| 1. |
- Alsiö, Åsa, 1965, et al.
(author)
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Early quantification of HCV core antigen may help to determine the duration of therapy for chronic genotype 2 or 3 HCV infection
- 2012
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In: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 31:7, s. 1631-1635
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Journal article (peer-reviewed)abstract
- The aim of the present study was to evaluate the utility of hepatitis C virus (HCV) core antigen (coreAg) assessment for the identification of candidates for short-term therapy. Plasma samples from HCV genotype 2 or 3-infected patients participating in the NORDynamIC trial (n = 382) comparing 12 and 24 weeks of combination treatment with pegylated interferon-alpha 2a and a fixed dose of 800 mg ribavirin daily were analyzed for coreAg. Among the 126 patients (33% of the intention-to-treat population) achieving HCV coreAg levels in plasma below 0.2 pg/mL when assayed on treatment day 3, sustained viral response (SVR) rates of 86% and 84% were achieved in the 12- and 24-week arms, respectively. Similarly, among patients having received at least 80% of the target dose of both pegylated interferon alpha-2a and of ribavirin for at least 80% of the target treatment duration (per-protocol analysis), the SVR rates were 89% and 95%, respectively. Twelve weeks of combination treatment may be sufficient for genotype 2 or 3-infected patients achieving HCV coreAg levels below 0.2 pg/mL by day 3, signaling a rapid clearance of HCV viremia.
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| 2. |
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| 3. |
- Alsiö, Åsa, 1965, et al.
(author)
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Nonresponder patients with hepatitis C virus genotype 2/3 infection: a question of low systemic interferon concentrations?
- 2010
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In: Clinical infectious diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 50:4
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Journal article (peer-reviewed)abstract
- Twelve of 303 per-protocol patients were nonresponders in a 12-week versus 24-week treatment study of hepatitis C virus (HCV) genotype 2/3 infection. The nonresponders had significantly lower interferon concentrations, as well as significantly greater mean age, body mass index, and viral load. Suboptimal drug concentrations may thus contribute to lack of response to therapy in patients with infection due to HCV genotype 2/3.
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| 4. |
- Askarieh, Galia, 1983, et al.
(author)
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Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C.
- 2010
-
In: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 51:5, s. 1523-1530
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Journal article (peer-reviewed)abstract
- High systemic levels of interferon-gamma-inducible protein 10 kDa (IP-10) at onset of combination therapy for chronic hepatitis C virus (HCV) infection predict poor outcome, but details regarding the impact of IP-10 on the reduction of HCV RNA during therapy remain unclear. In the present study, we correlated pretreatment levels of IP-10 in liver biopsies (n = 73) and plasma (n = 265) with HCV RNA throughout therapy within a phase III treatment trial (DITTO-HCV). Low levels of plasma or intrahepatic IP-10 were strongly associated with a pronounced reduction of HCV RNA during the first 24 hours of treatment in all patients (P < 0.0001 and P = 0.002, respectively) as well as when patients were grouped as genotype 1 or 4 (P = 0.0008 and P = 0.01) and 2 or 3 (P = 0.002, and P = 0.02). Low plasma levels of IP-10 also were predictive of the absolute reduction of HCV RNA (P < 0.0001) and the maximum reduction of HCV RNA in the first 4 days of treatment (P < 0.0001) as well as sustained virological response (genotype 1/4; P < 0.0001). To corroborate the relationship between early viral decline and IP-10, pretreatment plasma samples from an independent phase IV trial for HCV genotypes 2/3 (NORDynamIC trial; n = 382) were analyzed. The results confirmed an association between IP-10 and the immediate reduction of HCV RNA in response to therapy (P = 0.006). In contrast, pretreatment levels of IP-10 in liver or in plasma did not affect the decline of HCV RNA between days 8 and 29, i.e., the second-phase decline, or later time points in any of these cohorts. CONCLUSION: In patients with chronic hepatitis C, low levels of intrahepatic and systemic IP-10 predict a favorable first-phase decline of HCV RNA during therapy with pegylated interferon and ribavirin for genotypes of HCV.
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| 5. |
- Pedersen, C., et al.
(author)
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Ribavirin plasma concentration is a predictor of sustained virological response in patients treated for chronic hepatitis C virus genotype 2/3 infection
- 2011
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In: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 18:4, s. 245-51
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Journal article (peer-reviewed)abstract
- In hepatitis C virus (HCV) genotype 1 infection, the likelihood of obtaining sustained virological response (SVR) is associated with higher ribavirin exposure. Such an association has not been demonstrated for HCV genotype 2/3 infection, where a fixed 800 mg daily dosing of ribavirin is generally recommended. The primary aim of this study was to investigate the correlation between ribavirin concentration at day 29 and therapeutic response in patients with HCV genotype 2/3 infection. A total of 382 patients were randomized to 12 or 24 weeks of treatment with pegylated interferon-alfa 2a 180 μg weekly and 800 mg ribavirin daily. Trough plasma concentration of ribavirin was measured at day 29 and week 12 and the primary outcome was SVR (HCV-RNA undetectable 24 weeks after treatment). Of the 382 patients, 355 had a ribavirin concentration available at day 29. SVR was 84% among patients with a ribavirin concentration ≥2 mg/L at day 29 compared to 66% in those with concentrations <2 mg/L (P = 0.002). The corresponding figures in the 12-week treatment group were 74% and 57% (P = 0.12), and in the 24-week treatment group 91% and 75% (P = 0.02), respectively. In a multivariate analysis, ribavirin concentration at day 29 was an independent predictor of SVR (P = 0.002). In conclusion, a higher plasma ribavirin concentration is associated with an increased likelihood of achieving SVR in HCV genotype 2/3 infection. Individualization of ribavirin dosing may be helpful in improving outcome, especially in the presence of unfavourable baseline characteristics. This, however, requires evaluation in a prospective trial.
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| 6. |
- Rembeck, Karolina, et al.
