Browsing by Author "Gregson, Dan"

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    Application of Epidemiology and Biostatistics to Malaria Diagnosis in Returning Travellers
    (2019-07-04) Cheaveau, James; Pillai, Dylan; Deardon, Rob; Gregson, Dan
    Today, malaria elimination is back on the agenda but for this to be feasible, there must be a coordinated global effort utilizing all available tools. Portable, sensitive diagnostics with a low limit of detection are required to detect the malaria reservoir, and novel antimalarials are required to combat the threat of artemisinin resistance. Returning travellers are a good population in which to investigate malaria physiology and diagnostics because there is a good supply of study participants and an abundance of easily available data. In Canada, a combination of microscopy and rapid diagnostic tests are used to diagnose malaria, but these lack sensitivity and require repeated testing to rule out the condition. A prospective diagnostic trial of the illumigene Malaria, loop-mediated isothermal amplification (LAMP) assay, manufactured by Meridian Bioscience was conducted in symptomatic returning travellers between June 2017 and January 2018. After discrepant resolution with RT-PCR, LAMP had a sensitivity of 100% (95% CI; 95.8-100) and a specificity of 100% (95% CI; 98.7-100). In symptomatic returning travellers, LAMP has the potential to replace traditional malaria diagnostics, allowing for malaria to be ruled out in a timely manner. It is unclear if uncomplicated malaria causes deranged liver enzymes, which has implications for antimalarial drug development. A retrospective cohort study was evaluated in returning travellers (n=4548) who underwent a malaria test and had liver enzymes measured within 31 days from 2010-2017. After adjusting for gender, age, and use of hepatotoxic medications, returning travellers testing positive for malaria had higher odds of having an abnormal TB [(OR: 12.64, 95% CI: 6.32 – 25.29), p<0.001] but not ALP [(OR: 0.32, 95% CI: 0.09 – 1.10), p=0.072], ALT [(OR: 1.01, 95% CI: 0.54 – 1.89), p=0.978] or AST [(OR: 1.26, 95% CI: 0.22 – 7.37), p=0.794], compared to those who tested negative. This is most likely to be due to haemolysis, which normalizes following treatment. LAMP can be used in the diagnosis of malaria in returning travellers, and it may have a role in malaria elimination. Uncomplicated malaria does not appear to cause raised aminotransferases in returning travellers, and consideration must be given to this in antimalarial drug development.
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    Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia without Evidence of Antecedent Viral Upper Respiratory Infection
    (2014-01-01) Toro, Cristina Moran; Janvier, Jack; Zhang, Kunyan; Fonseca, Kevin; Gregson, Dan; Church, Deirdre; Laupland, Kevin; Rabin, Harvey; Elsayed, Sameer; Conly, John
    BACKGROUND: USA300 community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains causing necrotizing pneumonia have been reported in association with antecedent viral upper respiratory tract infections (URI).METHODS: A case series of necrotizing pneumonia presenting as a primary or coprimary infection, secondary to CA-MRSA without evidence of antecedent viral URI, is presented. Cases were identified through the infectious diseases consultation service records. Clinical and radiographic data were collected by chart review and electronic records. MRSA strains were isolated from sputum, bronchoalveolar lavage, pleural fluid or blood cultures and confirmed using standard laboratory procedures. MRSA strains were characterized by susceptibility testing, pulsed-field gel electrophoresis, spa typing, agr typing and multilocus sequence typing. Testing for respiratory viruses was performed by appropriate serological testing of banked sera, or nucleic acid testing of nasopharyngeal or bronchoalveloar lavage specimens.RESULTS: Ten patients who presented or copresented with CA necrotizing pneumonia secondary to CA-MRSA from April 2004 to October 2011 were identified. The median length of stay was 22.5 days. Mortality was 20.0%. Classical risk factors for CA-MRSA were identified in seven of 10 (70.0%) cases. Chest tube placement occurred in seven of 10 patients with empyema. None of the patients had historical evidence of antecedent URI. In eight of 10 patients, serological or nucleic acid testing testing revealed no evidence of acute viral coinfection. Eight strains were CMRSA-10 (USA300). The remaining two strains were a USA300 genetically related strain and a USA1100 strain.CONCLUSION: Pneumonia secondary to CA-MRSA can occur in the absence of an antecedent URI. Infections due to CA-MRSA are associated with significant morbidity and mortality. Clinicians need to have an awareness of this clinical entity, particularly in patients who are in risk groups that predispose to exposure to this bacterium.
