background Severe acute respiratory syndrome (SARS) is a condition of unknown cause that has recently been recognized in patients in Asia, North America, and Europe. This report summarizes the initial epidemiologic findings, clinical description, and diagnostic findings that followed the identification of SARS in Canada. methods SARS was first identified in Canada in early March 2003. We collected epidemiologic, clinical, and diagnostic data from each of the first 10 cases prospectively as they were identified. Specimens from all cases were sent to local, provincial, national, and international laboratories for studies to identify an etiologic agent. results The patients ranged from 24 to 78 years old; 60 percent were men. Transmission occurred only after close contact. The most common presenting symptoms were fever (in 100 percent of cases) and malaise (in 70 percent), followed by nonproductive cough (in 100 percent) and dyspnea (in 80 percent) associated with infiltrates on chest radiography (in 100 percent). Lymphopenia (in 89 percent of those for whom data were available), elevated lactate dehydrogenase levels (in 80 percent), elevated aspartate aminotransferase levels (in 78 percent), and elevated creatinine kinase levels (in 56 percent) were common. Empirical therapy most commonly included antibiotics, oseltamivir, and intravenous ribavirin. Mechanical ventilation was required in five patients. Three patients died, and five have had clinical improvement. The results of laboratory investigations were negative or not clinically significant except for the amplification of human metapneumovirus from respiratory specimens from five of nine patients and the isolation and amplification of a novel coronavirus from five of nine patients. In four cases both pathogens were isolated. conclusions SARS is a condition associated with substantial morbidity and mortality. It appears to be of viral origin, with patterns suggesting droplet or contact transmission. The role of human metapneumovirus, a novel coronavirus, or both requires further investigation.

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Identification of Severe Acute Respiratory Syndrome in Canada

Background We sought to determine the role of human metapneumovirus in lower respiratory tract illness in previously healthy infants and children. Methods We tested nasal-wash specimens, obtained over a 25-year period from otherwise healthy children presenting with acute respiratory tract illness, for human metapneumovirus. Results A viral cause other than human metapneumovirus was determined for 279 of 687 visits for acute lower respiratory tract illness (41 percent) by 463 children in a population of 2009 infants and children prospectively seen from 1976 to 2001. There were 408 visits for lower respiratory tract illness by 321 children for which no cause was identified. Of these 321 children, specimens from 248 were available. Forty-nine of these 248 specimens (20 percent) contained human metapneumovirus RNA or viable virus. Thus, 20 percent of all previously virus-negative lower respiratory tract illnesses were attributable to human metapneumovirus, which means that 12 percent of all lower respiratory ...

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Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children.

Summary: Clinical laboratories historically diagnose seven or eight respiratory virus infections using a combination of techniques including enzyme immunoassay, direct fluorescent antibody staining, cell culture, and nucleic acid amplification tests. With the discovery of six new respiratory viruses since 2000, laboratories are faced with the challenge of detecting up to 19 different viruses that cause acute respiratory disease of both the upper and lower respiratory tracts. The application of nucleic acid amplification technology, particularly multiplex PCR coupled with fluidic or fixed microarrays, provides an important new approach for the detection of multiple respiratory viruses in a single test. These multiplex amplification tests provide a sensitive and comprehensive approach for the diagnosis of respiratory tract infections in individual hospitalized patients and the identification of the etiological agent in outbreaks of respiratory tract infection in the community. This review describes the molecular methods used to detect respiratory viruses and discusses the contribution that molecular testing, especially multiplex PCR, has made to our ability to detect respiratory viruses and to increase our understanding of the roles of various viral agents in acute respiratory disease.

Detection of Respiratory Viruses by Molecular Methods

We evaluated the percentage of hospitalizations for acute respiratory tract infections in children <3 years of age attributable to human metapneumovirus (HMPV) and other respiratory viruses in a prospective study during winter and spring 2002. We used real-time polymerase chain assays and other conventional diagnostic methods to detect HMPV, human respiratory syncytial virus (HRSV), and influenza viruses in nasopharyngeal aspirates of children. HMPV was detected in 12 (6%) of the 208 children hospitalized for acute respiratory tract infections, HRSV in 118 (57%), and influenza A in 49 (24%). Bronchiolitis was diagnosed in 8 (68%) and pneumonitis in 2 (17%) of HMPVinfected children; of those with HRSV infection, bronchiolitis was diagnosed in 99 (84%) and pneumonitis in 30 (25%). None of the HMPV-infected children was admitted to an intensive-care unit, whereas 15% of those with HRSV or influenza A infections were admitted. HMPV is an important cause of illness in young children with a similar, although less severe, clinical presentation to that of HRSV.

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Human metapneumovirus infections in hospitalized children.

During a 17-month period, we performed retrospective analyses of the prevalence of and clinical symptoms associated with human metapneumovirus (hMPV) infection, among patients in a university hospital in The Netherlands. All available nasal-aspirate, throat-swab, sputum, and bronchoalveolar-lavage samples (N=1515) were tested for hMPV RNA by reverse-transcriptase polymerase chain reaction. hMPV RNA was detected in 7% of samples from patients with respiratory tract illnesses (RTIs) and was the second-most-detected viral pathogen in these patients during the last 2 winter seasons. hMPV was detected primarily in very young children and in immunocompromised individuals. In young children, clinical symptoms associated with hMPV infection were similar to those associated with human respiratory syncytial virus (hRSV) infection, but dyspnea, feeding difficulties, and hypoxemia were reported more frequently in hRSV-infected children. Treatment with antibiotics and corticosteroids was reported more frequently in hMPV-infected children. From these data, we conclude that hMPV is an important pathogen associated with RTI.

