent syndromes were AJ between 2009 and 2012 (59.5–48.7%), AFVR between 2013 and 2014 (54.5–59%), AFR between 2015 and 2016 (67.6–65.9%), and AFVR in 2017 (62.2%). There were increases in the prevalence of AFR, with the monthly number of cases being 37.7 ± 6.1 during 2015–2016; this could be related to the measles outbreak in Mongolia during that period. The AFVR incidence rate showed winter’s multiplicative seasonal fluctuations with a peak of 10.6 ± 2 cases per 10,000 population in 2017. AJ outbreaks were identified in 2010, 2011, and 2012, and these could be associated with hepatitis A outbreaks. Prospective time series forecasting showed increasing trends in the rates of AFVR and ABD. Conclusions The evidence-based method for infectious disease syndromes was useful in gaining an understanding of the current situation, and predicting the future trends of various infectious diseases in Mongolia.…

Abstract Background Hepatitis C virus (HCV) is a major public health problem in correctional settings. HCV treatment is often not possible in U.S. jails due to short lengths of stay. Linkage to care is crucial in these settings, but competing priorities complicate community healthcare engagement and retention after incarceration. Methods We conducted a single arm clinical trial of a combined transitional care coordination (TCC) and patient navigation intervention and assessed the linkage rate and factors associated with linkage to HCV care after incarceration. Results During the intervention, 84 participants returned to the community after their index incarceration. Most participants were male and Hispanic, with a history of mental illness and a mean age of 45 years. Of those who returned to the community, 26 (31%) linked to HCV care within a median of 20.5 days; 17 (20%) initiated HCV treatment, 15 (18%) completed treatment, 9 (11%) had a follow-up lab drawn to confirm sustained virologic response (SVR), and 7 (8%) had a documented SVR. Among those with follow-up labs the known SVR rate was (7/9) 78%. Expressing a preference to be linked to the participant’s existing health system, being on methadone prior to incarceration, and feeling that family or a loved one were concerned about the participant’s wellbeing were associated with linkage to HCV care. Reporting drinking alcohol to intoxication prior to incarceration was negatively associated with linkage to HCV care. Conclusion We demonstrate that an integrated strategy with combined TCC and patient navigation may be effective in achieving timely linkage to HCV care. Additional multicomponent interventions aimed at treatment of substance use disorders and increasing social support could lead to further improvement. Trial registration Clinicaltrials.gov NCT04036760 July 30th, 2019 (retrospectively registered).…

Abstract Background Hepatitis C infection is a major public health concern globally. In Ireland, like other European countries, people who use drugs (PWUD) and prisoners carry a larger HCV disease burden than the general population. Recent advances in HCV management have made HCV elimination across Europe a realistic goal. Engaging these two marginalised and underserved populations remains a challenge. The aim of this review was to map key findings and identify gaps in the literature (published and unpublished) on HCV infection in Irish PWUD and prisoners. Methods A scoping review guided by the methodological framework set out by Levac and colleagues (based on previous work by Arksey & O’Malley). Results A total of 58 studies were identified and divided into the following categories; Epidemiology, Guidelines and Policy, Treatment Outcomes, HCV-related Health Issues and qualitative research reporting on Patients’ and Health Providers’ Experiences. This review identified significantly higher rates of HCV infection among Irish prisoners and PWUD than the general population. There are high levels of undiagnosed and untreated HCV infection in both groups. There is poor engagement by Irish PWUD with HCV services and barriers have been identified. Prison hepatology nurse services have a positive impact on treatment uptake and outcomes. Identified gaps in the literature include; lack of accurate epidemiological data on incident infection, untreated chronic HCV infection particularly in PWUD living outside Dublin and those not engaged with OST. Conclusion Ireland like other European countries has high levels of undiagnosed and untreated HCV infection. Collecting, synthesising and identifying gaps in the available literature is timely and will inform national HCV screening, treatment and prevention strategies.…

G. Dennis Shanks

Abstract. Early trials of killed, whole-cell typhoid vaccine indicated a paradoxical, positive effect on malaria infections. British soldiers in India in 1898 reported > 90% decrease in malaria recurrences after receiving an investigational typhoid vaccine despite no intention or expectation to observe such an outcome. In the 1940s, multiple doses of intravenous typhoid vaccine appeared to control parasitemia and limit reinfection in three syphilis patients purposefully infected with Plasmodium vivax. Several modern vaccines (against human papillomavirus, hepatitis B virus, and malaria) use a detoxified lipid A derived from Salmonella as an immune adjuvant. Early typhoid vaccines could have plausibly functioned as an innate immune stimulus, leading to some protection against malaria.…

Sun L, Fan J, Gao H, et al.

Abstract Background The epidemiology and risk factors for hepatitis C virus (HCV) infection in Rwanda are not well known; however, this information is crucial to shaping the country’s public health approach to hepatitis C control. Methods A HCV screening campaign was conducted in the general population in 24 districts previously identified to have a high HCV disease burden. At the time of sample collection, sociodemographic information and self-reported risk factors were collected. Bivariate and multivariate logistic regressions were conducted to assess risk factors independently associated with hepatitis C antibodies (HCVAb) seroprevalence. Results Out of a total of 326,263 individuals screened for HCVAb, 22,183 (6.8%) were positive. In multivariate analysis, risk factors identified as statistically associated with HCVAb Seroprevalence include history of traditional operation or scarification (OR = 1.09, 95% CI: 1.05–1.14), presence of viral hepatitis in the family (OR = 1.27, 95% CI: 1.15–1.40), widowed or separated/divorced (OR = 1.36, 95% CI: 1.26–1.47), Southern province (OR = 1.98, 95% CI: 1.88–2.08) and aged 65 years and older (OR = 4.86, 95% CI: 4.62–5.11). Ubudehe category 3 (OR = 0.97, 95% CI: 0.93–1.01) and participants using RAMA (Health insurances for employees of public and private sectors) insurance (OR = 0.76, 95% CI: 0.70–0.85) had lower odds of HCV seroprevalence. Conclusions Our findings provide important information for Rwanda’s strategy on prevention and case-finding. Future prevention interventions should aim to reduce transmission through targeted messaging around traditional healing practices and case-finding targeting individuals with a history of exposure or advanced age.…

Wang K, Lin W, Kuang Z, et al.

