Predictors for MTB Culture-Positivity among HIV-Infected Smear-Negative Presumptive Tuberculosis Patients in Uganda: Application of New Tuberculosis Diagnostic Technology.

The existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce delays in TB diagnosis in HIV-infected smear-negative presumptive TB. We sought to determine predictors for MTB culture-positivity among these patients.This study was nested into a prospective evaluation of HIV-infected outpatients and inpatients clinically suspected to have TB who were screened by smear-microscopy on two spot sputum samples. Data on socio-demographics, clinical symptoms, antiretroviral therapy, CXR, CD4 count, mycobacterial sputum and blood cultures and TB-LAM were collected. Logistic regression and conditional inference tree analysis were used to determine the most predictive indicators for MTB culture-positivity.Of the 418 smear-negative participants [female, 64%; median age (IQR) 32 (28-39) years, median CD4 106 (IQR 22 - 298) cells/mm3], 96/418 (23%) were sputum and/ or blood culture-positive for Mycobacterium tuberculosis (MTB) complex. Abnormal CXR (aOR 3.68, 95% CI 1.76- 7.71, p=0.001) and positive urine TB-LAM (aOR 6.21, 95% CI 3.14-12.27, p< 0.001) were significantly associated with MTB culture-positivity. Previous TB treatment (aOR 0.41, 95% CI 0.17-0.99, p=0.049) reduced the likelihood of a positive MTB culture. A conditional inference tree analysis showed that positive urine TB-LAM and abnormal CXR were the most predictive indicators of MTB culture-positivity. A combination of urine TB-LAM test and CXR had sensitivity and specificity of 50% and 86.1% respectively overall, and 70.8% and 84.1% respectively among those with CD4<100 cells/mm3.A positive urine TB-LAM test and an abnormal CXR significantly predict MTB culture-positivity among smear-negative HIV-infected presumptive TB patients while previous TB treatment reduces the likelihood of a positive MTB culture. Validation studies to assess the performance of diagnostic algorithms that include urine TB-LAM in the diagnosis of smear-negative TB in HIV-infected individuals are warranted

Performance of the urine TB-LAM test in the diagnosis of smear-negative TB among inpatients and outpatients stratified by CD4 cell count.

<p><b>Abbreviations</b>: TB, tuberculosis; LAM, lipoarabinomannan; CXR, Chest X-ray; PPV, positive predictive value; NPV, negative predictive value; LR, likelihood ratio</p><p>Performance of the urine TB-LAM test in the diagnosis of smear-negative TB among inpatients and outpatients stratified by CD4 cell count.</p

Logistic regression analysis for predictors of MTB culture-positive TB in sputum smear-negative HIV-infected presumptive TB^**.

<p>** N = 381 with complete records.</p><p>The model adjusted for CD4 cell count, previous TB treatment, antiretroviral therapy, CXR findings, ART therapy and urine TB-LAM test</p><p><b>Abbreviations</b>: TB, tuberculosis; ART, antiretroviral therapy; CXR, chest X-ray; LAM, lipoarabinomannan; IQR, inter-quartile range; OR, odds ratio; CI, confidence intervals.</p><p>Logistic regression analysis for predictors of MTB culture-positive TB in sputum smear-negative HIV-infected presumptive TB^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133756#t002fn001" target="_blank">**</a>}.</p

Performance of the urine TB-LAM test in the diagnosis of smear-negative TB stratified by CD4 cell count.

<p><b>Abbreviations</b>: TB, tuberculosis; LAM, lipoarabinomannan; CXR, Chest X-ray; PPV, positive predictive value; NPV, negative predictive value; LR, likelihood ratio</p><p>Performance of the urine TB-LAM test in the diagnosis of smear-negative TB stratified by CD4 cell count.</p

Participant flow diagram and MTB culture results distribution.

<p>Participant flow diagram and MTB culture results distribution.</p

A plot of a conditional inference tree showing the most predictive indictors for MTB culture-positivity.

<p>The model was fitted on the 381 participants with complete records.</p

Logistic regression analysis for predictors of MTB culture-positive TB in sputum smear-negative HIV-infected presumptive TB^**.

<p>** N = 381 with complete records.</p><p>The model adjusted for CD4 cell count, previous TB treatment, antiretroviral therapy, CXR findings, ART therapy and urine TB-LAM test</p><p><b>Abbreviations</b>: TB, tuberculosis; ART, antiretroviral therapy; CXR, chest X-ray; LAM, lipoarabinomannan; IQR, inter-quartile range; OR, odds ratio; CI, confidence intervals.</p><p>Logistic regression analysis for predictors of MTB culture-positive TB in sputum smear-negative HIV-infected presumptive TB^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133756#t002fn001" target="_blank">**</a>}.</p