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Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data

Barr, David A, Lewis, Joseph ORCID:, Feasey, Nicholas ORCID:, Schutz, Charlotte, Kerkhoff, Andrew D, Jacob, Shevin ORCID:, Andrews, Ben, Kelly, Paul, Lakhi, Shabir, Muchemwa, Levy, Bacha, Helio A, Hadad, David J, Bedell, Richard, van Lettow, Monique, Zachariah, Rony, Crump, John A, Alland, David, Corbett, Elizabeth L, Gopinath, Krishnamoorthy, Singh, Sarman, Griesel, Rulan, Maartens, Gary, Mendelson, Marc, Ward, Amy M, Parry, Christopher, Talbot, Elizabeth A, Munseri, Patricia, Dorman, Susan E, Martinson, Neil, Shah, Maunank, Cain, Kevin, Heilig, Charles M, Varma, Jay K, Gottberg, Anne von, Sacks, Leonard, Wilson, Douglas, Squire, Bertie ORCID:, Lalloo, David ORCID:, Davies, Gerry and Meintjes, Graeme (2020) 'Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data'. Lancet Infectious Diseases, Vol 20, Issue 6, pp. 742-752.

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The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis blood stream infection (MTB-BSI) is incompletely understood. We hypothesised that MTB-BSI prevalence has been underestimated, that MTB-BSI independently predicts death, and sputum Xpert has suboptimal diagnostic yield for MTB-BSI.
We conducted a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood-culture (TBBC). Harmonised inclusion criteria were applied to IPD: age ≥13 years, HIV-positivity, available CD4 count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of MTB-BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum (Xpert or culture if Xpert unavailable) and urine-lipoarabinomannan for MTB-BSI were obtained by two-level random-effect meta-analysis, mortality hazard of MTB-BSI by mixed-effect Cox proportional-hazard modelling, and effect of treatment delay with propensity-score analysis. PROSPERO registration: CRD42016050022·
We identified 23 data sets for inclusion (20 published and 3 unpublished at time of search), and obtained data from 20, representing 96% of eligible IPD. 5751 patients met inclusion criteria. Predicted probability of MTB-BSI was 45% (95%CI 38-52%) for danger-sign positive tuberculosis inpatients with cohort median CD4 count of 76 cells/L. Diagnostic yield of sputum was 77% (95%CI 63–87%), rising to 89% (95%CI 80-94%) when combined with urine-lipoarabinomannan testing. Presence of MTB-BSI compared to absence in patients with HIV-associated tuberculosis increased hazard of death before 30-days (aHR 2·5, 95%CI 2·1–3·1) but the effect waned after 30 days (aHR 1.25 95% 0.84-2.49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased with anti-tuberculosis treatment delay >4 days in the subgroup with MTB-BSI (OR 3·2, 95%CI 1·1–10·3) but not convincingly in the overall cohort (OR 1.25 95% CI 0.68 – 2.25).
In critically-ill adults with HIV-tuberculosis, MTB-BSI is a frequent manifestation of tuberculosis and strongly predicts mortality within 30 days. Better diagnostic yield in patients with MTB-BSI can be achieved by parallel use of sputum-Xpert and urine-LAM. Anti-tuberculosis treatment delay may increase mortality hazard.

Item Type: Article
Subjects: QW Microbiology and Immunology > Viruses > QW 160 Viruses (General). Virology
W General Medicine. Health Professions > W 20.5 Biomedical research
WA Public Health > Statistics. Surveys > WA 950 Theory or methods of medical statistics. Epidemiologic methods
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI):
Depositing User: Stacy Murtagh
Date Deposited: 07 May 2020 14:07
Last Modified: 31 Jul 2020 09:19


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