(author)
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Impact of IL28B-related single nucleotide polymorphisms on liver histopathology in chronic hepatitis C genotype 2 and 3.
- 2012
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:1
-
Journal article (peer-reviewed)abstract
- Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of HCV infection as well as outcome following peginterferon and ribavirin therapy among HCV genotype 1 infected patients. The present study aimed to evaluate the impact of IL28B SNP variability on liver histology in the context of a phase III treatment trial (NORDynamIC) for treatment-naïve patients with chronic HCV genotype 2 or 3 infection, where pretreatment liver biopsies were mandatory.
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| 7. |
- Ydreborg, Magdalena, 1974, et al.
(author)
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Look-back screening for the identification of transfusion-induced hepatitis C virus infection in Sweden
- 2011
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In: Scandinavian Journal of Infectious Diseases. - 0036-5548. ; 43:6-7, s. 522-527
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Journal article (peer-reviewed)abstract
- Background: Following the discovery of the hepatitis C virus (HCV) in 1989, screening of all blood donors for antibodies became mandatory in Sweden as of 1 January 1992. Methods: Serum samples were collected from patients who had received a blood transfusion in the period prior to 1992 in western Sweden. The prevalence of HCV infection was assessed by antibody screening. Results: Of 13,573 screening serologies, 124 patients (0.9%) had antibodies against HCV; 113 (0.8%) had detectable HCV RNA indicating an ongoing infection. Ninety-one (73%) were female, of whom 32 had been transfused in conjunction with childbirth. A review of the 32 liver biopsy reports available showed that 2 patients had cirrhosis and an additional 9 patients had periportal or septal fibrosis. Conclusion: A considerable portion of screened patients had an ongoing HCV infection and were eligible for antiviral treatment. Look-back screening for HCV among recipients of blood transfusions prior to 1992 is meaningful and should include women transfused in childbirth.
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| 8. |
- Alestig, Erik, 1973, et al.
(author)
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Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection
- 2011
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In: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 11
-
Journal article (peer-reviewed)abstract
- Background: Patients infected with hepatitis C virus (HCV) genotype 1 respond poorly to standard treatment with 50% or less achieving sustained virologic response. Predicting outcome is essential and could help avoid unnecessary treatment and reduce health cost. Recently, an association of amino acid substitutions in the core region and treatment outcome was observed in Japanese patients. In the present study, the impact of these mutations on response kinetics and treatment outcome was explored in Caucasian patients. Methods: The core region of HCV pre-treatment samples obtained from 50 patients treated with peginterferon/ribavirin in a previous Swedish clinical trial with genotype 1 infection were sequenced. The alleles at rs12979860, a single nucleotide polymorphism (SNP), were assessed in order to identify any co-association with this strong response predictor. Results: No association between treatment response and substitutions of core residue 91 was found. In contrast, substitutions of core residue 70 were observed in 6/21 (29%) non-responders, but only in one of 29 responders (p = 0.03), and were more common in subgenotype 1b (R70Q in 6 of 13 strains) than in 1a (R70P in 1 of 37 strains, p = 0.004). The rs12979860 SNP upstream of the IL28B gene was overall the strongest response predictor (p = 0.0001). Core 70 substitutions were associated with poorer response kinetics in patients carrying the CT genotype at rs12979860. Conclusions: The results indicate that substitutions of core residue 70 are related to treatment response in Caucasian patients with HCV-1b infection, but are of less importance than IL28B polymorphism.
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| 9. |
- Guedj, H., et al.
(author)
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The impact of fibrosis and steatosis on early viral kinetics in HCV genotype 1-infected patients treated with Peg-IFN-alfa-2a and ribavirin
- 2012
-
In: Journal of Viral Hepatitis. - : Wiley. - 1352-0504. ; 19:7, s. 488-496
-
Journal article (peer-reviewed)abstract
- . Hepatitis C viral (HCV) kinetics after initiation of interferon-based therapy provide valuable insights for understanding virus pathogenesis, evaluating treatment antiviral effectiveness and predicting treatment outcome. Adverse effects of liver fibrosis and steatosis on sustained virological response have been frequently reported, yet their impacts on the early viral kinetics remain unclear. In this study, associations between histology status and early viral kinetics were assessed in 149 HCV genotype 1infected patients treated with pegylated interferon alfa-2a and ribavirin (DITTO trial). In multivariate analyses adjusted for critical factors such as IL28B genotype and baseline viral load, presence of significant fibrosis (Ishak stage > 2) was found to independently reduce the odds of achieving an initial reduction (calculated from day 0 to day 4) in HCV RNA of =2 logIU/mL (adjusted OR 0.03, P = 0.004) but was not associated with the second-phase slope of viral decline (calculated from day 8 to day 29). On the contrary, presence of liver steatosis was an independent risk factor for not having a rapid second-phase slope, that is, =0.3 logIU/mL/week (adjusted OR 0.22, P = 0.012) but was not associated with the first-phase decline. Viral kinetic modelling theory suggests that significant fibrosis primarily impairs the treatment antiviral effectiveness in blocking viral production by infected cells, whereas the presence of steatosis is associated with a lower net loss of infected cells. Further studies will be necessary to identify the biological mechanisms underlain by these findings.
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| 10. |
- Jerkeman, Anna, et al.
