ORIGINAL STUDIES

A Population-Based Study of Tuberculosis in Children and

Adolescents in Ontario
Wanatpreeya Phongsamart, MD,*†‡ Ian Kitai, MB, BCH, FRCPC,*† Michael Gardam, MD,†§
Jun Wang, MSc,¶ and Kamran Khan, MD, MPH, FRCPC†¶

experience with TB on all-cause mortality in 1154 cases of active

Background: There are few population-based data on presentation and
treatment of tuberculosis (TB) in children and adolescents in Ontario.
Methods: We analyzed data from 121 patients less than 17 years of age
with TB disease reported to the Province of Ontario between 1999 and
2002. Physician provider data were obtained from the College of Physi-
cians and Surgeons of Ontario.
Results: Of the 121 patients, 84 (69.4%) patients were foreign born. The
median time of residence in Canada before diagnosis was 2.7 years (range,
7 days–16 years). Diagnosis was made by symptoms in 78 (64.5%), by
contact investigation in 25 (20.7%), and by immigration screening in 5
(4.1%) patients. Pulmonary TB occurred in 94 (77.7%) patients. When
cases detected by contact tracing and screening were excluded, isolated
extrapulmonary TB was present in 4 (23.5%), 6 (35.0%), and 19 (37.0%)
of young children (0 – 4 years), older children (5–12 years), and adolescents
(13–17 years), respectively. Eleven patients (9.1%) had drug-resistant
strains. Eighty (66.1%) patients received directly observed therapy (DOT).
Prescribed treatment was completed in 105 (86.8%) patients with a trend
toward higher completion rates in those receiving DOT (P ⫽ 0.07). Of 57
physician providers, 50 (87.7%) had treated less than 1 pediatric TB
patient/year during the study period.
Conclusions: Extrapulmonary disease accounted for a high proportion of
TB in older children and adolescents who presented with symptoms.
One-third of patients did not receive DOT and most were cared for by
physicians with limited experience in managing TB. Further studies are
needed to determine whether these factors influence outcome in pedi-
atric TB.
Key Words: tuberculosis, children, adolescent, population-based study,
extrapulmonary disease
(Pediatr Infect Dis J 2009;28: 416 – 419)
T uberculosis (TB) is a globally significant cause of morbidity
and mortality for children. During the past 50 years, the overall
incidence of TB in Canada has decreased.1 Rates in Canadian
children younger than 15 years of age decreased from 6.6 per
100,000 in 1970 to 1.9 per 100,000 in 2001.2 As TB incidence
rates decline in Canada, fewer physicians are managing active TB
cases on a regular basis. A lack of experience among physicians
may have contributed to a low level of suspicion for, and a delay
in diagnosis of TB.1 Khan et al3 studied the impact of physician
Accepted for publication October 21, 2008.
From the *Division of Infectious Diseases, the Hospital for Sick Children,
Toronto, Ontario; †University of Toronto, Ontario, Canada; ‡Division of
Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Siriraj
Hospital, Mahidol University, Bangkok, Thailand; §University Health Net-
work; and ¶Centre for Research on Inner City Health, St. Michael’s
Hospital, Ontario, Canada.
Address for correspondence: Ian Kitai, MB, BCH, FRCPC, Division of Infec-
tious Diseases, The Hospital for Sick Children, 555 University Ave,
Toronto, Ontario M5G 1X8, Canada. E-mail: ianwilkitai@rogers.com.
Copyright © 2009 by Lippincott Williams & Wilkins
ISSN: 0891-3668/09/2805-0416
DOI: 10.1097/INF.0b013e3181920d4d
TB reported to Toronto Public Health and demonstrated that
greater TB-specific experience was associated with improved pa-
tient survival. Pediatric TB presents unique challenges in terms of
diagnosis and therapeutic options. The difficulty of obtaining
adequate specimens and low rate of bacteriologic confirmation are
well documented, especially in infants and young children.4 – 6
Understanding the clinical presentations of children and adoles-
cents with TB is crucial for early diagnosis and control. There are
few detailed population-based data on TB in children and adoles-
cents in North America that consider physician provider charac-
teristics. A recent study of active TB among adolescents in
Toronto revealed significant diagnostic delays despite multiple
physician visits with the average time from symptom onset to the
diagnosis of TB of 5.2 months.7 Extrapulmonary TB occurred in
57% of adolescents, which may have contributed to this diagnostic
delay. However, results from this study might have been may be
biased, given that the analysis was restricted to TB patients
managed at a tertiary care hospital. We therefore conducted a
population-based study to determine clinical features, diagnosis,
and treatment of TB, as well as the characteristics of physician
providers managing children and adolescents with TB.
MATERIALS AND METHODS
We reviewed all patients with active TB less than 17 years
of age who were diagnosed on microbiologic or clinical grounds
and reported to 6 public health units in Ontario which accounted
for 80% of TB cases in the province between July 1, 1999, and
June 30, 2002. Patient demographic, clinical, treatment, and out-
come data were obtained from each health unit’s reportable disease
database and complemented with TB case management files.
These data sources were also used to identify the treating physi-
cians of record for reported cases and to determine the number of
active TB cases managed by each physician during the study
period. Data pertaining to physician’s undergraduate and postgrad-
uate medical training were obtained from the physician database of
the College of Physicians and Surgeons of Ontario. Physicians
were considered TB “specialists” if they completed postgraduate
training in respiratory medicine or infectious diseases. The study
was approved by the ethics review board of the Hospital for Sick
Children. Statistical comparisons were made using ␹2 test.
RESULTS
A total of 121 patients were identified. Their baseline
characteristics are shown in Table 1. The median age of the
patients at the time of TB diagnosis was 13 years (range, from
newborn to 17 years). Individuals between the ages of 13 and 17
years accounted for 53.7% of the total. Eighty-four patients
(69.4%) were foreign born; of these the median time of residence
in Canada before diagnosis was 2.7 years (range, 7 days–16 years).
Most of these patients were originally from Asia (36/84 关42.9%兴),
followed by Middle East (28/84 关33.3%兴) and Africa (13/84
关15.5%兴), respectively. Countries of origin of the foreign born
cases are shown in Table 2. Only 4 patients had underlying

