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Serious Fungal Infections in Canada

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Serious Fungal Infections in Canada Eur J Clin Microbiol Infect Dis DOI 10.1007/s10096-017-2922-y ORIGINAL ARTICLE Serious fungal infections in Canada S. F. Dufresne1 & D. C. Cole 2 & D. W. Denning 3 & D. C. Sheppard4 Received: 21 December 2016 /Accepted: 21 December 2016 # Springer-Verlag Berlin Heidelberg 2017 Abstract There are currently no nationwide epidemiological of cryptococcosis. These estimates warrant validation through data on fungal infections in Canada. We estimated the burden more formal epidemiological studies in Canada. of serious fungal diseases using literature review and model- ing, as per a methodology previously described by the LIFE program (http://www.LIFE-worldwide.org). Among the Introduction population of Canada (35.5 million in 2014), it was estimated that approximately 1.8% are affected by a serious Canada is a high-income country with a gross domestic fungal infection. Recurrent vulvovaginal candidiasis, severe product of 1551 billion dollars (USD) in 2015 (GDP per asthma with fungal sensitization, and allergic capita, 43,249). Several studies have examined the epide- bronchopulmonary aspergillosis are the most frequent miology of fungal infections in Canada, but most were infections, with population prevalences of 498,688 local (single-centered, regional, or provincial) and focused (1403/100,000), 73,344 (206/100,000), and 61,854 (174/ on individual infections in specific populations. A single 100,000) cases, respectively. Over 3000 invasive fungal study reported on the burden of invasive fungal infections infections are estimated to occur annually, with incidences of at the national level; however, these data are over 20 years 2068 cases (5.8/100,000) of invasive candidiasis, 566 cases old [1] and relied largely on clinical microbiology labora- (1.6/100,000) of invasive aspergillosis, 252 cases (0.71/ tory records review. Since that time, the Canadian popula- 100,000) of Pneumocystis pneumonia, 99 cases (0.28/ tion has expanded by 26%; use of immunosuppressive 100,000) of endemic mycoses, and 63 cases (0.18/100,000) therapies that increase the risk of fungal infection have risen in importance, e.g., solid organ and stem cell trans- plantation and immunosuppressive biologic therapies; fun- * S. F. Dufresne gal diagnostics have improved; and medical care practices [email protected] have evolved greatly. Hence, we sought to provide an estimate of the national burden of serious fungal infections. 1 Department of Infectious Diseases and Medical Microbiology, Maisonneuve-Rosemont Hospital Research Center, Université de Montréal, Montréal, Canada 2 Dalla Lana School of Public Health, University of Toronto, Materials and methods Toronto, Canada 3 The National Aspergillosis Centre, University Hospital of South The current study targeted serious fungal infections, which Manchester, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK were defined as fungal-associated syndromes (infection or hypersensitivity) causing significant morbidity or mortality. 4 Department of Microbiology and Immunology and Department of Medicine, Infectious Diseases and Immunity in Global Health The LIFE methodology (http://www.LIFE-worldwide.org) Program, Research Institute of the McGill University Health Center, was followed as described previously [2, 3], with some McGill University, Montréal, Canada modifications. Eur J Clin Microbiol Infect Dis In brief, an annual burden was estimated for each targeted Table 1 Estimated annual burden of serious fungal diseases in Canada serious fungal disease and presented as: (i) absolute number of Serious fungal infection categories Proportion affected No. of cases per year in Canada (representing either incident or prev- and types (per 100,000 cases alent cases, depending on the nature of the infection) and (ii) population) annual rates (incidence or prevalence), using the annual number Opportunistic invasive fungal 8.28 2949 of cases as the numerator and the entire Canadian population as infections the denominator. For simplicity, the 2014 Canadian population Invasive candidiasis (IC) without 2.91 1034 (n = 35,540,419 [4]) was used regardless of the year from candidemia which the numerator data originated. To calculate the absolute Candidemia 2.91 1034 number of cases per year in Canada, data derived from various Invasive aspergillosis (IA) 1.59 566 sources were aggregated in a step-wise hierarchic fashion, Pneumocystis pneumonia (PCP) 0.71 252 starting with notifiable fungal diseases obtained directly from Cryptococcosis 0.18 63 national and provincial public health agencies, followed by Endemic mycoses 0.28 99 local data from individual centers or health authorities cited in Blastomycosis 0.18 63 peer review or gray literature