Browsing by Author "Parkins, Michael D."
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Item Open Access Clinical epidemiology and impact of Haemophilus influenzae airway infections in adults with cystic fibrosis(2024-10-27) Weyant, R. Benson; Waddell, Barbara J.; Acosta, Nicole; Izydorczyk, Conrad; Conly, John M.; Church, Deirdre L.; Surette, Michael G.; Rabin, Harvey R.; Thornton, Christina S.; Parkins, Michael D.Abstract Background Haemophilus influenzae is prevalent within the airways of persons with cystic fibrosis (pwCF). H. influenzae is often associated with pulmonary exacerbations (PEx) in pediatric cohorts, but in adults, studies have yielded conflicting reports around the impact(s) on clinical outcomes such as lung function decline. Accordingly, we sought to discern the prevalence, natural history, and clinical impact of H. influenzae in adult pwCF. Methods This single-centre retrospective cohort study reviewed all adult pwCF with H. influenzae sputum cultures between 2002 and 2016. From this cohort, persistently infected subjects (defined as: ≥2 samples with the same pulsotype and > 50% sputum culture-positive for H. influenzae in each year) were matched (1:2) to controls without H. influenzae. Demographic and clinical status (baseline health or during periods of PEx) were obtained at each visit that H. influenzae was cultured. Yearly biobank isolates were typed using pulsed-field gel electrophoresis (PFGE) to assess relatedness. Results Over the study period, 30% (n = 70/240) of pwCF were culture positive for H. influenzae, of which 38 (54%) were culture-positive on multiple occasions and 12 (17%) had persistent infection. One hundred and thirty-seven isolates underwent PFGE, with 94 unique pulsotypes identified. Two (1.5%) were serotype f with the rest non-typeable (98.5%). H. influenzae isolation was associated with an increased risk of PEx (RR = 1.61 [1.14–2.27], p = 0.006), however, this association was lost when we excluded those who irregularly produced sputum (i.e. only during a PEx). Annual lung function decline did not differ across cohorts. Conclusions Isolation of H. influenzae was common amongst adult pwCF but often transient. H. influenzae infection was not associated with acute PEx or chronic lung function decline.Item Open Access Development and application of ultra-sensitive tools for the detection of malaria(2020-01) Mohon, Md Abu Naser; Pillai, Dylan R.; Wasmuth, James D.; Parkins, Michael D.The goal to eliminate malaria has been challenged by the lack of accurate diagnostic tools to identify symptomatic, asymptomatic, and drug-resistant malaria carriers. In this dissertation, we have shown the potential of the Loop-mediated Isothermal Amplification (LAMP)-based diagnostic approaches to be a powerful tool available for malaria elimination. We have validated the combination of the Non-instrumented Nucleic Acid (NINA) platform heater (PATH, Seattle) with a commercial LAMP kit (LoopAmp malaria Pan/Pf detection kit), with a view to deploying it in extremely resource-limited settings in the future. An ultrasensitive (US)-LAMP assay was also developed and validated to identify asymptomatic malaria reservoirs. Moreover, a novel strategy for detecting single nucleotide polymorphisms (SNPs) by the LAMP method was designed and deployed for spotting artemisinin resistance in P. falciparum. We conclude that the NINA-LAMP assay can be a convenient test for detecting symptomatic malaria cases with a sensitivity of 100% and specificity of 98.6% compared to the gold standard nested PCR. Additionally, the US-LAMP assay was able to achieve a limit of detection (LOD) between 25 to 100 parasites/mL from dried blood spots. We have also found that the overall prevalence of asymptomatic malaria was 22.1% in the Gambella region of Ethiopia, detected by the US-LAMP assay. The sensitivity and the specificity of the US-LAMP assay were 92.6% and 97.1%, respectively compared to an ultrasensitive quantitative reverse transcriptase PCR. Additionally, the SNP-LAMP assay was 100% sensitive and 97.3% specific to identify the C580Y mutation in the kelch 13 propeller gene, which is known as the major genetic determinant of artemisinin resistance in Southeast Asia. Furthermore, we conclude that artemisinin resistance-linked kelch 13 propeller mutations are absent in the Bangladeshi P. falciparum isolates. However, two cases of the A578S SNP in the kelch 13 propeller gene were found in those P. falciparum isolates, although this SNP was not associated with artemisinin resistance. In conclusion, as the LAMP-based diagnostic approaches are simple, low-cost, and accurate compared to currently available nucleic acid tests, they can be used at different aspects to diagnose malaria and expedite elimination.Item Open Access The effects of diketopiperazines on the virulence of Burkholderia cepacia complex species(2021-01-15) Jervis, Nicole Marie; Storey, Douglas G.; Harrison, Joe J.; Parkins, Michael D.; Savchenko, Alexei; Storey, Douglas G.Recognized as a novel class of quorum sensing inhibitors (QSIs), 2,5-diketopiperazines (DKPs) are small, organic molecules that hold many