Aerosol generation during coughing: an observational study.

OBJECTIVE: Coronavirus disease 2019 has highlighted the lack of knowledge on aerosol exposure during respiratory activity and aerosol-generating procedures. This study sought to determine the aerosol concentrations generated by coughing to better understand, and to set a standard for studying, aerosols generated in medical procedures. METHODS: Aerosol exposure during coughing was measured in 37 healthy volunteers in the operating theatre with an optical particle sizer, from 40 cm, 70 cm and 100 cm distances. RESULTS: Altogether, 306 volitional and 15 involuntary coughs were measured. No differences between groups were observed. CONCLUSION: Many medical procedures are expected to generate aerosols; it is unclear whether they are higher risk than normal respiratory activity. The measured aerosol exposure can be used to determine the risk for significant aerosol generation during medical procedures. Considerable variation of aerosol generation during cough was observed between individuals, but whether cough was volitional or involuntary made no difference to aerosol production.

Low efficacy of three non-alcohol-based hand disinfectants utilizing silver polymer, lactic acid and benzalkonium chloride on inactivation of bacteria on the fingertips of healthcare workers.

BACKGROUND: Recently, new non-alcohol-based hand disinfection formulae have come to the market. Although they have passed the EN1500 test, data on their clinical efficacy compared with alcohol-based hand rubs are scarce, mainly covering benzalkonium chloride (BAC). AIM: To test the efficacy of silver-polymer-based, lactic-acid-based and BAC-based hand disinfectant foams and an alcohol-based hand rub gel to reduce bacterial counts on the fingertips of healthcare workers working on hospital wards. METHODS: Each of the 84 participants tested one of the four products during their morning shift on a hospital ward using the 'fingertips on Petri dish' method before and after rubbing their hands with the product. After incubation, two independent readers assessed bacterial counts on the culture plates. FINDINGS: The alcohol-based hand rub efficiently reduced bacteria on testers' fingertips in the test situation, whereas the lactic-acid- and BAC-based disinfectants did not have any detectable efficacy. The silver-polymer-based formula had some effect but requires further study. CONCLUSION: Non-alcohol-based hand rubs require careful consideration and further study before they can be accepted for clinical use.

Isolation precautions cause minor delays in diagnostics and treatment of non-COVID patients.

BACKGROUND: Isolation precautions are essential prevent spread of COVID-19 infection but may have a negative impact on inpatient care. The impact of these measures on non-COVID-19 patients remains largely unexplored. AIM: This study aimed to investigate diagnostic and treatment delays related to isolation precautions, the associated patient outcome, and the predisposing risk factors for delays. METHODS: This observational study was conducted in seven Helsinki region hospitals during the first wave of the COVID-19 pandemic in Finland. The study used data on all non-COVID-19 inpatients, who were initially isolated due to suspected COVID-19, to estimate whether isolation precautions resulted in diagnostic or treatment delays. RESULTS: Out of 683 non-COVID-19 patients, 33 (4.8%) had delays related to isolation precautions. Clinical condition deteriorated non-fatally in seven (1.0%) patients. The following events were associated with an increased risk of treatment or a diagnostic delay: more than three ward transfers (P = 0.025); referral to an incorrect speciality in the emergency department (P = 0.004); more than three SARS-CoV-2 RT-PCR tests performed (P = 0.022); and where cancer was the final diagnosis (P = 0.018). In contrast, lower respiratory tract symptoms (P = 0.013) decreased the risk. CONCLUSIONS: The use of isolation precautions for patients who did not have COVID-19 had minor negative effects on patient outcomes. The present study underlines the importance of targeting diagnostic efforts to patients with unspecified symptoms and to those with a negative SARS-CoV-2 test result. Thorough investigations to achieve an accurate diagnosis improves the prognosis of patients and facilitates appropriate targeting of hospital resources.

Routine wastewater-based monitoring of antibiotic resistance in two Finnish hospitals: focus on carbapenem resistance genes and genes associated with bacteria causing hospital-acquired infections.