416 The Pediatric Infectious Disease Journal • Volume 28, Number 5, May 2009
The Pediatric Infectious Disease Journal • Volume 28, Number 5, May 2009 Pediatric TB in Ontario

TABLE 1. Baseline Characteristics of 121 Children TABLE 3. Primary Site of TB Involvement

and Adolescents With Active TB
No. (%) Patients
Site
No. (%) Patients (n ⫽ 121)
Characteristic
(n ⫽ 121)
Pulmonary TB 85 (70.2)
Age Extra-pulmonary TB 27 (22.3)
0 – 4 yr 29 (24.0) TB lymphadenitis 18
5–12 yr 27 (22.3) TB bone and joint 3
13–17 yr 65 (53.7) Abdominal TB 2
Sex CNS TB 1
Male 53 (43.8) Disseminated/miliary TB 3
Female 68 (56.2) Both pulmonary and extrapulmonary TB 9 (7.5)
Country of origin
Canada 37 (30.6)
Others (foreign-born) 84 (69.4)
Underlying medical condition 4 (3.3)
English speaking 107 (88.4) diagnosis and treatment. Diagnosis was confirmed microbiologi-
cally in 68 (56.2%) patients. Seventeen (37.8%) of 45 patients had
positive smears for acid-fast bacilli. Eleven patients (9.1%) had
drug resistant strains. Isoniazid, pyrazinamide, and streptomycin
TABLE 2. Countries of Origin of the 84 Foreign-Born resistance was found in 9 (7.4%), 1 (0.8%), and 1 (0.8%) strains,
Cases respectively. All but 2 patients with drug resistant TB were foreign
born. There was no multidrug resistant TB in this cohort. Eighty
Countries of Origin (No. Cases) No. (%) (66.1%) patients received directly observed therapy (DOT). Ideal
Asia 36 (42.9)
length of treatment according to the Canadian TB Standards8 and
Bangladesh (2), Hong Kong (1), India (6), American Thoracic Society, Centers for Disease Control and
South Korea (3), Myanmar (1), Philippines (16), Prevention, and Infectious Diseases Society of America TB treat-
Sri Lanka (1), Taiwan (1), Vietnam (5) ment guidelines9 was completed in 105 (86.8%) patients. A trend
Middle East and North Africa 28 (33.3) toward higher treatment completion rates was observed in those
Afghanistan (1), Iran (1), Jordan (1), Pakistan receiving DOT (77/80 关96.3%兴 vs. 36/41 关87.8%关on self-adminis-
(12), Somalia (13)
tered therapy; P ⫽ 0.07).
Europe 2 (2.4)
Portugal (1), United kingdom of Great Britain (1)
Of 57 physician providers, 63.8% were TB specialists.
Twenty-five physicians (43.9%) had treated fewer than 1 active TB
North America 1 (1.2)
United States (1) patient/year and 50 (87.7%) had treated fewer than 1 pediatric TB
Central America and the Caribbean 2 (2.4)
patient/year during the study period.
Grenada (1), Nicaragua (1)
South America 2 (2.4) DISCUSSION
Columbia (1), Peru (1) This is the first detailed population-based study of TB in
Africa 13 (15.4) children and adolescents in Canada that also describes physician
Angola (1), Central Africa Republic (1), Republic provider characteristics. It provides a more comprehensive picture of
of the Congo (1), Ethiopia (2), Kenya (3),
Nigeria (3), Rwanda (1), Sudan (1)
TB in children and adolescents than previous hospital-based studies.