AbstractBackgroundLittle is known about cause and intervention for alanine aminotransferase (ALT) elevation after complete viral suppression in patients with chronic hepatitis B (CHB).MethodsIn this prospective cohort study, patients with CHB who were treated with nucleos(t)ide analogs and maintained undetectable levels of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) for at least 6 months were enrolled. Patients were followed up at 6-month intervals, and anthropometric, biochemical, and virological assessments were performed.ResultsOf 1965 patients with median follow-up of 18.36 months, one third of patients experienced ALT elevation. Baseline high body mass index ([BMI] defined as ≥25 kg/m2), younger age, and liver cirrhosis independently increased the risk of longitudinal ALT elevation. At the end of follow-up, 89 (4.8%) patients reverted to low BMI, and 92 (5.0%) developed to high BMI. Compared with persistent high BMI, reversion to low BMI reduced the risk of ALT elevation (adjusted odds ratio [aOR], 0.38; 95% confidence interval [CI], 0.19–0.77); compared with persistent low BMI, onset of high BMI increased the risk of ALT elevation (aOR, 1.78; 95% CI, 1.02–3.11).ConclusionsHigh BMI is an independent predictor for ALT elevation after complete HBV DNA suppression. Improvement of BMI may have a beneficial effect on ALT normalization and even long-term outcomes.

Abstract Background Hepatitis E virus (HEV) infection is now recognized as a major cause of acute hepatitis worldwide. HEV specific antibodies develop shortly after infection and are thought to confer protection. Case presentation We report an immunocompromised patient who developed chronic HEV infection despite the presence of high level antibodies. HEV infection was detected using RT-PCR upon diagnostic evaluation due to increased liver enzymes. Upon retrospective analysis of stored serum samples we found that the patient was HEV RNA positive since 7 months. Chronic HEV infection was successfully treated with ribavirin. Conclusions In conclusion, the patient suffered from a chronic course of HEV infection, which was successfully treated with ribavirin. Our case underlines the importance of RT-PCR for HEV diagnostics in immunosuppressed patients and supports the notion that HEV antibodies do not confer universal protection. Counseling patients at risk for chronic HEV infection seems advisable. The role of the humoral and T-cell mediated immune response in cases of HEV reinfection deserves further study.…

Colson, Philippe; Decoster, Claire

Purpose of review Hepatitis E virus (HEV) has gained increased global recognition in recent years, particularly in developed countries. We summarized here a selection of the literature published since the 1st of June, 2017. Recent findings Longitudinal studies are increasingly conducted in Europe, to determine trends in HEV prevalence. The spectrum of mammals infected with HEV and potentially capable to transmit it to humans has widened. New virological data on HEV repCon and pathogenicity have been reported and clinical features of HEV infections have been precised or newly described. Finally, there are some new data on the therapeutic management of HEV infections in various clinical settings. Summary HEV emergence in developed countries appears to be based on improved diagnosis tools and increased awareness of clinicians that HEV transmission is essentially autochthonous and is a possible cause of life-threatening acute hepatitis, chronic hepatitis, cirrhosis, and extra-hepatic symptoms. In addition, the distribution of HEV strains evolves. Ribavirin remains to date the only specific treatment recommended for HEV infection, being efficient in the majority but not in all cases. Correspondence to Philippe Colson, PharmD, PhD, IHU - Méditerranée Infection, 19-21 boulevard Jean Moulin, 13005 Marseille, France. Tel: +33 413 732 401; fax: +33 413 732 402; e-mail: philippe.colson@ap-hm.fr Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Safreed-Harmon K, Blach S, Aleman S, et al.

AbstractCascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate in simple terms the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of HCV-infected individuals to diagnosis, treatment and cure. The value of reporting would be enhanced if reporting entities utilized a standardized approach for generating their CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and ensuring the accurate monitoring of progress toward WHO’s 2030 hepatitis C elimination targets.

Shing J, Ly K, Xing J, et al.

AbstractBackgroundHepatitis 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.MethodsUsing 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.ResultsFrom 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.ConclusionOne-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.

Akiyama M, Lipsey D, Heo M, et al.

AbstractBackgroundDirect acting antiviral (DAA) therapy is highly effective in PWID; however, rates, specific injection behaviors, and social determinants of drug use associated with HCV reinfection following DAA therapy among PWID on opioid agonist therapy (OAT) are poorly understood.MethodsPREVAIL was a randomized control trial that assessed models of HCV care for 150 PWID on OAT. Those who achieved SVR (n=141; 94%) were eligible for this extension study. Interviews and assessments of recurrent HCV viremia occurred at 6-month intervals for up to 24 months following PREVAIL. We used survival analysis to analyze variables associated with time to reinfection.ResultsOf 141 who achieved SVR, 114 had a least one visit in the extension study (62% male, mean age 52). Injection drug use (IDU) after SVR24 was reported in 19% (n=22). HCV reinfection was observed in three participants. Over 246 person-years of follow-up, the incidence of reinfection was 1.22/100 person-years (95% CI 0.25-3.57). All reinfections occurred among participants reporting ongoing IDU. The incidence of reinfection in participants reporting ongoing IDU (41 person-years of follow-up) was 7.4/100 person-years (95% CI 1.5-21.6). Reinfection was associated with reporting ongoing IDU in the follow-up period (p

, Owens DK, Davidson KW, et al.

This 2019 Recommendation Statement from the US Preventive Services Task Force reaffirms the prior recommendation to screen pregnant women for hepatitis B virus infection at their first prenatal visit (A recommendation).

Jin J.

This JAMA Patient Page describes the US Preventive Services Task Force’s recommendations on screening for hepatitis B virus infection in pregnant women.

Henderson JT, Webber EM, Bean SI.

This systematic review to support the 2019 US Preventive Services Task Force Recommendation Statement on screening for hepatitis B infection in pregnant women summarizes published evidence on the benefits and harms of hepatitis B infection screening and case management in pregnant women.

Silverman NS.

Contemporary clinicians who provide obstetric care acknowledge screening of pregnant women for perinatally transmissible infectious diseases as a routine component of prenatal care, although this has not always been the case. For example, prenatal screening for hepatitis B virus (HBV) infection only began to be discussed after rigorous trials conducted in the 1970s and 1980s in high-endemic areas demonstrated that identification of chronically infected pregnant women followed by targeted neonatal immunoprophylaxis (hepatitis B immunoglobulin and the first dose of HBV vaccine) significantly lowered the risk of chronic infection in these children from 90% to approximately 5% to 15%.

Marks K, Naggie S.

This JAMA Insights Clinical Update reviews current standards of management of HCV infection, including use of antibody and RNA tests to identify infected patients, use of direct acting antivirals (DAAs) to obtain sustained viral response (SVR), and management of treatment failure.