(author)
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Chronic hepatitis C in Swedish subjects receiving opiate substitution therapy-Factors associated with advanced fibrosis
- 2014
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In: Scandinavian Journal of Infectious Diseases. - : Informa Healthcare. - 0036-5548 .- 1651-1980. ; 46, s. 340-347
-
Journal article (peer-reviewed)abstract
- Background: Opiate substitution therapy (OST) reduces the risk of death from directly drug-related causes in heroin users, allowing other chronic health problems to emerge. People who inject drugs (PWID) are exposed to hepatitis C virus (HCV), with an associated risk of chronic liver disease. We investigated HCV prevalence and liver-related morbidity in a cohort of OST recipients, and analyzed factors associated with significant hepatic fibrosis. Methods: All patients registered on 1 April 2008 in 4 clinics providing OST in the 3 largest cities in Sweden were eligible for inclusion. HCV viremic subjects were evaluated for fibrosis stage by liver biopsy, transient elastometry (TE), and/or a biochemical fibrosis index (Göteborg University Cirrhosis Index; GUCI). Factors associated with severity of fibrosis were determined by logistic regression analysis. Results: Out of 524 eligible patients, 277 consented to enrolment. Two hundred and thirty-six subjects (88%) were anti-HCV-positive, and 162 of these were viremic (69%). Significant liver fibrosis (defined as Ishak stages F3-F6, TE value ≥ 8.85 kPa, or GUCI > 0.33) was found in 69 out of 103 (67%) tested viremic patients, and was associated with alcohol intake (p = 0.03), higher body mass index (BMI; p = 0.04), and the presence of anti-HBc antibodies (indicating exposure to hepatitis B virus (HBV); p = 0.02). Conclusions: Significant liver fibrosis was detected in two-thirds of HCV viremic OST recipients in this cohort, and was associated with alcohol use, high BMI, and exposure to HBV. These findings indicate that the management of HCV and associated risk factors should be emphasized in Swedish OST programs. © 2014 Informa Healthcare.
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| 11. |
- Jerkeman, A., et al.
(author)
-
Treatment for chronic hepatitis C in a cohort of opiate substitution therapy recipients in three Swedish cities - completion rates and efficacy
- 2014
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In: European Journal of Gastroenterology & Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0954-691X. ; 26:5, s. 523-531
-
Journal article (peer-reviewed)abstract
- Objectives Opiate substitution treatment (OST) programs could provide opportunities for management of comorbidities, such as hepatitis C virus (HCV) infection, in people who inject drugs. We aimed to prospectively evaluate the real-life feasibility of interferon/ribavirin-based HCV treatment in OST recipients, with a special focus on psychiatric status and health-related quality of life. Patients from a cohort of OST recipients from three cities in Sweden were selected for HCV treatment on the basis of structured investigation for HCV-related liver disease. Therapy was delivered in collaboration between infectious disease and OST clinics, with monitoring for completion and adherence, treatment response, adverse events, health-related quality of life (HRQoL) (SF-36) and signs of depression (MADRS-S), or relapse into drug abuse. The primary endpoint was completion of prescribed treatment; the secondary endpoints were sustained virological response (SVR), adherence, and incidence of depression. Among 69 patients with an indication for antiviral therapy, 41 initiated treatment; 34/41 (83%) completed treatment and 19/41 (46%) achieved SVR. Adequate adherence was observed in 29/41 patients (71%). Two serious adverse events occurred, including one death because of liver failure. Baseline scores for self-assessed health were low, with a significant reduction during treatment. Seventy-one percent of patients (29/41) fulfilled the criteria for clinically significant depression at some time point during treatment. Baseline scores for HRQoL/MADRS-S were associated with treatment completion, SVR, and depression during treatment. Despite the low HRQoL and the high occurrence of depression, HCV treatment was feasible and showed satisfactory rates of completion in this cohort of unselected OST recipients.
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| 12. |
- Lagging, Martin, 1965, et al.
(author)
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Reply.
- 2014
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In: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 60:6, s. 2130-1
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Journal article (other academic/artistic)
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| 13. |
- Lagging, Martin, 1965, et al.
(author)
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Response prediction in chronic hepatitis C by assessment of IP-10 and IL28B-related single nucleotide polymorphisms.
- 2011
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:2
-
Journal article (peer-reviewed)abstract
- High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients.
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| 14. |
- Lagging, Martin, 1965, et al.
(author)
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Retreatment with peg-interferon and ribavirin in patients with chronic hepatitis C virus genotype 2 or 3 infection with prior relapse
- 2013
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 48:7, s. 839-847
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Journal article (peer-reviewed)abstract
- Objectives. Uncertainty remains regarding the efficacy of retreatment with current standard-of-care peg-interferon (peg-IFN) and ribavirin among patients infected with hepatitis C virus (HCV) genotypes 2 or 3 with relapse after prior therapy. Materials and methods. Seventy-one patients with chronic HCV genotype 2/3 with prior relapse were enrolled in a phase III multicenter study. Patients were retreated with peg-IFN alpha-2a 180 mu g per week and ribavirin 1000/1200 mg daily. Patients having received previous therapy for 24 weeks were retreated for 48 weeks (Group A), whereas patients having received at least 12 weeks but less than 24 weeks of treatment were allocated to either 48 (Group B) or 24 weeks (Group C) on the basis of whether they had achieved rapid virological response (RVR). Results. Sustained virological response (SVR) rates of 53%, 81% and 75% were achieved in groups A, B and C, respectively. Patients with favorable baseline characteristics, e. g., less advanced liver fibrosis, age < 40 years, duration of infection < 20 years, or BMI < 25 kg/m(2), tended to have more favorable outcomes. All patients achieving HCV RNA below 1000 IU/mL day 6 achieved SVR in contrast to none of the patients with detectable HCV RNA at week 12. Conclusions. Retreatment with peg-IFN and ribavirin for 24-48 weeks entails SVR among the majority of HCV genotype 2/3 infected patients with prior relapse. However, in light of the prolonged treatment duration, moderate effect and considerable side effects, deterring therapy until new options are available may be preferential, particularly in patients previously treated for 24 weeks.
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| 15. |
- Lindh, Magnus, 1960, et al.
(author)
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Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin
- 2013
-
In: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 20:4
-
Journal article (peer-reviewed)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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| 16. |
- Lindh, Magnus, 1960, et al.
(author)
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Hepatitis C treatment response kinetics and impact of baseline predictors.