The distribution of primary sites of infection in our study paralleled
that reported in previous studies in North America (pulmonary
72.9%– 80.2%, lymphadenitis 16.7%–21.4%, bone and joints 0.9%–
medical conditions; of these 1 patient had HIV coinfection. TB 1%, central nervous system 0%–3.3%, miliary 1.3%–2.8%).5,10,11 In
diagnosis was made on the basis of symptoms in 78 (64.5%). analyzing the data we excluded cases detected by contact tracing to
Twenty-five (20.7%) cases were detected by contact investigation, better elucidate how patients presented to clinicians. We documented
5 (4.1%) cases by immigration screening, 5 (4.1%) cases by a trend toward higher prevalence of isolated extrapulmonary disease
screening for other reasons, 7 (5.8%) cases were diagnosed for in older children (35.0%) and adolescents (37.0%) than in young
unknown reasons, and 1 very premature infant with congenital TB children (23.5%), the group previously described as having the high-
was diagnosed postmortem. Eighty-five (70.2%) of 121 patients est prevalence of extrapulmonary disease. Our population-based study
had only pulmonary disease. Twenty-seven (22.3%) patients had confirms the high prevalence of extrapulmonary disease in adoles-
only extrapulmonary disease and 9 (7.5%) patients had both cents that was described in recent hospital-based studies in Toronto
pulmonary and extrapulmonary TB. TB lymphadenitis was the and Paris.7,12 The diagnosis of extrapulmonary TB poses a particular
most common presentation of extrapulmonary TB. Details of the challenge for clinicians because of the protean ways in which the
primary site of disease are shown in Table 3. disease presents.
To elucidate how the patients presented to clinicians, we From 1994 to 2004, the proportion of TB cases attributable
excluded all cases detected by contact investigation and other to the foreign-born population exceeded 50% for the leading
screening methods and stratified patients into 3 age groups; young immigrant-receiving provinces (Ontario– 82%, British Columbia–
children (0 – 4 years), older children (5–12 years), and adolescents 68%, Alberta– 60%, Quebec–52%).13 In our study, most children
(13–17 years). When the 85 remaining patients were examined, the and adolescents in Ontario who developed TB were foreign-born
prevalence of extrapulmonary disease in older children (35.0%) and became symptomatic several years (median 2.7 years) after
and adolescents (37.0%) was higher than in young children immigration. Chest radiography for applicants 11 years and above
(23.5%) although it was nonstatistically significant (P ⫽ 0.2715). has been the mainstay of TB screening as a part of immigration
Primary site of TB by age group is shown in Figure 1. Forty-two medical examination and assessment (IME) in Canada. Routine
patients (34.7%) were admitted to hospital during the course of TB screening for latent tuberculosis infection using the tuberculin skin

