Background The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in implementation of public health measures worldwide to mitigate disease spread, including; travel restrictions, lockdowns, messaging on handwashing, use of face coverings and physical distancing. As the pandemic progresses, exceptional decreases in seasonal respiratory viruses are increasingly reported. We aimed to evaluate the impact of the pandemic on laboratory confirmed detection of seasonal non-SARS-CoV-2 respiratory viruses in Canada. Methods Epidemiologic data were obtained from the Canadian Respiratory Virus Detection Surveillance System. Weekly data from the week ending 30 th August 2014 until the week ending the 13 th March 2021 were analysed. We compared trends in laboratory detection and test volumes during the 2020/2021 season with pre-pandemic seasons from 2014 to 2019. Findings We observed a dramatically lower percentage of tests positive for all seasonal respiratory viruses during 2020-2021 compared to pre-pandemic seasons. For influenza A and B the percent positive decreased to 0•0015 and 0•0028 times that of pre-pandemic levels respectively and for RSV, the percent positive dropped to 0•0169 times that of pre-pandemic levels. Ongoing detection of enterovirus/rhinovirus occurred, with regional variation in the epidemic patterns and intensity. Interpretation We report an effective absence of the annual seasonal epidemic of most seasonal respiratory viruses in 2020/2021. This dramatic decrease is likely related to implementation of multi-layered public health measures during the pandemic. The impact of such measures may have relevance for public health practice in mitigating seasonal respiratory virus epidemics and for informing responses to future respiratory virus pandemics. Funding No additional funding source was required for this study.

The biocide chlorhexidine (CHX) as well as additional membrane-active agents were shown to induce expression of the mexCD-oprJ multidrug efflux operon, dependent upon the AlgU stress response sigma factor. Hyperexpression of this efflux system in nfxB mutants was also substantially AlgU dependent. CHX resistance correlated with efflux gene expression in various mutants, consistent with MexCD-OprJ being a determinant of CHX resistance.Pseudomonas aeruginosa is an opportunistic human pathogen characterized by an innate resistance to multiple antimicrobials (13), resistance increasingly attributable to the operation of broadly specific, tripartite multidrug efflux systems of the resistance-nodulation-division (RND) family (35,36). One of these, MexCD-OprJ, was originally identified as a determinant of fluoroquinolone resistance (17) but is known to accommodate a variety of clinically relevant antimicrobials (35, 36) as well as biocides (5), dyes, detergents, and organic solvents (27,45,46). MexCD-OprJ is typically quiescent in wild-type cells (20,46), with expression following mutation of the nfxB gene (16,22,23,50) that is divergently transcribed from the mexCDoprJ operon and encodes a repressor of mexCD-oprJ expression (37). Little is known about the signal(s) to which this regulator responds in naturally promoting efflux gene expression, although mexCD-oprJ is inducible by the biocides benzalkonium chloride and chlorhexidine (CHX) (33). These biocides are known to interact with and disrupt bacterial membranes (8), with the possibility that mexCD-oprJ expression is a response to membrane damage/envelope stress. Envelope stress responses (ESRs) are well documented in bacteria (40, 41), with the extracytoplasmic sigma factor RpoE being a key regulator of ESRs in Escherichia coli and other gram-negative bacteria (1,40,41). The RpoE homologue in P. aeruginosa is AlgU, first identified as a regulator of alginate production in mucoid isolates recovered from the lungs of cystic fibrosis patients (15, 28) and shown to be functionally interchangeable with RpoE (51). This study was undertaken to assess the contribution of MexCD-OprJ to biocide resistance in P. aeruginosa and its possible regulation as part of an ESR.Bacterial strains and plasmids used in this study are listed in Table 1. Bacteria were cultivated at 37°C in Luria broth (LB) (34) supplemented with antibiotics to maintain plasmids as needed (for pEX18Tc and derivatives, tetracycline was used [10 g/ml for E. coli and 50 to 100 g/ml for P. aeruginosa]; for pMMB206 and derivatives, chloramphenicol was used [10 g/ml for E. coli and 150 g/ml for P. aeruginosa]; for pK18MobSacB and derivatives, kanamycin was used [50 g/ml for E. coli and 750 to 1,500 g/ml for P. aeruginosa as indicated]; for miniCTX-lacZ and derivatives, tetracycline was used [10 g/ml for E. coli and 25 g/ml for P. aeruginosa]; and for pUC19 and derivatives, ampicillin was used [100 g/ml for E. coli]). AlgU-encoding plasmid pSF02 was constructed by amplifying the algU gene from the chromosome (isol...