- 2011
-
In: Journal of Viral Hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 18:6, s. 400-407
-
Journal article (peer-reviewed)abstract
- Summary. The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics and treatment outcome. Patients treated with peginterferon alfa-2a and ribavirin in standard dosing were included: 49 with genotype 1 treated for 48 weeks and 139 with genotype 2 or 3 treated for 24 weeks. The reduced SVR rates in patients older than 45 years, with severe liver fibrosis or pretreatment viraemia above 400 000 IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24 weeks.
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| 17. |
- Lindh, Magnus, 1960, et al.
(author)
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IL28B polymorphisms determine early viral kinetics and treatment outcome in patients receiving peginterferon/ribavirin for chronic hepatitis C genotype 1
- 2011
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In: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 18:7
-
Journal article (peer-reviewed)abstract
- Single nucleotide polymorphisms (SNPs) upstream of IL28B predict the outcome of treatment in chronic hepatitis C virus (HCV) infection, but their impact on viral kinetics and relation to other predictors are not well known. Here, two SNPs, rs12979860 and rs8099917, were analysed and related to early viral kinetics during treatment in 110 patients with HCV genotype 1 infection. The reduction of HCV RNA after 7days of therapy was more pronounced (P<0.0001) in patients with CC(rs12979860) or TT(rs8099917) than in patients carrying TT(rs12979860) or GG(rs8099917), respectively. The two SNPs were in linkage disequilibrium (d' =1, r2 = 0.44), but CC(rs12979860) was less common (43% vs. 71%) than TT(rs8099917). Patients carrying both CC(rs12979860) and TT(rs8099917) genotypes achieved lower levels of HCV RNA at week 4 than those with CT or TT at rs12979860 and TT(rs8099917) (P=0.0004). The viral elimination was significantly influenced by rs12979860 independently of baseline viral load, age or fibrosis. This translated into high rates of sustained viral response (SVR) among patients carrying CC(rs12979860) despite the presence of high viral load at baseline (SVR 74%), high age (SVR 79%) or severe liver fibrosis (SVR 83%). We conclude that the IL28B variability influences the antiviral efficiency of interferon/ribavirin therapy and has a strong impact on SVR, independently of traditional response predictors. A combined assessment of these SNPs in conjunction with other response predictors may better predict outcome in difficult-to-treat patients.
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| 18. |
- Lindh, Magnus, 1960, et al.
(author)
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Interleukin 28B Gene Variation at rs12979860 Determines Early Viral Kinetics During Treatment in Patients Carrying Genotypes 2 or 3 of Hepatitis C Virus
- 2011
-
In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 203:12, s. 1748-1752
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Journal article (peer-reviewed)abstract
- Single-nucleotide polymorphisms upstream of the interleukin 28B (interferon lambda 3) gene (IL28B) strongly influence treatment efficacy in patients carrying hepatitis C virus (HCV) of genotype 1. In patients receiving 12 or 24 weeks of interferon-ribavirin therapy for infection with genotype 2 or 3 (n = 341), we found that rs12979860 strikingly determined the first phase of viral elimination (P < .001). In patients treated for 24 weeks, rs12979860 also predicted the rate of sustained virologic response (P = .02), especially among those with high baseline HCV RNA levels (P = .002) or older than 45 years (P = .01). Patients carrying CCrs12979860 had higher baseline HCV RNA levels (P < .001) and did not, when treated for 12 weeks, achieve sustained virologic response more often than those carrying CTrs1297986 or TTrs1297986. The results indicate that IL28B gene testing may identify patients carrying genotype 2 or 3 who could benefit from extended treatment.
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| 19. |
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| 20. |
- Rembeck, Karolina, et al.
(author)
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PNPLA 3 I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection.
- 2012
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In: BMC medical genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13:1
-
Journal article (peer-reviewed)abstract
- ABSTRACT: BACKGROUND: Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients. METHODS: Three hundred and eighty-two treatment naive HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study), in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients. RESULTS: In HCV genotype 2 infected patients carrying the PNPLA3 148 M allele, there was significantly increased insulin resistance (P = 0.023) and lower viral load (P = 0.005) at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients. CONCLUSIONS: Our results suggest a possible association between the PNPLA3 148 M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.
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| 21. |
- Rembeck, Karolina, et al.
(author)
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Variants of the inosine triphosphate pyrophosphatase gene are associated with reduced relapse risk following treatment for HCV genotype 2/3.
- 2014
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In: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 59:6, s. 2131-2139
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Journal article (peer-reviewed)abstract
- The present study evaluated the impact of variations in the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) on treatment outcome in patients with hepatitis C virus (HCV) genotype 2/3 infection receiving peginterferon-α2a and lower, conventional 800 mg daily dose of ribavirin. Previous studies using higher, weight-based ribavirin dosing report that patients carrying polymorphisms encoding reduced predicted ITPase activity show decreased risk of ribavirin-induced anemia but increased risk of thrombocytopenia, with no impact on elimination of virus. Three hundred fifty-four treatment naïve HCV genotype 2/3 infected patients, enrolled in a phase III trial (NORDynamIC), were genotyped for ITPA (rs1127354 and rs7270101). Homo- or heterozygosity at Ars1127354 or Crs7270101, entailing reduced ITPase activity, was observed in 37% of patients and was associated with increased likelihood of achieving sustained virological response (SVR) (P=0.0003 in univariate and multivariate analyses) accompanied by a reduced risk of relapse among treatment-adherent patients. The association between ITPA variants and SVR remained significant when patients were subdivided by the 12- and 24-week treatment duration arms, HCV genotype, fibrosis stage and IL28B genotype, and was not secondary to improved adherence to therapy or less pronounced anemia. Gene variants predicting reduced predicted ITPase activity also were associated with decreased risk of anemia (P<0.0001), increased risk of thrombocytopenia (P=0.007), and lower ribavirin concentrations (P=0.02). Conclusion: These findings demonstrate a novel ribavirin-like association between polymorphisms at ITPA and treatment efficacy in chronic hepatitis C mediated by reduced relapse risk. We hypothesize that patients (63%) being homozygous for both major alleles, leading to normal ITPase activity, may benefit more from the addition of ribavirin to present and future treatment regimens for HCV in spite of concomitant increased risk of anemia.
