Genotype 1b Research Articles

Characteristics of Hepatitis C Epidemic Process in the Republic of Belarus

Relevance. The medical and social significance of hepatitis C (HC) is determined by its widespread distribution, the involvement of the working-age population in the epidemic process, the multiplicity of transmission routes of the pathogen, a variety of clinical forms, and a high frequency of chronicity and malignancy of the process.The purpose of the study- to characterize epidemic process of HC in the Republic of Belarus, based on long-term observations.Materials and methods. Assessment of the incidence of HS in the population as a whole and in individual groups was carried out according to the data of the state statistical reporting form «Report on individual infectious, parasitic diseases and their carriers» in 1996-2019. Genotyping was carried out in the core/E1 and NS5B areas; for bioinformation analysis, BoiEdit v.7.2.5, SeqA6, SeqScape v.3, and Mega 6 were used. Statistical calculations were performed using the software Statistica V.6.1 (Statsoft, USA). Credibility of long-term assessment was proved using the Spearman correlation coefficient Rs.Results. The incidence of acute hepatitis during the 24-year epidemiological observation period decreased 3.5 times from 2.68 cases per 100 ths people in 1996 to 0.76 per 100 ths people in 2019. With a downward trend in number of carriers of hepatitis C -6.34% (p < 0.05) there is still a moderate upward tendency in the incidence of chronic hepatitis C (+4.37%, p < 0.05). The age group of 21-39 years is the main cohort in the structure of patients with acute hepatitis (1.1-2.5 per 100 ths). 68.8% of all patients with chronic as well as latently occurring forms of HC are people aged 21-49, the incidence in this age group ranges from 61.3-186.2 per 100 ths and exceeds 1.3-4.5 times the incidence among the total population of Belarus. During 2018-2019 among the selected isolates, the hepatitis C was dominated by the 1st genotype represented by 1a (10.3 ± 1.7%) and 1b (51.7 ± 2.9%) subtypes and genotype 3a (31.8 ± 2.7%).Conclusion. In the Republic of Belarus the decrease in the incidence of acute hepatitis (decrease rate of -6.09% p < 0.05) comes along with the increase in the incidence of chronic hepatitis C (increase rate + 4.37% p < 0.05). The main risk group for hepatitis C is 21-49 years old. Thus, the largest share (about 70%) of disease falls on socially active population in the reproductive age with the highest labor potential (21-49 years old). The proclaimed and widely manifested decrease in the incidence of acute hepatitis is shadowed by the continued growth of newly diagnosed chronic hepatitis C in high-risk groups and it will surely worsen epidemiological situation with a large number of chronic sources of infection. The results of molecular genetic monitoring show that in the period from 2018 to 2019 the genetic structure of hepatitis C virus isolates is not different to the period of 2004-2015, and the prevailing types are still the 1b, 1a, and 3a subgenotypes of Hepatitis C virus. This knowledge is necessary for the planning, implementation and development of the Program for Elimination of Hepatitis C in the Republic of Belarus for 2019-2028, which aims to reduce HC virus infection by its prevention, detection and antiviral treatment. An expected result of the Program is a substantial decrease in mortality, disability as well as long-term job disqualification among the population of the Republic of Belarus.

Required concentration index quantifies effective drug combinations against hepatitis C virus infection

Successful clinical drug development requires rational design of combination treatments based on preclinical data. Anti-hepatitis C virus (HCV) drugs exhibit significant diversity in antiviral effect. Dose-response assessments can be used to determine parameters profiling the diverse antiviral effect during combination treatment. In the current study, a combined experimental and mathematical approaches were used to compare and score different combinations of anti-HCV treatments. A “required concentration index” was generated and used to rank the antiviral profile of possible double- and triple-drug combinations against HCV genotype 1b and 2a. Rankings varied based on target HCV genotype. Interestingly, multidrug (double and triple) treatment not only augmented antiviral activity, but also reduced genotype-specific efficacy, suggesting another advantage of multidrug treatment. The current study provides a quantitative method for profiling drug combinations against viral genotypes, to better inform clinical drug development.

Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries: A Dutch Nationwide Cohort Study.