important physiochemical properties which has led to recent inquiries into their effects towards limiting the pathogenicity of multi-drug resistant bacterial pathogens. Species within the Burkholderia cepacia complex (Bcc) are one such group of pathogens that require attention towards the development of alternative therapeutic strategies given their detrimental clinical outcomes, particularly in patients with cystic fibrosis. By targeting Bcc QS regulation, our data demonstrated DKPs, cyclo(-D-ala-val), cyclo(-pro-val), cyclo(-leu-pro), and cyclo(-phe-pro) to alter the production of extracellular virulence factors and to decrease the production of biofilm-associated factors which comprise the protective extracellular matrix of Bcc biofilms. Further analysis demonstrated these DKPs to also possess antibiotic potentiator activity, enhancing the antimicrobial activity of ceftazidime, meropenem, and tobramycin. Taken together, the data collected in this study offers an initial step towards understanding the potential role of DKPs in the development of alternative therapeutics.Item Open Access Epidemiology and risk factors for pyogenic liver abscess in the Calgary Health Zone revisited: a population-based study(2021-09-10) Losie, Jennifer A.; Lam, John C.; Gregson, Daniel B.; Parkins, Michael D.Abstract Background Pyogenic liver abscess (PLA), although uncommon in North America, is associated with significant morbidity and mortality. We sought to re-examine the epidemiology, risk factors, and outcomes of PLA in a large, diverse Canadian health zone. Methods All Calgary Health Zone (CHZ) residents aged ≥20 with PLA between 2015 and 2017 were identified. Incidence and mortality rates were calculated using census data. Risk factors for PLA were identified using a multivariate analysis. Data was compared to 1999–2003 data, also collected in the CHZ. Results There were 136 patients diagnosed with PLA between 2015 and 2017. Incidence rate during this period increased significantly relative to 1999–2003 (3.7 vs 2.3 cases/100,000 population, p < 0.01), however, mortality rates remained similar. The microbiological composition of PLA did not change over this 15-year time period but the number of antimicrobial resistant isolates did increase (8% vs 1%, p = 0.04). The greatest risk factors for PLA relative to general populations included current malignancy, liver-transplant, end-stage renal disease, and cirrhosis. Thirty-day mortality was 7.4% and independent risk factors included polymicrobial bacteremia, absence of abscess drainage, congestive-heart failure, a history of liver disease, and admission bilirubin. Conclusions Pyogenic liver abscess is a health concern with rising incidence rate. The increasing prevalence of comorbidities in our population and factors that are associated with risk of PLA suggests this will continue to be an emerging diagnosis of concern. Increasing prevalence of antibiotic resistant organisms compounding unclear optimal treatment regimens is an issue that requires urgent study.Item Open Access Exploring the Effects of Inhaled Antibiotics on the Cystic Fibrosis Lung Microbiome and Pseudomonas aeruginosa Population Diversity and their Clinical Implications(2020-01-20) Heirali, Alya; Parkins, Michael D.; Storey, Douglas G.; van Marle, Guido; Surette, Michael G.The CF lung microbiome is composed of a diverse group of microorganisms. Where the constituents of the microbiome originate from remains poorly understood. The work presented herein shows that the home environment may serve as a reservoir for infection in patients with CF. Researchers have demonstrated that the CF lung microbial communities are dynamic and complex. As patients age and disease progression occurs the diversity of organisms colonizing the lower airways generally decreases and patients become dominated by organisms such as Pseudomonas aeruginosa. Several studies have attempted to increase our understanding of the shifts in the microbial communities prior to pulmonary exacerbations. However, there is a tremendous knowledge gap on how the microbiome changes through chronic suppressive inhaled antibiotics used by the majority of CF patients in Canada. Accordingly, we sought to investigate how inhaled aztreonam and tobramycin affect the CF lung microbiome and whether the microbiome can be used as a tool to predict patient response. We showed that the lung microbiome is relatively fixed in adults with CF despite potent inhaled antibacterial therapy. The relative abundance of Staphylococcus was associated with response in all three studies assessing the effects of inhaled antibiotics on the lung microbiome. Specifically, a higher abundance of Staphylococcus at baseline was associated with non-response to inhaled aztreonam and response to inhaled tobramycin – mirroring expected antibacterial activity and suggesting a potential biomarker for treatment response. Keywords: lung microbiome, cystic fibrosis, inhaled antibiotics, Staphylococcus, P. aeruginosa, biomarkerItem Open Access Gene expression in pseudomonas aeruginosa biofilms(2000) Parkins, Michael D.; Storey, Douglas G.Item Open Access