BACKGROUND: Wastewater-based monitoring represents a useful tool for antibiotic resistance surveillance. AIM: To investigate the prevalence and abundance of antibiotic resistance genes (ARGs) in hospital wastewater over time. METHODS: Wastewater from two hospitals in Finland (HUS1 and HUS2) was monitored weekly for nine weeks (weeks 25-33) in summer 2020. A high-throughput real-time polymerization chain reaction (HT-qPCR) system was used to detect and quantify 216 ARGs and genes associated with mobile genetic elements (MGEs), integrons, and bacteria causing hospital-acquired infections (HAIs), as well as the 16S rRNA gene. Data from HT-qPCR were analysed and visualized using a novel digital platform, ResistApp. Eight carbapenem resistance genes (blaGES, blaKPC, blaVIM, blaNDM, blaCMY, blaMOX, blaOXA48, and blaOXA51) and three genes associated with bacteria causing HAIs (Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were studied. FINDINGS: There was a significantly higher number of ARGs at both hospitals in weeks 27-30 (174-191 genes) compared to other sampling weeks (151-171 genes). Our analyses also indicated that the two hospitals, which used different amounts of antibiotics, had significantly different resistance gene profiles. Carbapenem resistance genes were more prevalent and abundant in HUS1 than HUS2. Across both hospitals, blaGES and blaVIM were the most prevalent and abundant. There was also a strong positive association between blaKPC and K. pneumoniae in HUS1 wastewater. CONCLUSION: Routine wastewater-based monitoring using ResistApp can provide valuable information on the prevalence and abundance of ARGs in hospitals. This helps hospitals understand the spread of antibiotic resistance in hospitals and identify potential areas for intervention.

Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland.

Reports on real-world experience on efficacy of bezlotoxumab (BEZ) has been lacking thus far. We retrospectively studied the efficacy and safety of BEZ in preventing the recurrence of Clostridium difficile infection (CDI) in five university hospitals in Finland. Seventy-three percent of our 46 patients remained free of recurrence in the following 3 months and the performance remained as 71% effective also among immunocompromised patients. In severe CDI, BEZ prevented recurrence in 63% of cases. From our study patients, 78% had three or more known risk factors for recurrence of CDI. Eight of our patients were waiting for fecal microbiota transplantation but after stopping the antibiotics that were continued to prevent recurrence of CDI and after receiving BEZ, all remained free of recurrence and did not need the procedure. Success with BEZ as an adjunctive treatment in preventing recurrence of CDI in high-risk patients may be rated as high. Among a subgroup of our patients, those already evaluated to be in need of fecal microbiota transplantation, BEZ seems to be an alternative option.

Clinical use of fungal PCR from deep tissue samples in the diagnosis of invasive fungal diseases: a retrospective observational study.

OBJECTIVES: To assess the clinical use of panfungal PCR for diagnosis of invasive fungal diseases (IFDs). We focused on the deep tissue samples. METHODS: We first described the design of panfungal PCR, which is in clinical use at Helsinki University Hospital. Next we retrospectively evaluated the results of 307 fungal PCR tests performed from 2013 to 2015. Samples were taken from normally sterile tissues and fluids. The patient population was nonselected. We classified the likelihood of IFD according to the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG), comparing the fungal PCR results to the likelihood of IFD along with culture and microscopy results. RESULTS: There were 48 positive (16%) and 259 negative (84%) PCR results. The sensitivity and specificity of PCR for diagnosing IFDs were 60.5% and 91.7%, respectively, while the negative predictive value and positive predictive value were 93.4% and 54.2%, respectively. The concordance between the PCR and the culture results was 86% and 87% between PCR and microscopy, respectively. Of the 48 patients with positive PCR results, 23 had a proven or probable IFD. CONCLUSIONS: Fungal PCR can be useful for diagnosing IFDs in deep tissue samples. It is beneficial to combine fungal PCR with culture and microscopy.

The long-term effects of faecal microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent Clostridium difficile infection.

BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection. In short-term the treatment has been shown to be safe, however, there are no large, long-term follow-up studies looking into the potential adverse effects. AIM: To analyse the long-term effect of FMT treatment in patients with recurrent C. difficile infection and to compare the outcome to antibiotic treated patients. METHODS: Altogether 84 patients of which 45 received a FMT treatment and 39 served as controls receiving antibiotics for the infection were followed on average for 3.8 years. Their recovery and medical status was evaluated using a retrospective questionnaire, determining their quality of life, gastrointestinal symptoms and new diseases potentially related to the FMT. RESULTS: There was no difference in the incidence of severe diseases (inflammatory bowel disease, cancer, autoimmune disease, allergy, neurological diseases) between the patient groups. In addition, weight gain did not differ between treatment groups. The FMT treated patients reported that their bowel habits improved significantly faster, they had less irregular bowel function and less symptoms of upper GI-tract when compared to the patients treated with antibiotics. Significantly more patients in FMT-group reported that their mental health improved after the treatment. The willingness to receive FMT treatment for potential new C. difficile infection was significantly higher in both treatment groups compared to other treatment options. CONCLUSION: Our study highlights that FMT is a durable, safe and acceptable treatment option for patients with recurrent C. difficile infection also in long term, and it shows potential benefits over antimicrobial treatment.

