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- Lindh, Magnus, 1960, et al.
(författare)
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Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin
- 2013
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 20:4
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Tidskriftsartikel (refereegranskat)abstract
- The treatment durations for hepatitis C are guided by the analysis of hepatitis C virus (HCV) RNA in blood at certain time points. This multicentre, randomized open label trial evaluated the utility and performance of individualized treatment durations guided by viral decline rates in 103 patients with HCV genotype 1 infection. Pegylated interferon 2a and ribavirin were given as standard of care (SOC) for 24, 48 or 72 weeks or as dynamic treatment (DT) for 24–72 weeks. The DT duration was based on the time point when log HCV RNA would reach 0 log copies/mL, as estimated by the second-phase decline. The rate of sustained virologic response was 63% for SOC and 54% for DT, but this difference was not significant in multiple regression analysis taking predictive factors such as interleukin-28B genotypes, age and baseline viremia into account (P = 0.45). The mean required treatment time per cured patient was 51 weeks for DT as compared with 58 weeks for SOC (P = 0.22) when given per protocol (n = 95) and was significantly shorter (42 vs 51 weeks) among patients who achieved undetectable HCV RNA (P = 0.01). We conclude that DT was feasible and increased efficiency. The estimated time point for 0 log viral copies/mL is a new and quantitative response variable, which may be used as a complement to the qualitative variable rapid virologic response. The outcome parameter treatment weeks per cured patient could become a useful tool for comparing treatment efficiency also in the era of directly acting antivirals.
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| 2. |
- Waldenström, Jesper, 1985, et al.
(författare)
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Absence of interferon-lambda 4 enhances spontaneous clearance of acute hepatitis C virus genotypes 1-3 infection
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Absence of a functional interferon-lambda 4 (IFN-lambda 4) gene (IFNL4) predicts spontaneous resolution of acute hepatitis C virus (HCV) infections in regions with a predominance of genotype 1, whereas variants of the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) entailing reduced activity associate with increased sustained virologic response rates following some therapeutic regimens. This study aimed at investigating the impact of IFNL4 on acute HCV genotype 2 or 3 infections, and whether ITPase activity influenced outcome. Materials and Methods Two hundred and seven people who injected drugs (PWID) with documented anti-HCV seroconversion, and 57 PWID with reinfection with HCV were analyzed regarding IFNL4 (rs368234815 and rs12979860) and ITPA (rs1127354 and rs7270101), and longitudinally followed regarding HCV RNA. Results The spontaneous clearance of HCV infection in anti-HCV seronegative PWID was enhanced when IFN-lambda 4 was absent (44% vs. 20% for IFNL4 TT/TTrs1368234815 and Delta G(rs1368234815) respectively, p < .001; OR 3.2) across genotypes 1-3. The proportion lacking IFN-lambda 4 was further increased following resolution of repeated re-exposure to HCV (74% among re-infected participants who had cleared at least two documented HCV infections). ITPA genetic variants did not independently impact on the outcome, but among males lacking IFN-lambda 4, reduced ITPase activity markedly augmented the likelihood of resolution (65% vs. 29% for <100% and 100% ITPase activity, p = .006). Conclusions Absence of IFN-lambda 4 entails an enhanced likelihood of spontaneous resolution both following primary acute infection and repeated re-exposure to HCV across genotypes 1-3. Among men lacking IFN-lambda 4, reduced ITPase activity improved outcome.
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| 3. |
- Widell, Anders, et al.
(författare)
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Epidemiologic and molecular investigation of outbreaks of hepatitis C virus infection on a pediatric oncology service
- 1999
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819. ; 130:2, s. 130-134
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite screening of blood donors, hepatitis C virus (HCV) infection can occur in patients who receive multiple transfusions. OBJECTIVE: To clarify mechanisms of nosocomial transmission of HCV. DESIGN: Epidemiologic and molecular analyses of hepatitis C outbreaks. SETTING: Pediatric oncology ward. PATIENTS: Children with cancer. MEASUREMENTS: Epidemiologic analysis, HCV RNA detection, genotyping, and hypervariable region 1 (HVR1) sequencing. RESULTS: Ten cases of infection with acute HCV genotype 3a occurred between 1990 and 1993. Sequencing of HVR1 revealed three related strains. Despite an overhaul of hygiene procedures, a patient infected with genotype 1b generated nine subsequent infected patients in 1994. Several patients had high virus titers and strongly delayed anti-HCV antibody responses. All had permanent intravenous catheters. Multidose vials used for flushing or treatment had probably been contaminated during periods of overlapping treatment. CONCLUSIONS: Contamination of multidose vials was the most likely mode of HCV transmission; therefore, use of such vials should be restricted. Rigorous adherence to hygiene routines remains essential to preventing transmission of bloodborne infections.