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    Point Prevalence Study of Antibiotic Susceptibility of Genital Group B Streptococcus Isolated from Near-Term Pregnant Women in Calgary, Alberta
    (2012-01-01) Church, Deirdre; Carson, Julie; Gregson, Dan
    BACKGROUND: Genital group B streptococcus (GBS) may be transmitted from a colonized mother to her infant if appropriate intrapartum antibiotic prophylaxis is not given. A recent case of GBS neonatal sepsis occurred due to an erythromycin-intermediate strain after empirical use of this drug as intrapartum prophylaxis.OBJECTIVE: To determine the regional antibiotic resistance rates of genital GBS isolates to penicillin, erythromycin and clindamycin.METHODS: A total of 309 genital GBS strains cultured from vaginal/rectal swabs were prospectively isolated and randomly selected between March and May 2011. Etest strips (bioMèrieux, France) were used to determine the minimum inhibitory concentrations to penicillin, erythromycin and clindamycin according to standard methods. All isolates that either demonstrated intermediate or full resistance to erythromycin had a D-test performed to detect inducible resistance to clindamycin. The resistance mechanism for each isolate was inferred from its antibiogram phenotype.RESULTS: All genital GBS isolates were susceptible to penicillin, but high rates of resistance were found to both erythromycin (25%) and clindamycin (22%), mainly due to acquisition of erythromycin ribosomal methylation genes (erm) that result in the MLSB resistance phenotype. Most often the MLSB resistance phenotype was constitutive (MLSB-C; 14.2%) rather than inducible (MLSB-I; 8.1%), and an efflux mechanism (msrA; 3%) was much less common.DISCUSSION: The present article is the first point prevalence study of genital GBS antibiogram profile that has been reported from a Canadian health care region. The high rates of resistance of genital GBS to both erythromycin and clindamycin is mainly due to the acquisition and spread of erm genes conveying the MSLB phenotype.CONCLUSION: Changes to clinical and laboratory practice in the Calgary, Alberta, region were made to prevent additional cases of neonatal GBS sepsis due to inappropriate intrapartum antibiotic prescription.
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    Prevalence of USA300 Colonization or Infection and Associated Variables During an Outbreak of Community-Associated Methicillin-Resistant Staphylococcus aureus in a Marginalized Urban Population
    (2007-01-01) Gilbert, Mark; MacDonald, Judy; Louie, Marie; Gregson, Dan; Zhang, Kunyan; Elsayed, Sameer; Laupland, Kevin; Nielsen, Diane; Wheeler, Virginia; Lye, Tara; Conly, John
    BACKGROUND: In 2004, an outbreak of the USA300 strain of methicillin-resistant Staphylococcus aureus (MRSA) was identified in persons with histories of homelessness, illicit drug use or incarceration in the Calgary Health Region (Calgary, Alberta). A prevalence study was conducted to test the hypotheses for factors associated with USA300 colonization or infection.METHODS: Participants were recruited at sites accessed by this marginalized population. Health care staff administered a questionnaire and collected crack pipes and nasal, axillary and skin infection swabs. Pipes and swabs were cultured according to standard techniques. MRSA isolates were further characterized by polymerase chain reaction (mecA, Panton-Valentine leukocidin and Staphylococcal cassette chromosome mec) and typing methods (pulsed-field gel electrophoresis, staphylococcal protein A typing and multilocus sequence typing). Colonization or infection was determined by having any one of nasal, axillary, skin infection or pipe swabs positive for USA300. Colonized participants had one or more nasal, axillary or pipe swab positive for USA300; infected participants had one or more skin infection swab positive for USA300.RESULTS: The prevalence of USA300 colonization or infection among 271 participants was 5.5% (range 3.1% to 9.0%). USA300 cases were more likely to report manipulation of skin infections (OR 9.55; 95% CI 2.74 to 33.26); use of crack pipes was not significant despite identification of the USA300 strain on two of four crack pipes tested. USA300 cases were more likely to report drug use between sex trade workers and clients (OR 5.86; 95% CI 1.63 to 21.00), and with casual sex partners (OR 5.40; 95% CI 1.64 to 17.78).CONCLUSION: Ongoing efforts to promote the appropriate treatment of skin infections in this population are warranted. The association of USA300 colonization or infection and drug use with sexual partners suggest a role for sexual transmission of the USA300 strain of MRSA.