Abstract Background Although significant improvement in efficacy measured by a sustained virological response, the high acquisition costs of direct-acting antivirals limit the access for patients and influence the costs of healthcare resource utilisation in hepatitis C. It is important to have the latest estimates of prevalence, especially in high-risk groups, for cost of illness, cost-effectiveness and budget impact studies. Methods Original studies on the estimates of the prevalence among general and high-risk groups in the European Union/European Economic Area (EU/EEA) were retrieved from Medline and Embase for the period from 2015 to 2018. All included studies were evaluated for risk of selection bias and summarised together in a narrative form. Results from previous reviews and updated searches were compared per country among different populations, respectively. Results Among the 3871 studies identified, 46 studies were included: 20 studies were used for the estimate of the general population; 3 for men who have sex with men (MSM); 6 for prisoners; and 17 for people who inject drugs (PWID). Compared with the results reported in previous systematic reviews, the updated estimates were lower than previously in most available countries. Anti-HCV general population prevalence estimates ranged from 0.54 to 1.50% by country. The highest prevalence of anti-HCV was found among PWID (range of 7.90–82.00%), followed by prisoners (7.00–41.00%), HIV-positive MSM (1.80–7.10%), HIV-negative MSM (0.20–1.80%), pregnant women (0.10–1.32%) and first-time blood donors (0.03–0.09%). Conclusions Our study highlights the heterogeneity in anti-HCV prevalence across different population groups in EU/EEA. The prevalence also varies widely between European countries. There are many countries that are not represented in our results, highlighting the need for the development of robust epidemiological studies.…

Archampong, Timothy; Ojewale, Oluwayemisi; Bears, Kristi; Chen, Yiqing; Lartey, Margaret; Sagoe, Kwamena W.; Obo-Akwa, Adjoa; Gong, Yan; Langaee, Taimour; Kwara, Awewura

Background: Incomplete hepatitis B virus (HBV) suppression during antiretroviral therapy (ART) in human immunodeficiency virus (HIV) and HBV co-infected patients is common, but underlying factors are not fully elucidated. We hypothesize that genetic factors that influence nucleoside analog pharmacokinetics will affect HBV treatment response. Methods: HIV/HBV co-infected patients on tenofovir disoproxil fumarate/lamivudine ((TDF/3TC)-containing ART were enrolled. Selected ABCC4 single nucleotide polymorphisms (SNPs) with known effects on nucleoside pharmacokinetics were genotyped using TaqMan® assays. Relationship between ABCC4 SNPs and unsuppressed HBV DNA (HBV DNA ≥ 20 IU/mL) were examined. Results: Of the 50 participants on TDF/3TC-containing ART for a median (range) of 1.5 (1 to 7.4) years, 20 (40%) had unsuppressed HBV DNA. Participants with unsuppressed compared to those with suppressed HBV DNA were more likely to have negative HBe antibody, lower body mass index (BMI) and lower CD4 count at enrolment. Carriers of ABCC4 rs11568695 (G3724A) variant allele were more likely than non-carriers to have unsuppressed HBV (61.1% vs. 29.0%, P = 0.038). Among 36 patients with suppressed HIV RNA (presumed good ART adherence), ABCC4 rs11568695 variant carriers were more likely than non-carriers to have unsuppressed HBV (58.8% vs. 20.0% P=0.021). Logistic regression analysis that included genetic and non-genetic factors identified ABCC4 rs11568695 variant allele, BMI and male sex as predictors of unsuppressed HBV DNA. Conclusion: We identified a novel association between ABCC4 rs11568695 SNP and poor HBV treatment response. If confirmed in further studies, ABCC4 genotyping could be used to identify individuals who may need intensified HBV therapy. Corresponding author and request for reprints: Dr. Awewura Kwara University of Florida College of Medicine, Emerging Pathogens Institute, 2055 Mowry Road, P.O. Box 103600, Gainesville, FL 32610, USA Telephone: +1 325 273-9501 Fax: +1 352 273-9275 Email: awewura.kwara@medicine.ufl.edu Conflict of interest: The authors have declared that no competing interests exist. Authors’ contribution: TNA, ML and AK contributed to the study design of the initial study, acquisition of data, analysis and interpretation of data, and drafting of the manuscript. OO, TL and AK contributed to design of the current study and acquisition of data for the current analysis. KWC and AOA contributed to acquisition of clinical and laboratory data. KB and TL performed DNA genotyping. YC and YG contributed to statistical analysis, drafting of the manuscript. All authors critically reviewed the manuscript and approved the final version. Source of funding: This work was supported in part by the Gatorade Trust through funds distributed by the University of Florida, Department of Medicine. The initial study that obtained the DNA samples was funded by a Developmental Grant from the Lifespan/Tufts/Brown CFAR (P30AI042853) to Dr. Archampong. Dr. Kwara received support from Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health [grant number HD071779] and Fogarty International Center [grant number TW010055]. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background Hepatitis A, caused by the hepatitis A virus (HAV), is a vaccine preventable disease. In Low and Middle-Income Countries (LMICs), poor hygiene and sanitation conditions are the main risk factors contributing to HAV infection. There have been, however, notable improvements in hygiene and sanitation conditions in many LMICs. As a result, there are studies showing a possible transition of some LMICs from high to intermediate HAV endemicity. The World Health Organization (WHO) recommends that countries should routinely collect, analyse and review local factors (including disease burden) to guide the development of hepatitis A vaccination programs. Up-to-date information on hepatitis A burden is, therefore, critical in aiding the development of country-specific recommendations on hepatitis A vaccination. Methods We conducted a systematic review to present an up-to-date, comprehensive synthesis of hepatitis A epidemiological data in Africa. Results The main results of this review include: 1) the reported HAV seroprevalence data suggests that Africa, as a whole, should not be considered as a high HAV endemic region; 2) the IgM anti-HAV seroprevalence data showed similar risk of acute hepatitis A infection among all age-groups; 3) South Africa could be experiencing a possible transition from high to intermediate HAV endemicity. The results of this review should be interpreted with caution as the reported data represents research work with significant sociocultural, economic and environmental diversity from 13 out of 54 African countries. Conclusions Our findings show that priority should be given to collecting HAV seroprevalence data and re-assessing the current hepatitis A control strategies in Africa to prevent future disease outbreaks.…

Cedarbaum, Emily; Ma, Yifei; Scherzer, Rebecca; Price, Jennifer C.; Adimora, Adaora A.; Bamman, Marcas; Cohen, Mardge; Fischl, Margaret A.; Matsushita, Kunihiro; Ofotokun, Igho; Plankey, Michael; Seaberg, Eric C.; Yin, Michael T.; Grunfeld, Carl; Vartanian, Shant; Sharma, Anjali; Tien, Phyllis C.

