High real-world effectiveness of 12-week elbasvir/grazoprevir without resistance testing in the treatment of patients with HCV genotype 1a infection in Norway.

BACKGROUND AND AIMS: The recommended treatment duration of hepatitis C virus (HCV) genotype 1a (GT1a) infection with elbasvir/grazoprevir (EBR/GZR) in the presence of a high baseline viral load and resistance associated substitutions (RAS) is 16 weeks with ribavirin added. The objective of this study was to evaluate the real-world effectiveness of 12 weeks of EBR/GZR without ribavirin and regardless of baseline viral load and RAS testing. METHOD: This retrospective, observational cohort study was performed at five Norwegian hospitals that did not systematically utilize RAS testing. All adult patients with chronic HCV GT1a and compensated liver disease who had received 12 weeks of EBR/GZR without ribavirin and baseline RAS testing, were included. The primary endpoint was sustained virologic response at week 12 (SVR12), or if not available, at week 4 (SVR4). RESULTS: We included 433 patients and attained SVR data on 388. The mean age was 45.7 years (22-73 years). 67.2% were male. HIV co-infection was present in 3.8% (16/424) and cirrhosis in 4% (17/424). The viral load was >800 000 IU/mL in 55.0% (235/427) of patients. Overall SVR was achieved in 97.2% (377/388). SVR was achieved in 98.3% (169/172) of those with viral load ≤800 000 IU/mL and in 96.2% (202/210) of those with viral load >800 000 IU/mL. CONCLUSION: We observed high SVR rates among patients with HCV GT1a infection treated with EBR/GZR for 12 weeks without ribavirin, with no regard to baseline viral load and no RAS testing.

Aetiology and risk factors of community-acquired pneumonia in hospitalized patients in Norway.

BACKGROUND AND AIMS: In Norway, data on the aetiology of community-acquired pneumonia (CAP) in hospitalized patients are limited. The aims of this study were to investigate the bacterial aetiology of CAP in hospitalized patients in Norway, risk factors for CAP and possible differences in risk factors between patients with Legionnaire's disease and pneumonia because of other causes. METHODS: Adult patients with radiologically confirmed CAP admitted to hospital were eligible for the study. Routine aerobic and Legionella culture of sputum, blood culture, urinary antigen test for Legionella pneumophila and Streptococcus pneumoniae, polymerase chain reaction detection of Chlamydophila pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis from throat specimens, and serology for L. pneumophila serogroup 1-6 were performed. A questionnaire, which included demographic and clinical data, risk factors and treatment, was completed. RESULTS: We included 374 patients through a 20-month study period in 2007-2008. The aetiological agent was detected in 37% of cases. S. pneumoniae (20%) was the most prevalent agent, followed by Haemophilus influenzae (6%) and Legionella spp. (6%). Eight Legionella cases were diagnosed by urinary antigen test, of which four also had positive serology. In addition, 13 Legionella cases were diagnosed by serology. The degree of comorbidity was high. An increased risk of hospital-diagnosed Legionella pneumonia was found among patients with a diagnosis of chronic congestive heart failure. CONCLUSION: Our results indicate that S. pneumoniae is the most common bacterial cause of pneumonia in hospitalized patients, and the prevalence of Legionella pneumonia is probably higher in Norway than recognized previously.

Characterization of the extent of a large outbreak of Legionnaires' disease by serological assays.

BACKGROUND: In May 2005, a long-distance outbreak of Legionnaires' disease (LD) caused by Legionella pneumophila serogroup 1 occurred in south-east Norway. The initial outbreak investigation without serology identified 56 laboratory-confirmed LD cases of whom 10 died. However, 116 patients with community-acquired pneumonia might belong to the outbreak based on epidemiological investigations, but acute laboratory tests other than serology were negative or not performed. To assess the true extent of the outbreak, we evaluated two serological assays in order to reclassify the 116 patients with indeterminate case status. METHODS: Two polyvalent antibody tests, a serogroup 1-6 immunofluorescence assay (IFA) and a serogroup 1-7 enzyme-linked immunosorbent assay (ELISA) were used. They were evaluated with cases defined as culture- or urinary antigen positive LD patients (n=40) and non-cases defined as confirmed non-LD patients (n=39) and healthy control subjects (n=62). The 116 patients, who were negative in culture, polymerase chain reaction and/or urinary antigen tests, were analysed by the same serological assays. Antibodies to the outbreak strain were determined by immunoblotting. RESULTS: In the evaluation study, the sensitivity and specificity of a ≥4-fold IFA titre change was 38% and 100%, respectively, with corresponding values of 30% and 99% for seroconversion in ELISA. A single high positive IFA titre yielded sensitivity and specificity of 73% and 97%, respectively, with corresponding values of 68% and 96% for a single high immunoglobulin (Ig) G and/or IgM in ELISA. Based on this evaluation, the following serological testing identified 47 more LD cases, and the outbreak thus comprised 103 cases with a case fatality rate of 10%. About the same proportion (70%) of the urinary antigen positive and negative LD cases had antibodies to the serogroup-specific lipopolysaccharide of the outbreak strain. In addition to the 103 LD cases, Legionella infection could not be verified or excluded in 32 patients based on epidemiology and/or lack of microbiological sampling. CONCLUSIONS: The acute-phase tests (culture, polymerase chain reaction, and urinary antigen) identified less than 55% of the 103 patients in this outbreak. Serological testing thus remains an important supplement for diagnosis of LD and for determination of outbreak cases.

An outbreak of legionnaires disease caused by long-distance spread from an industrial air scrubber in Sarpsborg, Norway.

BACKGROUND: On 21 May 2005, the Norwegian health authorities were alerted by officials from a local hospital that several recent patients had received the diagnosis of legionnaires disease; all patients resided in 2 neighboring municipalities. We investigated the outbreak to identify the source and to implement control measures. METHODS: We interviewed all surviving case patients and investigated and harvested samples from 23 businesses with cooling towers and other potential infection sources. The locations of the businesses and the patients' residences and movements were mapped. We calculated attack rates and risk ratios among people living within various radii of each potential source. Isolates of Legionella pneumophila were compared using molecular methods. RESULTS: Among 56 case patients, 10 died. The case patients became ill 12-25 May, resided up to 20 km apart, and had not visited places in common. Those living up to 1 km from a particular air scrubber had the highest risk ratio, and only for this source did the risk ratio decrease as the radius widened. Genetically identical L. pneumophila serogroup 1 isolates were recovered from patients and the air scrubber. The air scrubber is an industrial pollution-control device that cleans air for dust particles by spraying with water. The circulating water had a high organic content, pH of 8-9, and temperature of 40 degrees C. The air was expelled at 20 m/s and contained a high amount of aerosolized water. CONCLUSIONS: The high velocity, large drift, and high humidity in the air scrubber may have contributed to the wide spread of Legionella species, probably for >10 km. The risk of Legionella spread from air scrubbers should be assessed.