Clinical efficacy of seasonal influenza vaccination: characteristics of two outbreaks of influenza A(H1N1) in immunocompromised patients.

BACKGROUND: Influenza A(H1N1) causes serious complications in immunocompromised patients. The efficacy of seasonal vaccination in these patients has been questioned. AIM: To describe two outbreaks of influenza A(H1N1) in immunocompromised patients. METHODS: Two outbreaks of influenza A(H1N1) occurred in our institution: on the kidney transplant ward in 2014 including patients early after kidney or simultaneous pancreas-kidney transplantation, and on the oncology ward in 2016 including patients receiving chemotherapy for malignant tumours. Factors leading to these outbreaks and the clinical efficacy of seasonal influenza vaccination were analysed. FINDINGS: Altogether 86 patients were exposed to influenza A(H1N1) during the outbreaks, among whom the seasonal influenza vaccination status was unknown in 10. Only three out of 38 vaccinated patients were infected with influenza A(H1N1), compared with 20 out of 38 unvaccinated patients (P = 0.02). The death of one out of 38 vaccinated patients was associated with influenza, compared with seven out of 38 unvaccinated patients (P = 0.06). Shared factors behind the two outbreaks included outdated facilities not designed for the treatment of immunosuppressed patients. Vaccination coverage among patients was low, between 40% and 70% despite vaccination being offered to all patients free of charge. Vaccination coverage of healthcare workers on the transplant ward was low (46%), but, despite high coverage on the oncology ward (92%), the outbreak occurred. CONCLUSION: Seasonal influenza vaccination was clinically effective with both a reduced risk of influenza infection and a trend towards reduced mortality in these immunocompromised patients. Several possible causes were identified behind these two outbreaks, requiring continuous awareness in healthcare professionals to prevent further outbreaks.

Parainfluenza 3 Infections Early After Kidney or Simultaneous Pancreas-Kidney Transplantation.

Parainfluenza virus (PIV) can cause serious infections after hematopoietic stem cell or lung transplantation. Limited data exist about PIV infections after kidney transplantation. We describe an outbreak of PIV-3 in a transplant unit. During the outbreak, 45 patients were treated on the ward for postoperative care after kidney or simultaneous pancreas-kidney (SPK) transplantation. Overall, 29 patients were tested for respiratory viruses (12 patients with respiratory symptoms, 17 asymptomatic exposed patients) from nasopharyngeal swabs using polymerase chain reaction. PIV-3 infection was confirmed in 12 patients. One patient remained asymptomatic. In others, symptoms were mostly mild upper respiratory tract symptoms and subsided within a few days with symptomatic treatment. Two patients suffered from lower respiratory tract symptoms (dyspnea, hypoxemia, pulmonary infiltrates in chest computed tomography) and required supplemental oxygen. Four of six SPK patients and eight of 39 of kidney transplant patients were infected with PIV (p = 0.04). In patients with follow-up tests, PIV-3 shedding was still detected 11-16 days after diagnosis. Despite rapid isolation of symptomatic patients, PIV-3 findings were diagnosed within 24 days, and the outbreak ceased only after closing the transplant ward temporarily. In conclusion, PIV-3 infections early after kidney or SPK transplantation were mostly mild. PIV-3 easily infected immunosuppressed transplant recipients, with prolonged viral shedding.

Increase of prostate biopsy-related bacteremic complications in southern Finland, 2005-2013: a population-based analysis.