BackgroundThe majority of hepatitis C virus (HCV) infections are found in low- and middle-income countries, which harbor many region-specific HCV subtypes. Nevertheless, direct-acting antiviral (DAA) trials have almost exclusively been conducted in high-income countries, where mainly epidemically spread HCV subtypes are present. Recently, several studies have demonstrated suboptimal DAA efficacy for certain nonepidemic subtypes, which could hamper global HCV elimination. Therefore, we aimed to evaluate DAA efficacy in patients treated for a nonepidemic HCV genotype infection in the Netherlands.MethodsWe performed a nationwide retrospective study including patients treated with interferon-free DAAs for an HCV genotype other than 1a/1b/2a/2b/3a/4a/4d. The genotype was determined by NS5B region phylogenetic analysis. The primary end point was SVR-12. If stored samples were available, NS5A and NS5B sequences were obtained for resistance-associated substitutions (RAS) evaluation.ResultsWe included 160 patients, mainly infected with nonepidemic genotype 2 (41%) and 4 (31%) subtypes. Most patients were from Africa (45%) or South America (24%); 51 (32%) were cirrhotic. SVR-12 was achieved in 92% (140/152) of patients with available SVR-12 data. Only 73% (8/11) genotype 3–infected patients achieved SVR-12, the majority being genotype 3b patients with 63% (5/8) SVR. Regardless of SVR, all genotype 3b patients had 30K and 31M RAS.ConclusionsThe DAA efficacy we observed in most nonepidemic genotypes in the Netherlands seems reassuring. However, the low SVR-12 rate in subtype 3b infections is alarming, especially as it is common in several HCV-endemic countries. Alongside earlier results, our results indicate that a remaining challenge for global HCV elimination is confirming and monitoring DAA efficacy in nonepidemic genotypes.

Focus on hepatitis C virus genotype distribution in Tunisia prior to elimination: a 16-year retrospective study.

With the introduction of direct-acting antiviral treatment (DAA), Tunisia has committed to achieving the international goal of eliminating viral hepatitis. Because the specific DAA prescribed depends on viral genotype, viral genotyping remains of great importance. The aim of the present study was to outline the trends in the distribution of HCV genotypes from 2002 to 2017 in the Tunisian general population in order to guide authorities towards the most appropriate therapeutic strategies for preventing HCV infection. A total of 2532 blood samples were collected over a 16-year period and from all regions of Tunisia. Genotyping showed that genotype 1 (subtype 1b) was the most prevalent genotype in the country (n = 2012; 79.5%), followed by genotype 2 (n = 339; 13.3%). Genotypes 3, 4 and 5 were detected in 4.8%, 2.2% and 0.1% of the country's population, respectively. Mixed infections with different HCV genotypes were detected in 0.1% of the population (one case each of genotypes 1b + 4, 1b + 2 and 2 + 4). Interestingly, a significant increase in genotypes 2, 3 and 4 was observed over time (p = 0.03). Sixteen different subtypes were detected over the study period, most of which were subtypes of genotype 2, and some of these subtypes appeared to be new. Patients infected with genotypes 1a, 3 and 4 were significantly younger than those infected with genotypes 1b and 2 (p < 0.01). Furthermore, genotypes 1b and 2 were detected more often in women than men, while genotypes 1a and 3 were detected mostly in men (P < 0.01). Our study confirms a large predominance of genotype1/subtype1b in Tunisia and shows a significant increase in the prevalence of other genotypes over time. These findings reinforce the need for an additional HCV genotype survey to improve the design of treatment strategies in Tunisia.

Prevalence and Genotype Distribution of Hepatitis C Virus from 1,668 Individuals of Sichuan Area in China.

Hepatitis C virus (HCV) is one of the main causes of liver fibrosis, chronic hepatitis, and liver cirrhosis. The aim of this study is to determine the prevalence of HCV, age-dependent prevalence and genotypes distribution in a large number of clinical samples in Sichuan area of China. In the past five years from 2014 to 2018, a total number of 4,508 individuals received the serum HCV-RNA analysis in the Sichuan Provincial People's Hospital. Viral nucleic acid was extracted from the serum samples and amplified using COBAS AmpliPre/COBAS TaqMan Detection Platform. Five HCV genotypes (1b, 2a, 3a, 3b, and 6a) of serum samples from 469 HCV positive individuals collected from 2016 to 2018 were analyzed using the PCR-fluorescence probe technique. A total of 1,668 individuals had positive results by high precision HCV-RNA quantitative technique, corresponding to a crude prevalence of 37.0% (95% confidence interval: 33.6 - 40.3%). The majority of HCV positive individuals were aged over 41 years, accounting for 80.7% (1,346/1,668, CI: 72.3 - 87.1%). Among the nine age groups, the 41 - 50-year age group had the highest HCV prevalence of 29.8% (497/1,668, CI: 25.6 - 32.3%). Of the 469 HCV-RNA positive serum samples collected in 2016 - 2018, genotype 1b was the most frequent type found in 357 individuals, corresponding to a prevalence of 76.1% (CI: 72.3 - 80.0%). Positive rates of HCV in the years of 2014 to 2018 showed a downward trend year by year, of which a majority of positive cases were aged over 41 years. HCV was distributed with multi-genotype features while genotype 1b yielded a very high prevalence in the Sichuan area. The results have potential for prevention and treatment of HCV infection, as well as epidemiological research.

