Research Interests

• Antifungal resistance in Candida species - in vitro/in vivo correlation
• Molecular mechanisms of resistance to azole antifungals
• Rapid diagnosis of invasive fungal infections in the immunocompromised host
• Strain typing of Candida species
• Risk factors and long-term neurological outcome of neonatal candiasis

Research Activities

Improvements in the diagnosis and understanding of pediatric infectious diseases

Infections in children are very common and differ in important ways from those seen in adults. Infections are a common cause of visits to and admissions to Sick Kids in children who suffer from chronic conditions and diseases that impair their immune system, and also in otherwise healthy children. Our goal is to improve the diagnosis of these infections, so that every child with a probable infection stands the best chance of having that infection diagnosed. To do this we apply our understanding of the basic disease process that we observe combined with the latest research techniques.

Two main areas in which we are making progress are in the diagnosis of pediatric respiratory infections (i.e. colds, flu-like illnesses) and serious, life-threatening fungal infections in patients with cancer. Based on our experience with SARS in 2003, we have determined what are the best and quickest methods to diagnose respiratory infections from samples taken from different areas of the body. We are using very sensitive techniques based on detecting very small amounts of genetic material of the viruses in question. This will permit us to rapidly detect cases of newly emerging infections such as SARS and avian influenza and to distinguish them from other less severe infections such as RSV and parainfluenza infection. This will have a significant impact on the control of the spread of these infections should they be introduced or re-introduced into our community.

Children with impairment of their immune systems, such as extremely premature newborns and those who are being treated for cancer, can develop severe infections with a number of microorganisms, including fungi. The more quickly these infections can be diagnosed and treated, the better the outcome. We are applying molecular techniques to diagnose and track these infections. In addition, we are studying premature babies who become infected with the yeast, here and at other children’s hospitals across Canada. We will shortly begin an analysis of the risk factors for acquiring this infection, and of the long-term outcome on growth and development of these babies who have had this serious infection in infancy.

Fungal Infections in the Immunocompromised Host

The focus of this work is on the pathogenesis, diagnosis, treatment and outcome of serious invasive fungal infections that occur primarily in the immunocommpromised host. These infections are increasing as the population of successfully treated cancer and transplant patients increases, with their concomitant immunosuppression. The work in our laboratory includes the development of techniques for the rapid detection of invasive fungal infections, the development of strain typing systems for the 5 most common species involved in invasive candidiasis, and the study of trends in susceptibility to antifungal agents of Candida species.

Resistance of fungi to antifungal agents is an increasing problem, and we are concerned with developing optimal methods for its detection and for correlating the laboratory findings of resistance with clinical outcome. We are working on the expression of various resistance genotypes in Candida species, and the correlation with reference antifungal susceptibility testing.

Neonatal candidiasis is a serious problem in pre-term infants, and is increasing in incidence with the successful resuscitation of ever younger, smaller and more immature babies. We are studying the risk factors associated with the acquisition of this infection and its long term neuro-physiological outcome. We are also looking at the role of differences in species, strains and resistance to antifungals of the Candida species isolated from these infections

External Funding

1. Katz K, Richardson SE, McGeer A, Simor A, Sarabia A, Borgundvaag B, Ellis P, Saunders A, Rutledge T, Lee J, Goldman R, Rizos J, Currie A, Drews S, Jamieson F. Prevalence of CA-MRSA in purulent skin and soft tissue infections in patients presenting at emergency departments in the greater Toronto area. Wyeth Pharmaceuticals. March 2007 to February 2009.
2. Tran D, Paterson A, Ipp M, Bitnun A, Richardson SE. Genetic determinants of influenza severity in children: A pre-pandemic community-based feasibility study. Canadian Institutes of Health Research. March 2008 to February 2009.
3. Petrich A, Smieja M, Drews S, Fox J, Hatchette T, Mahony J, Petric M, Richardson S. Rapid molecular diagnostics for influenza. Canadian Institutes of Health Research. April 2008 to March 2011.
4. Tran D, Richardson SE, et al. Severe influenza in children: Genetic determinants and related epidemiology. SickKids Foundation and Canadian Institutes of Health Research. April 2008 to March 2010.

