Alex Marchand-Austin

Pulmonary Nontuberculous Mycobacterial Disease, Ontario, Canada, 1998–2010

We measured the prevalence and temporal trends of pulmonary nontuberculous mycobacterial disease among residents of Ontario, Canada, during 1998–2010. Five-year prevalence increased from 29.3 cases/100,000 persons in 1998–2002 to 41.3/100,000 in 2006–2010 (p<0.0001). Improved laboratory methods did not explain this increase, suggesting a surge in disease prevalence.

Increased risk of mycobacterial infections associated with anti-rheumatic medications

Rationale Anti-tumour necrosis factor (TNF) agents and other anti-rheumatic medications increase the risk of TB in rheumatoid arthritis (RA). Whether they increase the risk of infections with nontuberculous mycobacteria (NTM) is uncertain. Objectives To determine the effect of anti-TNF therapy and other anti-rheumatic drugs on the risk of NTM disease and TB in older patients with RA. Methods Population-based nested case–control study among Ontario seniors aged ≥67 years with RA who were prescribed at least one anti-rheumatic medication between 2001 and 2011. We identified cases of TB and NTM disease microbiologically and identified drug exposures using linked prescription drug claims. We estimated ORs using conditional logistic regression, controlling for several potential confounders. Measurements and main results Among 56 269 older adults with RA, we identified 37 cases of TB and 211 cases of NTM disease; each case was matched to up to 10 controls. Individuals with TB or NTM disease were both more likely to be using anti-TNF therapy (compared with non-use); adjusted ORs (95% CIs) were 5.04 (1.27 to 20.0) and 2.19 (1.10 to 4.37), respectively. Exposure to leflunomide and other anti-rheumatic drugs with high immunosuppressing potential also were associated with both TB and NTM disease, while oral corticosteroids and hydroxychloroquine were associated with NTM disease. Conclusions Anti-TNF use is associated with increased risk of both TB and NTM disease, but appears to be a relatively greater risk for TB. Several other anti-rheumatic drugs were also associated with mycobacterial infections.

Rhinovirus outbreaks in long-term care facilities, Ontario, Canada.

Diagnostic difficulties may have led to underestimation of rhinovirus infections in long-term care facilities. Using surveillance data, we found that rhinovirus caused 59% (174/297) of respiratory outbreaks in these facilities during 6 months in 2009. Disease was sometimes severe. Molecular diagnostic testing can differentiate these outbreaks from other infections such as influenza.

Deriving Group A Streptococcus Typing Information from Short-Read Whole Genome Sequencing Data

ABSTRACT Typing of group A Streptococcus (GAS) is crucial for infection control and epidemiology. While whole-genome sequencing (WGS) is revolutionizing the way that bacterial organisms are typed, it is necessary to provide backward compatibility with currently used typing schemas to facilitate comparisons and understanding of epidemiological trends. Here, we sequenced the genomes of 191 GAS isolates representing 42 different emm types and used bioinformatics tools to derive commonly used GAS typing information directly from the short-read WGS data. We show that emm typing and multilocus sequence typing can be achieved rapidly and efficiently using this approach, which also permits the determination of the presence or absence of genes associated with GAS tissue tropism. We also report on how the WGS data analysis was instrumental in identifying ambiguities present in the commonly used emm type database hosted by the U.S. Centers for Disease Control and Prevention.

High Incidence of Invasive Group A Streptococcus Disease Caused by Strains of Uncommon emm Types in Thunder Bay, Ontario, Canada

ABSTRACT An outbreak of type emm59 invasive group A Streptococcus (iGAS) disease was declared in 2008 in Thunder Bay District, Northwestern Ontario, 2 years after a countrywide emm59 epidemic was recognized in Canada. Despite a declining number of emm59 infections since 2010, numerous cases of iGAS disease continue to be reported in the area. We collected clinical information on all iGAS cases recorded in Thunder Bay District from 2008 to 2013. We also emm typed and sequenced the genomes of all available strains isolated from 2011 to 2013 from iGAS infections and from severe cases of soft tissue infections. We used whole-genome sequencing data to investigate the population structure of GAS strains of the most frequently isolated emm types. We report an increased incidence of iGAS in Thunder Bay compared to the metropolitan area of Toronto/Peel and the province of Ontario. Illicit drug use, alcohol abuse, homelessness, and hepatitis C infection were underlying diseases or conditions that might have predisposed patients to iGAS disease. Most cases were caused by clonal strains of skin or generalist emm types (i.e., emm82, emm87, emm101, emm4, emm83, and emm114) uncommonly seen in other areas of the province. We observed rapid waxing and waning of emm types causing disease and their replacement by other emm types associated with the same tissue tropisms. Thus, iGAS disease in Thunder Bay District predominantly affects a select population of disadvantaged persons and is caused by clonally related strains of a few skin and generalist emm types less commonly associated with iGAS in other areas of Ontario.