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| 22. |
- Söderholm, Jonas, 1978, et al.
(author)
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Impact of Soluble CD26 on Treatment Outcome and Hepatitis C Virus-Specific T Cells in Chronic Hepatitis C Virus Genotype 1 Infection
- 2013
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
-
Journal article (peer-reviewed)abstract
- Background Interferon and ribavirin therapy for chronic hepatitis C virus (HCV) infection yields sustained virological response (SVR) rates of 50–80%. Several factors such as non-1 genotype, beneficial IL28B genetic variants, low baseline IP-10, and the functionality of HCV-specific T cells predict SVR. With the pending introduction of new therapies for HCV entailing very rapid clearance of plasma HCV RNA, the importance of baseline biomarkers likely will increase in order to tailor therapy. CD26 (DPPIV) truncates the chemokine IP-10 into a shorter antagonistic form, and this truncation of IP-10 has been suggested to influence treatment outcome in patients with chronic HCV infection patients. In addition, previous reports have shown CD26 to be a co-stimulator for T cells. The aim of the present study was to assess the utility of CD26 as a biomarker for treatment outcome in chronic hepatitis C and to define its association with HCV-specific T cells. Methods Baseline plasma from 153 genotype 1 and 58 genotype 2/3 infected patients enrolled in an international multicenter phase III trial (DITTO-HCV) and 36 genotype 1 infected patients participating in a Swedish trial (TTG1) were evaluated regarding baseline soluble CD26 (sCD26) and the functionality of HCV-specific CD8+ T cells. Results Genotype 1 infected patients achieving SVR in the DITTO (P = 0.002) and the TTG1 (P = 0.02) studies had lower pretreatment sCD26 concentrations compared with non-SVR patients. Sixty-five percent of patients with sCD26 concentrations below 600 ng/mL achieved SVR compared with 39% of the patients with sCD26 exceeding 600 ng/mL (P = 0.01). Patients with sCD26 concentrations below 600 ng/mL had significantly higher frequencies of HCV-specific CD8+ T cells (P = 0.02). Conclusions Low baseline systemic concentrations of sCD26 predict favorable treatment outcome in chronic HCV infection and may be associated with higher blood counts of HCV-specific CD8+ T cells.
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| 23. |
- Westin, Johan, 1965, et al.
(author)
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Are FoxP3(+) cells involved in hyporesponsiveness to interferon/ribavirin therapy in chronic hepatitis C?
- 2011
-
In: Journal of viral hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 18:2, s. 149-151
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Journal article (peer-reviewed)abstract
- Summary. We aimed to clarify the role of liver-infiltrating FoxP3(+)T cells for the response to therapy in chronic hepatitis C. Liver biopsies from 52 patients were collected prior to the start of interferon/ribavirin treatment, and the kinetics of viral decay during treatment were compared in patients with high and low infiltration of FoxP3(+) cells. These groups did not differ with respect to the effectiveness of early viral clearance or the frequency of sustained viral response. Our data imply that FoxP3(+) cell-mediated immunosuppression is not a major mechanism of hyporesponsiveness to interferon-based therapy in chronic hepatitis C.
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| 24. |
- Ydreborg, Magdalena, 1974, et al.
(author)
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A Novel Fibrosis Index Comprising a Non-Cholesterol Sterol Accurately Predicts HCV-Related Liver Cirrhosis
- 2014
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4
-
Journal article (peer-reviewed)abstract
- Diagnosis of liver cirrhosis is essential in the management of chronic hepatitis C virus (HCV) infection. Liver biopsy is invasive and thus entails a risk of complications as well as a potential risk of sampling error. Therefore, non-invasive diagnostic tools are preferential. The aim of the present study was to create a model for accurate prediction of liver cirrhosis based on patient characteristics and biomarkers of liver fibrosis, including a panel of non-cholesterol sterols reflecting cholesterol synthesis and absorption and secretion. We evaluated variables with potential predictive significance for liver fibrosis in 278 patients originally included in a multicenter phase III treatment trial for chronic HCV infection. A stepwise multivariate logistic model selection was performed with liver cirrhosis, defined as Ishak fibrosis stage 5-6, as the outcome variable. A new index, referred to as Nordic Liver Index (NoLI) in the paper, was based on the model:Log-odds (predicting cirrhosis) =-12.17+ (agex0.11) + (BMI (kg/m(2))x0.23) + (D-7-lathosterol (mu g/100 mg cholesterol)x(-0.013)) + (Platelet count (x10(9)/L)x(-0.018)) + (Prothrombin-INRx3.69). The area under the ROC curve (AUROC) for prediction of cirrhosis was 0.91 (95% CI 0.86-0.96). The index was validated in a separate cohort of 83 patients and the AUROC for this cohort was similar (0.90; 95% CI: 0.82-0.98). In conclusion, the new index may complement other methods in diagnosing cirrhosis in patients with chronic HCV infection.
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| 25. |
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| 26. |
- Ydreborg, Magdalena, 1974, et al.
(author)
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Impact of IL28B-Related Single Nucleotide Polymorphisms on Liver Transient Elastography in Chronic Hepatitis C Infection
- 2013
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
-
Journal article (peer-reviewed)abstract
- Background and Aims: Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV) infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography. Methods: Seven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan (R) in the context of a real-life trial had samples available for IL28B genotyping (rs12979860) and HCV genotyping. Results: CCrs12979860 was more common among HCV genotype 2 or 3 infected treatment-naive patients than among those infected with genotype 1 (P<0.0001). Additionally CCrs12979860 among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004), and higher AST to platelet ratio index (APRI; p = 0.02) as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CCrs12979860 was significantly associated with higher viral load (P = 0.001), with a similar non-significant trend noted among HCV genotype 3 infected patients. Conclusion: This study confirms previous reports that the CCrs12979860 SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.
