Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. The Pediatric Infectious Disease Journal •  Volume 35, Number 1, January 2016 www.pidj.com | 13 ORIGINAL STUDIES Background: Few data relate Mycobacterium tuberculosis (Mtb) lineage and disease phenotype in the pediatric population or examine the contribu- tion of travel to the tuberculosis (TB)-endemic country in North America. We examined clinical, demographic and Mtb genotype data from patients with TB who were treated in Toronto between 2002 and 2012. Methods: Consecutive Mtb culture-positive, pediatric patients were included. Clinical data were collected from a prospectively populated clinical database. Mtb case isolate genotypes were identified using Myco- bacterial Interspersed Repetitive Units–Variable Number Tandem Repeat (MIRU-VNTR) and spoligotyping and were categorized into phylogeo- graphic lineages for analysis. Results: The 77 patients included 30.4% of all culture-positive pediatric TB cases in Ontario from 2002 to 2012. Seventy-six (99%) patients were first or second generation Canadians. Foreign-born patients were more likely to have extrathoracic disease [odds ratios (OR) = 3.0; 95% confidence interval (CI): 1.04–8.71; P < 0.05] and less likely to have a genotype match in the Pub- lic Health Ontario Laboratories database [OR = 0.32 (95% CI: 0.11–0.90); P < 0.05] than Canadian-born patients. For those without a known TB con- tact, Canadian-born patients were more likely to have travelled to a TB- endemic country [OR = 13.0 (95% CI: 2.5–78.5); P < 0.001]. Extrathoracic disease was less likely in patients infected with the East Asian Mtb lineage [OR = 0.1 (95% CI: 0.01–0.9); P < 0.05] and more likely in those infected with the Indo-Oceanic Mtb lineage [OR = 5.4 (95% CI: 1.5–19.2); P < 0.05]. Conclusions: Travel to TB-endemic countries likely plays an important part in the etiology of pediatric TB infection and disease, especially in Cana- dian-born children. Mtb lineage seems to contribute to disease phenotype in children as it has been described in adults. Key Words: tuberculosis, pediatric, lineage, travel (Pediatr Infect Dis J 2016;35:13–18) T he clinical manifestations of pediatric tuberculosis (TB) dis- ease are wide ranging and distinct from adult disease. 1 Host factors that contribute to TB disease phenotype include age, socioeconomic status, nutritional status and comorbid medical conditions, especially HIV infection. 1 Specific polymorphisms of genes involved in the host immune response have been associated with disease phenotypes (reviewed by Di Pietranto- nio and Schurr 2 ). Different strain types or lineages of Mycobacterium tuber- culosis (Mtb) vary in virulence. 3 Advances in genetic and bioin- formatic techniques have allowed for standardized classification of Mtb isolates into phylogeographic lineages, 4,5 and the intrinsic biol- ogy of these lineages may play a role in the clinical manifestations of TB disease. 6–9 There are few data linking Mtb lineage and clinical disease phenotype in the pediatric population. 10 History of host travel to a TB-endemic country is an impor- tant risk factor for TB infection and disease. 11,12 However, a detailed travel history is not systematically collected on patients with TB in the US and Canada. Our institution is a major pediatric TB referral centre in Ontario, treating approximately 15–20 new cases of TB disease per year (30%–40% of all pediatric cases in Ontario). Demographic and other data including travel history are prospectively collected at clinic entry for all TB patients. In addition, Public Health Ontario Laboratories (PHOL) have maintained a database [the Ontario Uni- versal Typing-Tuberculosis (OUT-TB) program 13 ] and an archive of all isolates from culture-positive TB cases in Ontario since 1997. Genotype data are available since 1997 and for 92% of culture- confirmed cases since 2007. This study is a retrospective analysis of all culture-positive pediatric TB cases managed at our institution over an 11-year period, between 2002 and 2012. The objectives of this study were to describe the clinical and patient demographic features of these cases, to determine the Mtb lineage distribution of the case isolates and to identify potential associations of these features with disease phenotype. We also compared the Mtb lineage distribution of the case isolates in our population with the adult data collected in OUT- TB. Finally, we sought to explore the differences between foreign- born and Canadian-born patients in their disease characteristics and potential sources of TB acquisition. MATERIALS AND METHODS Study Setting This study was undertaken at The Hospital for Sick Children (SickKids) in Toronto, Ontario, Canada. Public health units in the Greater Toronto Area make referrals to the SickKids TB program for evaluation of childhood TB contacts and for management of TB disease. Study Design This was a retrospective study that included consecutive patients with a clinical diagnosis of TB and a positive culture for Mtb between January 1, 2002 and December 31, 2012. Inclusion criteria were a clinical diagnosis of TB, age younger than 18 years at the time of diagnosis, at least 1 TB clinic visit at SickKids or 1 inpatient infectious disease service consultation and at least 1 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0891-3668/16/3501-0013 DOI: 10.1097/INF.0000000000000915 Culture-positive Pediatric Tuberculosis in Toronto, Ontario Sources of Infection and Relationship of Birthplace and Mycobacterial Lineage to Phenotype Jonathan H. Rayment, MDCM, MSc,* Jennifer L. Guthrie, MSc,‡ Karen Lam, BSc,‡ Michael Whelan, MSc,‡ Brenda Lee, MHSc,‡ Frances B. Jamieson, MD, MHSc, FRCP(C),‡§ and Ian Kitai, MB, BCh, FRCP(C)†¶ Accepted for publication September 9, 2015. From the Divisions of *Respiratory Medicine and †Infectious Diseases, The Hospital For Sick Children; ‡Public Health Ontario Laboratories, Public Health Ontario; and Departments of §Laboratory Medicine and Pathobiology and ¶Pediatrics, University of Toronto, Toronto, Ontario, Canada. J.H.R. and J.L.G. contributed equally to this work. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Jonathan H Rayment, MDCM, MSc, The Hospital For Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. E-mail: jonathan.rayment@sickkids.ca. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).