Journal Article

Characteristics and Early Outcomes of Patients With Xpert MTB/RIF-Negative Pulmonary Tuberculosis Diagnosed During Screening Before Antiretroviral Therapy

Stephen D. Lawn, Andrew D. Kerkhoff, Monica Vogt, Yonas Ghebrekristos, Andrew Whitelaw and Robin Wood

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 54, issue 8, pages 1071-1079
Published in print April 2012 | ISSN: 1058-4838
Published online February 2012 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1093/cid/cir1039

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Background. A proportion of patients with tuberculosis diagnosed by sputum culture during screening before antiretroviral therapy (ART) have false-negative Xpert MTB/RIF assay results (Xpert-negative tuberculosis). We determined the characteristics and early ART program outcomes of such patients.

Methods. Adult patients who enrolled in a South African township ART service were systematically screened for pulmonary tuberculosis regardless of symptoms by testing paired sputum samples with Xpert MTB/RIF and liquid culture. The ART service provided follow-up for all patients, and early (90-day) programmatic outcomes were determined.

Results. Among 602 patients screened, 523 had ≥1 Xpert and culture result, yielding 89 culture-positive tuberculosis diagnoses. Of these, 37 (42%) of the patients with tuberculosis were Xpert-negative when a single sputum sample was tested, compared with 25 (28%) when 2 samples were tested. Compared with patients with Xpert-positive tuberculosis, those with Xpert-negative tuberculosis (using either definition) had substantially higher CD4 cell counts, lower plasma viral loads, higher hemoglobin concentrations, and higher body mass index. Their tuberculosis was also less advanced, with a lower frequency of prolonged cough (≥2 weeks), less extensive radiographic abnormalities, and a lower frequency of detectable lipoarabinomannan antigenuria and mycobacteriuria. Xpert-negative cases were all sputum smear negative with prolonged time to culture positivity (median, 21 days). Despite greater delays in starting tuberculosis treatment, Xpert-negative patients were less likely to die during follow-up.

Conclusions. Compared to patients with Xpert-positive tuberculosis diagnosed during pre-ART screening, Xpert-negative cases had less advanced immunosuppression and less advanced tuberculosis and did not have adverse outcomes despite substantial delays in starting tuberculosis treatment.

Journal Article.  4566 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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