© 2009 Lippincott Williams & Wilkins 417

Phongsamart et al The Pediatric Infectious Disease Journal • Volume 28, Number 5, May 2009
(Excluding cases identified through contact tracing, screening or post mortem)
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
0- 4 5-12
FIGURE 1. Primary site of TB disease by age group (n ⫽ 85).
test is not mandated as part of the IME.14 As such, the IME misses
signs of active or inactive pulmonary TB in children younger than
11 years, may miss extrapulmonary disease, and is not designed to
detect latent tuberculosis infection in children and adolescents.
Clinicians should consider the diagnosis of TB in foreign-born
individuals, even years or decades after immigration. Contact
tracing detected 20.7% of all cases of TB in this study, a finding
similar to previous studies in which investigation of contacts of
adult source cases detected 19% to 28% of TB in children and
adolescents.12,15 A recently published study of 14 years experience
of pediatric TB in Alberta, Canada showed that approximately
75% of pediatric cases were detected by contact tracing. However,
pediatric TB in Alberta was mainly the result of ongoing trans-
mission in Aboriginal communities.11 The difference, therefore,
may be due to the fact that in our population, TB disease is likely
the result of reactivation in latently infected children rather than
ongoing transmission in the community. Contact tracing is an estab-
lished effective method for detecting and preventing active TB.16
Using DOT has been associated with a decreased risk of
death,3 improvement in treatment success rates,17 shorter treat-
ment duration,18 and less acquired drug resistance.19 We found a
trend toward a higher rate of treatment completion in those who
received DOT than in those with self-administered therapy. How-
ever, only 66.1% of children and adolescents with TB in Ontario
received DOT. Expanding DOT to all children and adolescents
might improve TB treatment outcomes and TB control in Ontario.
A survey of physician’s knowledge, attitudes, and practice
conducted in San Diego county in 1995–1997 revealed that pulmo-
nary medicine and infectious diseases specialists, and physicians who
treated 6 or more TB patients in the past 2 years were more likely to
conform to health department guidelines, which were closely based
on American Thoracic Society/Centers for Disease Control and Pre-
vention guidelines.20 Although two-thirds of physician providers in
our population were infectious diseases or respiratory specialists, most
of these providers had treated fewer than 1 pediatric TB patient per
year during the past 3 years. Recently, Khan et al3 demonstrated that
patient survival for adults with TB was influenced not only by patient
characteristics, but also by features of the treating physician. Greater
TB-specific experience of physicians was associated with improved
survival at 1 year. Although a significant proportion of children in our
418
Both
Extrapulmonary TB
Pulmonary TB
1 3- 17 Age group (years)
study were cared for by physicians with limited experience in man-
aging pediatric TB we do not have sufficient data to determine
whether this affected outcome. Further studies are needed to elucidate
whether provider characteristics may account for different outcomes
in the management of pediatric TB.
ACKNOWLEDGMENTS
The authors are indebted to the public health units of
Toronto, Peel, York, Durham, Hamilton, and Ottawa for providing
