Intensified tuberculosis case-finding in HIV-positive adults managed at Ethiopian health centers: diagnostic yield of Xpert MTB/RIF compared with smear microscopy and liquid culture

PLoS One. 2014 Jan 22;9(1):e85478. doi: 10.1371/journal.pone.0085478. eCollection 2014.

Abstract

Background: Detection of active tuberculosis (TB) before antiretroviral therapy (ART) initiation is important, but optimal diagnostic methods for use in resource-limited settings are lacking. We assessed the prevalence of TB, evaluated the diagnostic yield of Xpert MTB/RIF in comparison with smear microscopy and culture, and the impact of Xpert results on clinical management in HIV-positive adults eligible for ART at health centers in a region of Ethiopia.

Methods: Participants were prospectively recruited and followed up at 5 health centers. Trained nurses collected data on socio-demographic characteristics, medical history and symptoms, and performed physical examination. Two paired morning sputum samples were obtained, and lymph node aspirates in case of lymphadenopathy. Diagnostic yield of Xpert MTB/RIF in sputum was compared with smear microscopy and liquid culture.

Results: TB was diagnosed in 145/812 participants (17.9%), with bacteriological confirmation in 137 (16.9%). Among bacteriologically confirmed cases, 31 were smear-positive (22.6%), 96 were Xpert-positive (70.1%), and 123 were culture-positive (89.8%). Xpert MTB/RIF increased the TB detection rate by 64 cases (47.4%) compared with smear microscopy. The overall sensitivity of Xpert MTB/RIF was 66.4%, and was not significantly lower when testing one compared with two samples. While Xpert MTB/RIF was 46.7% sensitive among patients with CD4 cell counts >200 cells/mm(3), this increased to 82.9% in those with CD4 cell counts ≤100 cells/mm(3). Compared with Xpert-positive TB patients, Xpert-negative cases had less advanced HIV and TB disease characteristics.

Conclusions: Previously undiagnosed TB is common among HIV-positive individuals managed in Ethiopian health centers. Xpert MTB/RIF increased TB case detection, especially in patients with advanced immunosuppression. An algorithm based on the use of a single morning sputum sample for individuals with negative sputum smear microscopy could be considered for intensified case finding in patients eligible for ART. However, technical and cost-effectiveness issues relevant for low-income countries warrant further study.

Trial registration: ClinicalTrials.gov NCT01433796.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibiotics, Antitubercular / pharmacology
  • Bacteriological Techniques / methods
  • Drug Resistance, Bacterial
  • Ethiopia / epidemiology
  • Female
  • HIV Infections / complications*
  • Humans
  • Male
  • Mass Screening / methods*
  • Microscopy / methods
  • Molecular Diagnostic Techniques / methods
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics
  • Nucleic Acid Amplification Techniques / methods
  • Prevalence
  • Prospective Studies
  • Reproducibility of Results
  • Rifampin / pharmacology
  • Sensitivity and Specificity
  • Sputum / microbiology
  • Tuberculosis / complications
  • Tuberculosis / diagnosis*
  • Tuberculosis / epidemiology*

Substances

  • Antibiotics, Antitubercular
  • Rifampin

Associated data

  • ClinicalTrials.gov/NCT01433796

Grants and funding

The Swedish International Development Cooperation Agency (SIDA), the Swedish Civil Contingency Agency (MSB) and the Swedish Medical Society have provided funding for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.