Tuberculosis screening in HIV-positive hospitalized patients: a systematic review and meta-analysis of individual participant data

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Evidence before this study

Tuberculosis is the leading cause of hospitalization and death in hospital among people living with HIV and often goes undiagnosed. Since 2011, WHO has recommended that people living with HIV (including HIV-positive hospitalized patients) be routinely screened for TB with the WHO Four Symptom Screen (W4SS; including any symptoms of cough, fever, night sweats or weight loss). ; if W4SS is positive, a rapid molecular diagnostic test recommended by WHO (e.g. Xpert MTB/RIF [Xpert] or Xpert MTB/RIF Ultra [Xpert Ultra]) should be done. However, hospitalized patients with other HIV-related opportunistic illnesses often have a positive W4SS. Additionally, the diagnostic accuracy of alternative tests and screening strategies in HIV-positive hospitalized patients is unclear. To inform updated WHO guidelines on TB screening, we performed a meta-analysis of individual participant data among HIV-positive inpatients who were enrolled regardless of signs and symptoms of TB. We searched MEDLINE, Embase and the Cochrane Library from 1 January 2011 to 1 March 2020, with search terms related to ‘human immunodeficiency virus’, ‘tuberculosis’, ‘screening’, ‘algorithm’, “sensitivity” and “specificity”. We calculated the proportion of hospitalized patients eligible for the Xpert test using the WHO algorithm (W4SS followed by Xpert); assessed the accuracy of the W4SS and alternative screening and strategies to guide diagnostic testing; and compared the accuracy of the WHO Xpert algorithm (W4SS followed by Xpert) with Xpert for All.

Added value of this study

We used individual participant data from six studies of HIV-positive inpatients admitted to hospital regardless of signs and symptoms of TB. We found that 90% of all HIV-positive hospitalized patients were eligible for the Xpert test using the WHO algorithm. Among screening tests to guide further diagnostic testing, W4SS and C-reactive protein concentration (≥5 mg/L) had the highest sensitivities but low specificities. Cough (≥ 2 weeks), hemoglobin concentration (

Implications of all available evidence

Based on these results, WHO has strongly recommended performing a rapid molecular diagnostic test (e.g., with Xpert) for tuberculosis in all hospitalized HIV-positive patients in high prevalence settings (>10 % prevalence of tuberculosis). Rapid molecular diagnostic tests in all HIV-positive hospitalized patients would reduce the current diagnostic gap; however, a negative result does not exclude tuberculosis.

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