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| 27. |
- Andreasson, Thomas, et al.
(author)
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Evaluation of anamnestic criteria for the identification of patients with acute community onset viral gastroenteritis in the emergency department-A prospective observational study.
- 2014
-
In: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 46:8, s. 561-565
-
Journal article (peer-reviewed)abstract
- Background: To our knowledge no clinical criteria for the identification of community onset viral gastroenteritis in individual patients have been evaluated systematically with modern PCR-based diagnostic assays as gold standard. Objective: The aim of this study was to identify factors independently associated with the detection of virus by PCR in rectal swab samples from patients with acute community onset gastroenteritis. Methods: A prospective observational study was conducted from December 2010 through March 2011 at the emergency department (ED) of a large teaching hospital. All patients who reported vomiting and/or diarrhoea up to 48 h prior to their visit to the ED were asked to participate. A rectal swab sample was obtained from each patient. Symptoms, date of onset, and epidemiological data were recorded. Samples were analysed with a multiple real-time PCR targeting 6 viral agents (astrovirus, adenovirus, rotavirus, sapovirus, and norovirus GI and GII). Results: Two hundred and five patients fulfilled the inclusion criteria, of whom 66 agreed to participate; their median (IQR) age was 65 (38-84) y and 43 (65%) were females. Thirty-one (47%) were positive by PCR for at least 1 of the agents examined (26 norovirus, 2 sapovirus, 2 rotavirus, and 1 adenovirus). Diarrhoea and a short duration of symptoms (≤ 2 days) were independently associated with a positive rectal swab sample, with odds ratios of 7.5 (95% confidence interval (CI) 2.0-28) and 10.4 (95% CI 1.9-56), respectively (p < 0.01 for both). A multivariate model including these 2 variables had a sensitivity of 81% (25/31) and a specificity of 69% (24/35). Conclusions: Diarrhoea and a short duration of symptoms were the only anamnestic criteria independently associated with acute community onset viral gastroenteritis confirmed by PCR.
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| 28. |
- Brittain-Long, Robin, 1969, et al.
(author)
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Access to a polymerase chain reaction assay method targeting 13 respiratory viruses can reduce antibiotics: a randomised, controlled trial.
- 2011
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In: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 9
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Viral respiratory infections are common worldwide and range from completely benign disease to life-threatening illness. Symptoms can be unspecific, and an etiologic diagnosis is rarely established because of a lack of suitable diagnostic tools. Improper use of antibiotics is common in this setting, which is detrimental in light of the development of bacterial resistance. It has been suggested that the use of diagnostic tests could reduce antibiotic prescription rates. The objective of this study was to evaluate whether access to a multiplex polymerase chain reaction (PCR) assay panel for etiologic diagnosis of acute respiratory tract infections (ARTIs) would have an impact on antibiotic prescription rate in primary care clinical settings. METHODS: Adult patients with symptoms of ARTI were prospectively included. Nasopharyngeal and throat swabs were analysed by using a multiplex real-time PCR method targeting thirteen viruses and two bacteria. Patients were recruited at 12 outpatient units from October 2006 through April 2009, and samples were collected on the day of inclusion (initial visit) and after 10 days (follow-up visit). Patients were randomised in an open-label treatment protocol to receive a rapid or delayed result (on the following day or after eight to twelve days). The primary outcome measure was the antibiotic prescription rate at the initial visit, and the secondary outcome was the total antibiotic prescription rate during the study period. RESULTS: A total sample of 447 patients was randomised. Forty-one were excluded, leaving 406 patients for analysis. In the group of patients randomised for a rapid result, 4.5% (9 of 202) of patients received antibiotics at the initial visit, compared to 12.3% (25 of 204) (P = 0.005) of patients in the delayed result group. At follow-up, there was no significant difference between the groups: 13.9% (28 of 202) in the rapid result group and 17.2% (35 of 204) in the delayed result group (P = 0.359), respectively. CONCLUSIONS: Access to a rapid method for etiologic diagnosis of ARTIs may reduce antibiotic prescription rates at the initial visit in an outpatient setting. To sustain this effect, however, it seems necessary to better define how to follow and manage the patient according to the result of the test, which warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01133782.
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| 29. |
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| 30. |
- Brittain-Long, Robin, 1969, et al.
(author)
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Seasonal variations of 15 respiratory agents illustrated by the application of a multiplex polymerase chain reaction assay.
- 2011
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In: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548.
-
Journal article (peer-reviewed)abstract
- Abstract Background: Nucleic acid amplification tests are increasingly being used to diagnose viral and bacterial respiratory tract infections. The high sensitivity of these tests affects our understanding of the epidemiology of respiratory tract infections. We have assessed the detection rate of a multiplex real-time polymerase chain reaction (PCR) test, with emphasis on epidemiology and seasonal distribution of the most common respiratory tract infections. Methods: Seven thousand eight hundred and fifty-three nasopharyngeal samples from 7220 patients (age range 0-98 y, median 22 y) obtained during 36 consecutive months (November 2006-October 2009), were analyzed with a multiplex PCR panel including influenza A (IfA) and B (IfB) virus, parainfluenza virus (PIV) 1-3, respiratory syncytial virus (RSV), human rhinovirus (HRV), human coronavirus (CoV) OC43, NL63, and 229E, human metapneumovirus (HMPV), adenovirus (AdV), enterovirus (EV), and 2 bacteria - Mycoplasma pneumoniae and Chlamydophila pneumoniae. Results: Of the total samples, 44.5% (n = 3496) were positive for at least 1 agent, with HRV being the most common (n = 1482, 38.0%), followed by RSV (n = 526, 13.5%) and IfA (n = 403, 10.3%). The diagnostic yield was significantly higher during the winter and early spring compared to the summer (n = 2439 of 4458 samples, 54.7% and n = 1057 of 3395 samples, 31.1%, respectively; p < 0.001). Conclusions: The diagnostic yield was highly dependent on the month of sampling and the age of the patient. However, the overall detection rate per month was above 30%, apart for August and September. Our findings support the use of similar tests in routine clinical care all year round. HRV was the most common finding in the respiratory tract, independent of season.