Анализ эффективности противовирусной терапии хронического гепатита С у детей

Objective. To analyze the efficacy of antiviral therapy for chronic hepatitis C (HCV) in children. Patients and methods. This study included 58 children aged between 3 and 17 years who had never received antiviral therapy (AVT) before and were treated in the Pediatric Department for Infectious Diseases, N.A.Semashko City Clinical Hospital No 2 (Samara). The inclusion criteria were as follows: confirmed CHC diagnosis and follow-up for at least one year. We analyzed treatment outcomes during an 8-year period, as well as the dynamics of clinical and biochemical parameters in children with HCV depending on their response to AVT. Results. Sustained virologic response (SVR) was achieved in 19 out of 58 children (32.8%) after 24 weeks of therapy and 30 out of 58 children (51.7%) after 48 weeks of therapy. In these children, viral genotypes were distributed as follows: 1b genotype in 19 participants (32.7%), 2a genotype in 4 participants (6.9%), and 3a genotype in 7 participants (12.1%). Twenty-eight patients (71.8%) remained HCV RNA positive, including 1 child with 2a genotype (2.6%), 3 children with 3a genotype (7.7%), and 24 children with 1b genotype (61.5%). Three years after treatment completion, 25 out of 58 patients (43.1%) had SVR. During 8 years of follow-up, 17 out of 30 children (56.7%) maintained SVR. Conclusion. Five out of 58 study participants (8.6%) developed F1–F2 liber fibrosis (METAVIR scale) over 8 years of follow-up. Two out of 58 children with HCV (3,5%) were found to have liver cirrhosis 6.6 ± 1.15 years after the disease onset (minimum – 4 years; maximum – 8 years). New drugs and treatment regimens are needed to increase the SVR rate in children. Key words: children, outcomes, sustained virologic response, chronic hepatitis C

The Impact of Hepatitis C Virus Genotypes on Oxidative Stress Markers and Catalase Activity.

Hepatitis C virus (HCV) is a major cause of liver disease worldwide. Chronic HCV infections are usually associated with increased oxidative stress in the liver tissue. The intensity of oxidative stress may be a detrimental factor in liver injury and may determine the severity of the disease. The aim of the present case-control study was to determine the level of lipid peroxidation (TBARS), protein oxidative modification (AOPP), and catalase activity in sera of patients infected with HCV, in relation to different HCV genotypes and viral load. Considering the HCV patients with chronic hepatitis C (52) and control subject (50) recruitment, the study was designed as a case–control-type. The HCV RNA isolation, viral load, and HCV genotyping were performed according to the standard protocols. A significant difference compared to control healthy subjects was reported for TBAR (p < 0.001), AOPP (p = 0.001), and catalase activity (p = 0.007). In a gender-based comparison, a significantly higher level of AOPP for females was reported (p < 0.001). As stratified by HCV genotype, the most common was HCV-1 (HCV-1a and HCV 1b), with the overall participation of more than 60%, followed by genotype 3, while the least represented was genotype 2. No significant difference was documented among genotypes in regard to oxidative stress markers, although somewhat higher TBARS level, but not significant, was registered in patients infected with genotype 1b. A statistically significant positive correlation was found between the concentration of HCV genome copies and AOPP (r = 0.344; p = 0.012). A high level of HCV viral load was more likely to have a higher TBARS, but still without statistical significance (p = 0.072). In conclusion, the results obtained confirmed an imbalance between the ROS production and antioxidative defense system in HCV-infected patients. Since oxidative stress may have a profound influence on disease progression, fibrosis, and carcinogenesis, our results may meet the aspirations of mandatory introduction of antioxidants as early HCV therapy to counteract ROS consequences.

Clinical Characteristics and Treatment Outcomes of Patients with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection: Experience at a Single Center in Korea.