Incidence, susceptibility and outcomes of candidemia in adults living in Calgary, Alberta, Canada (2010–2018)(2023-02-20) Bourassa-Blanchette, Samuel; Biesheuvel, Marit M.; Lam, John C.; Kipp, Alexander; Church, Deirdre; Carson, Julie; Dalton, Bruce; Parkins, Michael D.; Barkema, Herman W.; Gregson, Daniel B.Abstract Background Candidemia is increasing in frequency and is associated with high mortality. We sought to determine the burden of illness, the population it affects and its resistance profile in our region. Methods The Calgary Zone (CZ) provides all care for residents of Calgary and surrounding communities (~ 1.69 million) via five tertiary hospitals each served by a common single laboratory for acute care microbiology. All adult patients in the CZ with at least one Candida spp.-positive blood culture between January 1, 2010, and December 31, 2018, were identified using microbiological data from Calgary Lab Services, the laboratory that processes > 95% of all blood culture samples in the CZ, were reviewed for the study. Results The overall annual incidence of candidemia among individuals living in the CZ was 3.8 per 100,000 persons (Median age 61 years (IQR 48–72) and 221/455 (47.4%) were female). C. albicans was the most common species (50.6%), followed by C. glabrata, (24.0%). No other species accounted for more than 7% of cases. Overall mortality at 30, 90, and 365 days was 32.2, 40.1, and 48.1% respectively. Mortality rate did not differ by Candida species. Of individuals who developed candidemia, more than 50% died within the next year. No new resistance pattern has emerged in the most common Candida species in Calgary, Alberta. Conclusions In Calgary, Alberta, the incidence of candidemia has not increased in the last decade. C. albicans was the most common species and it remains susceptible to fluconazole.Item Open Access Metastatic Bladder Cancer Presenting with Persistent Hematuria in Young Man with Cystic Fibrosis(2013-05-14) Patel, Premal; Rabin, Harvey R.; Vickers, Michael M.; Parkins, Michael D.We report a case of metastatic bladder cancer developing in a young man with cystic fibrosis (CF) that was initially diagnosed as ureterolithiasis and managed as renal colic. With the improved survival of patients with CF, an increasing burden of extrapulmonary disease manifestations is apparent. Renal colic is observed at an increased frequency in patients with CF relative to the general population and is a commonly recognized cause of hematuria. However, CF patients harboring a malignancy are recognized to be at increased risk of delayed identification owing to atypical symptoms and lack of demographic risk factors. This case illustrates how investigations to rule out malignancy are warranted in those CF patients not responding to therapies directed towards presumptive diagnoses.Item Open Access Systematic review: cystic fibrosis in the SARS-CoV-2/COVID-19 pandemic(2021-05-20) Mathew, Hannah R.; Choi, May Y.; Parkins, Michael D.; Fritzler, Marvin J.Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the development of life-threatening COVID-19 are believed to disproportionately affect certain at-risk populations. However, it is not clear whether individuals with cystic fibrosis (CF) are at a higher risk of COVID-19 or its adverse consequences. Recurrent respiratory viral infections are often associated with perturbation and pulmonary exacerbations of CF as evidenced by the significant morbidity observed in CF individuals during the 2009 H1N1 pandemic. The primary goal of this review was to systematically survey published accounts of COVID-19 in CF and determine if individuals with CF are disproportionally affected by SARS-CoV-2 and development of COVID-19. Methods We conducted a systematic literature search using EMBASE and Medline between April 28 and December 10, 2020. Six evaluable studies reporting on a total of 339 individuals with CF who developed COVID-19 were included in this study. Results We found that although individuals with CF generally experience acute exacerbations of lung disease from infectious agents, COVID-19 incidence estimates in CF appear to be lower than in the general population. However, there are reports of subsets of CF, such as those who had organ transplants, that may experience a more severe COVID-19 course. Potential protective mechanisms in the CF population include pre-pandemic social isolation practices, infection prevention and control knowledge, altered expression of angiotensin-converting enzyme, and the use of certain medications. Conclusions Although individuals with CF are at risk of acute exacerbations often precipitated by respiratory tract viral infections, published evidence to date indicated that individuals with CF do not experience higher risks of contracting SARS-CoV-2 infection. However, there is evidence that some subsets within the CF population, including those post-transplantation, may experience a more severe clinical course. As SARS-CoV-2 variants are identified and the pandemic goes through additional waves of disease outbreaks, ongoing monitoring of the risk of COVID-19 in individuals with CF is required.