Immigrant screening for latent tuberculosis infection: numbers needed to test and treat, a Norwegian population-based cohort study

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Abstract

Objectives

To estimate the number needed to screen (NNS) and the number needed to treat (NNT) to prevent one tuberculosis (TB) case in the Norwegian immigrant latent tuberculosis infection (LTBI) screening programme and to explore the effect of delay of LTBI treatment initiation.

Design

Population-based, prospective cohort study.

Participants

Immigrants to Norway.

Outcome

Incident TB.

Methods

We obtained aggregated data on immigration to Norway in 2008–2011 and used data from the Norwegian Surveillance System for Infectious Diseases to assess the number of TB cases arising in this cohort within 5 years after arrival. We calculated the average NNS and NNT for immigrants from the top 10 source countries for TB in Norway and by estimated TB incidence rates in source countries. We explored the sensitivity of these estimates with regard to test performance, treatment efficacy and treatment adherence using an extreme value approach, and assessed the effects of emigration, time to TB diagnosis (to define incident TB) and intervention timing.

Results

NNS and NNT were overall high, with substantial variation. NNT showed numerically stronger negative correlation with TB notification rate in Norway (−0.75 [95% CI −1.00 to −0.44]) than with the WHO incidence rate (IR) (−0.32 [95% CI −0.93 to 0.29]). NNT was affected substantially by emigration and the definition of incident TB. Estimates were lowest for Somali (NNS 99 [70–150], NNT 27 [19–41]) and highest for Thai immigrants (NNS 585 [413–887], NNT 111 [79–116]). Implementing LTBI treatment in immigrants sooner after arrival may improve the effectiveness of the programme.

Conclusion

Using TB notifications in Norway, rather than IR in source countries, would improve targeting of immigrants for LTBI management. However, the overall high NNT is a concern and challenges the scale-up of preventive LTBI treatment for significant public health impact. Better data are urgently needed to monitor and evaluate NNS and NNT in countries implementing LTBI screening.

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Most cited references 20

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An assessment of clinically useful measures of the consequences of treatment.

A Laupacis, D L Sackett, R Roberts (1988)

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Evidence-based comparison of commercial interferon-gamma release assays for detecting active TB: a metaanalysis.

Roland Diel, Robert Loddenkemper, Albert Nienhaus (2010)

Test accuracy of interferon-gamma release assays (IGRAs) for diagnosing TB differs when using older or precommercial tools and inconsistent diagnostic criteria. This metaanalysis critically appraises studies investigating sensitivity and specificity of the commercial T-Spot.TB and the QuantiFERON-TB Gold In-Tube Assay (QFT-IT) among definitely confirmed TB cases. We searched Medline, EMBASE, and Cochrane bibliographies of relevant articles. Sensitivities, specificities, and indeterminate rates were pooled using a fixed effect model. Sensitivity of the tuberculin skin test (TST) was evaluated in the context of IGRA studies. In addition, the rates of indeterminates of both IGRAs were assessed. The pooled sensitivity of TST was 70% (95% CI, 0.67-0.72) compared with 81% (95% CI, 0.78-0.83) for the QFT-IT and 88% (95% CI, 0.85-0.90) for the T-Spot.TB. Sensitivity increased to 84% (95%CI, 0.81-0.87) and 89% (95% CI, 0.86-0.91) for the QFT-IT and T-Spot.TB, respectively, when restricted to performance in developed countries. In contrast, specificity of the QFT-IT was 99% (95% CI, 0.98-1.00) vs 86% for the T-Spot.TB (95% CI, 0.81-0.90). The pooled rate of indeterminate results was low, 2.1% (95% CI, 0.02-0.023) for the QFT-IT and 3.8% (95% CI, 0.035-0.042) for the T-Spot.TB, increasing to 4.4% (95% CI, 0.039-0.05) and 6.1% (95% CI, 0.052-0.071), respectively, among immunosuppressed hosts. The newest commercial IGRAs are superior, in comparison with the TST, for detecting confirmed active TB disease, especially when performed in developed countries.