BackgroundBecause of the very low incidence of human immunodeficiency virus (HIV) coinfection in Korea, data on hepatitis C virus (HCV)/HIV coinfection are limited. This study aimed to investigate the clinical characteristics and treatment outcomes of patients with HCV/HIV coinfection in Korea.MethodsWe performed a retrospective cohort study of all HCV-monoinfected and HCV/HIV-coinfected patients treated with antivirals at National Medical Center in Seoul, Korea, between January 2009 and March 2020.ResultsWe enrolled 220 HCV-monoinfected and 23 HCV/HIV-coinfected patients treated with antivirals. The HCV/HIV-coinfected patients were younger (HCV vs. HCV/HIV: 57.3 ± 11.3 vs. 40.7 ± 10.1 years, P < 0.001) and had a higher proportion of men (HCV vs. HCV/HIV: 54.5% [n = 120] vs. 91.3% [n = 21], P < 0.001) than the HCV-monoinfected patients. Genotype 1b and 2 were most common in both HCV monoinfection and HCV/HIV coinfection groups. HCV-monoinfected patients had a higher incidence of genotype 1b and 2 than HCV/HIV-coinfected patients (HCV vs. HCV/HIV: 95.4% [n = 210] vs. 73.9% [n = 17], P < 0.001), while the HCV/HIV-coinfected patients had genotype 1a (HCV vs. HCV/HIV: 1.8% [n = 4] vs. 21.7% [n = 5], P < 0.001). The fibrosis-4 index was significantly lower in the HCV/HIV-coinfected patients than in the HCV-monoinfected patients (HCV vs. HCV/HIV: 3.81 ± 3.38 vs. 1.66 ± 1.10, P < 0.001). Among the direct-acting antivirals (DAA)-treated patients, the sustained viral response (SVR) rate did not differ significantly between both groups (HCV vs. HCV/HIV: 94.9% [93/99] vs. 90.9% [10/11], P = 0.480).ConclusionIn Korea, the HCV/HIV-coinfected patients who received antiviral treatment were younger, had higher proportion of men and incidence of genotype 1a, and had less advanced fibrosis than the HCV-monoinfected patients. In actual clinical settings, HCV/HIV-coinfected patients show excellent SVR to DAA treatment, similar to HCV-monoinfected patients.

Measles outbreak related to healthcare transmission

IntroductionMeasles has a high transmission rate among susceptible populations. Healthcare facilities can play an important role in measles transmission. The aim of this study is to describe a measles outbreak in a highly immunized community and the implication of healthcare workers in the transmission of the disease. MethodsDescriptive study of measles outbreak linked to hospital setting with sociodemographic, clinical, virological and immunization variables studied. Cases were confirmed by RT-PCR in clinical specimens and genotyped by nucleotide sequencing. Association was assessed by chi2, Fisher's exact and z test. Statistical significance at p=0.05. Results47 suspected measles cases were reported from March to June 2018 at Terres de l’Ebre, Catalonia. Fourteen cases were confirmed, 8 cases (57%) were men; median age of cases 33y (range 16–46 y). Hospital associated transmission was confirmed in 13 (93%) cases, 8 (61.5%) were hospital staff. Five (38.5%) were healthcare workers (HCW), three (23%) non-healthcare workers (non-HCW) and 6 (46%) were patients attended at the hospital. Four cases (28.5%) were immunized with 2 doses of measles virus containing vaccine (MCV); 3 (75%) were HCW. No statistical difference observed among hospital staff and community cases as to immunization (OR 2.4 95%CI: 0.17–32.88; p=0.49). Genotype B3 MVs/Dublin.IRL/8.16-variant was obtained from confirmed cases. ConclusionSuspecting measles diagnosis, allows for immediate airborne isolation, and retrieving measles immunity records for healthcare facility employees and contacts. Vaccination of HCW and the adoption of good infection control will minimize nosocomial transmission and spreading of the virus to the community.

Acute Hepatitis C Virus Infections in Spouses: The Utility of a Genetic Analysis of the Hepatitis C Virus Hypervariable Region Sequence for Identifying the Infectious Source

A married couple who developed hepatitis was referred to our hospital. The husband was diagnosed with acute hepatitis C virus (HCV) infection based on HCV RNA positivity and seroconversion to HCV antibody. The wife was also diagnosed with HCV-related hepatitis; however, she could not be confirmed to have acute hepatitis due to the lack of information on her HCV negativity just before this event. The HCV strains recovered from the couple were genotype 2b and shared 100% identities within the 5’-untranslated region-core region sequence (655 nucleotides/nt) and non-structural (NS)5B region sequence (502 nt). The amplified hypervariable region 1 (HVR-1) sequence indicated that all 10 clones from the wife shared 100% identity and were identical to 3 of 10 heterogeneous clones (separable into 4 groups) from the husband. The husband had a history of intravenous drug use. These results suggested that one of four quasispecies 2b HCV strains was transmitted from the husband to the wife, with the husband being the infectious source for acute HCV infection in the wife, most likely via sexual intercourse. A sequence analysis of the HCV genomes and the further comparison of the HVR-1 amino acid sequence variability may be useful for defining the infectious source of HCV, especially in couples or cluster cases.