Objectives: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have been associated with cardiovascular disease (CVD), but it is unclear whether HIV and HCV are also associated with peripheral artery disease (PAD). We examined the association of HIV, HCV, and traditional CVD risk factors with PAD in the Women's Interagency HIV Study (WIHS), a multicenter U.S. cohort. Methods: In this cross-sectional study, ankle-brachial index (ABI) was estimated using Doppler ultrasound and manual sphygmomanometer in 1,899 participants aged >40 years with HIV/HCV coinfection, HCV or HIV monoinfection, or neither infection. Multivariable logistic regression was used to estimate the odds of PAD (ABI≤0.9) after controlling for demographic, behavioral, and CVD risk factors. Results: Over two-thirds were African-American, median age was 50 years, and PAD prevalence was 7.7% with little difference by infection status. After multivariable adjustment, neither HIV nor HCV infection was associated with greater odds of PAD. Factors associated with PAD included older age [adjusted(a) OR:2.15 for age>61-70 vs 40-50 years;95%CI:1.13,4.11)], Black race (aOR:2.24;95%CI:1.12,4.47), smoking (aOR:1.25 per 10-pack-year increment;95%CI:1.07,1.45), and higher systolic blood pressure (aOR:1.14 per 10mmHg;95%CI:1.02,1.29). Conclusions: The high PAD prevalence in this nationally representative cohort of women with or at risk for HIV is on par with general population studies in individuals a decade older than our study's median age. HIV and HCV infection are not associated with greater PAD risk relative to uninfected women with similar risk factors. Modifiable traditional CVD risk factors may be important early intervention targets in women with and at risk for HIV. Correspondence to Phyllis C. Tien, University of California, San Francisco, VAMC, Infectious Disease Section, 111W, 4150 Clement Street, San Francisco, CA 94121. Tel: +415 221 4810; ext 22577; fax: +415 379 5523; (e-mail: Phyllis.tien@ucsf.edu), Emily R. Cedarbaum, MD, MPH, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143, Tel: +360 480 9600; fax: +415 379 5523; (e-mail: emily.cedarbaum@ucsf.edu). Received 27 February, 2019 Revised 28 May, 2019 Accepted 16 June, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

de Lazzari, Elisa; Lonca, Montserrat; Rojas, Jhon; Gonzalez-Cordon, Ana; Blanch, Jordi; Inciarte, Alexy; Tricas, Amparo; Rodriguez, Ana; Martinez-Rebollar, Maria; Laguno, Montserrat; Mallolas, Josep; Sanchez-Palomino, Sonsoles; Plana, Montserrat; Blanco, Jose L.; Martinez, Esteban

Background: There is an increasing interest in two-drug regimens. We hypothesized that maintenance therapy with raltegravir plus lamivudine would keep HIV-1 suppressed and be well tolerated. Methods: Virally suppressed HIV-1-infected adults without previous viral failures or known resistance mutations to integrase inhibitors or 3TC/FTC or chronic hepatitis B were randomized 2:1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. Primary outcome was the proportion of patients free of therapeutic failure (defined as viral failure, change in treatment for any reason, consent withdrawal, loss to follow-up or death) at week 24. Secondary outcomes were changes in laboratory, body composition, sleep quality, adherence, and adverse effects. Results: There were 75 patients included: men 78%; median age 50 years; median CD4 622/mm3. At week 24, 7 (9%) patients had therapeutic failure: raltegravir plus lamivudine 2 (4%) vs. control 5 (20%). The difference in proportions of therapeutic failures raltegravir plus lamivudine minus control was -0.159 (95% confidence interval: -0.353; -0.012). There was a trend to more weight gain with raltegravir plus lamivudine, but no significant changes in other secondary outcomes. Sixty four percent of patients in each arm had at least one adverse effect. Two (6%) patients in control arm and 4 (7%) patients in raltegravir plus lamivudine arm had severe adverse effects. Conclusion: This pilot study suggests that switching to raltegravir plus lamivudine in patients with viral suppression maintains efficacy and is well tolerated. A larger study of longer duration is required to confirm these findings. Correspondence to Esteban Martinez, PhD, Senior Consultant & Associate Professor of Medicine, Infectious Diseases Unit, Hospital Clínic & University of Barcelona, 08036 Barcelona, Spain. Tel: +34 93 227 55 74; fax: +34 93 451 44 38; e-mail: estebanm@clinic.cat Received 21 December, 2018 Revised 1 May, 2019 Accepted 26 May, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.

Abstract Background The virological or clinical relapse is common in chronic hepatitis B (CHB) patients after stopping long-term nucleos(t)ide analogue (NA) therapy. Soluble growth stimulation expressed gene 2 (sST2), one of the Toll-like/interleukin-1 receptor members, is involved in a variety of inflammatory processes and immune responses. However, the expression and function of serum sST2 in CHB patients after stopping NA treatment remains unknown. Methods A total of 91 non-cirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed up to 240 weeks. All patients were divided into clinical relapse group and non-clinical relapse (including sustained virological response and only virological relapse) group according HBV DNA and ALT levels. The serum levels of sST2 of all participants were determined by ELISA and compared between each two groups. Results Clinical relapse occurred in 26 patients and virological relapse occurred in 57 patients. We found that there was a positive correlation between sST2 expression and HBsAg, ALT, HBV DNA, and anti-HBc levels in CHB patients after discontinuation of NA treatment. Levels of serum sST2 in clinical relapse patients showed a rising trend and most patients showed peak sST2 levels at the point of clinical relapse. Moreover, the sST2 levels of clinical relapse group at week 12, week 24 and week 48 were relatively higher than non-clinical relapse group. However, the level of sST2 at the end of treatment was not an effective biological marker for the early prediction of clinical relapse after discontinuation of long-term NA therapy. Conclusions In conclusion, we found that an increase in sST2 in clinical relapse patients might be associated with an inflammation-related immune response after discontinuation of NA treatment. Trial registration The trial was retrospectively registered at Chinese Clinical Trial Registry: ChiCTR-OOC-17013970. Registration date: December 15, 2017.…

Abstract Background Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality. High HBV prevalence in immigrants and ethnic minorities and numerous barriers to healthcare access are associated with serious health disparities in the United States. Reportedly, self-awareness of HBV infection is low, suggesting a greater need for effective screening and education. Further, low levels of linkage to care (LTC) (completion of a first doctor’s visit after the diagnosis of chronic HBV infection) may be responsible for the lack of engagement over the continuum of care and for needed services. Methods Demographics and survey data were obtained from 97 Korean American adults chronically infected with HBV, initially identified through a series of community screening events in northern New Jersey between Dec. 2009 and June 2015. Eight year follow-up on these HBV-infected individuals was obtained to determine their access to care, and thus the efficacy of a campaign to improve LTC. The participants’ self-awareness of HBV infection and other factors for LTC were also evaluated. Results Of a total of 97 HBV-infected participants (age range 30 to 79), 74 were aware of their infections at screening. The remaining 23 had been unaware of their infections until screening. Eight years after the campaign, some 66 of these 97 individuals accessed care (LTC rate 68%). Health insurance status, presence or absence of symptoms and level of knowledge of CHB were among the most significant factors in LTC. Conclusion A community-based hepatitis B screening and education campaign can be instrumental in prompting HBV infected individuals to access care, as demonstrated in the cumulative increase in LTC in our cohort. Despite many years of awareness of HBV infection, many are not accessing care owing to a lack of health insurance, suggesting a pressing need for advocacy and health education to improve access to affordable coverage in the Asian American population. Community efforts and strategies similar to the ones employed in the current study may serve as a model to improve the engagement of HBV-infected individuals in high risk immigrant populations.…

