Explore the vast range of titles available.

To facilitate HCV diagnosis, we developed an HCV-RNA testing service, which involved home-sampled dried blood spots (DBS). The main objective of this study was to evaluate the feasibility of self-sampling at home. Furthermore, to optimise the processing of DBS samples for RNA detection, we evaluated two elution buffers: phosphate-buffered saline (PBS) and L6-buffer. 27 HCV-RNA and 12 HIV-1 RNA positive patients were included. Laboratory spotted DBS (LabDBS) were made by a technician from blood samples drawn at inclusion. Patients received a DBS home-sampling kit and were requested to return their self-sampled DBS (ssDBS) by mail. We compared the RNA load of PBS and L6-eluted labDBS, and of L6-eluted ssDBS, L6-eluted labDBS and plasma. LabDBS load measurements were repeated after 7-13 and 14-21 days to evaluate RNA stability. All 39 plasma samples provided quantifiable RNA loads. In 1/39 labDBS sample, RNA could not be detected (plasma HCV load: 2.98 log10 IU/ml). L6-eluted samples gave a 0.7 log10 and 0.6 log10 higher viral load for HCV and HIV-1 respectively, compared to PBS-eluted samples. Strong correlations were found between labDBS and ssDBS HCV RNA (r = 0.833; mean difference 0.3 log10 IU/mL) and HIV-1 RNA results (r = 0.857; mean difference 0.1 log10 copies/mL). Correlations between labDBS and plasma values were high for HCV (r = 0.958) and HIV-1 (r = 0.844). RNA loads in DBS remained stable over 21 days. Our study demonstrates that self-sampling dried blood spots at home is a feasible strategy for the detection of HCV and HIV-1 RNA. This could facilitate one-step diagnostics and treatment monitoring in communities with high HCV prevalence.

miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1). We enrolled men and postmenopausal or hysterectomised women (aged 18–65 years) with chronic HCV genotype 1, 3, or 4 infection diagnosed at least 24 weeks before screening who were either treatment naive to or relapsed after interferon-α based therapy. Patients with co-infection (hepatitis B virus or HIV infection), evidence of decompensated liver disease, or a history of hepatocellular carcinoma were excluded. Randomisation was done by an independent, unblinded, statistician using the SAS procedure Proc Plan. The first cohort received one subcutaneous injection of 2 mg/kg RG-101 or placebo; the second cohort received one subcutaneous injection of 4 mg/kg or placebo. Patients were followed up for 8 weeks (all patients) and up to 76 weeks (patients with no viral rebound and excluding those who were randomised to the placebo group) after randomisation. The primary objective was safety and tolerability of RG-101. This trial was registered with EudraCT, number 2013-002978-49. Between June 4, 2014, and Oct 27, 2014, we enrolled 32 patients with chronic HCV genotype 1 (n=16), 3 (n=10), or 4 (n=6) infections. In the first cohort, 14 patients were randomly assigned to receive 2 mg/kg RG-101 and two patients were randomly assigned to receive placebo, and in the second cohort, 14 patients were randomly assigned to receive 4 mg/kg RG-101 and two patients were randomly assigned to receive placebo. Overall, 26 of the 28 patients dosed with RG-101 reported at least one treatment-related adverse event. At week 4, the median viral load reduction from baseline was 4·42 (IQR 3·23–5·00) and 5·07 (4·19–5·35) log10 IU/mL in patients dosed with 2 mg/kg RG-101 or 4 mg/kg RG-101. Three patients had undetectable HCV RNA levels 76 weeks after a single dose of RG-101. Viral rebound at or before week 12 was associated with the appearance of resistance associated substitutions in miR-122 binding regions in the 5′ UTR of the HCV genome. This study showed that one administration of 2 mg/kg or 4 mg/kg RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated anti-miR-122 oligonucleotide, was well tolerated and resulted in substantial viral load reduction in all treated patients within 4 weeks, and sustained virological response in three patients for 76 weeks. Regulus Therapeutics, Inc.