Effectiveness of pertussis vaccination and duration of immunity

Background: A resurgence of pertussis cases among both vaccinated and unvaccinated people raises questions about vaccine effectiveness over time. Our objective was to study the effectiveness of the pertussis vaccine and characterize the effect of waning immunity and whole-cell vaccine priming. Methods: We used the test-negative design, a nested case–control study with test-negative individuals as controls. We constructed multivariable logistic regression models to estimate odds ratios (ORs). Vaccine effectiveness was calculated as (1 – OR) × 100. We assessed waning immunity by calculating the odds of developing pertussis per year since last vaccination and evaluated the relative effectiveness of priming with acellular versus whole-cell vaccine. Results: Between Dec. 7, 2009, and Mar. 31, 2013, data on 5867 individuals (486 test-positive cases and 5381 test-negative controls) were available for analysis. Adjusted vaccine effectiveness was 80% (95% confidence interval [CI] 71% to 86%) at 15–364 days, 84% (95% CI 77% to 89%) at 1–3 years, 62% (95% CI 42% to 75%) at 4–7 years and 41% (95% CI 0% to 66%) at 8 or more years since last vaccination. We observed waning immunity with the acellular vaccine, with an adjusted OR for pertussis infection of 1.27 (95% CI 1.20 to 1.34) per year since last vaccination. Acellular, versus whole-cell, vaccine priming was associated with an increased odds of pertussis (adjusted OR 2.15, 95% CI 1.30 to 3.57). Interpretation: We observed high early effectiveness of the pertussis vaccine that rapidly declined as time since last vaccination surpassed 4 years, particularly with acellular vaccine priming. Considering whole-cell vaccine priming and/or boosters in pregnancy to optimize pertussis control may be prudent.

SEVERE HUMAN RHINOVIRUS OUTBREAK ASSOCIATED WITH FATALITIES IN A LONG-TERM CARE FACILITY IN ONTARIO, CANADA

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The risk of mycobacterial infections associated with inhaled corticosteroid use

Inhaled corticosteroid (ICS) use is associated with an increased risk of pneumonia. This study was performed to determine if ICS use is associated with an increased risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) or tuberculosis (TB). We conducted a population-based nested case–control study using linked laboratory and health administrative databases in Ontario, Canada, including adults aged ≥66 years with treated obstructive lung disease (i.e. asthma, chronic obstructive pulmonary disease (COPD) or asthma–COPD overlap syndrome) between 2001 and 2013. We estimated odds ratios comparing ICS use with nonuse among NTM-PD and TB cases and controls using conditional logistic regression. Among 417 494 older adults with treated obstructive lung disease, we identified 2966 cases of NTM-PD and 327 cases of TB. Current ICS use was associated with NTM-PD compared with nonuse (adjusted OR (aOR) 1.86, 95% CI 1.60–2.15) and was statistically significant for fluticasone (aOR 2.09, 95% CI 1.80–2.43), but not for budesonide (aOR 1.19, 95% CI 0.97–1.45). There was a strong dose–response relationship between incident NTM-PD and cumulative ICS dose over 1 year. There was no significant association between current ICS use and TB (aOR 1.43, 95% CI 0.95–2.16). This study suggests that ICS use is associated with an increased risk of NTM-PD, but not TB. Inhaled corticosteroid use in older adults with obstructive lung disease increases with risk of NTM lung infection http://ow.ly/k2mL30cDO1b

Risk of nontuberculous mycobacterial pulmonary disease with obstructive lung disease

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasingly prevalent [1] and especially common in the elderly [2]. It is usually chronic, requiring complex therapy with suboptimal outcomes [3]. Risk factors for NTM-PD may be covert, presumably disordered mucociliary defences, or overt structural lung abnormalities. In one study, 56% of NTM-PD patients had unexplained nontuberculous mycobacteria (NTM) and among the rest with structural lung disease, chronic obstructive pulmonary disease (COPD) was the most common predisposing condition [4]. High incidence of NTM pulmonary disease in people with COPD and asthma (142 and 53 per 100 000 person-years) http://ow.ly/2laN300kLOV

Human metapneumovirus prevalence and molecular epidemiology in respiratory outbreaks in Ontario, Canada

Human metapneumovirus (hMPV) has been identified previously as a cause of respiratory outbreaks in adults, including the elderly. The objective of this study was to document respiratory outbreaks that were caused by hMPV in Ontario, Canada and to identify the various circulating genotypes during April 2009–February 2012. The majority of the outbreaks that were part of this study were in adults (>65 years). Total nucleic acid extraction was done on 123 residual anonymized clinical specimens from 51 different respiratory outbreaks. Specimens were subjected to PCR amplification and Sanger sequencing targeting the F and G genes of hMPV. Phylogenetic analysis was performed to identify genotypes. HMPV accounted for 195 (8.5%) of 2,292 respiratory outbreaks. Genotype A2b was most prevalent, detected in 28 (54.9%) of 51 typed hMPV‐positive outbreaks. The genotype A2b2 that was described recently was also identified. In earlier reports, subtype A1 was reported in Canada which was absent in the specimens typed in this study. This shift in genotype may be significant in terms of disease severity, and for any future vaccine considerations. Regular testing for hMPV should be done as part of outbreak investigation. J. Med. Virol. 87:269–274, 2015.