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Towards the elimination of paediatric tuberculosis in high-income, immigrant-receiving countries: a 25-year conventional and molecular epidemiological case study

Vivek Dhawan, Jennifer Bown, Angela Lau, Deanne Langlois-Klassen, Dennis Kunimoto, Ravi Bhargava, Linda Chui, Simon M. Collin, Richard Long
ERJ Open Research 2018 4: 00131-2017; DOI: 10.1183/23120541.00131-2017
Vivek Dhawan
1Dept of Medicine, University of Alberta, Edmonton, AB, Canada
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Jennifer Bown
1Dept of Medicine, University of Alberta, Edmonton, AB, Canada
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Angela Lau
1Dept of Medicine, University of Alberta, Edmonton, AB, Canada
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Deanne Langlois-Klassen
1Dept of Medicine, University of Alberta, Edmonton, AB, Canada
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Dennis Kunimoto
1Dept of Medicine, University of Alberta, Edmonton, AB, Canada
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Ravi Bhargava
2Dept of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada
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Linda Chui
3Dept of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
4Provincial Laboratory for Public Health, Alberta Health Services, Edmonton, AB, Canada
5Provincial Laboratory for Public Health, Alberta Health Services, Calgary, AB, Canada
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Simon M. Collin
6Centre for Child and Adolescent Health, School of Social and Community Medicine, University of Bristol, Bristol, UK
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Richard Long
1Dept of Medicine, University of Alberta, Edmonton, AB, Canada
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  • FIGURE 1
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    FIGURE 1

    Age- and sex-adjusted incidence of paediatric tuberculosis (TB) by population group and time period in Alberta, 1990–2014. Population figures are from Statistics Canada. CBO: Canadian-born “other”; RFN: registered First Nations; FB: foreign born.

  • FIGURE 2
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    FIGURE 2

    Paediatric tuberculosis (TB) cases by 5-year period and population group in Alberta, 1990–2014. CBO-CB: Canadian-born “other” with Canadian-born parents; CBO-FB: Canadian-born “other” with one or more foreign-born parents; RFN: registered First Nations; FB: foreign born.

  • FIGURE 3
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    FIGURE 3

    Paediatric tuberculosis (TB) in Alberta by method of detection and strategically placed TB elimination activities. The dotted lines highlight contacts with a single International Classification of Diseases Ninth Revision (ICD-9) code of 010.0 (primary tuberculous complex). Of the CBO-FB children without a source case in Alberta (n=9), five could, on the basis of their travel history or their unique Mycobacterium tuberculosis DNA fingerprints, be reasonably said to have acquired their infection overseas. PTB: pulmonary TB; CBO-CB: Canadian-born “other” with Canadian-born parents; CBO-FB: Canadian-born “other” with one or more foreign-born parents; RFN: registered First Nations; FB: foreign born; ME: molecular epidemiology; CNS: central nervous system; LTBI: latent TB infection.

Tables

  • Figures
  • TABLE 1

    The incidence of paediatric tuberculosis (TB) in Alberta by population group and age, 1990–2014

    GroupingCases n (%)Observation person-years (×100 000)#Incidence rateRRadj (95% CI)
    UnadjustedAdjusted (95% CI)¶
    By population group
     Overall176 (100)159.371.101.20 (1.01–1.20)
     CBO61 (36)143.850.420.54 (0.39–0.66)1.00
     RFN56 (34)7.507.468.34 (6.13–11.07)16.37 (10.91–24.48)
     FB59 (30)8.017.369.29 (6.43–12.95)18.25 (11.59–28.30)
    By age and population group
     0–4 years
      Overall78 (100)5.311.471.47 (1.16–1.83)
      CBO39 (50)4.950.790.79 (0.56–1.08)1.00
      RFN23 (29)0.2210.4810.48 (6.64–15.72)13.31 (7.59–22.85)
      FB16 (21)0.1312.2212.22 (6.99–19.85)15.53 (8.10–28.44)
     5–14 years
      Overall98 (100)10.630.920.92 (0.75–1.12)
      CBO22 (22)9.430.230.23 (0.15–0.35)1.00
      RFN33 (34)0.536.216.22 (4.29–8.75)26.70 (15.10–48.10)
      FB43 (44)0.676.416.41 (4.64–8.64)27.50 (16.09–48.28)

    RRadj: age-sex adjusted incidence rate ratio; CBO: Canadian-born “other”; RFN: registered First Nations; FB: foreign born. #: based upon Canadian censuses conducted in 1986, 1991, 1996, 2001, 2006 and 2011, as well as registered First Nations population estimates provided by Indian and Northern Affairs Canada; ¶: adjusted rates by population group were standardised by age and sex, while adjusted rates by age and population group were standardised by sex.

