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Multidrug-resistant tuberculosis in Finland: treatment outcome and the role of whole-genome sequencing

Virve Korhonen, Pia Kivelä, Marjo Haanperä, Hanna Soini, Tuula Vasankari
ERJ Open Research 2022 8: 00214-2022; DOI: 10.1183/23120541.00214-2022
Virve Korhonen
1Department of Respiratory Medicine, Tampere University Hospital, Tampere, Finland
2Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland
3Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
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  • ORCID record for Virve Korhonen
Pia Kivelä
4Department of Infectious Diseases, Helsinki University Hospital, Helsinki, Finland
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Marjo Haanperä
2Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland
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Hanna Soini
2Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland
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Tuula Vasankari
5Finnish Lung Health Association (Filha), Helsinki, Finland
6Faculty of Medicine, University of Turku, Turku, Finland
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  • For correspondence: virve.korhonen@tuni.fi
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  • FIGURE 1
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    FIGURE 1

    Steps in identifying multidrug-resistant tuberculosis (MDR-TB) cases with treatment started in Finland in 2007–2016. NIDR: National Infectious Diseases Register; XDR: extensively drug-resistant. #: culture-negative cases with diagnoses based on radiology as well as 1) a positive nucleic acid amplification test result with rifampicin resistance and 2) a Finnish-born child with interferon-γ release assay (IGRA) positivity and a known exposure to MDR-TB; ¶: strains resistant to rifampicin and isoniazid; +: MDR-TB with additional resistance to any fluoroquinolone or injectable drug; §: MDR-TB with additional resistance to at least one fluoroquinolone and one injectable agent.

  • FIGURE 2
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    FIGURE 2

    Concordance of the phenotypic and genotypic (whole-genome sequencing) drug susceptibility testing results of the sequenced isolates (n=45).

Tables

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  • TABLE 1

    Risk factors for non-successful outcome among multidrug-resistant (MDR) tuberculosis cases diagnosed and treatment started in Finland in 2007–2016

    VariableAllSuccessfulNon-successfulUnivariate OR (95% CI)Univariate p-valueMultivariate OR (95% CI)Multivariate p-value
    Subjects473512
    Age years, median343038.5
     Age/1 year1.0 (0.99–1.05)0.251.0 (0.96–1.05)0.85
    Sex
     Male2922 (75.9)7 (24.1)RefRef
     Female1813 (72.2)5 (27.8)1.2 (0.3–4.4)0.764.6 (0.79–48.8)0.09
    Origin
     Foreign3329 (87.9)4 (12.1)RefRef
     Finnish146 (42.9)8 (57.1)8.6 (2.2–39.0)0.00212.8 (2.0–142.9)0.006
    Site of disease
     Extrapulmonary98 (88.9)1 (11.1)RefRef
     Pulmonary38#27 (71.1)11 (28.9)2.4 (0.4–24.1)0.331.5 (0.2–22.1)0.71
    Resistance
     MDR4335 (81.4)8 (18.6)RefRef
     XDR40 (0)4 (100)37.6 (3.5–5167.1)0.00162.3 (2.8–12 291.9)0.006
    Immunocompromised¶
     No4030 (75.0)10 (25.0)RefRef
     Yes75 (71.4)2 (28.6)1.3 (0.2–6.3)0.773.1 (0.38–27.0)0.28

    Data are presented as n or n (%), unless otherwise stated. Ref: reference; XDR: extensively drug-resistant. #: concomitant extrapulmonary tuberculosis n=8 out of 38 (21.1%); ¶: HIV (n=2), immunosuppressive medication (n=4), uncontrolled diabetes mellitus type 1 (n=1).

    • TABLE 2

      Multidrug-resistant tuberculosis (MDR-TB) treatment data for the 43 cases diagnosed and treated in Finland, 2007–2016#

      Cases, n (%)Duration, median (IQR)Adverse events, n (%)Drugs, median (IQR)
      Injectable drug¶39 (90.7)6.2 (5.2–7.4) months22 (56.4)
      Linezolid38 (88.4)9.6 (5.6–14.8) months26 (68.4)
      Fluoroquinolone+40 (93.0)23.3 (15.8–24.8) months10 (25.0)
      Clofazimine23 (53.5)12.3 (5.6–21.1) months2 (8.7)
      Bedaquiline§5 (11.6)5.9 (4.5–15.6) months0 (0)
      Duration of effective MDR-TB treatment23.8 (17.8–25.8) months
      Adverse event for any drug38 (88.4)
      Number of drugs in intensive phase6 (5–6)
      Number of drugs in continuation phase4 (4–5)
      Duration of hospitalisation50 (38–108) days
      Cases with all MDR-TB medicines paused14 (32.6)
      Duration of pauses for cases with pauses in medication9.0 (5.5–14.0) days
      DOT used42 (97.7)

      IQR: interquartile range; DOT: directly observed treatment. #: cases that received only standard tuberculosis treatment with first-line drugs (n=1) or left Finland during MDR-TB treatment (n=3) were excluded; ¶: amikacin (n=37), streptomycin (n=2), non-recipient of an injectable drug due to drug resistance (n=3) and due to young age (n=1); +: non-recipient of fluoroquinolone due to drug resistance (n=3); §: extensively drug-resistant (n=3), pre-extensively drug-resistant (n=1), MDR (n=1).

      • TABLE 3

        Treatment outcomes for multidrug-resistant tuberculosis cases in Finland by different definitions, 2007–2016

        OutcomeCases, n (%)
        Treatment outcome (WHO/ECDC)#
         Cured19 (40.4)
         Treatment completed16 (34.0)
         Failed0 (0)
         Lost to follow-up6 (12.8)
         Died3 (6.4)
         Not evaluated3 (6.4)
        Treatment outcome for pulmonary cases (TBNET)¶
         Cured20 (52.6)
         Failed1 (2.6)
         Lost to follow-up1 (2.6)
         Died3 (7.9)
         Undeclared13 (34.2)

        WHO: World Health Organization; ECDC: European Centre for Disease Prevention and Control; TBNET: Tuberculosis Network European Trials group. #: outcome assessed for all multidrug-resistant cases (n=47); ¶: outcome assessed for pulmonary multidrug-resistant cases only (n=38).

        Supplementary Materials

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          Supplementary material 00214-2022.SUPPLEMENT

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        Multidrug-resistant tuberculosis in Finland: treatment outcome and the role of whole-genome sequencing
        Virve Korhonen, Pia Kivelä, Marjo Haanperä, Hanna Soini, Tuula Vasankari
        ERJ Open Research Oct 2022, 8 (4) 00214-2022; DOI: 10.1183/23120541.00214-2022

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        Multidrug-resistant tuberculosis in Finland: treatment outcome and the role of whole-genome sequencing
        Virve Korhonen, Pia Kivelä, Marjo Haanperä, Hanna Soini, Tuula Vasankari
        ERJ Open Research Oct 2022, 8 (4) 00214-2022; DOI: 10.1183/23120541.00214-2022
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