Tuberculosis screening among HIV-positive inpatients: a systematic review and individual participant data meta-analysis

Ashar Dhana, Yohhei Hamada, Andre P. Kengne, Andrew D. Kerkhoff, Molebogeng X. Rangaka, Tamara Kredo, Annabel Baddeley, Cecily Miller, Ankur Gupta-Wright, Katherine Fielding, Robin Wood, Helena Huerga, Sekai Chenai Mathabire Rücker, Christine Heidebrecht, Douglas Wilson, Stephanie Bjerrum, Isik S. Johansen, Swe Swe Thit, Mar Mar Kyi, Josh HansonDavid A. Barr, Graeme Meintjes, Gary Maartens*

*Kontaktforfatter

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Background: Since 2011, WHO has recommended that HIV-positive inpatients be routinely screened for tuberculosis with the WHO four-symptom screen (W4SS) and, if screened positive, receive a molecular WHO-recommended rapid diagnostic test (eg, Xpert MTB/RIF [Xpert] assay). To inform updated WHO tuberculosis screening guidelines, we conducted a systematic review and individual participant data meta-analysis to assess the performance of W4SS and alternative screening tests to guide Xpert testing and compare the diagnostic accuracy of the WHO Xpert algorithm (ie, W4SS followed by Xpert) with Xpert for all HIV-positive inpatients. Methods: We searched MEDLINE, Embase, and Cochrane Library from Jan 1, 2011, to March 1, 2020, for studies of adult and adolescent HIV-positive inpatients enrolled regardless of tuberculosis signs and symptoms. The separate reference standards were culture and Xpert. Xpert was selected since it is most likely to be the confirmatory test used in practice. We assessed the proportion of inpatients eligible for Xpert testing using the WHO algorithm; assessed the accuracy of W4SS and alternative screening tests or strategies to guide diagnostic testing; and compared the accuracy of the WHO Xpert algorithm (W4SS followed by Xpert) with Xpert for all. We obtained pooled proportion estimates with a random-effects model, assessed diagnostic accuracy by fitting random-effects bivariate models, and assessed diagnostic yield descriptively. This systematic review has been registered on PROSPERO (CRD42020155895). Findings: Of 6162 potentially eligible publications, six were eligible and we obtained data for all of the six publications (n=3660 participants). The pooled proportion of inpatients eligible for an Xpert was 90% (95% CI 89–91; n=3658). Among screening tests to guide diagnostic testing, W4SS and C-reactive protein (≥5 mg/L) had highest sensitivities (≥96%) but low specificities (≤12%); cough (≥2 weeks), haemoglobin concentration (<8 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had higher specificities (61–90%) but suboptimal sensitivities (12–57%). The WHO Xpert algorithm (W4SS followed by Xpert) had a sensitivity of 76% (95% CI 67–84) and specificity of 93% (88–96; n=637). Xpert for all had similar accuracy to the WHO Xpert algorithm: sensitivity was 78% (95% CI 69–85) and specificity was 93% (87–96; n=639). In two cohorts that had sputum and non-sputum samples collected for culture or Xpert, diagnostic yield of sputum Xpert was 41–70% and 61–64% for urine Xpert. Interpretation: The W4SS and other potential screening tests to guide Xpert testing have suboptimal accuracy in HIV-positive inpatients. On the basis of these findings, WHO now strongly recommends molecular rapid diagnostic testing in all medical HIV-positive inpatients in settings where tuberculosis prevalence is higher than 10%. Funding: World Health Organization.

OriginalsprogEngelsk
TidsskriftThe Lancet HIV
Vol/bind9
Udgave nummer4
Sider (fra-til)e233-e241
ISSN2352-3018
DOI
StatusUdgivet - apr. 2022

Bibliografisk note

Funding Information:
This work was supported by WHO. AD received training in research that was supported by the Fogarty International Center of the US National Institutes of Health (D43 TW010559) and National Research Foundation of South Africa. GMe and GMa were supported by core funding from the Wellcome Centre for Infectious Diseases Research in Africa (203135/Z/16/Z). GMe was supported by the Wellcome Trust (214321/Z/18/Z) and the South African Research Chairs Initiative of the Department of Science and Technology and NRF of South Africa (64787). One funder (WHO) had a role in the study design, data collection, data analysis, data interpretation, and writing of this report. TK is partly supported by the Research, Evidence and Development Initiative (READ-It; 300342?104), funded by UK aid from the UK Government. We thank Joy Oliver (Cochrane South Africa and South African Medical Research Council, Cape Town, South Africa) who assisted with the searches for the systematic review and Amanda Jackson (The Wellcome Centre for Infectious Diseases Research in Africa, Cape Town, South Africa) who assisted with standardising individual participant data. AB and CM are currently staff members of WHO. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy, or views of WHO.

Funding Information:
This work was supported by WHO. AD received training in research that was supported by the Fogarty International Center of the US National Institutes of Health (D43 TW010559) and National Research Foundation of South Africa. GMe and GMa were supported by core funding from the Wellcome Centre for Infectious Diseases Research in Africa (203135/Z/16/Z). GMe was supported by the Wellcome Trust (214321/Z/18/Z) and the South African Research Chairs Initiative of the Department of Science and Technology and NRF of South Africa (64787). One funder (WHO) had a role in the study design, data collection, data analysis, data interpretation, and writing of this report. TK is partly supported by the Research, Evidence and Development Initiative (READ-It; 300342–104), funded by UK aid from the UK Government. We thank Joy Oliver (Cochrane South Africa and South African Medical Research Council, Cape Town, South Africa) who assisted with the searches for the systematic review and Amanda Jackson (The Wellcome Centre for Infectious Diseases Research in Africa, Cape Town, South Africa) who assisted with standardising individual participant data. AB and CM are currently staff members of WHO. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy, or views of WHO.

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