Widespread hepatitis C virus transmission network among people who inject drugs in Kenya.

Objectives: Hepatitis C virus (HCV) disproportionately affects people who inject drugs (PWID) worldwide. Despite carrying a high HCV burden, little is known about transmission dynamics in low- and middle-income countries.

Methods: We recruited PWID from Nairobi and coastal cities and towns of Mombasa, Kilifi, and Malindi in Kenya at needle and syringe programs.

Polyvalent immunization elicits a synergistic broadly neutralizing immune response to hypervariable region 1 variants of hepatitis C virus.

A hepatitis C virus (HCV) vaccine is urgently needed. Vaccine development has been hindered by HCV's genetic diversity, particularly within the immunodominant hypervariable region 1 (HVR1). Here, we developed a strategy to elicit broadly neutralizing antibodies to HVR1, which had previously been considered infeasible.

A Novel Information-Theory-Based Genetic Distance That Approximates Phenotypic Differences.

Application of genetic distances to measure phenotypic relatedness is a challenging task, reflecting the complex relationship between genotype and phenotype. Accurate assessment of proximity among sequences with different phenotypic traits depends on how strongly the chosen distance is associated with structural and functional properties. In this study, we present a new distance measure Mutual Information and Entropy H (MIH) for categorical data such as nucleotide or amino acid sequences.

SOPHIE: Viral outbreak investigation and transmission history reconstruction in a joint phylogenetic and network theory framework.

Genomic epidemiology is now widely used for viral outbreak investigations. Still, this methodology faces many challenges. First, few methods account for intra-host viral diversity.

Hepatitis C virus transmission cluster among injection drug users in Pakistan.

Hepatitis C virus (HCV) infections are public health problem across the globe, particularly in developing countries. Pakistan has the second highest prevalence of HCV infection worldwide. Limited data exist from Pakistan about persons who inject drugs (PWID) and are at significant risk of exposure to HCV infection and transmission.

Primary case inference in viral outbreaks through analysis of intra-host variant population.

Background: Investigation of outbreaks to identify the primary case is crucial for the interruption and prevention of transmission of infectious diseases. These individuals may have a higher risk of participating in near future transmission events when compared to the other patients in the outbreak, so directing more transmission prevention resources towards these individuals is a priority. Although the genetic characterization of intra-host viral populations can aid the identification of transmission clusters, it is not trivial to determine the directionality of transmissions during outbreaks, owing to complexity of viral evolution.

Raman and XANES Spectroscopic Study of the Influence of Coordination Atomic and Molecular Environments in Biomimetic Composite Materials Integrated with Dental Tissue.

In this work, for the first time, the influence of the coordination environment as well as Ca and P atomic states on biomimetic composites integrated with dental tissue was investigated. Bioinspired dental composites were synthesised based on nanocrystalline calcium carbonate-substituted hydroxyapatite Ca4ICa6IIPO46-xCO3x+yOH2-y (nano-cHAp) obtained from a biogenic source and a set of polar amino acids that modelled the organic matrix. Biomimetic composites, as well as natural dental tissue samples, were investigated using Raman spectromicroscopy and synchrotron X-ray absorption near edge structure (XANES) spectroscopy.

Changing Molecular Epidemiology of Hepatitis A Virus Infection, United States, 1996-2019.

Hepatitis A virus (HAV) genotype IA was most common among strains tested in US outbreak investigations and surveillance during 1996-2015. However, HAV genotype IB gained prominence during 2016-2019 person-to-person multistate outbreaks. Detection of previously uncommon strains highlights the changing molecular epidemiology of HAV infection in the United States.

Quantitative differences between intra-host HCV populations from persons with recently established and persistent infections.

Detection of incident hepatitis C virus (HCV) infections is crucial for identification of outbreaks and development of public health interventions. However, there is no single diagnostic assay for distinguishing recent and persistent HCV infections. HCV exists in each infected host as a heterogeneous population of genomic variants, whose evolutionary dynamics remain incompletely understood.

Convex hulls in hamming space enable efficient search for similarity and clustering of genomic sequences.

Background: In molecular epidemiology, comparison of intra-host viral variants among infected persons is frequently used for tracing transmissions in human population and detecting viral infection outbreaks. Application of Ultra-Deep Sequencing (UDS) immensely increases the sensitivity of transmission detection but brings considerable computational challenges when comparing all pairs of sequences. We developed a new population comparison method based on convex hulls in hamming space.

Accurate spatiotemporal mapping of drug overdose deaths by machine learning of drug-related web-searches.

Persons who inject drugs (PWID) are at increased risk for overdose death (ODD), infections with HIV, hepatitis B (HBV) and hepatitis C virus (HCV), and noninfectious health conditions. Spatiotemporal identification of PWID communities is essential for developing efficient and cost-effective public health interventions for reducing morbidity and mortality associated with injection-drug use (IDU). Reported ODDs are a strong indicator of the extent of IDU in different geographic regions.

Complex genetic encoding of the hepatitis B virus on-drug persistence.

Tenofovir disoproxil fumarate (TDF) is one of the nucleotide analogs capable of inhibiting the reverse transcriptase (RT) activity of HIV and hepatitis B virus (HBV). There is no known HBV resistance to TDF. However, detectable variation in duration of HBV persistence in patients on TDF therapy suggests the existence of genetic mechanisms of on-drug persistence that reduce TDF efficacy for some HBV strains without affording actual resistance.