Abstract Background In light of increasing complexity of identifying and treating malaria cases in low transmission settings, operational solutions are needed to increase effective delivery of interventions. Community engagement (CE) is at the forefront of this conversation given the shift toward creating local and site-specific solutions. Malaria programmes often confuse CE with providing information to the community or implementing community-based interventions. This study seeks to expand on CE approaches for malaria by looking to a variety of health and development programmes for lessons that can be applied to malaria elimination. Methods Qualitative data was collected from key informant interviews and community-based focus group discussions. Manual analysis was conducted with a focus on key principles, programme successes and challenges, the operational framework, and any applicable results. Results Ten programmes were included in the analysis: Ebola, HIV/Hepatitis C, Guinea worm, malaria, nutrition, and water, sanitation and hygiene. Seven focus group discussions (FGDs) with 69 participants, 49 key informant (KI) interviews with programme staff, and 7 KI interviews with thought leaders were conducted between October–April 2018. Participants discussed the critical role that village leaders and community health workers play in CE. Many programmes stated understanding community priorities is key for CE and that CE should be proactive and iterative. A major theme was prioritizing bi-directional interpersonal communication led by local community health workers. Programmes reported that measuring CE is difficult, particularly since CE is ongoing and fluid. Conclusions Results overwhelmingly suggest that CE must be an iterative process that relies on early involvement, frequent feedback and active community participation to be successful. Empowering districts and communities in planning and executing community-based interventions is necessary. Communities affected by the disease will ultimately achieve malaria elimination. For this to happen, the community itself must define, believe in, and commit to strategies to interrupt transmission.…

Abstract Background We describe a case of severe Guillain-Barre syndrome (GBS) associated with chronic active hepatitis C and mixed cryoglobulinemia (MC). To our knowledge, this association between GBS and hepatitis C virus (HCV) infection has been rarely reported. Case presentation A 56-year-old man developed symmetrical muscle weakness in all extremities, areflexia and sensorial disorder followed by acute respiratory failure associated with chronic active hepatitis C, which was confirmed by the presence of anti-HCV antibodies in the serum and persistence of HCV RNA viral load for more than 6 months. Chronic hepatitis C was further complicated by type 3 MC. Electromyography showed peripheral nerve injury (mainly in axon). A severe acute motor sensory axonal neuropathy (AMSAN) was diagnosed. After treatment with intravenous immunoglobulin and plasma exchange followed by antiviral therapy by direct-acting antiviral agent, patient showed progressive recovery and was transferred 3 months after his first admission to a rehabilitation center. Conclusions Our case reported a severe GBS associated with HCV infection and MC. EMG classified for the first time the subtype of GBS (severe AMSAN) correlated with severe clinical form. HCV infection should be screened in high-risk patients to prevent silent progression of the chronic hepatitis C and its potentially severe extra-hepatic manifestations.…

Abstract Background Hepatitis B virus (HBV) testing in oral fluid samples may provide advantages in diagnosis, screening or prevalence studies, especially among individuals with venous access difficulties. This study aims to optimize one commercially available assay for detecting total anti-HBc marker in oral fluid samples and to evaluate its utility under real life conditions in different settings for the purposes of prevalence and diagnostic studies. Methods Oral fluid was collected using a Salivette device and some parameters were initially evaluated: type of elution buffer and sample volume. Thereafter, the utility of oral fluid samples for detection of anti-HBc was evaluated in real life conditions in which, 1296 individuals gave serum and oral fluid samples. All serum samples were submitted to commercial EIAs to detect total anti-HBc, according to the manufacturer’s instructions and oral fluid samples according to previous optimization. Results In optimization evaluation, PBS/BSA 0.5% and 100 μL of oral fluid (volume was two-fold increased compared to serum in EIA) were chosen as transport buffer and sample volume. In the field study, anti-HBc was detected in 211 out of 1296 serum samples giving overall oral fluid sensitivity of 52.6% and specificity of 96%. Concordance was higher in ambulatory setting (67.7) compared to general population (31.8). Mean ± standard deviation values of optical density/cutoff (OD/CO) in serum samples were higher in false-negative oral fluid samples than those seen in true positive samples. Sensitivity was higher in those presenting active infection compared to anti-HBc isolate and past infection. Sensitivity also increased in the ambulatory group when HCV individuals were excluded. Conclusions It was possible to optimize a commercial EIA for detecting anti-HBc in oral fluid samples and where the highest concordance was found in ambulatory settings and among individuals with active infection.…

Abstract Background Elevated rates of Hepatitis C Virus (HCV) infection have been reported in epidemiological studies with people who used illicit drugs (PWUIDs) in different Brazilian regions. In Brazil’s Amazon region, studies have already identified the common use of illicit drugs among adolescents and the high prevalence of HCV infections among PWUIDs. However, all studies done with PWUIDs were conducted with small samples and within limited geographic coverage. This study determined the prevalence and risk factors for HCV infection in PWUIDs in the Amazon region, northern Brazil, as well as estimating the prevalence and factors associated with the HCV spontaneous clearance (HSC). Methods This cross-sectional study accessed 1666 PWUIDs from multiple municipalities of the Amazon region. Socio-demographic, economic, drug use and health-related information were collected through interviews. Blood samples collected were tested for the presence of anti-HCV antibodies and RNA-HCV. HCV genotypes were identified by real-time polymerase chain reaction (PCR). Logistic regressions were run to identify factors independently associated with HCV infection status and HSC. Results In total, 577 (34.6%) featured HCV antibodies, of which 384 (23.1%) had active HCV infection and 193 (11.6%) indicated HSC. Genotypes 1 (80.2%) and 3 (18.8%) were detected. HCV infection status was associated with the length of illicit drug use history, factors related to parenteral and sexual transmission, and factors of socio-economic marginalization leading to potential risk activities for HCV. HSC was associated with the ethnic (including indigenous) background of participants. Conclusions High levels of HCV infection were detected in PWUIDs. Genotype 1 was predominant. Intense use of illicit drugs, unprotected sexual intercourse, high number of sexual partners and social marginalization were associated with all HCV infection. HSC was associated with origin (Amazonian-born) and non-white (e.g., Black or Indigenous) of PWUIDs. These findings emphasize the need for improve HCV prevention and control services and care for PWUIDs in the Brazilian Amazon region.…

Gubareva L, Fry A.

Drug resistance is a topic of significant concern in the treatment of infectious diseases caused by rapidly evolving RNA viruses that can persist (eg, human immunodeficiency virus and hepatitis C virus) or reinfect (eg, influenza virus). Combination drug therapy is standard of care for the treatment of infections by rapidly mutating RNA viruses [1, 2]. However, it is not a common approach for treating influenza virus infections, partly because of the limited number of anti-influenza drugs and drug targets. We now know that all of the classes of anti-influenza drugs—M2 blockers, neuraminidase inhibitors (NAIs), and the newly licensed cap-dependent endonuclease inhibitor (baloxavir marboxil)—have low genetic barriers to resistance: 1 or 2 amino acid substitutions are sufficient to gain resistance [3, 4].