Scavenger receptor class B type I is more conducive for genotype 1b hepatitis C virus internalization than low-density lipoprotein receptor.

The current limited understanding of HCV entry mechanisms hinders the development of specific antiviral drug screening techniques and vaccine assessment. HCV subtypes and cellular surface proteins both can affect virus tropism. Human factors such as low-density lipoprotein receptor (hLDLR), CD81 (hCD81), scavenger receptor class B type I (hSR-BI), claudin 1 (hCLDN1), and occludin (hOCLN) assist HCV entry into hepatocytes. Here, we studied the importance of five human proteins in the process of cell culture-derived (HCVcc) and serum-derived (HCV-sd) HCV entry using constructed humanized mouse hepatocytes and mouse models. We determined that unlike hLDLR, hSR-BI was an indispensable factor for 1b genotype HCV adsorption. Furthermore, this attachment can be completely prevented by treatment with a monoclonal antibody targeting hSR-BI. Our data support the idea that SR-BI is an essential factor in HCV infection, particularly during the initial HCV particle-binding step. This novel finding will facilitate the development of antiviral drugs and vaccines. Keywords: hepatitis C virus; virus internalization; model construction; hSR-BI.

Extended panel of biomarkers for long term monitoring of effectiveness of 3 direct antiviral regimen in HCV genotype 1b infection: results from a Romanian infectious disease hospital

Abstract Background: Hepatitis C virus can be eradicated with antiviral therapy, thus reducing the risk of disease progression and death associated with the final stage of liver disease. Methods: 241 patients received PrOD+RBV for 12 weeks. Clinical and laboratory data were assessed at baseline, week 4, 8, 12 (end of treatment, EOT), and 12 weeks after therapy (sustained virological response, SVR). Subsequently, biological and virological measurements were performed at least 48 weeks after obtaining SVR12 in responder patients. Results: Per protocol SVR12 rate was 97,6%. Severe adverse events were reported in 3 patients (1.24%) and led to treatment discontinuation (liver decompensation). One 58-year-old patient who completed the treatment died before SVR evaluation due to acute mesenteric ischemia (not related to antiviral therapy). Baseline total bilirubin above 2 mg/dl can be considered a predictive factor for non-response to PrOD+RBV treatment (p = 0.004). Of the 30 patients evaluated at least 48 weeks after SVR no one presented relapses, with no statistically significant differences in biological parameters changes and no adverse events were noted during the 48-week follow up period. Conclusion: Our study revealed the high effectiveness and good safety profile of PrOD +RBV in patients with genotype-1b HCV compensated cirrhosis (Child Pugh A) which were maintained during a 48-week period after treatment finalization.

Hepatitis C virus genotype and its correlation with viral load in patients from Kathmandu, Nepal.

Knowledge about the distribution of hepatitis C virus (HCV) genotype and its correlation with viral load are important for the decision of treatment and the prediction of disease progression, however such information is very limited in Nepal. Here, we investigated the distribution of HCV genotypes and viral load for HCV-infected patients from Kathmandu, Nepal. Ninety-six patients with HCV infection and not on antiviral therapy were enrolled from three different medical centers in Kathmandu valley, Nepal. Demographics were recorded and blood samples were collected. Plasma was separated and HCV RNA was extracted. Reverse transcriptase PCR (RT-PCR) was performed to measure the viral load, and virus genotype was determined. Genotype 3a (n = 53, 55.2%) was the most prevalent, followed by 1b (n = 19, 19.8%), 1a (n = 18, 18.8%), 5a (n = 3, 3.1%), and mix types (n = 3, 3.1%). The median viral load for HCV genotype 1a was 770,942 IU/mL (IQR, 215,268-3,720,075), 1b was 700,000 IU/mL (IQR, 431,560-919,000), 3a was 1,060,000 IU/mL (IQR, 641,050-6,063,500), 5a was 673,400 IU/mL, and mixed was 6,428,000 IU/mL. A correlation between genotype and viral load was observed (p = 0.02), of which genotype 3a showed a high viral load. HCV genotypes 1a, 1b, 3a, and 5a were identified in Kathmandu, Nepal, and mixed genotype patients were observed in the patients studied. HCV genotype showed a correlation with viral load in patient plasma. This finding may contribute to the treatment and prevention of hepatitis C in Kathmandu, Nepal.