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| 31. |
- Gustavsson, Lars, et al.
(author)
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Excess mortality following community-onset norovirus enteritis in the elderly.
- 2011
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In: The Journal of hospital infection. - : Elsevier BV. - 1532-2939 .- 0195-6701. ; 79:1, s. 27-31
-
Journal article (peer-reviewed)abstract
- Norovirus has been associated with excess deaths. A retrospective study of mortality following norovirus enteritis (NVE) was undertaken. All hospitalized adult patients with a stool sample positive for norovirus genogroup II on polymerase chain reaction, treated at Sahlgrenska University Hospital, Gothenburg, Sweden between August 2008 and June 2009, were included as cases (N=598, aged 18-101 years). Matched controls without enteritis (N=1196) were selected for comparison. Medical records were reviewed and deaths up to 90 days following positive sampling were noted, as well as comorbidities and length of hospital stay. Thirty- and 90-day survival rates were calculated. Total 30-day mortality was 7.6% and no deaths were recorded in cases aged 18-59 years. Thirty-day mortality was higher in cases with underlying medical conditions compared with those without these comorbidities (age 60-101 years: 89.5% vs 94.7% alive at Day 30, respectively; P<0.05). In cases aged >80 years, mortality was higher in those with community-onset NVE (N=64) compared with hospital-onset NVE (N=305) (81.2% vs 90.2% alive at Day 30, respectively; P<0.05), and compared with controls (N=128) (81.2% vs 91.4% alive at Day 30, respectively; P<0.05). Median length of hospital stay was 20 [interquartile range (IQR) 12-29] days for cases with hospital-onset NVE, and seven (IQR 2-13) days for controls (P<0.001). In conclusion, community-onset NVE requiring hospitalization was associated with higher mortality compared with hospital-onset NVE and matched controls in hospitalized elderly patients.
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| 32. |
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| 33. |
- Gustavsson, Lars, et al.
(author)
-
Rectal swabs can be used for diagnosis of viral gastroenteritis with a multiple real-time PCR assay
- 2011
-
In: Journal of Clinical Virology. - 1386-6532. ; 51, s. 275-278
-
Journal article (peer-reviewed)abstract
- Background: Viral agents, especially norovirus, are the most common cause of nosocomial spread of epidemic gastroenteritis (GE). Rapid and reliable detection of these agents could reduce the risk of outbreaks. Objective: To evaluate the diagnostic performance of rectal swab samples compared to standard stool samples for detection of agents causing viral GE by PCR. Study design: Complete pairs of rectal swab and stool samples, obtained simultaneously from patients with symptoms of acute onset GE, were analysed with a multiple real-time PCR targeting six different gastroenteritis agents (astro-, adeno-, rota-, sapo- and norovirus GI and II). Cycle threshold (Ct) values were registered for positive samples. A positive PCR result in either sample for any virus was considered gold standard. Results: 69 sample pairs were included of which 29 were negative in both sample types and 38 were positive in both sample types. One pair was positive in the stool sample only and another pair was positive in the rectal swab sample only. Sensitivity for both sample types was 97.5% (39/40). Conclusion: Rectal swab samples are as reliable as stool samples for PCR-based diagnosis of viral gastroenteritis in patients with a short duration of symptoms and may be used as a complement to stool samples, especially when immediate sampling is desirable.
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| 34. |
- Gustavsson, Lars, et al.
(author)
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Venous lactate levels can be used to identify patients with poor outcome following community-onset norovirus enteritis
- 2012
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 44:10, s. 782-787
-
Journal article (peer-reviewed)abstract
- Background: Norovirus enteritis (NVE) can be fatal in frail patients. High blood lactate levels indicate hypoperfusion and predict mortality in many infectious diseases. The objective was to determine the frequency and association with mortality of elevated lactate levels in patients with community-onset NVE. Methods: A retrospective cohort study was performed. All hospitalized adult patients with community-onset NVE verified by polymerase chain reaction during the period August 2008 to June 2009 were included. Vital signs and venous lactate on arrival, co-morbid conditions, and time of death were registered. The outcome measure was 30-day all-cause mortality. Results: Eighty-two patients with a median age of 77 y (interquartile range (IQR) 53-86 y) were included, of whom 47 (57%) were female and 49 (60%) had at least 1 major co-morbid condition. Lactate levels were above the upper limit of normal (ULN; 1.6 mmol/l) in 45 patients (55%). The overall 30-day mortality rate was 7% (6/82). Mortality was 18% (5/28) with lactate >= 2.4 mmol/l (> 50% above the ULN) on admission compared to 2% (1/54) with lactate < 2.4 mmol/l (p < 0.05). Patients who died had a higher median lactate level compared to survivors: 4.5 (IQR 2.7-7.9) mmol/l vs 1.7 (IQR 1.3-2.5) mmol/l, respectively (p < 0.01). The adjusted odds ratio for death within 30 days for a 1 mmol/l increase in lactate was 2.5 (95% confidence interval 1.003-6.3, p = 0.049). Conclusions: We observed a high proportion of patients with elevated lactate levels in community-onset NVE. Lactate elevation could predict mortality. Measurement of blood lactate may be a valuable tool in the clinical management of patients with a suspected norovirus infection.
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| 35. |
- Magnusson, Jesper, et al.
(author)
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The Impact of Viral Respiratory Tract Infections on Long-Term Morbidity and Mortality following Lung Transplantation: A Retrospective Cohort Study Using a Multiplex PCR Panel.