Martin N, Jansen K, an der Heiden M, et al.

AbstractBackgroundDespite high hepatitis C virus (HCV) treatment rates, HCV incidence among HIV-positive men who have sex with men (HIV+ MSM) in Germany rose prior to HCV direct-acting antivirals (DAAs). We model what intervention can achieve the World Health Organization (WHO) elimination target of 80% incidence reduction by 2030 among HIV+ MSM in Berlin.MethodsAn HCV transmission model among HIV-diagnosed MSM was calibrated to Berlin (rising HCV incidence and high HCV testing/treatment). We modelled HCV incidence among HIV-diagnosed MSM in Berlin until 2030 (relative to 2015 WHO baseline) under scenarios of DAA scale-up with/without behavior change (among HIV-diagnosed MSM and/or all MSM).ResultsContinuing current treatment rates will marginally reduce HCV incidence among HIV-diagnosed MSM in Berlin by 2030. Scaling-up DAAs to 100% within 3 months of diagnosis and 25%/year of previously diagnosed and untreated from 2018 could reduce incidence by 61% (2.5-97.5%Interval 55.4-66.7%) by 2030. The WHO target would likely be achieved by combining DAA scale-up with 40% HCV transmission risk reduction among HIV-diagnosed MSM and 20% transmission reduction from HIV-undiagnosed or negative MSM.DiscussionHCV elimination among HIV+ MSM in Berlin likely requires combining DAA scale-up with moderately effective behavioral interventions to reduce risk among all MSM.

Abstract Background In the United States Hepatitis C virus (HCV) viral clearance is estimated to range between 20 and 30%. The objective of this study was to estimate the frequency of HCV clearance and identify correlates of viral clearance among patients newly identified as HCV antibody positive in a large urban health system in Los Angeles, California. Methods We identified patients between November 2015 and September 2017 as part of a newly implemented HCV screening and linkage-to-care program at University of California Los Angeles (UCLA) Health System. All patients were eligible for screening, though there were additional efforts to screen patients born between 1945 and 1965. We reviewed Medical records to categorize anti-HCV antibody positive patients as having spontaneously cleared HCV infection (HCV RNA not detected) or not (HCV RNA detected). We excluded those with a prior history of anti-HCV positivity or history of HCV treatment. We compared differences between those with and without detectable HCV RNA using chi-square test, Fisher’s exact test, and t-test as appropriate. We assessed factors associated with HCV clearance using logistic regression analysis. Results Among the 320 patients included in this study, 56% were male. Baby boomers (52–72 years of age) comprised the single largest age group (62%). We found spontaneous HCV clearance in 58% (n = 185). HCV viral clearance was slightly higher among women as compared to men (63% vs. 53%; p value = 0.07) and varied by race/ethnicity: clearance among Blacks/African Americans was 37% vs. 58% among whites (p value = 0.02). After adjusting for age, race/ethnicity, and sex we found that those diagnosed with chronic kidney disease had a tendency of decreased HCV viral clearance (adjusted OR = 0.34; 95% CI 0.14–1.03). Conclusion Of those patients newly identified as anti-HCV positive, 58% had cleared HCV virus, while the rest showed evidence of active infection. In addition, we found that clearance varied by race/ethnicity and clinical characteristics.…

Abstract Background To evaluate the efficacy and safety of telbivudine in chronic hepatitis B women during the second and third trimesters of pregnancy. Methods The week 12–34 of pregnant women were screened in this prospective non-intervention study, with HBV DNA > 106 IU/mL and alanine aminotransferase > 50 IU/L. The patients were received telbivudine treatment as a treatment group or without antiviral treatment as a control group. All infants were received recombinant hepatitis B vaccine 10 μg within 12 h of birth, at week 4 and week 24, immunoglobulin G within 12 h of birth and were detected HBV markers at the range from 7 to 12 months after delivery. Results A total of 241 patients were finally enrolled, 139 patients in telbivudine group and 102 patients in control group. HBsAg negative rate of infants was 99.3% (135/136) in telbivudine group and was 91.9% (91/99) in control group after 7 months (P = 0.005), respectively. The incidence of undetectable HBV DNA levels (47.5%) was significantly lower in telbivudine-treated mothers than that in the controls (0%), and 75.5% patients alanine aminotransferase returned to normal in telbivudine group, and 51% in control group at delivery (P 

Abstract Background The major infectious diseases of hepatitis B has constituted an acute public health challenge in China. An effective and affordable HBV control model is urgently needed. A national project of Community-based Collaborative Innovation HBV (CCI-HBV) demonstration areas has optimized the existing community healthcare resources and obtained initial results in HBV control. Methods Based on the existing community healthcare network, CCI-HBV project combined the community health management and health contract signing service for long-staying residents in hepatitis B screening. Moreover, HBV field research strategy was popularized in CCI-HBV areas. After screening, patients with seropositive results were enrolled in corresponding cohorts and received treatment at an early stage. And the uninfected people received medical supports including health education through new media, behavior intervention and HBV vaccinations. In this process, a cloud-based National Information Platform (NIP) was established to collect and store residents’ epidemiological data. In addition, a special quality control team was set up for CCI project. Results After two rounds of screening, HBsAg positive rate dropped from 5.05% (with 5,173,003 people screened) to 4.57% (with 3,819,675 people screened), while the rate of new HBV infections was 0.28 per 100 person-years in the fixed cohorts of 2,584,322 people. The quality control team completed PPS sampling simultaneously and established the serum sample database with 2,800,000 serum samples for unified testing. Conclusions CCI-HBV project has established a large-scale field research to conduct whole-population screening and intervention. We analyzed the HBsAg prevalence and new infection rate of HBV in the fixed population for the epidemic trend and intervention effect. The purpose of CCI-HBV project is to establish and evaluate a practical model of grid management and field strategy, to realize the new goal to control hepatitis B in China. To provide policymakers with a feasible model, our results are directly applicable. Trial registration The project was funded by the Major Projects of Science Research for the 11th and 12th five-year plans of China, entitled “The prevention and control of AIDS, viral hepatitis and other major infectious diseases”, Grant Nos. 2009ZX10004901, 2011ZX10004901, 2013ZX10004904, 2014ZX10004007 and 2014ZX10004008.…