access to their tuberculosis patient data.
REFERENCES
1. Phypers M. Tuberculosis in Canada 2002: executive summary. Can Com-
mun Dis Rep. 2005;31:45– 46.
2. Phypers M. Pediatric tuberculosis in Canada. Can Commun Dis Rep.
2003;29:139 –142.
3. Khan K, Campbell A, Wallington T, et al. The impact of physician training
and experience on the survival of patients with active tuberculosis. CMAJ.
2006;175:749 –753.
4. Kibel MA. Problems in the diagnosis of childhood tuberculosis. S Afr Med
J. 1990;70:379 –380.
5. Chaulk CP, Khoo L, Matuszak DL, et al. Case characteristics and trends in
pediatric tuberculosis, Maryland, 1986 –1993. Public Health Rep. 1997;
112:146 –152.
6. Zar HJ, Hanslo D, Apolles P, et al. Induced sputum versus gastric lavage for
microbiological confirmation of pulmonary tuberculosis in infants and
young children: a prospective study. Lancet. 2005;365:130 –134.
7. Kam A, Ford-Jones L, Malloy P, et al. Active tuberculosis among adoles-
cents in Toronto, Canada: clinical features and delays in diagnosis. Pediatr
Infect Dis J. 2007;26:355–356.
8. Kitai I, Malloy P, Kowalczyk A, et al. Pediatric tuberculosis. In: Long R,
Ellis E, eds. The Canadian Tuberculosis Standards. 6th ed. Ottawa, Can-
ada: Health Canada and the Canadian Lung Association; 2007:182–199.
9. American Thoracic Society, CDC, and Infectious Diseases Society of
America. Treatment of Tuberculosis. MMWR. 2003;52(RR11):1–77.
10. Snider DE Jr, Rieder HL, Combs D, et al. Tuberculosis in children. Pediatr
Infect Dis J. 1988;7:271–278.
11. Yip D, Bhargava R, Yao Y, et al. Pediatric tuberculosis in Alberta:
epidemiology and case characteristics (1990 –2004). Can J Public Health.
2007;98:276 –280.
12. de Pontual L, Balu L, Ovetchkine P, et al. Tuberculosis in adolescents: a
French retrospective study of 52 cases. Pediatr Infect Dis J. 2006;25:930 –
932.
© 2009 Lippincott Williams & Wilkins
The Pediatric Infectious Disease Journal • Volume 28, Number 5, May 2009
13. Phypers M, Kunimoto D, Behr M, et al. Epidemiology of tuberculosis in
Canada. In: Long R, Ellis E, eds. The Canadian Tuberculosis Standards.
6th ed. Ottawa, Canada: Health Canada and the Canadian Lung Associa-
tion; 2007:1–16.
14. Gushulak B, Martin S. Immigration and tuberculosis control in Canada. In:
Long R, Ellis E, eds. The Canadian Tuberculosis Standards. 6th ed. Ottawa,
Canada: Health Canada and the Canadian Lung Association; 2007:308–319.
15. Yeo IK, Tannenbaum T, Scott AN, et al. Contact investigation and geno-
typing to identify tuberculosis transmission to children. Pediatr Infect Dis
J. 2006;25:1037–1043.
16. Dasgupta K, Menzies D. Cost-effectiveness of tuberculosis control strate-
gies among immigrants and refugees. Eur Respir J. 2005;25:1107–1116.
© 2009 Lippincott Williams & Wilkins
Pediatric TB in Ontario
17. Soares EC, Pacheco AG, Mello FC, et al. Improvements in treatment
success rates with directly observed therapy in Rio DeJaneiro City. Int J
Tuberc Lung Dis. 2006;10:690 – 695.
18. Davidson BL. A controlled comparison of directly observed therapy vs self
administered therapy for active tuberculosis in the urban United States.
Chest. 1998;114:1239 –1243.
19. Yew WW. Directly observed therapy, short-course: the best way to
prevent multidrug-resistant tuberculosis. Chemotherapy. 1999;45(suppl 2):
26–33.
20. LoBue PA, Moser K, Catanzaro A. Management of tuberculosis in San
Diego County: a survey of physicians’ knowledge, attitudes and practices.
Int J Tuberc Lung Dis. 2001;5:933–938.
419