and extrapolated to the total Histoplasmosis 0.08 27 Canadian population (with the exception of geographically con- Coccidioidomycosis 0.03 9 fined infections, Cryptococcus gattii, and endemic mycoses) Non-invasive pulmonary aspergillosis 381.79 135,690 and, finally, extrapolations from other countries’ estimates. Severe asthma with fungal sensitization 206.37 73,344 Sources included: Statistics Canada (total and adult female (SAFS) Allergic bronchopulmonary aspergillosis 174.04 61,854 population [4], asthma prevalence [5]), the Canadian Cancer (ABPA) Society (acute leukemia [6] and overall cancer incidence [7]), Chronic pulmonary aspergillosis (CPA) 1.38 492 the Canadian Institute for Health Information (number of solid Mucosal candidiasis 1446.94 514,250 organ transplants) [8], the Canadian Blood and Marrow Recurrent vulvovaginal candidiasis 1403.16 498,688 Transplant Group (number of hematopoietic stem cell trans- (RVVC) plants), the Organisation for Economic Co-operation and Oropharyngeal candidiasis (OC) 43.67 15,519 Development (number of chronic obstructive pulmonary disease Esophageal candidiasis (EC) 0.12 43 [COPD] admissions) [9], the Public Health Agency of Canada (human immunodeficiency virus [HIV] prevalence and acquired immune deficiency syndrome [AIDS] incidence) [10], the World year period, based on blood and cerebrospinal fluid culture Health Organization (pulmonary tuberculosis incidence) [11], (approximately 93% of cases were candidemia). Of note, the and Cystic Fibrosis Canada (cystic fibrosis prevalence) [12]. Of incidence was significantly higher (3.7/100,000) during the note, AIDS cases from the province of Québec are not currently latter 3 years of the study. In the second study, the reported reported to the Public Health Agency of Canada, so the number annual incidence of candidemia was 3 cases per 100,000 pop- was estimated at pro rata of the Québec population, assuming the ulation, with 50% of cases arising from intensive care units. same incidence as the rest of the country. These rates translate to at least 1034 cases of candidemia each A map showing the geographic distribution of endemic year in Canada. Deep-seated Candida infections such as peri- mycoses was created using SmartDraw (SmartDraw tonitis and endophthalmitis are accompanied by positive Software, LLC, San Diego, CA, USA). blood cultures in, at most, 50% of cases [15]. This observation is consistent with a recent nationwide German study which reported that the incidence of IC without candidemia was the Results and discussion same as candidemia [3]. Applying this ratio, a total of 2068 IC cases are estimated to occur annually in Canada. Estimated annual numbers of cases of serious fungal diseases Invasive aspergillosis (IA) was largely reported in the main and the corresponding population rates are summarized in high-risk populations, including patients with hematologic Table 1. The distribution of geographically confined mycoses malignancies, hematopoietic stem cell transplant (HSCT) re- is shown in Fig. 1. cipients, and solid organ transplant (SOT) recipients, as well as patients with severe COPD. A recent study from a Montreal Opportunistic invasive fungal infections center found an incidence of 8.9% among adult acute leuke- mia patients (both myelogenous [AML] and lymphocytic The burden of invasive candidiasis (IC) was extrapolated from [ALL]) [16], consistent with other international reports [17]. data reported from the Calgary health region and the Province There were 1215 cases of AML in Canada in 2010 [6], corre- of Québec [13, 14]. In the first study, candidemia incidence sponding to approximately 108 cases of IA that year. Since was estimated at 2.8 cases per 100,000 person-years over a 5- AML and ALL were reported to account for approximately Eur J Clin Microbiol Infect Dis Fig. 1 Localization of geographically confined mycoses in Canada. The colored areas represent the approximate geographic distribution of three fungal infections: light gray Cryptococcus gattii; dark gray blastomycosis; hatched blastomycosis and histoplasmosis Yukon Northwest Territories Nunavut British Columbia Alberta Newfoundland and Labrador Manitoba Saskatchewan Ontario Quebec Prince Edward Island Nova Scotia New Brunswick 75% of IA cases occurring among patients with hematologic Over a 10-year period (2003–2012), 264 cases of malignancies [18], an additional 36 IA cases are estimated to Pneumocystis pneumonia (PCP) were diagnosed in single ter- occur in patients with other hematologic malignancies. The tiary care center in Montreal (personal communication, Dr M. incidence of IA amongst patients undergoing SOT was esti- Laskine, Centre Hospitalier de l’Université de Montréal). mated using data from a prospective North American cohort Using this center’s estimated catchment population
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