Abstract Background Hepatitis B virus (HBV) is a hepatotropic deoxyribonucleic acid (DNA) virus which causes death. More than 300 million people have chronic liver infections globally and about 600,000 people die annually from acute or chronic complications of hepatitis B infection. Recent studies conducted in Ethiopia showed moderate endemicity (3–7.8%) of HBV among pregnant women. However, there is paucity of information on sero- prevalence of HBV and associated factors among pregnant women at Gambella town. The aim of this study is to assess sero-prevalence of hepatitis surface antigen (HBsAg) and associated factors among pregnant women in Gambella Hospital. Methods Hospital based cross-sectional study was conducted in a total of 253 pregnant women from March 10–April 15, 2017. Socio-demographic characteristics and risk factors were collected through face to face interview using structured questionnaire. HBV infection was determined using Eugene strip test. Logistic regression analysis was used to determine association between HBsAg sero-positivity and various factors. Findings were presented using 95% CI of Crude Odds Ratios (COR) and Adjusted Odds Ratios (AOR). Result The overall sero- prevalence of HBV infection was 7.9% (95% CI, 4.7–11.9), which indicates intermediate endemicity. History of abortion (AOR = 3.56:1: 95% CI, 1.24–10.22), occupation (AOR = 8.36:95% CI, 1.67–41.96) and multiple sexual partner (AOR = 17.38: 95% CI, 4.48–67.49) had statistical significant association with HBsAg sero-positivity. Conclusion HBV sero-prevalence in pregnant women shows intermediate endemicity. Hence health education on having single sexual partner and risk factors of abortion should be given. In addition, routine screening and immunization of pregnant women for HBV infection should be strengthen.…

Poudyal, Deepak; Yang, Jun; Chen, Qian; Goswami, Suranjana; Adelsberger, Joseph W.; Das, Sudipto; Herman, Andrew; Hornung, Ronald L.; Andresson, Thorkell; Imamichi, Tomozumi

Objectives: IL-27 is known as an antiviral cytokine that inhibits HIV, hepatitis C virus, and other viruses. We have previously demonstrated that, IL-27 posttreatment after HIV-infection inhibits viral replication in primary CD4+ T cells. Design: Here, we evaluated the anti-HIV effect of IL-27 pretreatment in CD4+ T cells from healthy donors prior to HIV infection with HIVNL4.3 or vesicular stomatitis virus G glycoprotein (VSV-G)-pseudotyped HIV-luciferase virus (HIV-LUC-V). Methods: IL-27-treated CD4+ T cells were infected with HIVNL4.3 or HIV-LUC-V and assessed the anti-HIV effect. HIV infection was monitored by p24 antigen ELISA or luciferase assay. HIV fusion/entry and uncoating were determined by BlaM-Vpr assay and HIV fate of capsid and/or HIV Entry/Uncoating assay based on core-packaged RNA availability and Translation assay, respectively. HIV proviral copy number was determined by real-time PCR. Gene expression profile from IL-27-pretreated CD4+ T cells was determined using Genechip array. Posttranslational modification of global proteins from IL-27-pretreated CD4+ T cells was determined by a combination of 2-dimensional difference-in-gel-electrophoresis (2D-DIG), western-blot and protein mass spectrometry. Results: IL-27 pretreatment inhibited HIVNL4.3 and HIV-LUC-V infection in CD4+ T cells. HIV copy assay demonstrated that IL-27-treatment suppressed an early step of reverse transcription during HIV infection. A combination of 2D-DIG-electrophoresis and western blot assays demonstrated that IL-27-treatment induces a change in posttranslational modification of Y box binding protein-1 (YB-1). Overexpression of domain negative YB-1 mutants illustrated that a residue Lysine at 118 plays a key role in supporting HIV infection in CD4+ T cells. Conclusion: IL-27-pretreatment inhibits HIV-1 infection by suppressing an HIV-reverse transcription product formation/uncoating step by suppressing the acetylation of YB-1 in primary CD4+ T cells. Correspondence to Tomozumi Imamichi, Building 550, Room 126, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. E-mail: timamichi@mail.nih.gov Received 25 January, 2019 Revised 2 June, 2019 Accepted 7 June, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 Copyright © 2019 Wolters Kluwer Health, Inc.

Natalia Romero-Sandoval, Lizeth Cifuentes, Gabriela León, Paola Lecaro, Claudia Ortiz-Rico, Philip Cooper and Miguel Martín

Abstract. Waterborne pathogens, associated with poverty and poor sanitary conditions, are a major cause of morbidity and mortality worldwide. There are limited data on the epidemiology of waterborne pathogens in indigenous populations living in the Amazon region. We did a cross-sectional survey in two indigenous Shuar communities in the Amazon region of Ecuador in which we documented the presence of pathogens representing different sources of environmental contamination of water. We detected protozoa and soil-transmitted helminths by microscopy of fecal samples and the presence of IgG antibodies to hepatitis A and Leptospira spp. in blood samples from individuals older than 2 years and collected data by questionnaire on sociodemographic factors and knowledge of infectious diseases. Seroprevalence for hepatitis A and Leptospira spp. were 98.1% (95% CI: 97.0–99.8) and 50.0% (95% CI: 43.3–56.6), respectively, whereas 62.6% (95% CI: 55.8–69.4) had enteric parasites in stool samples. In participants older than 6 years, eight of 10 had evidence of infection with or exposure to at least one of the pathogens studied. Although prevalence of pathogens varied by age, it did not vary significantly by gender, temporal migration, illiteracy, perceived morbidity, receipt of conditional cash transfers, water boiling practices, poor housing conditions, and anthropometric status. These findings indicate a high level of contamination of drinking water by human pathogens in these indigenous communities and the need for interventions to improve access to and use of clean drinking water in these marginalized communities.…

Cooper C.

HCVHIVDirect Acting Antivirals…

Mocroft A, Lundgren J, Gerstoft J, et al.

AbstractBackgroundHepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers but its impact on clinical endpoints among treated HIV/HCV coinfected persons is unclear.MethodsHIV-positive persons from EuroSIDA with known HCV status after January 2001 were classified into strata based on time-updated HCV-RNA measurements and HCV treatment: HCV antibody negative, spontaneously resolved HCV, chronic untreated HCV, cured HCV (HCV-RNA-negative), HCV treatment failures (HCV-RNA-positive). Poisson regression compared incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-AIDS defining malignancy (NADM; excluding HCC) and cardiovascular disease (CVD).Results16618 persons were included (median follow-up 8.3 (interquartile range 3.1–13.7) years). There were 887 CVD, 902 NADM and 436 ESLD events; crude incidence rates/1000 person-years follow-up (95% confidence interval [CI]) were 6.4 (6.0–6.9) CVD, 6.5 (6.1–6.9) NADM and 3.1 (2.8–3.4) ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the five groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22 95% CI 0.14–0.34) and those with spontaneous clearance (aIRR 0.61; 95% CI 0.36–1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic untreated HCV infection (aIRR 1.47; 95% CI 1.02–2.13) or treatment failure (aIRR 1.80; 95% CI 1.22–2.66) had significantly raised rates of ESLD compared to those cured.ConclusionsIncidence of NADM or CVD was independent of HCV group whereas those cured had a substantially lower incidence of ESLD, underlining the importance of successful HCV treatment for reducing ESLD.