Investigation of Genotype Distribution in Hepatitis C Patients in Giresun Province

Introduction: HCV infections are an important public health problem due to their high chronicity, cirrhosis and advanced complications like hepatocellular carcinoma. In HCV infections, it is important and necessary to determine genotypes before treatment because treatment times and protocols vary according to genotypes. The aim of this study was to determine the distribution of HCV genotypes in HCV-RNA positive individuals in Giresun province and to investigate whether there was a statistically significant difference between genotypes and patient ages. Materials and Methods: HCV-RNA level and HCV genotype of 147 patients were included in the study. HCV RNA levels of the samples were studied by QIAsymphony SP (Qiagen) automated device, genotype determination by Rotor Gene Q (Qiagen) automated device by “real-time polymerase chain reaction (PCR)” method. Each sample was tested for HCV genotypes 1a, 1b, 2, 3, 4, 5a and 6. Results: Of the 147 patients genotyped; 128 (87%) genotype 1b, 9 (6%) genotype 1a, 8 (6%) genotype 3, 2 (1%) genotype 2 were detected. Genotypes 4, 5a and 6 were not detected. According to the HCV genotype distribution, median age and range (min.-max.) of the patients weren50 (30-83) for 1a, 70 (22-87) for 1b, 48.5 (36-61) for 2 and 33 (25-52) for 3. HCV RNA levels were between 37 and 12.630.170 IU/mL. Conclusion: The predominant genotype in the world and Turkey is genotype 1b. In our study, the most common genotype was also genotype 1b (87%), consistent with other studies in our country. This study contributed to HCV genotype distribution data in our region and country.

Directly Acting Antiviral-Based Treatment for HCV-Infected Persons Who Inject Drugs: A Multicenter Real-Life Study.

Background: We aimed to evaluate the factors associated with a virological response in a cohort of Hepatitis C virus (HCV)-infected people who inject drugs (PWID) treated with direct acting antivirals (DAAs). Methods: We conducted a multicenter retrospective cohort study enrolling HCV-infected PWID treated with DAAs. The primary outcome evaluated was the sustained virological response (SVR12) rate. Results: Five hundred and twenty HCV-infected PWID treated with all-oral DAA-based regimens were enrolled; a total of 168 (32.3%) patients presented genotype 1a, 109 (21.0%) genotype 1b, and 174 (33.5%) genotype 3; a total 152 of the 520 subjects (29.2%) were cirrhotics; a total 118 (22.7%) and 373 (71.7%) were treated with DAA regimens of second and third generation, respectively; a total 169 (33.6%) patients were receiving an opioid agonist at the start of antiviral therapy. Only 11 subjects (2.1%) did not show an SVR12. A significant correlation was found between treatment with opioid substitution therapy (p < 0.001), Human Immunodeficiency Virus (HIV) coinfection (p = 0.002), and treatment with first- or second-generation regimens (p = 0.0015) and HCV failure. Upon multivariate analysis, treatment with a first- or second-generation DAA was the only factor independently associated with failure (OR 10.4, 95% CI: 1.43 to 76.1, p = 0.02). Conclusions: Treatment with DAAs led to a high SVR12 rate (97.9%) in a large cohort of HCV-infected PWID. The only predictor of viral failure found in our analysis was treatment with first- and second-generation DAA.

Phylogenetic Characterization of the 5′ Untranslated Region of Untypable HCV Genotypes Circulating in Pakistan

Introduction: Commercial methods for HCV genotyping is challenged by the increased prevalence of untypable genotypes in Pakistan. Objective: The aim of the current study was to perform nucleotide sequencing of 5′ UTR region for genotyping of viral isolates circulating in Peshawar, Pakistan. Methods: The total number of commercially untypable samples were 94 in which 18 samples were sequenced for the characterization of 5′ UTR region. Post-sequencing analysis was performed for genotype identification (n = 18) and molecular phylogenetic analysis. Results: The current study reveals different genotypes, that is, 10/18 viral isolates were found to be genotype 3a (55.55%), 3 isolates (genotype 3b, 16.66%), 2 isolates (genotype 6h/6g, 11.11%), 2 (6g/d, 11.11%), and 1 sample (genotype 1c, 5.55%). In addition, genotype 3a is the dominant representative of HCV circulating in Pakistan and has been increasing across the country. Conclusion: The current study also reveals that genotype 6 (2 were genotype 6h/6g and 2 were 6g/d) is also circulating in Pakistan and not restricted to South China and Hong Kong.