    • TABLE 2

      Demographic and clinical characteristics of paediatric tuberculosis (TB) cases by population group in Alberta, 1990–2014

      CharacteristicsPopulation groupTotalp-value#
      RFNCBO-CBCBO-FBFB
      Cases56184359176
      Age years0.001
       <523 (41)10 (56)29 (67)16 (27)78 (44)
       5–1433 (59)8 (44)14 (33)43 (73)98 (56)
      Sex0.09
       Female25 (45)10 (56)30 (70)35 (59)100 (57)
       Male31 (55)8 (44)13 (30)24 (41)76 (43)
      Disease site0.03
       Pulmonary51 (91)14 (78)36 (84)41 (70)142 (81)
       Extrapulmonary¶5 (9)4 (22)7 (16)18 (31)34 (19)
      Method of detection<0.001
       Contact tracing52 (93)14 (78)27 (63)15 (25)108 (61)
       Symptoms4 (7)4 (22)14 (33)37 (63)59 (34)
       Other screening+0 (0)0 (0)2 (5)7 (12)9 (5)
      Culture status0.47
       Positive22 (39)6 (33)16 (37)34 (58)78 (44)
       Negative32 (57)9 (50)24 (56)25 (42)90 (51)
       Unknown§2 (4)3 (17)3 (7)0 (0)8 (5)

      Data are presented as n or n (%), unless otherwise stated. CBO-CB: Canadian-born “other” with Canadian-born parents; CBO-FB: Canadian-born “other” with foreign-born parents; RFN: registered First Nations; FB: foreign born. #: Pearson's Chi-squared test or Fisher's exact test if cells contain values <5; ¶: Extrapulmonary includes all cases with an International Classification of Diseases Ninth Revision (ICD-9) code of 013 (TB of meninges and the central nervous system) and/or 018 (miliary TB) with or without disease in other sites. It also includes the single ICD-9 codes 014 (TB of the intestines, peritoneum and mesenteric glands), 015 (TB of the bones and joints), 016 (TB of the genito-urinary system) and 017 (TB of other organs); +: other screening includes immigration medical evaluations, international adoptee screening and incidental findings; §: unknown means that no diagnostic specimens were submitted.

      • TABLE 3

        Culture status of paediatric tuberculosis (TB) cases in Alberta by demographic and clinical characteristics, 1990–2014

        CharacteristicsTotalCulture specimenp-value#OR (95% CI)
        NegativePositive
        Cases16890 (54)78 (46)
        Age years0.01
         <57146 (65)25 (35)1
         5–149744 (45)53 (55)2.21 (1.16–4.21)
        Sex0.23
         Female9346 (50)47 (51)1
         Male7544 (59)31 (41)0.69 (0.37–1.27)
        Population group0.20
         CBO-CB159 (60)6 (40)1
         CBO-FB4024 (60)16 (40)1.00(0.30–3.36)
         RFN5432 (59)22 (41)0.97(0.30–3.11)
         FB5925(42)34(58)0.49(0.15–1.56)
        Disease site0.02
         Pulmonary13679 (58)57 (42)1
         Extrapulmonary3211 (34)21 (66)0.38 (0.17–0.85)
        Method of detection<0.001
         Symptoms5819 (33)39 (67)1
         Contact tracing¶10169 (68)32 (32)0.22 (0.11–0.45)
         Other screening+92 (22)7 (78)1.71 (0.32–9.01)

        Data are presented as n or n (%), unless otherwise stated. CBO-CB: Canadian-born “other” with Canadian-born parents; CBO-FB: Canadian-born “other” with foreign-born parents; RFN: registered First Nations; FB: foreign born; OR: odds ratio (crude and unadjusted for any other variables in the table). #: Pearson's Chi-squared test or Fisher's exact test if cells contain values <5. ¶: of the 101 children whose method of detection was contact tracing and who had one or more specimens submitted for culture, 85 had primary pulmonary TB complex alone (see figure 3). Of these only 22 (25.9%) were culture-positive. +: other screening includes immigration medical evaluations, international adoptee screening and incidental findings.