Achievements

2007 AMMI Canada Distinguished Service Award
Association of Medical Microbiology and Infectious Disease (AMMI) Canada

John B. Walter Prize for Course Design and Development. Department of Laboratory Medicine and Pathobiology, University of Toronto. 2001.

Publications

Adam H, Groenewald M, Mohan S, Richardson S, Bunn U, Gibas CFC, Poutanen S and Sigler L. Identification of a new species, Candida subhashii, as a cause of peritonitis. Medical Mycology 2008; e-pub DOI: 10.1080/13693780802380545. First Published on: 16 September 2008

Drews SJ, Richardson SE, Wray R, Freeman R, Goldman C, Streitenberger L, Stephens D, Goia C, Kovach D, Brophy J, Matlow AG, and the VRE outbreak management team. An outbreak of vancomycin-resistant Enterococcus faecium (VRE) in an acute care paediatric hospital: lessons from environmental screening and a case control study. Canadian Journal of Infectious Diseases and Medical Microbiology 2008; 19(3):233-236

Gharabaghi F, Tellier R, Cheung R, Collins C, Broukhanski G, Drews SJ, Richardson SE. Comparison of a commercial qualitative real-time RT-PCR Kit with direct immunofluorescence assay (DFA) and cell culture for detection of influenza A and B in children. J Clin Virol 2008; Epub 2008, March 26

Amin R, Ford-Jones E, Richardson SE, MacGregor D, Tellier R, Heurter H, Fearon M, Bitnun A. Acute childhood encephalitis and encephalopathy associated with influenza: a prospective 11-year review. Pediatric Infectious Disease Journal 2008; 27(5):390-395

Zhang SX, Parisian F, Yau Y, Fuller JD, Poutanen SM, Richardson SE. Narrow-spectrum cephalosporin susceptibility testing of escherichia coli with the BD Phoenix automated system: questionable utility of cephalothin as a predictor of cephalexin swusceptibility. J Clin Microbiol 2007; 45(11):3762-3763

Cameron MJ, Ran L, Xu L, Danesh A, Bermejo-Martin JF, Cameron CF, Muller MP, Gold WL, Richardson SE, Poutanen SM, Willey BM, DeVries ME, Fang Y, Seneviratne C, Bosinger SE, Persad D, Wilkinson P, Greller LD, Somogyi R, Humar A, Louie M, Loeb MB, Brunton J, McGeer AJ and Kelvin DJ, for the Canadian SARS Research Network. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in severe acute respiratory syndrome (SARS) patients. J Virol 2007; 81(16):8692-8706

Tansey CM, Louie M, Loeb M, Gold WL, Muller MP, deJager J, Cameron JI, Tomlinson G, Mazzulli T, Walmsley SL, Rachlis AR, Mederski BD, Silverman M, Shainhouse Z, Ephtimios I, Avendano M, Downey J, Styra R, Webster P, Yamamura D, Gerson M, Stanbrook MB, Marras TK, Phillips EJ, Zamel N, Richardson SE, Slutsky AS, Herridge MS. One-year outcomes and health care utilization in survivors of severe acute respiratory syndrome (SARS). Archives of Internal Medicine 2007; 167(12):1312-1320

Elbers JM, Bitnun A, Richardson SE, Ford-Jones EL, Tellier R, Wald RM, Petric M, Kolski H, Heurter H, MacGregor D. A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease? Pediatrics 2007; 119:399-407

Yea C, Adachi D, Johnson G, Nagy E, Gharabaghi F, Petric M, Richardson SE, Tellier R. Design of a single tube RT-PCR assay for the diagnosis of human infection with highly pathogenic influenza A(H5) viruses. J Virol Methods 2007; Feb 139(2):220-6

Louie L, Simor AE, Chong S, Luinstra K, Petrich A, Mahony J, Smieja M, Johnson G, Gharabaghi F, Tellier R, Willey BM, Poutanen S, Mazzulli T, Broukhanski G, Jamieson F, Louie M, Richardson S. Detection of severe acute respiratory syndrome coronavirus in stool specimens by commercially available real-time reverse transcriptase PCR assays. J Clin Microbiol 2006; 44(11):4193-6