Colonial History and Contemporary Transmission Shape the Genetic Diversity of Hepatitis C Virus Genotype 2 in Amsterdam

Evolutionary analysis of hepatitis C virus (HCV) genome sequences has provided insights into the epidemic history and transmission of this widespread human pathogen. Here we report an exceptionally diverse set of 178 HCV genotype 2 (HCV-2) isolates from 189 patients in Amsterdam, comprising 8 distinct HCV subtypes and 10 previously not recognized, unclassified lineages. By combining study subjects' demographic information with phylogeographic and molecular clock analyses, we demonstrate for the first time that the trans-Atlantic slave trade and colonial history were the driving forces behind the global dissemination of HCV-2. We detect multiple HCV-2 movements from present-day Ghana/Benin to the Caribbean during the peak years of the slave trade (1700 to 1850) and extensive transfer of HCV-2 among the Netherlands and its former colonies Indonesia and Surinam over the last 150 years. The latter coincides with the bidirectional migration of Javanese workers between Indonesia and Surinam and subsequent immigration to the Netherlands. In addition, our study sheds light on contemporary trends in HCV transmission within the Netherlands. We observe multiple lineages of the epidemic subtypes 2a, 2b, and 2c (together 67% of HCV-2 infections in Amsterdam), which cluster according to their suspected routes of transmission, specifically, injecting drug use (IDU) and contaminated blood/blood products. Understanding the epidemiological processes that generated the global pattern of HCV diversity seen today is critical for exposing associations between populations, risk factors, and specific HCV subtypes and might help HCV screening and prevention campaigns to minimize the future burden of HCV-related liver disease

Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries: A Dutch Nationwide Cohort Study (vol 8, ofab006, 2021)

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Bryde's whale (Balaenoptera edeni) in the southwestern Gulf of California: Relationship with ENSO variability and prey availability

Interannual changes in the occurrence of Bryde’s whale (Balaenoptera edeni) have been observed in La Paz Bay (southwestern Gulf of California, Mexico) over the last 20 years. We suggest that these changes could be driven by natural fluctuations in food resources that are related to climate variability. We compared monthly Bryde’s whale occurrence in La Paz Bay from 1988 to 2006 to climate variability at seasonal and interannual time scales and its effect on prey availability. The results showed that Bryde’s whales do not have a well-defined pattern of seasonal occurrence; however, large numbers of whales were consistently recorded during La Niña conditions when the Gulf of California sardine population is distributed further south within the gulf. In contrast, fewer whales were recorded during El Niño and neutral conditions. This indicates that changes in the occurrence of Bryde’s whales at La Paz Bay are driven by the El Niño-Southern Oscillation interannual variability and are probably mediated by their prey availability

Pharmacokinetics and antiviral activity of PHX1766, a novel HCV protease inhibitor, using an accelerated Phase I study design

Background: PHX1766 is a novel HCV NS3/4 protease inhibitor with robust potency and high selectivity in replicon studies (50% maximal effective concentration 8 nM). Two clinical trials investigated the safety, tolerability, pharmacokinetics and antiviral activity of PHX1766 in healthy volunteers (HV) and chronic hepatitis C patients, by use of a dose-adaptive overlapping clinical trial design. Methods: Two randomized, double-blind, placebo-controlled clinical trials were conducted. Single doses of PHX1766 or placebo were administered to 25 HV and six HCV genotype 1-infected patients (50 mg once daily -1,000 mg once daily, 250 mg twice daily and 100 mg of a new formulation of PHX1766 once daily). Multiple doses of PHX1766 or placebo were administered to 32 HV and seven HCV genotype 1-infected patients (50 mg once daily -800 mg twice daily). Results: Oral administration of PHX1766 was safe and well tolerated at all dose levels wit