TY - JOUR
T1 - Treatment decisions and mortality in HIV-positive presumptive smear-negative TB in the Xpert™ MTB/RIF era
T2 - A cohort study
AU - Hermans, Sabine M.
AU - Babirye, Juliet A.
AU - Mbabazi, Olive
AU - Kakooza, Francis
AU - Colebunders, Robert
AU - Castelnuovo, Barbara
AU - Sekaggya-Wiltshire, Christine
AU - Parkes-Ratanshi, Rosalind
AU - Manabe, Yukari C.
N1 - Funding Information:
Xpert® MTB/RIF test cartridges were supplied by a project of the University of Antwerp funded by the Flemish Interuniversity Council. This study was supported by the Infectious Diseases Network for Treatment and Research in Africa (INTERACT) programme, funded by the Netherlands Organization for Scientific Research – WOTRO Science for Global Development: NACCAP [grant number W07.05.20100] and the European Union [grant number SANTE/2006/105–316]. Salary support to SH was provided by the INTERACT programme followed by a European Union Marie Curie International Outgoing Fellowship for Career Development [PIOF-GA-2012-332,311]. Support was also provided under the National Institutes of Health (DMID under the Tuberculosis Clinical Diagnostics Research Consortium [NIH/NIAID], HHSN272200900050C for YM) and the Office of the Global AIDS Coordinator-funded Medical Education Partnership Initiative-Medical Education for Services to all Ugandans (RFA-TW-10-008) for YM and CSW, and the NIH Fogarty International Center (D43TW009771) for YM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© The Author(s). 2017.
PY - 2017
Y1 - 2017
N2 - Background: The Xpert™ MTB/RIF (XP) has a higher sensitivity than sputum smear microscopy (70% versus 35%) for TB diagnosis and has been endorsed by the WHO for TB high burden countries to increase case finding among HIV co-infected presumptive TB patients. Its impact on the diagnosis of smear-negative TB in a routine care setting is unclear. We determined the change in diagnosis, treatment and mortality of smear-negative presumptive TB with routine use of Xpert MTB/RIF (XP). Methods: Prospective cohort study of HIV-positive smear-negative presumptive TB patients during a 12-month period after XP implementation in a well-staffed and trained integrated TB/HIV clinic in Kampala, Uganda. Prior to testing clinicians were asked to decide whether they would treat empirically prior to Xpert result; actual treatment was decided upon receipt of the XP result. We compared empirical and XP-informed treatment decisions and all-cause mortality in the first year. Results: Of 411 smear-negative presumptive TB patients, 175 (43%) received an XP; their baseline characteristics did not differ. XP positivity was similar in patients with a pre-XP empirical diagnosis and those without (9/29 [17%] versus 14/142 [10%], P = 0.23). Despite XP testing high levels of empirical treatment prevailed (18%), although XP results did change who ultimately was treated for TB. When adjusted for CD4 count, empirical treatment was not associated with higher mortality compared to no or microbiologically confirmed treatment. Conclusions: XP usage was lower than expected. The lower sensitivity of XP in smear-negative HIV-positive patients led experienced clinicians to use XP as a "rule-in" rather than "rule-out" test, with the majority of patients still treated empirically.
AB - Background: The Xpert™ MTB/RIF (XP) has a higher sensitivity than sputum smear microscopy (70% versus 35%) for TB diagnosis and has been endorsed by the WHO for TB high burden countries to increase case finding among HIV co-infected presumptive TB patients. Its impact on the diagnosis of smear-negative TB in a routine care setting is unclear. We determined the change in diagnosis, treatment and mortality of smear-negative presumptive TB with routine use of Xpert MTB/RIF (XP). Methods: Prospective cohort study of HIV-positive smear-negative presumptive TB patients during a 12-month period after XP implementation in a well-staffed and trained integrated TB/HIV clinic in Kampala, Uganda. Prior to testing clinicians were asked to decide whether they would treat empirically prior to Xpert result; actual treatment was decided upon receipt of the XP result. We compared empirical and XP-informed treatment decisions and all-cause mortality in the first year. Results: Of 411 smear-negative presumptive TB patients, 175 (43%) received an XP; their baseline characteristics did not differ. XP positivity was similar in patients with a pre-XP empirical diagnosis and those without (9/29 [17%] versus 14/142 [10%], P = 0.23). Despite XP testing high levels of empirical treatment prevailed (18%), although XP results did change who ultimately was treated for TB. When adjusted for CD4 count, empirical treatment was not associated with higher mortality compared to no or microbiologically confirmed treatment. Conclusions: XP usage was lower than expected. The lower sensitivity of XP in smear-negative HIV-positive patients led experienced clinicians to use XP as a "rule-in" rather than "rule-out" test, with the majority of patients still treated empirically.
KW - Empirical treatment
KW - HIV Infections/complications
KW - Molecular diagnostic techniques/methods
KW - Pulmonary/diagnosis
KW - Pulmonary/epidemiology
KW - Tuberculosis
KW - Tuberculosis
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U2 - 10.1186/s12879-017-2534-2
DO - 10.1186/s12879-017-2534-2
M3 - Article
C2 - 28622763
AN - SCOPUS:85027564019
SN - 1471-2334
VL - 17
JO - BMC infectious diseases
JF - BMC infectious diseases
IS - 1
M1 - 433
ER -