Clinical and Radiographic Factors Do Not Accurately Diagnose Smear-Negative Tuberculosis in HIV-infected Inpatients in Uganda: A Cross-Sectional Study

J Lucian Davis,William Worodria,Harriet Kisembo,Michael Kawooya,Samuel Yoo,Richard Okello,John Z Metcalfe,Laurence Huang,Saskia Den Boon,Rachel Kyeyune,Krista Powell,Adithya Cattamanchi,Philip Campbell Hill

doi:10.1371/journal.pone.0009859

Abstract

BackgroundAlthough World Health Organization guidelines recommend clinical judgment and chest radiography for diagnosing tuberculosis in HIV-infected adults with unexplained cough and negative sputum smears for acid-fast bacilli, the diagnostic performance of this approach is unknown. Therefore, we sought to assess the accuracy of symptoms, physical signs, and radiographic findings for diagnosing tuberculosis in this population in a low-income country with a high incidence of tuberculosis.MethodologyWe performed a cross-sectional study enrolling consecutive HIV-infected inpatients with unexplained cough and negative sputum smears for acid-fast bacilli at Mulago Hospital in Kampala, Uganda. Trained medical officers prospectively collected data on standard symptoms and signs of systemic respiratory illness, and two radiologists interpreted chest radiographs in a standardized fashion. We calculated positive- and negative-likelihood ratios of these factors for diagnosing pulmonary tuberculosis (defined when mycobacterial cultures of sputum or bronchoalveolar lavage fluid were positive). We used both conventional and novel regression techniques to develop multivariable prediction models for pulmonary tuberculosis.Principal FindingsAmong 202 enrolled HIV-infected adults with negative sputum smears for acid-fast bacilli, 72 (36%) had culture-positive pulmonary tuberculosis. No single factor, including respiratory symptoms, physical findings, CD4+ T-cell count, or chest radiographic abnormalities, substantially increased or decreased the likelihood of pulmonary tuberculosis. After exhaustive testing, we were also unable to identify any combination of factors which reliably predicted bacteriologically confirmed tuberculosis.Conclusions and SignificanceClinical and radiographic criteria did not help diagnose smear-negative pulmonary tuberculosis among HIV-infected patients with unexplained cough in a low-income setting. Enhanced diagnostic methods for smear-negative tuberculosis are urgently needed.

Highlights

The lack of accurate, rapid, inexpensive tests for the diagnosis of pulmonary tuberculosis (TB) remains a major obstacle to effective TB control, especially in high-burden countries in sub-Saharan Africa where HIV co-infection is common
[1] clinicians must either use individual judgment to decide whether to treat empirically for TB or to refer to a higher level of care without treatment. Both approaches are sanctioned by major international guidelines [2,3], there are limited data on how well clinical and radiographic factors perform for TB diagnosis in HIV-infected patients relative to established gold standards such as mycobacterial culture. [4,5] Since existing data may not apply to the referral hospital setting envisaged in guidelines, we designed a diagnostic cross-sectional study with two-month follow-up of HIVinfected Ugandan adults with unexplained cough and negative sputum smears for acid-fast bacilli (AFB)
Of the 35 sputum smear-negative patients missing chest radiography results, one had an uninterpretable chest radiograph, and 34 never underwent chest radiography, most commonly because the radiology department was too busy at the time of admission or because the patient was too weak to travel there from the emergency ward

Summary

Introduction

The lack of accurate, rapid, inexpensive tests for the diagnosis of pulmonary tuberculosis (TB) remains a major obstacle to effective TB control, especially in high-burden countries in sub-Saharan Africa where HIV co-infection is common. [1] clinicians must either use individual judgment to decide whether to treat empirically for TB or to refer to a higher level of care without treatment. Both approaches are sanctioned by major international guidelines [2,3], there are limited data on how well clinical and radiographic factors perform for TB diagnosis in HIV-infected patients relative to established gold standards such as mycobacterial culture. World Health Organization guidelines recommend clinical judgment and chest radiography for diagnosing tuberculosis in HIV-infected adults with unexplained cough and negative sputum smears for acid-fast bacilli, the diagnostic performance of this approach is unknown. We sought to assess the accuracy of symptoms, physical signs, and radiographic findings for diagnosing tuberculosis in this population in a low-income country with a high incidence of tuberculosis

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