Stool Xpert MTB/RIF and urine lipoarabinomannan for the diagnosis of tuberculosis in hospitalized HIV-infected children

• Authors: Sylvia M. LaCourse, University of Washington; Patricia B. Pavlinac, University of Washington; Lisa Cranmer, Emory University; Irene N. Njuguna, University of Washington; Cyrus Mugo, University of Nairobi; John Gatimu, University of Nairobi; Joshua Stern, University of Washington; Judd L. Walson, University of Washington; Elizabeth Maleche-Obimbo, University of Nairobi; Julius Oyugi, University of Nairobi; Dalton Wamalwa, University of Nairobi; Grace John-Stewart, University of Washington
• Journal Title: AIDS
• Volume: Volume 32, Number 1
• Publisher: Lippincott, Williams & Wilkins | 2018-01-02, Pages 69-78
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1097/QAD.0000000000001662
• Subjects: Health Sciences, Immunology; Biology, Virology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Infectious Diseases; Virology; children; GeneXpert MTB/RIF; HIV; lipoarabinomannan; stool; tuberculosis; urine; CLINICAL CASE DEFINITIONS; PULMONARY TUBERCULOSIS; INTRATHORACIC TUBERCULOSIS; RAPID DIAGNOSIS; METAANALYSIS; ASSAY; CLASSIFICATION; PERFORMANCE; SETTINGS; ACCURACY

Abstract

Background: Tuberculosis (TB) causes substantial morbidity and mortality in HIV-infected children. Sample collection and the paucibacillary nature of TB in children makes diagnosis challenging. Rapid diagnostic tools using easily obtained specimens are urgently needed. Methods: Hospitalized, HIV-infected children aged 12 years or less enrolled in a randomized controlled trial (NCT02063880) comparing urgent to post-stabilization antiretroviral therapy initiation in Kenya underwent TB evaluation. At enrollment, sputum or gastric aspirates were collected for TB culture and Xpert, stool for Xpert, and urine for lipoarabinomannan (LAM). When possible, a second sputum/gastric aspirate for culture was obtained. Stool Xpert and urine LAM performance were compared to reference sputum/gastric aspirate culture. Results: Among 165 HIV-infected children, median age was 24 months [interquartile range (IQR) 13-58], median CD4 + % was 14.3 (IQR 8.9-22.0%), and 114 (69.5%) had severe immunosuppression. Thirteen (7.9%) children had confirmed TB (positive culture and/or Xpert). Sputum/gastric aspirate Xpert, stool Xpert, and urine LAM sensitivities were 60% [95% confidence interval (CI) 26-88%], 63% (95% CI 25-92%), and 43% (95% CI 10-82%), respectively. Specificity was 98% (95% CI 94-100%) for sputum/gastric aspirate Xpert, 99% (95% CI 95-100%) for stool Xpert, and 91% (95% CI 84-95%) for urine LAM. Stool Xpert and urine LAM sensitivity increased among children with severe immunosuppression [80% (95% CI 28-100) and 60% (95% Cl 15-95%)]. Conclusion: Stool Xpert had similar performance compared with sputum/gastric aspirate Xpert to detect TB. Urine LAM had lower sensitivity and specificity, but increased among children with severe immunosuppression. Stool Xpert and urine LAM can aid rapid detection of TB in HIV-infected children using easily accessible samples.