BACKGROUND: The most severe manifestations of prostate biopsy complications are bacteremic infections. These complications are increasing alarmingly. METHODS: A retrospective cohort study of 17 183 transrectal prostate biopsies performed at the Helsinki and Uusimaa hospital district in southern Finland during 2005-2013. Biopsies were linked to a database of positive blood cultures, yielding 111 bacteremic cases, and yearly bacteremia rates were determined. By multiple regression analysis, demographic risk factors of the whole biopsy cohort for developing bacteremia or fluoroquinolone (FQ)-resistant bacteremia were studied. Clinical risk factors for bacteremia caused by an FQ-resistant organism and for serious bacteremic outcomes were studied by univariate and multivariate analyzes. RESULTS: The average bacteremia rate was 0.7% (111 of 17 183 biopsies) and an increase was observed from 0.5% in 2005 (95% confidence interval (CI): 0.3-0.9) to 1.2% in 2012 (95% CI 0.8-1.8); 53.2% were caused by an FQ-resistant organism. In univariate regression analysis, previous biopsy sessions and increasing calendar year of biopsy associated with the risk of developing bacteremia (odds ratio (OR) 1.232, 95% CI: 1.020-1.488, P=0.030 and OR 1.164, 95% CI: 1.079-1.255, P<0.001, respectively), but only increasing calendar year of biopsy remained statistically significant (OR 1.155, 95% CI: 1.070-1.247, P<0.001) in multivariate analysis. Foreign travel within 3 months was associated with FQ resistance in multivariate analysis (OR 7.158, 95% CI: 1.042 to infinite, P=0.045). The study failed to show any significant clinical risk factors for serious bacteremic outcomes (requiring intensive care, developing deep infection foci or death). CONCLUSIONS: The postbiopsy bacteremia rate doubled during the study period and half of the cases were caused by FQ-resistant organisms. Recent foreign travel increased the risk for FQ resistance. Future research efforts should be aimed at better identifying risk factors, targeted prophylaxis and reducing the need for biopsies.

Outbreak of Influenza A(H1N1) in a Kidney Transplant Unit-Protective Effect of Vaccination.

Seasonal influenza vaccination is recommended for patients with end-stage renal disease (ESRD), despite suggested inferior efficacy among these patients. We characterize an outbreak of influenza A(H1N1) in a kidney transplant unit. Altogether 23 patients were treated on the ward for postoperative care after kidney transplantation during the outbreak. After the first positive case, all patients were tested with nasopharyngeal swab tests and 7 patients were diagnosed with influenza A(H1N1). Altogether 17/23 patients had received adequate seasonal influenza vaccination, of whom 2/17 tested positive for influenza (one asymptomatic, one with mild cough). Five of six unvaccinated patients were diagnosed with influenza A(H1N1); 3/5 suffered from severe respiratory failure and were treated with ventilator support in the ICU, but all died due to acute respiratory distress syndrome, whereas 2/5 suffered from mild viral pneumonitis and recovered fully. The risk of influenza infection and mortality was significantly increased in unvaccinated patients (odds ratio 37.5 [95% CI 2.7-507.5, p = 0.01] and 6.7 [95% CI 2.3-18.9, p = 0.003], respectively). Influenza A(H1N1) had a high mortality in our cohort of nonvaccinated immunosuppressed patients early after kidney transplantation. None of the vaccinated patients developed serious disease, supporting the role of vaccination also for ESRD patients.

Rifaximin in the treatment of recurrent Clostridium difficile infection.

BACKGROUND: Clostridium difficile can cause severe antibiotic-associated colitis. Conventional treatments with metronidazole and vancomycin improve symptoms, but after discontinuation of treatment, C. difficile infection (CDI) recurs in a number of patients. Rifaximin is a rifamycin-based non-systemic antibiotic that has effect against C. difficile. AIM: To assess the effectiveness of rifaximin in recurrent C. difficile infection. METHODS: We retrospectively evaluated the records of 32 patients who were treated with rifaximin for recurrent C. difficile infection. The symptoms were evaluated 12 weeks after the start of treatment and patient records were followed up until 1 year after treatment. RESULTS: The mean age of the patients was 55 years (median 64, range: 19-84 years). Before the initiation of rifaximin therapy, the patients had undergone, on the average, 4.4 (range: 2-12) antimicrobial courses for C. difficile infection. C. difficile strain typing was performed in 27 patients. Eight (30%) patients had a strain with a DNA profile compatible with the BI/NAP1/027 ribotype. Antibiotic susceptibilities were determined of isolates from 22 patients. Most isolates (68%) had very low MIC-values for rifampin (<0.002 µg/mL) and the highest MIC value was 3.0 µg/mL. Isolates with a DNA profile compatible with the BI/NAP1/027 ribotype had, on the average, higher MICs of rifampin. After 12 weeks 17 (53%) patients had no relapse. The MIC value of rifampin seemed to predict the response to rifaximin treatment. CONCLUSIONS: Rifaximin is a safe treatment for C. difficile infection. It has a reasonable effect in C. difficile infection and it can be considered as an optional treatment for recurrent C. difficile infection.