W. S. Probert et al.

Abstract Background Among people living with HIV (PLWH), the prevalence of non-HIV related co-morbidities is increasing. Aim of the present study is to describe co-morbidity and multi-morbidity, their clustering mode and the potential disease-disease interactions in a cohort of Italian HIV patients. Methods Cross-sectional analysis conducted by the Coordinamento Italiano per lo Studio di Allergia e Infezioni da HIV (CISAI) on adult subjects attending HIV-outpatient facilities. Non-HIV co-morbidities included: cardiovascular disease, diabetes mellitus, hypertension, oncologic diseases, osteoporosis, probable case of chronic obstructive pulmonary disease (COPD), hepatitis C virus (HCV) infection, psychiatric illness, kidney disease. Multi-morbidity was defined as the presence of two or more co-morbidities. Results One thousand and eighty-seven patients were enrolled in the study (mean age 47.9 ± 10.8). One hundred-ninety patients (17.5%) had no co-morbidity, whereas 285 (26.2%) had one condition and 612 (56.3%) were multi-morbid. The most recurrent associations were: 1) dyslipidemia + hypertension (237, 21.8%); 2) dyslipidemia + COPD (188, 17.3%); 3) COPD + HCV-Ab+ (141, 12.9%). Multi-morbidity was associated with older age, higher body mass index, current and former smoking, CDC stage C and longer ART duration. Conclusions More than 50% of PLHW were multi-morbid and about 30% had three or more concurrent comorbidities. The identification of common patterns of comorbidities address the combined risks of multiple drug and disease-disease interactions.…

Wade A, Doyle J, Gane E, et al.

AbstractBackgroundTo achieve the World Health Organization hepatitis C elimination targets, it is essential to increase access to direct acting antivirals (DAAs) – especially amongst people who inject drugs (PWID). We aimed to determine the effectiveness of providing DAAs in primary care compared with hospital-based specialist care.MethodsWe randomised PWID with hepatitis C attending primary care sites in Australia or New Zealand to receive DAAs at their primary care site or local hospital (standard of care (SOC)). The primary outcome was to determine if people treated in primary care had a non-inferior sustained virologic response at week 12 (SVR12) rate compared to historical controls (consistent with DAA trials at the time of study design); secondary outcomes included comparison of treatment initiation, SVR12 rates, and the care cascade by study arm.ResultsWe recruited 140 participants and randomised 136; 70 to primary care and 66 to SOC. The SVR12 rate (100%, 95% CI, 87.7-100) of people treated in primary care was non-inferior when compared to historical controls (85% assumed). Intention to treat analysis revealed that the proportion of participants commencing treatment in primary care (75%, 43/57) was significantly higher than in SOC (34%, 18/53) (p

Abstract Background Sofosbuvir is the keystone of direct antiviral agents for the chronic hepatitis C (CHC). The safety of sofosbuvir in patients with stage 4–5 chronic kidney disease (CKD) needs further observation in real world. Case presentation Thirty-three patients with stage 5 CKD and hepatitis C virus (HCV) infection from 2 hemodialysis centers accepted sofosbuvir based treatment as we reported previously. Serum potassium concentrations were tested every 4 weeks or on demand. Ten of 33 patients showed recurrence of hyperkalemia. We summarized the characteristics of hyperkalemia occurrence in these 10 patients. Overall, 24 episodes of hyperkalemia were observed in these 10 patients, 21 were under treatment and 3 were after treatment. Patients with or without hyperkalemia before sofosbuvir treatment didn’t show significantly differences in the median frequencies of hyperkalemia episodes during the observation period (3.5 vs. 2, p = 0.264). Conclusions Patients with stage 5 CKD and HCV infection treated with sofosbuvir based regimens, even halved sofosbuvir, should be taken caution and closely monitoring serum potassium and renal function is necessary.…

Abstract Background Hepatitis E is a liver disease caused by a small RNA virus known as hepatitis E virus (HEV). Four major genotypes infect humans, of which genotype 1 and 2 (HEV-1, HEV-2) are endemic mainly in Asia and responsible for waterborne epidemics. HEV-3 and HEV-4 are widely distributed in pigs and can be transmitted to humans mainly by undercooked meat, and contact with pigs. HEV-3 is the main genotype in industrialised countries with moderate climate conditions and object of this debate. Main text Whereas an HEV-3 infection in healthy humans is mostly asymptomatic, HEV-3 can induce chronic infection in immunocompromised individuals and acute-on-chronic liver failure (ACLF) in patients with underlying liver diseases. The number of reported cases of HEV-infections in industrialised nations increased significantly in the last years. Since HEV-3 has been transmitted by blood transfusion to other humans, testing of blood donors has been introduced or introduction is being discussed in some industrialised countries. In this article we summarise the arguments in favour of testing all blood donations for HEV-3. Conclusion The number of HEV infection in the population and the possibility of HEV transmission by blood transfusion are increasing. Transmission by blood transfusion can be dangerous for the recipients considering their immunosuppressive status, underlying disease or other circumstances requiring blood transfusion. This argues in favour of testing all blood donations for HEV-3 to prevent transmission.…

Abstract Background Distribution of Hepatitis C virus (HCV) genotypes varies significantly worldwide. Genomic diversity between genotypes has implications for treatment, vaccine development and optimal design of HCV diagnostic assays. Molecular characterization of HCV in different geographical areas is therefore very essential for management and public health control of HCV infection. This study investigated the molecular epidemiology and characteristics of HCV genotypes in healthy individuals in Accra, Ghana. Methods An experimental study was carried out on blood samples obtained from voluntary blood donors. Two hundred samples were initially screened for HCV antibodies and infection was confirmed by RNA detection through RT-PCR of the 5′-untranslated region (5’UTR). The core gene sequences were analysed for HCV genotype determination by genotype-specific PCR; and then by cloning and direct sequencing followed by phylogenetic analysis. The sequences were further analysed in detail by similarity plotting. Results Molecular diagnosis confirmed the presence of HCV RNA in 2 out of 200 (1%) blood donors. Initial genotyping by genotype-specific PCR identified all two infections as subtypes 2a and 2b of genotype 2. Extensive evolutionary and genetic analyses indicated two epidemiological profiles. First, phylogenetic tree topologies clearly showed that, collectively, the core sequences of the Ghanaian HCV isolates belong to a single, distinct genetic group within HCV genotype 2 cluster, with high genetic similarity and rapid sequence variation in a single individual. Second, the sequences are mosaics comprising 2e and other genotype 2 subtype fragments. The analyses underscore a unique and complex HCV genotype 2 core sequence profile of the Ghanaian isolates. Conclusions Analysis of HCV core encoding sequences from Ghanaian blood donors in Accra confirmed predominance of genotype 2 HCV among healthy individuals. However, the isolates could not be classified into subtypes, possibly due to their complex sequence pattern that might suggest high mutability of the prevailing genotype. The core region of Ghanaian HCV therefore may not be suitable for distinguishing subtypes. These findings extend those from previous studies and thus underscore the need to search for subtype-informative region of Ghanaian HCV to elucidate the genetic diversity and factors determining outcome of HCV infections in Ghana.…