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Prevalence and Clinical Symptoms of Human Metapneumovirus Infection in Hospitalized Patients

The virological features and clinical findings associated with the new human metapneumovirus (HMPV) were examined retrospectively in Canadian patients hospitalized for various respiratory conditions since 1993 Thirty-eight previously unidentified respiratory viruses isolated from rhesus monkey kindey (LLC-MK2) cells were found to be positive for HMPV by reverse-transcription polymerase chain reaction, and those strains clustered in 2 phylogenetic groups Children aged 65 years represented 351% and 459% of the HMPV-infected cases, respectively In hospitalized children, the most frequent diagnoses were pneumonitis (667%) and bronchiolitis (583%), whereas bronchitis and/or bronchospasm (60%) and pneumonitis (40%) were most commonly seen in elderly subjects Of the 15 patients with pneumonitis, 4 (267%) had immunosuppressive conditions and 6 (40%) were infants aged <15 months These findings suggest that HMPV can be associated with severe lower-respiratory-tract infections in very young children, the elderly, and immunocompromised patients

Virological Features and Clinical Manifestations Associated with Human Metapneumovirus: A New Paramyxovirus Responsible for Acute Respiratory-Tract Infections in All Age Groups

During the fall/winter season of 2004–05, we found 9 respiratory specimens positive for human parainfluenza virus type 4 (HPIV-4) in our laboratory (43% of all HPIVs) from patients with mild to moderate respiratory illnesses. Sequencing studies identified 8 different HPIV-4A strains and 1 HPIV-4B strain.

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Human parainfluenza type 4 infections, Canada.

The annual incidence rate of community-associated Clostridioides difficile infections in Quebec, Canada, has increased by 33.3%, from 0.51 (2008) to 0.68 (2015) cases/100,000 population, while incidence of healthcare-associated cases remained relatively stable. Possible causes include increased disease severity, increased antimicrobial drug use, emergence of virulent strains, and heightened physician awareness.

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Increased Community-Associated Clostridioides difficile Infections in Quebec, Canada, 2008-2015 1 .

Summary Background The incidence of health-care-associated Clostridioides difficile infections has been declining in the Canadian province of Quebec since 2015 We examined whether changes in high-risk antibiotic use could account for this decrease, as reported in other jurisdictions Methods We did a retrospective interrupted time-series analysis of 12 hospitals in the Canadian province of Quebec, representing a quarter of all health-care-associated C difficile infections in this region between April 1, 2012, and March 31, 2017 Data for high-risk antibiotic use (eg, amoxicillin–clavulanate, cephalosporins, fluoroquinolones, and clindamycin) in defined daily doses (DDDs) were extracted from local surveillance databases, and incidences of health-care-associated C difficile infections were extracted from provincial surveillance databases We used hierarchical segmented Poisson regression to assess whether variations in rates of health-care-associated C difficile infections followed variations in antibiotic use Findings Overall, 4455 health-care-associated C difficile infections and 6 281 960 patient-days were reported in the 12 participating hospitals, representing around a quarter of the provincial data A 50% decrease in the annual incidence of health-care-associated C difficile infections was recorded between 2012–13 and 2016–17 (9·4 infections per 10 000 patient-days vs 4·7 infections per 10 000 patient-days), and a 67% decrease in the proportion of these infections due to the NAP1/027 strain of C difficile was seen (64% in 2013 vs 21% in 2017) In total, 1 266 960 DDDs of high-risk antibiotics were distributed during the study period An increasing time trend was noted in high-risk antibiotic use, reaching a total of 223 DDDs per 1000 patient-days in 2016–17 An increase of one DDD per 1000 patient-days was associated with a 0·2% increase in the rate of health-care-associated C difficile infections in the following 4-week period A significant change in incidence of health-care-associated C difficile infections persisted despite adjustment for high-risk antibiotic use, as shown by a significant residual step change (0·825, 95% CI 0·731–0·932) and change in trend (0·987, 0·980–0·994) Interpretation Changes in use of high-risk antibiotics do not entirely account for the sudden decrease in health-care-associated C difficile infections in the Canadian province of Quebec since 2015 Further studies are needed to understand factors implicated in the change in epidemiology of health-care-associated C difficile infections Funding Institut National de Sante Publique du Quebec

Role of high-risk antibiotic use in incidence of health-care-associated Clostridioides difficile infection in Quebec, Canada: a population-level ecological study

Danielle Moisan

Papers

Virological Features and Clinical Manifestations Associated with Human Metapneumovirus: A New Paramyxovirus Responsible for Acute Respiratory-Tract Infections in All Age Groups

Human parainfluenza type 4 infections, Canada.

Increased Community-Associated Clostridioides difficile Infections in Quebec, Canada, 2008-2015 1 .

Role of high-risk antibiotic use in incidence of health-care-associated Clostridioides difficile infection in Quebec, Canada: a population-level ecological study