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Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis

Manish Pareek, John P Watson, L Peter Ormerod … (2011)

Summary Background Continuing rises in tuberculosis notifications in the UK are attributable to cases in foreign-born immigrants. National guidance for immigrant screening is hampered by a lack of data about the prevalence of, and risk factors for, latent tuberculosis infection in immigrants. We aimed to determine the prevalence of latent infection in immigrants to the UK to define which groups should be screened and to quantify cost-effectiveness. Methods In our multicentre cohort study and cost-effectiveness analysis we analysed demographic and test results from three centres in the UK (from 2008 to 2010) that used interferon-γ release-assay (IGRA) to screen immigrants aged 35 years or younger for latent tuberculosis infection. We assessed factors associated with latent infection by use of logistic regression and calculated the yields and cost-effectiveness of screening at different levels of tuberculosis incidence in immigrants' countries of origin with a decision analysis model. Findings Results for IGRA-based screening were positive in 245 of 1229 immigrants (20%), negative in 982 (80%), and indeterminate in two (0·2%). Positive results were independently associated with increases in tuberculosis incidence in immigrants' countries of origin (p=0·0006), male sex (p=0·046), and age (p<0·0001). National policy thus far would fail to detect 71% of individuals with latent infection. The two most cost-effective strategies were to screen individuals from countries with a tuberculosis incidence of more than 250 cases per 100 000 (incremental cost-effectiveness ratio [ICER] was £17 956 [£1=US$1·60] per prevented case of tuberculosis) and at more than 150 cases per 100 000 (including immigrants from the Indian subcontinent), which identified 92% of infected immigrants and prevented an additional 29 cases at an ICER of £20 819 per additional case averted. Interpretation Screening for latent infection can be implemented cost-effectively at a level of incidence that identifies most immigrants with latent tuberculosis, thereby preventing substantial numbers of future cases of active tuberculosis. Funding Medical Research Council and Wellcome Trust.

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Author and article information

Journal

Journal ID (nlm-ta): BMJ Open

Journal ID (iso-abbrev): BMJ Open

Journal ID (hwp): bmjopen

Journal ID (publisher-id): bmjopen

Title: BMJ Open

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2044-6055

Publication date Collection: 2019

Publication date (Electronic): 17 January 2019

Volume: 9

Issue: 1

Electronic Location Identifier: bmjopen-2018-023412

Affiliations

[1 ] departmentDepartment of Vaccine-Preventable Diseases , Norwegian Institute of Public Health , Oslo, Norway

[2 ] departmentDepartment of Infectious Disease Epidemiology and Modelling , Norwegian Institute of Public Health , Oslo, Norway

[3 ] departmentStatistics and Analysis Division , Norwegian Directorate of Immigration , Oslo, Norway

[4 ] departmentDivision of Infectious Diseases and Environmental Health , Norwegian Institute of Public Health , Oslo, Norway

[5 ] departmentInstitute of Health and Society , University of Oslo , Oslo, Norway

[6 ] departmentDepartment of Tuberculosis, Blood-Borne and Sexually Transmitted Infections , Norwegian Institute of Public Health , Oslo, Norway

Author notes

[Correspondence to ] Dr Brita Askeland Winje; brita.winje@ 123456fhi.no

Article

Publisher ID: bmjopen-2018-023412

DOI: 10.1136/bmjopen-2018-023412

PMC ID: 6340421

SO-VID: 82cd9f46-fd43-46a9-8ed4-8126afdfa1fc

License:

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 07 April 2018

Date revision received : 05 November 2018

Date accepted : 07 November 2018

Funding

Funded by: Norwegian Health association;

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special-feature unlocked

ScienceOpen disciplines: Medicine

Keywords: tuberculosis,latent tuberculosis infection,screening,number needed to treat,preventive treatment

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ScienceOpen disciplines: Medicine

Keywords: tuberculosis, latent tuberculosis infection, screening, number needed to treat, preventive treatment

Immigrant screening for latent tuberculosis infection: numbers needed to test and treat, a Norwegian population-based cohort study

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Conclusion

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Point-Of-Care Testing for Tuberculosis

Most cited references 20

An assessment of clinically useful measures of the consequences of treatment.

Evidence-based comparison of commercial interferon-gamma release assays for detecting active TB: a metaanalysis.

Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis

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