Low incidence of invasive aspergillosis in allogeneic stem cell transplant recipients receiving amphotericin B inhalation prophylaxis.

In this retrospective study we evaluated the impact of amphotericin B (AmB) deoxycholate inhalation prophylaxis on invasive aspergillosis (IA) in 611 allogeneic stem cell transplant (alloSCT) recipients and their tolerance of the inhalations. The inhalations were not used in 1996-2000 (Period I). In 2001-2005 (Period II) all patients with acute graft-versus-host disease treated with high-dose methylprednisolone used the inhalation prophylaxis with a dose of 25 mg daily. No systemic antifungal prophylaxis was routinely used during the study period. IA was detected in 17 (13 proven, 4 probable) out of 257 (6.6%) patients transplanted in Period I and in 9 (6 proven, 3 probable) out of 354 (2.5%) patients transplanted in Period II (P=0.007). The median time to the diagnosis of IA was 95 days and 155 days post transplant in the 2 periods (P=0.225). The mortality of the patients with IA was 94.1% and 66.6% in Period I and Period II. The median duration of AmB inhalation prophylaxis was 84 days. Breakthrough IA was detected in 1 of the 111 (1%) patients during the prophylaxis. No discontinuation of prophylaxis due to side effects was recorded. Overall, with a median follow-up of 3.5 and 4.6 years, 42.4% and 59% of the patients were alive in Period I and Period II, respectively (P=0.001). In conclusion, the incidence of IA fell during the AmB inhalation prophylaxis, and the inhalations were well tolerated. Mortality of patients with IA was high. The overall survival of patients was significantly higher in Period II, indicating the advances made in SCT therapy over the 10-year period.

Factors influencing the performance level of Candida mannan antigen testing in allogeneic stem cell transplant recipients not receiving fluconazole prophylaxis.

In this study, we evaluated the value of the Platelia(®) Candida mannan antigen (Ag) sandwich enzyme-linked immunosorbent assay test in the diagnosis of invasive candidiasis (IC) and the degree of oral colonization by Candida species in 102 allogeneic stem cell transplantation recipients who were not receiving fluconazole prophylaxis. Of the 2071 serum samples, 98 (4.7%) yielded positive and 78 (3.8%) borderline results with a cut-off value of 0.5 ng/mL. One patient had IC. In this patient, 6 out of 9 serum samples were positive, the first one 49 days before Candida albicans candidemia. False-positive results occurred in 92 (4.4%) samples and in 54 (52.9%) patients. Use of valacyclovir and acyclovir was associated with false-positive or borderline results. The median Ag concentration of the true-positive results was significantly higher than the concentration of the false-positive results (1.60 versus 0.62 ng/mL, P<0.001). With higher cut-off values of 0.75 and 1.0 ng/mL, false-positive Ag test results were seen in 17 and 7 patients, respectively. Of the 657 oral samples, a total of 92 (14%) samples in 39 (38.2%) patients turned out to be positive. C. albicans grew in 82 samples (89.1%), other Candida species in 9 (9.8%), and Aspergillus fumigatus in 1 sample (1.1%). In conclusion, despite the lack of fluconazole prophylaxis, the incidence of IC was low (1%). False-positive Ag test results were common with a test cut-off value of 0.5 ng/mL, and a single positive result does not seem to predict IC. Multiple positive results might predict IC, as 6 out of 9 samples were positive in the only patient with IC, the first one 7 weeks before positive blood cultures.

Deep, respiratory tract and ear infections caused by Pseudallescheria (Scedosporium) and Microascus (Scopulariopsis) in Finland. A 10-year retrospective multi-center study.

Deep, respiratory tract and ear infections due to Microascaceae (Pseudallescheria, Scedosporium, Microascus or Scopulariopsis) were studied nationwide in Finland during 1993-2002. The data were based on 52,000 fungal cultures that represented about 50% of all such specimens in Finland and included all Finnish cases of profound immunosuppression. There were 39 cases that were re-evaluated as clinically significant, i.e., three pneumonias, two deep pedal infections and five wound infections, 11 sinusitis and 18 ear infections. The pedal infections and most pneumonias occurred in immunocompromised patients. Most cases, except the ear infections, were due to Pseudallescheria boydii. Two patients had lethal P. boydii pneumonia and a deep P. boydii infection of the foot contributed to a third lethal case. Two of the patients with lethal outcomes had received an allogeneic haematopoietic stem cell transplantation (AHSCT). Two patients with haematological malignancies were cured of deep site infections by a prolonged course of itraconazole. Wound, sinus and ear infections were cured or improved by local surgery or topical therapy. There were 0.8-1.7 cases of any type of infection per million inhabitants per year (MY) and 3.4 cases/1000 AHSCT. Mortality associated with Microascaceae in any type of patient was 0.06-0.12 MY.