Introduction Hepatitis C virus (HCV) is a major public health threat. Although the recent availability of highly effective directly acting antivirals created optimism towards HCV elimination, there is ongoing transmission of HCV in men who have sex with men (MSM). We here report current epidemiological trends and synthesise evidence on behavioural, network, cellular and molecular host factors associated with sexual transmission of HCV, in particular the role of HIV‐1 co‐infection. We discuss prevention opportunities focusing on the potential of HCV treatment. Methods We searched MEDLINE, fact sheets from health professional bodies and conference s using appropriate keywords to identify and select relevant reports. Results and discussion Recent studies strongly suggest that HCV is transmitted via sexual contact in HIV‐positive MSM and more recently in HIV‐negative MSM eligible for or on pre‐exposure prophylaxis. The reinfection risk following clearance is about 10 times the risk of primary infection. International connectedness of MSM transmission networks might contribute to ongoing reinfection. Some of these networks might overlap with networks of people who inject drugs. Although, the precise mechanisms facilitating sexual transmission remain unclear, damage to the mucosal barrier in the rectum could increase susceptibility. Mucosal dendritic cell subsets could increase HCV susceptibility by retaining HCV and transmitting the virus to other cells, allowing egress into blood and liver. Early identification of new HCV infections is important to prevent onward transmission, but early diagnosis of acute HCV infection and prompt treatment is hampered by the slow rate of HCV antibody seroconversion, which in rare cases may take more than a year. Novel tests such as testing for HCV core antigen might facilitate early diagnosis. Conclusions High‐risk sexual behaviour, network characteristics, co‐infection with sexually transmitted infections like HIV‐1 and other concomitant bacterial and viral sexually transmitted infections are important factors that lead to HCV spread. Targeted and combined prevention efforts including effective behavioural interventions and scale‐up of HCV testing and treatment are required to halt HCV transmission in MSM.

Hepatitis C virus (HCV) infection affects approximately 58 million people and causes ~300,000 deaths yearly. The only target for HCV neutralizing antibodies is the highly sequence diverse E1E2 glycoprotein. Eliciting broadly neutralizing antibodies that recognize conserved cross-neutralizing epitopes is important for an effective HCV vaccine. However, most recombinant HCV glycoprotein vaccines, which usually include only E2, induce only weak neutralizing antibody responses. Here, we describe recombinant soluble E1E2 immunogens that were generated by permutation of the E1 and E2 subunits. We displayed the E2E1 immunogens on two-component nanoparticles and these nanoparticles induce significantly more potent neutralizing antibody responses than E2. Next, we generated mosaic nanoparticles co-displaying six different E2E1 immunogens. These mosaic E2E1 nanoparticles elicit significantly improved neutralization compared to monovalent E2E1 nanoparticles. These results provide a roadmap for the generation of an HCV vaccine that induces potent and broad neutralization. E1E2 spike on the hepatitis C virion is an important target for vaccine design. Here, the authors permute the subunits to generate E2E1 immunogens and show that mosaic nanoparticles displaying different E2E1 antigens elicit cross-neutralizing antibodies in rabbits.

Certain key populations have a high risk of hepatitis C virus (HCV) reinfection, which includes men who have sex with men (MSM) with HIV who continue to engage in behaviors associated with HCV acquisition following clearance. Among MSM with HIV, we aimed to identify longitudinal sexual behavior patterns and estimate reinfection risk within identified patterns. MSM with HIV from the longitudinal, prospective Dutch MOSAIC study (2009–2018) at risk for HCV reinfection were included. Follow-up started following HCV clearance. Risk behavior was assessed using the HCV-MOSAIC score (range = 0.0–7.0), where ≥2 indicates high risk of reinfection. Classes were inferred from the mean HCV-MOSAIC score over time using a latent process mixed-effects model with the covariates age, group sex and casual partnership. The association between classes and HCV reinfection risk was assessed using a joint survival model. In total, 123 MSM were included with a median follow-up of 2.7 years [interquartile range (IQR) = 1.2–4.7]. Two classes were identified: one with mostly lower (C1, n = 67) and one with mostly higher risk behavior (C2, n = 56). During follow-up, both classes had considerable variation in HCV-MOSAIC scores (C1, median = 1.1, IQR = 0.0–2.1 and C2, median = 3.0, IQR = 2.0–3.5). HCV reinfection probability was similar between both classes at year 3 of follow-up [C1, 17%, 95% confidence interval (CI) = 11%−35% and C2, 18%, 95%CI = 15%−47%], but became higher in C2 than C1 at year 5 (C1, 22%, 95%CI = 13%−39% and C2, 37%, 95%CI = 28%−69%). The variation in risk over time suggests that behavioral assessment is continually needed for early testing, treatment and offering behavioral inventions.

We studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination status among six ethnic groups in Amsterdam, the Netherlands. We analysed participants of the Healthy Life in an Urban Setting cohort who were tested for SARS-CoV-2 spike protein antibodies between 17 May and 21 November 2022. We categorized participants with antibodies as only infected, only vaccinated (≥1 dose), or both infected and vaccinated, based on self-reported prior infection and vaccination status and previous seroprevalence data. We compared infection and vaccination status between ethnic groups using multivariable, multinomial logistic regression. Of the 1,482 included participants, 98.5% had SARS-CoV-2 antibodies (P between ethnic groups = 0.899). Being previously infected and vaccinated ranged from 36.2% (95% confidence interval (CI) = 28.3–44.1%) in the African Surinamese to 64.5% (95% CI = 52.9–76.1%) in the Ghanaian group. Compared to participants of Dutch origin, participants of South-Asian Surinamese (adjusted odds ratio (aOR) = 6.74, 95% CI = 2.61–17.45)), African Surinamese (aOR = 23.32, 95% CI = 10.55–51.54), Turkish (aOR = 8.50, 95% CI = 3.05–23.68), or Moroccan (aOR = 22.33, 95% CI = 9.48–52.60) origin were more likely to be only infected than infected and vaccinated, after adjusting for age, sex, household size, trust in the government’s response to the pandemic, and month of study visit. SARS-CoV-2 infection and vaccination status varied across ethnic groups, particularly regarding non-vaccination. As hybrid immunity is most protective against coronavirus disease 2019, future vaccination campaigns should encourage vaccination uptake in specific demographic groups with only infection.

Abstract Background Despite recent breakthroughs in treatment of hepatitis C virus (HCV) infection, we have limited understanding of how virus diversity generated within individuals impacts the evolution and spread of HCV variants at the population scale. Addressing this gap is important for identifying the main sources of disease transmission and evaluating the risk of drug-resistance mutations emerging and disseminating in a population. Methods We have undertaken a high-resolution analysis of HCV within-host evolution from 4 individuals coinfected with human immunodeficiency virus 1 (HIV-1). We used long-read, deep-sequenced data of full-length HCV envelope glycoprotein, longitudinally sampled from acute to chronic HCV infection to investigate the underlying viral population and evolutionary dynamics. Results We found statistical support for population structure maintaining the within-host HCV genetic diversity in 3 out of 4 individuals. We also report the first population genetic estimate of the within-host recombination rate for HCV (0.28 × 10−7 recombination/site/year), which is considerably lower than that estimated for HIV-1 and the overall nucleotide substitution rate estimated during HCV infection. Conclusions Our findings indicate that population structure and strong genetic linkage shapes within-host HCV evolutionary dynamics. These results will guide the future investigation of potential HCV drug resistance adaptation during infection, and at the population scale. Using long-read serially sampled deep-sequenced data, we undertook a robust evolutionary analysis to formally evaluate, for the first time, whether or not HCV infection exhibits a structured viral population and the within-host HCV recombination rate.

Background Malaria and viral haemorrhagic fever (VHF) have overlapping symptomatology, creating clinical and diagnostic challenges within, and in travellers returning from, co-endemic areas. Rapid and accurate malaria diagnosis is critical, yet complicated by safety measures required for VHF. Methods Diagnostic accuracies of the rapid Alethia Malaria loop-mediated isothermal amplification (LAMP) assay and EasyNAT Malaria cross-primer assay (CPA) were assessed for the detection of malaria in whole blood mixed with guanidine isothiocyanate (GITC)-based virucidal DNA/RNA Shield buffer. Results Both the LAMP assay and the CPA performed excellent and detected DNA of Plasmodium spp. in all 47 mixtures. All mixtures without Plasmodium spp. DNA (n = 5) tested negative in both assays. Technical detection limit of both assays for P. falciparum was between 0.005 and 0.0005 parasites per microlitre of mixture. Conclusions Rapid and accurate malaria diagnosis remains possible on whole blood mixed with this virucidal buffer. The buffer is available in blood collection tubes, which allows for enhanced safety of sample handling from bedside to bench. These tubes can be used in patients with high suspicion of malaria, but in whom VHF cannot be completely excluded.