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

Lydia Nakiyingi,Jerry J Ellner,Susan E Dorman,Moses L Joloba,Yukari C Manabe,Willy Ssengooba,Gloria Lubega,Bruce J Kirenga,Pauline Byakika-Kibwika,Harriet Mayanja-Kizza,Damalie Nakanjako,Bareng A S Nonyane,Yoshihiko Hoshino

doi:10.1371/journal.pone.0133756

Abstract

BackgroundThe 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.MethodsThis 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.ResultsOf 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.ConclusionsA 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.

Highlights

Tuberculosis (TB) is a major cause of death among HIV-infected patients [1,2,3]
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 Chest X-ray (CXR) and positive urine TB-LAM were significantly associated with MTB culture-positivity

Summary

Introduction

Tuberculosis (TB) is a major cause of death among HIV-infected patients [1,2,3]. Early diagnosis of TB is essential for prompt initiation of therapy to reduce TB-associated morbidity and mortality as well as transmission. Several studies in sub-Saharan Africa (SSA) have found an increased prevalence of sputum smear-negative TB in HIV-infected patients [6] which is associated with high morbidity and mortality [7,8,9,10] as a consequence of delayed or missed diagnosis. This has emphasized the need for more rapid, sensitive and affordable TB diagnostic tools. We sought to determine predictors for MTB culture-positivity among these patients

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