Replication of Small Ruminant Lentiviruses in Aluminum Hydroxide-Induced Granulomas in Sheep: a Potential New Factor for Viral Dissemination.

Aluminum (Al)-based salts are widely used adjuvants in ruminants and other species to strengthen the immune response elicited against vaccine antigen(s). However, they can lead to the formation of long-lasting granulomas composed of abundant activated macrophages. Small ruminant lentiviruses (SRLV) are widely distributed macrophage-tropic retroviruses that cause persistent infections in sheep and goats. Infected monocytes/macrophages and dendritic cells establish an inflammatory microenvironment that eventually leads to clinical manifestations. The aim of this work was to study the effect of Al-induced granulomas in the replication and pathogenesis of SRLV. Eleven adult, naturally SRLV-infected sheep showing clinical arthritis were distributed in vaccine (n = 6), adjuvant-only (n = 3), and control (n = 2) groups and inoculated with commercial Al-based vaccines, Al hydroxide adjuvant alone, or phosphate-buffered saline, respectively. In vitro studies demonstrated viral replication in Al-induced granulomas in 5 out of 10 sheep. Immunohistochemistry (IHC) evinced granular, intracytoplasmic SRLV presence in macrophages within granulomas. Viral sequences obtained from granulomas, blood monocytes, and other tissues were highly similar in most animals, suggesting virus circulation among body compartments. However, notable differences between isolated strains in granulomas and other tissues in specific animals were also noted. Interestingly, the B2 subtype was the most commonly found SRLV genotype, reaching a wider body distribution than previously described. Recombination events between genotypes B2 and A3 along the gag region were identified in two sheep. Our results indicate that Al-hydroxide-derived granulomas may represent an ideal compartment for SRLV replication, perhaps altering natural SRLV infection by providing a new, suitable target tissue.IMPORTANCE Granulomas are inflammation-derived structures elicited by foreign bodies or certain infections. Aluminum adjuvants included in vaccines induce granulomas in many species. In sheep, these are persistent and consist of activated macrophages. Small ruminant lentiviruses (SRLV), which are macrophage-tropic lentiviruses, cause a chronic wasting disease affecting animal welfare and production. Here, we studied the occurrence of SRLV in postvaccination granulomas retrieved from naturally infected ewes after vaccination or inoculation with aluminum only. SRLV infection was confirmed in granulomas by identification of viral proteins, genomic fragments, and enzymatic activity. The infecting SRLV strain, previously found exclusively in carpal joints, reached the central nervous system, suggesting that occurrence of SRLV in postvaccination granulomas may broaden tissue tropism. SRLV recombination was detected in inoculated animals, a rare event in sheep lentiviruses. Potentially, virus-host interactions within granulomas may modify viral pathogenesis and lead to more widespread infection.

Molecular epidemiology of Hepatitis B virus, Hepatitis C virus, and Hepatitis D virus in general population of Afghanistan

This study gives a clue about genotypes, subgenotypes and subtypes of HBV, HCV and HDV viruses in general population of Afghanistan. A total of 234 HBsAg, 44 anti-HCV and 5 Anti-Delta positive patients belong to 25-70 age group were obtained through a rapid screening test among 5898 residents of Afghanistan. After quantifying viral load, genotyping of 61 HBV, 29 HCV and 1 HDV samples were accomplished by sequencing of a segment of the HBV Pre S, HCV NS5B, and HDV Delta antigen regions respectively. Clinically important variants of the HBV polymerase gene, the "a" determinant of HBsAg, HCV NS5B and NS3 regions were assessed. All HBV isolates were dispersed throughout the genotype D branch and ayw2 was the only subtypes found. The anti-HDV prevalence among HBsAg positive individuals was 2.2% and the single HDV sample, belonged to HDV genotype I. Analysis of HCV isolates revealed subtype HCV-1b in 75.86%, HCV-3a in 20.69% and HCV-3b in 3.44% patients. The observed mutant variants in the MHR of HBsAg were Y100 15%, Q101 5%, G102 15%, T115 45%, P120 5%, T131 5%. Likewise, S213T 10%, Q215P 5% and N248H 100% mutations were detected in the HBV polymerase region. C316N mutation was prevalent in 72.7% of HCV 1b participants. Genotypic variation in Afghan patients is in line with the ones existing in neighboring countries and regions. HBV genotypes D1, subtype ayw2, HDV RNA type I, and HCV RNA genotype 1b are likely to be dominant in Afghan patients.