        • TABLE 4

          Utility of conventional epidemiology (CE) for the identification of paediatric tuberculosis (TB) source cases

          CharacteristicTotalSource case identified by CEOR (95% CI)
          YesNo
          Cases176111 (63)65 (37)
          Age years
           <57854 (69)24 (31)1.0
           5–149857 (58)41 (42)1.62 (0.87–3.03)
          Sex
           Female10059 (59)41 (41)1.0
           Male7652 (68)24 (32)0.66 (0.35–1.24)
          Population group
           CBO6143 (71)18 (30)1.0
           RFN5653 (95)3 (5)0.14 (0.04–0.50)
           FB5915 (25)44 (75)7.01 (3.14–15.66)
          Method of detection
           Contact tracing108107 (99)1 (1)#
           Symptoms594 (4)¶55 (97)
           Other screening+90 (0)9 (100)

          Data is presented as n or n (%), unless otherwise stated. CBO: Canadian-born “other”; RFN: registered First Nations; FB: foreign born; OR: odds ratio. #: this child was a close contact of a relative who lived in a neighbouring province-there was no source case in Alberta; ¶: four children were index cases with symptoms and their source cases were identified through reverse contact tracing; +: other screening includes immigration medical evaluations, international adoptee screening and incidental findings.

          • TABLE 5

            Utility of molecular epidemiology (ME) for the identification of paediatric tuberculosis (TB) source cases

            CharacteristicTotal#Source case identified by CENo source case identified by CE
            SubtotalIdentified by MESubtotalIdentified by ME¶
            Cases783534 (97)436 (14)
            Age years
             <5251111 (100)144 (29)
             5–14532423 (96)292 (7)
            Sex
             Female472019 (95)273 (11)
             Male311515 (100)163 (19)
            Population group
             CBO221211 (92)104 (40)
             RFN222020 (100)21 (50)
             FB3433 (100)311 (3)
            Method of detection
             Symptoms3944 (100)356 (17)
             Contact tracing323130 (97)10 (0)
             Other screening+700 (0)70 (0)

            Data are presented as n or n (%), unless otherwise stated. CE: conventional epidemiology; CBO: Canadian-born “other”; RFN: registered First Nations; FB: foreign born. #: total culture-positive cases; ¶: odds ratios of paediatric TB cases with source cases identified by ME only versus paediatric TB cases without source cases identified by ME or CE for various characteristics are as follows: age 5–14 years (0.1852 (95% CI 0.03–1.17)); male sex (1.8462 (95% CI 0.33–10.49)); FB population group (0.0467 (95% CI 0.005–0.47)); detection by symptoms (3.7458 (95% CI 0.19–73.45)). +: other screening includes immigration medical evaluations, international adoptee screening and incidental findings.

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            Towards the elimination of paediatric tuberculosis in high-income, immigrant-receiving countries: a 25-year conventional and molecular epidemiological case study
            Vivek Dhawan, Jennifer Bown, Angela Lau, Deanne Langlois-Klassen, Dennis Kunimoto, Ravi Bhargava, Linda Chui, Simon M. Collin, Richard Long
            ERJ Open Research Apr 2018, 4 (2) 00131-2017; DOI: 10.1183/23120541.00131-2017

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            Towards the elimination of paediatric tuberculosis in high-income, immigrant-receiving countries: a 25-year conventional and molecular epidemiological case study
            Vivek Dhawan, Jennifer Bown, Angela Lau, Deanne Langlois-Klassen, Dennis Kunimoto, Ravi Bhargava, Linda Chui, Simon M. Collin, Richard Long
            ERJ Open Research Apr 2018, 4 (2) 00131-2017; DOI: 10.1183/23120541.00131-2017
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