- 2013
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In: Transplantation. - 1534-6080. ; 95:2, s. 383-388
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The major factor affecting morbidity and mortality after lung transplantation (LTX) is bronchiolitis obliterans syndrome. Earlier studies have suggested a connection between the presence of viral agents and morbidity in this patient group, but data are somewhat conflicting. The objective of this study was to investigate the development of bronchiolitis obliterans syndrome and graft loss after LTX in relation to the presence of respiratory viruses during the first year after LTX. METHOD: The study is a retrospective cohort study of 39 LTX recipients 11-13 years after surgery. Patients were operated between January 1, 1998 and December 31, 2000 at Sahlgrenska University Hospital. The presence of virus in bronchoalveolar lavage (BAL) fluids from patients during the first year after surgery was analyzed retrospectively using a multiplex polymerase chain reaction test capable of detecting 15 respiratory agents. The time to BOS or graft loss was analyzed in relation to the positive findings in BAL during the first year after LTX. RESULTS: Patients with one or more viruses detected in BAL during the first year after transplantation demonstrated a significantly faster development of BOS (P=0.005) compared with patients with no virus detected. No significant difference in graft survival was found. CONCLUSION: Our results suggest that the long-term prognosis after LTX may be negatively affected by viral respiratory tract infections during the first year after LTX.
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| 36. |
- Nenonen, Nancy P, 1943, et al.
(author)
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Norovirus GII.4 Detection in Environmental Samples from Patient Rooms during Nosocomial Outbreaks
- 2014
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In: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 52:7, s. 2352-2358
-
Journal article (peer-reviewed)abstract
- Norovirus (NoV) is an important cause of nosocomial gastroenteric outbreaks. This 5-month study was designed to characterize NoV contamination and airborne dispersal in patient rooms during hospital outbreaks. Air vents, overbed tables, washbasins, dust, and virus traps designed to collect charged particles from the air were swabbed to investigate the possibility of NoV contamination in patient rooms during outbreaks in seven wards and in an outbreak-free ward. Symptomatic inpatients were also sampled. Nucleic acid extracts of the samples were examined for NoV RNA using genogroup I (GI) and GII real-time reverse transcription-PCR (RT-PCR). The NoV strains were characterized by RT-PCR, sequencing, and phylogenetic analysis of the RNA-dependent RNA-polymerase-N/S capsid-coding region (1,040 nucleotides [nt]). Patient strains from two outbreaks in one ward were sequenced across the RNA-dependent-RNA-polymerase major capsid-coding region (2.5 kb), including the hypervariable P2 domain. In the outbreak wards, NoV GII was detected in 48 of 101 (47%) environmental swabs and 63 of 108 patients (58%); NoV genotype II.4 was sequenced from 18 environmental samples, dust (n = 8), virus traps (n = 4), surfaces (n = 6), and 56 patients. In contrast, NoV GII was detected in 2 (GII. 4) of 28 (7%) environmental samples and in 2 (GII. 6 and GII. 4) of 17 patients in the outbreak-free ward. Sequence analyses revealed a high degree of similarity (>99.5%, 1,040 nt) between NoV GII.4 environmental and patient strains from a given ward at a given time. The strains clustered on 11 subbranches of the phylogenetic tree, with strong correlations to time and place. The high nucleotide similarity between the NoV GII.4 strains from patients and their hospital room environment provided molecular evidence of GII.4 dispersal in the air and dust; therefore, interventional cleaning studies are justified.
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| 37. |
- Nilsson, Anna, et al.
(author)
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Frequent detection of respiratory agents by multiplex PCR on oropharyngeal samples in Swedish school-attending adolescents
- 2012
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 44, s. 393-397
-
Journal article (peer-reviewed)abstract
- Background: Respiratory agents may be detected in the oropharynx of healthy individuals. The extent of this condition and the reasons behind it are largely unknown. The objective of this study was to determine the factors associated with the presence of respiratory agents in the oropharynx of adolescents healthy enough to attend school activities. Methods: On a single day in December, samples from the posterior wall of the oropharynx of adolescents aged 1015 y were obtained using cotton-tipped swabs. The samples were analyzed by real-time polymerase chain reaction (PCR) for the presence of 13 respiratory viruses and 2 bacteria (Mycoplasma pneumoniae and Chlamydophila pneumoniae). Results: Out of the 232 adolescents sampled, 67 (29%) had any respiratory symptom. A positive PCR result was found in 50 individuals (22%). Human rhinovirus was the most commonly found agent. Respiratory agents were significantly more frequent in the younger age group (1013 y) than in the older age group (1415 y): 26% (38/148) vs 14% (12/84), respectively; p = 0.04. Cough was the only symptom that was more common among individuals with a positive PCR test than among those with a negative PCR test: 8/50 (16%) vs 11/182 (6%); p = 0.02. Family size and class size were not associated with the likelihood of a positive PCR test. Conclusions: The presence of respiratory agents in the oropharynx is a frequent finding among adolescents healthy enough to attend school activities. The high prevalence was found to be associated with young age, but not with the size of the family or class. © 2012 Informa Healthcare.
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| 38. |
- Olofsson, Sigvard, 1948, et al.
(author)
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PCR for detection of respiratory viruses: seasonal variations of virus infections
- 2011
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In: EXPERT REVIEW OF ANTI-INFECTIVE THERAPY. - 1478-7210. ; 9:8, s. 615-626
-
Research review (peer-reviewed)abstract
- Real-time PCR and related methods have revolutionized the laboratory diagnosis of viral respiratory infections because of their high detection sensitivity, rapidness and potential for simultaneous detection of 15 or more respiratory agents. Results from studies with this diagnostic modality have significantly expanded our knowledge about the seasonality of viral respiratory diseases, pinpointed the difficulties to make a reliable etiologic diagnosis without the aid of an unbiased multiplex molecular assay for respiratory viruses, and revealed previously unknown details as to possible infections with multiple agents as aggravating factors. The scope of this article is to review and discuss this new knowledge and its implications for diagnostic strategies and other measures essential for the clinical management of respiratory viral infections and for epidemiological surveillance of seasonal respiratory infections.
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| 39. |
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