Measles virus circulation between the State members of the Indian Ocean Commission?

Background: Despite the availability of safe and effective vaccines, measles resurgence has been observed worldwide in 2018 and 2019. In West Indian Ocean (WIO), almost all islands have reported measles cases during these years. Vaccine coverage was particularly low in Madagascar and Comoros Island, with a single dose provided by the Expanded Program on Immunization. Because of intense exchanges between WIO islands, outbreaks observed in WIO were probably related. Methods and materials: Thanks to the Epidemic Intelligence Unit and the SEGA-One Health network of the Indian Ocean Commission (IOC), composed of five countries (Comoros, Madagascar, Mauritius, France (Reunion), and Seychelles), epidemiological data from each surveillance system were shared. Results: Measles outbreaks have successively occurred in: Mauritius (W12/2018), Madagascar (W35/2018), Reunion (W51/2018) and Comoros (W21/2019; first cases were reported early 2019). As of W41/2019, Madagascar was the most affected island with 244 557 cases (attack rate around 929/100 000) and a case fatality rate of 0,4%. Attack rate was lower in Mauritius (117/100 000) were 1 482 and 4 deaths were reported. In Reunion and Comoros, respectively 96 and 132 cases (of whom 62 were confirmed) were reported; no deaths were reported. Two measles genotypes were circulating in the region: genotype B3 in Madagascar and Comoros; genotype D8 in Mauritius; in Reunion Island both genotypes were observed. Only one case was reported in December 2018 in Seychelles were 2-dose vaccine coverage reached 99% in 2017. Conclusion: Given starting date of each outbreak and circulating genotypes, it can be assumed that outbreaks were closely related, measles virus circulating especially between Mauritius and Reunion on the one hand, and between Madagascar, Comoros and Reunion on the other hand. WIO islands are considered as an epidemiological block where pathogens easily circulate through human and animal exchanges. This situation underlines the importance of the SEGA network which should be further strengthened. For example, development of biological cooperation between WIO islands could help comprehensive epidemiological analyses in the course of outbreaks.

Precipitating factors causing hyperbilirubinemia during chronic hepatitis C treatment with paritaprevir/ritonavir/ombitasvir and dasabuvir.

Hepatic decompensation is a fatal on-treatment side effect during chronic hepatitis C treatment with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Prompt bilirubin testing can reveal hepatic failure in susceptible patients, and clinical parameters precipitating early elevation of bilirubin can warn clinicians to avoid PrOD prescription. This retrospective study included 169 Hepatitis C virus (HCV)-genotype 1b patients who underwent a 12-week course of PrOD with or without ribavirin. Laboratory data underwent χ analysis with Fisher's exact test to determine the precipitating factors causing hyperbilirubinemia in patients who had received 1 week of treatment. Sustained viral response was achieved in 164 patients (97.0%). Total bilirubin was ≥2 mg/dL (21.3%) in 36 patients after 1 week of treatment. Pretreatment white blood cell (WBC) <4500/µL and platelet <100,000/µL correlated with total bilirubin ≥2 mg/dL (relative risk [RR]: 21.64, 95% CI: 5.23-89.64, p < 0.001) after 1 week of treatment. Pretreatment platelet ≥100 000/µL and WBC <4500/µL correlated with direct bilirubin ≥0.45 mg/dL (RR: 6.56, 95% CI: 1.42-30.38, p = 0.016) and indirect bilirubin ≥0.6 mg/dL (RR: 4.77, 95% CI: 1.03-22.15, p = 0.046). Pretreatment platelet <100,000/µL with F3/F4 fibrosis correlated with first week total bilirubin ≥2 mg/dL (RR: 3.57, 95% CI: 1.35-9.09, p = 0.010). PrOD is an effective antiviral regimen for HCV genotype 1b patients. Total bilirubin ≥2 mg/dL after 1 week of treatment serves as an early warning of irreversible progression toward hepatic decompensation, and the current study provides a guide by which to monitor chronic hepatitis C patients undergoing PrOD treatment.