Clinical characteristics, outcome and the role of viral load in nontransplant patients with Epstein-Barr viraemia.

Epstein-Barr virus (EBV) is important in the development of post-transplant lymphoproliferative disease in allogeneic stem cell and solid organ transplant recipients. We have studied the clinical significance of EBV DNAaemia among nontransplant patients in a tertiary referral hospital. We retrospectively reviewed the medical records for main diagnosis, outcome, immunosuppressive/cytotoxic chemotherapy and other opportunistic infections of the patients who were found positive in quantitative real-time PCR assay for EBV (EBV-qPCR) between the years 2000 and 2007. Allogeneic stem cell and solid organ transplant recipients were excluded, and all patients in nonsurgical adult wards were included. Altogether, 62 patients had at least one plasma sample positive with an EBV-qPCR. Fifteen were immunocompetent, most had primary EBV infection, and the outcome was good. On the other hand, 36 had malignant disease, seven had HIV infection and seven had immunosuppressive conditions of an other aetiology. All but one of the malignancies were of lymphoid origin, and most of these patients had a history of multiple cytotoxic treatments. Immunosuppressed patients had higher viral loads. EBV viraemia is associated with severe immunosuppression and lymphoid malignancies.

Invasive Aspergillus infections in allo-SCT recipients: environmental sampling, nasal and oral colonization and galactomannan testing.

A study was performed to investigate the air quality of a haematopoietic SCT ward, colonization of the upper airways with Aspergillus spp. and the role of galactomannan (GM) ELISA testing in serum in the diagnosis of invasive aspergillosis (IA). In 102 allo-SCT recipients, two cases of IA (one proven and one probable) were seen. Of 2071 serum samples, 12 were positive, two in a patient with proven IA and 10 in patients without IA. Of the 2059 negative samples, 22 were taken from the patient with probable IA. Of the 245 environmental samples, 20 (8.2%) were positive for filamentous fungi. Aspergillus fumigatus was seen in 14 samples. A total of 657 oral and nasal swabs were taken. Seven nasal samples and one oral sample were positive for Aspergillus species (A. fumigatus 4, A. niger 4) in four patients, one of whom had probable IA. In summary, most environmental samples were negative, colonization of the oral and nasal cavities was rare and IA was diagnosed in only 2% of patients. The GM ELISA test remained negative in one of two patients with IA and does not seem useful in a population of patients with a low incidence of IA.

Prolonged norovirus outbreak in a Finnish tertiary care hospital caused by GII.4-2006b subvariants.

Norovirus outbreaks are difficult to control in hospitals. Cohorting and contact isolation, disinfective surface cleaning and hand hygiene are key elements in outbreak control. A new norovirus variant, GII.4.-2006b, spreading across many continents, caused an exceptionally long epidemic period in Finland, from November 2006 to June 2007. Here, we describe the clinical and molecular characteristics of a norovirus outbreak in a large tertiary care hospital in Finland. Altogether 240 (18%) patients and 205 (19%) healthcare workers fell ill in the 504 bedded main building of Helsinki University Central Hospital during December 2006 to May 2007. The epidemic curve had three peaks in January, February and April, and different wards were affected each time. During the outbreak, 502 patient stool specimens were tested for norovirus RNA, 181 (36%) of which were positive. Molecular analysis of 48 positive specimens revealed three main subvariants of GII.4.-2006b circulating temporally within distinct wards. Of all microbiologically confirmed cases, 121 (67%) were nosocomial and nine (5%) died within 30 days of diagnosis. Molecular analysis suggested that the three main GII.4-2006b subvariants entered the hospital with gastroenteritis patients, and the nosocomial spread within wards coincided with the epidemic peaks. Active control measures, including temporary closure of the wards, ultimately confined the single-ward outbreaks. A prolonged outbreak in the community was probably the source for the prolonged outbreak period in the hospital.