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| 5. |
- Alsved, Malin, et al.
(författare)
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Aerosolization and recovery of viable murine norovirus in an experimental setup
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Noroviruses are the major cause for viral acute gastroenteritis in the world. Despite the existing infection prevention strategies in hospitals, the disease continues to spread and causes extensive and numerous outbreaks. Hence, there is a need to investigate the possibility of airborne transmission of norovirus. In this study, we developed an experimental setup for studies on the infectivity of aerosolized murine norovirus (MNV), a model for the human norovirus. Two aerosol generation principles were evaluated: bubble bursting, a common natural aerosolization mechanism, and nebulization, a common aerosolization technique in laboratory studies. The aerosolization setup was characterized by physical and viral dilution factors, generated aerosol particle size distributions, and the viral infectivity after aerosolization. We found a lower physical dilution factor when using the nebulization generator than with the bubble bursting generator. The viral dilution factor of the system was higher than the physical dilution; however, when comparing the physical and viral dilution factors, bubble bursting generation was more efficient. The infectivity per virus was similar using either generation principle, suggesting that the generation itself had a minor impact on MNV infectivity and that instead, the effect of drying in air could be a major reason for infectivity losses.
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| 9. |
- Alsved, Malin, et al.
(författare)
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Droplet, aerosol and SARS-CoV-2 emissions during singing and talking
- 2021
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Konferensbidrag (refereegranskat)abstract
- IntroductionAs the pandemic continues to spread, more knowledge is needed about the viral transmission routes. Several super spreading events during the Covid-19 pandemic have been linked to singing in choirs and talking loud. However, in the beginning of the pandemic there was only one study about emitted aerosols and droplets from singing, published in 1968, and only a handful on emissions from talking. Therefore, we conducted a study to measure the aerosol and droplet emissions from talking and singing. We also evaluated the emissions from singing when wearing a face mask.We have further developed our setup so that we collect the aerosol particles from Covid-19 infected patients that are talking and singing, and analyze our samples for SARS-CoV-2, the virus causing Covid-19.MethodTwelve healthy singers (7 professionals, 5 amateurs) were included in the first study part on quantifying the amount of emitted aerosols and droplets. The singers were singing or talking a short consonant rich text repeatedly at a constant pitch with their face in the opening of a funnel. The aerosol particle size and concentration was measured from the other end of the funnel using an aerodynamic particle sizer (APS, 3321, TSI Inc). In addition, the amount of un-evaporated droplets were captured with a high-speed camera and quantified using image analysis.During February and March 2021 we will collect aerosol particles from patients with confirmed Covid-19 that are singing and talking into a funnel. We will use a growth tube condensation collector, a BioSpot (Aerosol Devices), operating at 8 L min-1, and a NIOSH BC-251 cyclone sampler operating at 3.5 L min-1 (TISCH Environmental). The BioSpot collects the whole range of exhaled aerosol particles with high (95%) efficiency into liquid, and the NIOSH cyclone sampler collects particles into three size fractions: <1 µm (filter), 1-4 µm (liquid), >4 µm (liquid). The APS is again used to measure size and concentration of the emitted aerosol particles, so that emissions from infected test subjects can be compared with those of the healthy test subjects. Air samples will be analyzed for detection of SARS-CoV-2 genes, and if possible, SARS-CoV-2 infectivity in cell cultures.ResultsAerosol particle emissions from healthy test subjects were significantly higher during normal singing (median 690, range [320–2870] particles/s) than during normal talking (270 [120–1380] particles/s) (Wilcoxon’s signed rank test, p=0.002). Loud singing produced even more aerosol particles (980 [390–2870] particles/s) than normal singing (p=0.002). The amount of non-evaporated droplets detected by the high-speed camera setup showed similar results: more droplets during loud singing or talking. For both aerosol particle concentrations and droplet numbers, the levels were reduced by on average 70-80% when wearing a surgical face mask.ConclusionsSinging and talking give rise to high aerosol and droplet emissions from the respiratory tract. This is likely an important transmission route for Covid-19. In our upcoming part of the study we hope to determine how much SARS-CoV-2 that is emitted during these social activities.
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