Hepatitis B Virus Mutant Infections in Hemodialysis Patients: A Case Series.

Rationale & Objective: Hepatitis B virus (HBV) transmission in hemodialysis units has become a rare event since implementation of hemodialysis-specific infection control guidelines: performing hemodialysis for hepatitis B surface antigen (HBsAg)-positive patients in an HBV isolation room, vaccinating HBV-susceptible (HBV surface antibody and HBsAg negative) patients, and monthly HBsAg testing in HBV-susceptible patients. Mutations in HBsAg can result in false-negative HBsAg results, leading to failure to identify HBsAg seroconversion from negative to positive. We describe 4 unique cases of HBsAg seroconversion caused by mutant HBV infection or reactivation in hemodialysis patients.

A Phylogenetic Analysis of Hepatitis C Virus Transmission, Relapse, and Reinfection Among People Who Inject Drugs Receiving Opioid Agonist Therapy.

Background: Understanding hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is essential for HCV elimination. We aimed to differentiate reinfections from treatment failures and to identify transmission linkages and associated factors in a cohort of PWID receiving opioid agonist therapy (OAT).

Methods: We analyzed baseline and follow-up specimens from 150 PWID from 3 OAT clinics in the Bronx, New York.

Long-term virological and adherence outcomes to antiviral treatment in a 4-year cohort chronic HBV study.

Background: Chronic hepatitis B (CHB) treatment adherence has been poorly studied worldwide. We evaluated long-term virological and adherence outcomes to antiviral treatment in CHB patients.

Methods: A prospective 183 Brazilian CHB patient cohort treated with monotherapy or combination adefovir dipivoxil, entecavir, lamivudine and/or tenofovir disoproxil fumarate was studied in a reference tertiary centre.

Entropy of mitochondrial DNA circulating in blood is associated with hepatocellular carcinoma.

Background: Ultra-Deep Sequencing (UDS) enabled identification of specific changes in human genome occurring in malignant tumors, with current approaches calling for the detection of specific mutations associated with certain cancers. However, such associations are frequently idiosyncratic and cannot be generalized for diagnostics. Mitochondrial DNA (mtDNA) has been shown to be functionally associated with several cancer types.

HCV transmission in high-risk communities in Bulgaria.

Background: The rate of HIV infection in Bulgaria is low. However, the rate of HCV-HIV-coinfection and HCV infection is high, especially among high-risk communities. The molecular epidemiology of those infections has not been studied before.

A large HCV transmission network enabled a fast-growing HIV outbreak in rural Indiana, 2015.

Background: A high prevalence (92.3%) of hepatitis C virus (HCV) co-infection among HIV patients identified during a large HIV outbreak associated with injection of oxymorphone in Indiana prompted genetic analysis of HCV strains.

Methods: Molecular epidemiological analysis of HCV-positive samples included genotyping, sampling intra-host HVR1 variants by next-generation sequencing (NGS) and constructing transmission networks using Global Hepatitis Outbreak and Surveillance Technology (GHOST).

Automated quality control for a molecular surveillance system.

Background: Molecular surveillance and outbreak investigation are important for elimination of hepatitis C virus (HCV) infection in the United States. A web-based system, Global Hepatitis Outbreak and Surveillance Technology (GHOST), has been developed using Illumina MiSeq-based amplicon sequence data derived from the HCV E1/E2-junction genomic region to enable public health institutions to conduct cost-effective and accurate molecular surveillance, outbreak detection and strain characterization. However, as there are many factors that could impact input data quality to which the GHOST system is not completely immune, accuracy of epidemiological inferences generated by GHOST may be affected.

Fast estimation of genetic relatedness between members of heterogeneous populations of closely related genomic variants.

Background: Many biological analysis tasks require extraction of families of genetically similar sequences from large datasets produced by Next-generation Sequencing (NGS). Such tasks include detection of viral transmissions by analysis of all genetically close pairs of sequences from viral datasets sampled from infected individuals or studying of evolution of viruses or immune repertoires by analysis of network of intra-host viral variants or antibody clonotypes formed by genetically close sequences. The most obvious naïeve algorithms to extract such sequence families are impractical in light of the massive size of modern NGS datasets.

HCV adaptation to HIV coinfection.

Human immunodeficiency virus (HIV) infection is rising as a leading cause of morbidity and mortality among hepatitis C virus (HCV)-infected patients. Both viruses interact in co-infected hosts, which may affect their intra-host evolution, potentially leading to differing genetic composition of viral populations in co-infected (CIP) and mono-infected (MIP) patients. Here, we investigate genetic differences between intra-host variants of the HCV hypervariable region 1 (HVR1) sampled from CIP and MIP.

Intelligent Network DisRuption Analysis (INDRA): A targeted strategy for efficient interruption of hepatitis C transmissions.

Hepatitis C virus (HCV) infection is a global public health problem. The implementation of public health interventions (PHI) to control HCV infection could effectively interrupt HCV transmission. PHI targeting high-risk populations, e.

Reactivation of a Vaccine Escape Hepatitis B Virus Mutant in a Cambodian Patient During Anti-Hepatitis C Virus Therapy.

A 76-year-old Cambodian man co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) 6c-1 presented for care. HBV DNA was intermittently detectable despite anti-HBs levels being above the protective threshold. During treatment for HCV, HBV DNA levels increased.