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with SARS-CoV-2 is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay, and converted to estimated VL (copies/mL) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 vs. 197 ages 0-4; 79 vs 97 ages 5-9; 69 vs 75 ages 10-13; 73 vs 109 ages 14-17) were compared. The median adjusted Ct value in asymptomatic children was 10.3 cycles higher than for symptomatic children (p< 0.0001), and VL 3-4 logs lower (p<0.0001); differences were consistent (p<0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (OR 6.5, p = 0.01), recent contact (OR 2.3, p = 0.02), and testing for surveillance (OR 2.7, p = 0.005) had higher estimated risk of having a Ct value in the lowest quartile than children without, while immunocompromise had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in the nasopharynx/oropharynx than symptomatic children, but timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

No abstract

Introduction Annual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive. Aim We investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults. Methods We conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history. Results We included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1–3 (26%; 95%CI: 13 to 37%), 4–6 (24%; 95%CI: 15 to 33%), 7–8 (13%; 95%CI: 2 to 22%), or 9–10 (7%; 95%CI: −4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously. Conclusions Although VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.

No abstract

PURPOSE Seasonal influenza vaccination is recommended for patients with cancer despite concerns of disease or treatment-associated immunosuppression. The objective of this study was to evaluate vaccine effectiveness (VE) against laboratory-confirmed influenza for patients with cancer. PATIENTS AND METHODS We conducted an observational test-negative design study of previously diagnosed patients with cancer 18 years of age and older who underwent influenza testing during the 2010-2011 to 2015-2016 influenza seasons in Ontario, Canada. We linked individual-level cancer registry, respiratory virus testing, and health administrative data to identify the study population and outcomes. Vaccination status was determined from physician and pharmacist billing claims. We used multivariable logistic regression to estimate VE, adjusting for age, sex, rurality, income quintile, cancer characteristics, chemotherapy exposure, comorbidities, previous health care use, influenza season, and calendar time. RESULTS We identified 26,463 patients with cancer who underwent influenza testing, with 4,320 test-positive cases (16%) and 11,783 (45%) vaccinated. Mean age was 70 years, 52% were male, mean time since diagnosis was 6 years, 69% had solid tumor malignancies, and 23% received active chemotherapy. VE against laboratory-confirmed influenza was 21% (95% CI, 15% to 26%), and VE against laboratory-confirmed influenza hospitalization was 20% (95% CI, 13% to 26%). For patients with solid tumor malignancies, VE was 25% (95% CI, 18% to 31%), compared with 8% (95% CI, –5% to 19%) for patients with hematologic malignancies ( P = .015). Active chemotherapy usage did not significantly affect VE, especially among patients with solid tumor cancer. CONCLUSION Our results support recommendations for influenza vaccination for patients with cancer. VE was decreased for patients with hematologic malignancies, and there was no significant difference in VE among patients with solid tumor cancer receiving active chemotherapy. Strategies to optimize influenza prevention among patients with cancer are warranted.

Bacterial pneumonia complicating influenza is well-recognized as a severe manifestation of influenza, accounting for a substantial number of deaths from the 1918 influenza pandemic. Influenza-associated bacterial pneumonia remains a major contributor to the burden of influenza, and poses new challenges as antibiotic-resistant organisms such as methicillin-resistant Staphylococcus aureus spread. We provide an overview of the current state of knowledge of the epidemiology and co-pathogenesis of influenza-associated bacterial pneumonia, and outline management approaches and their limitations. We review preventative measures and discuss implications for pandemic planning. Knowledge gaps are underscored and future research directions are proposed.