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Author Notes:

Sylvia LaCourse, 325 9th Avenue, Box 359931, Seattle, WA 98104, sylvial2@uw.edu, (Tel) +1 206-616-5978, (Fax) +1 206-543-4818.

SML and PBP contributed equally to this work.

The authors wish to thank the parent PUSH study participants and their caregivers, without who this research would not be possible.

We thank the research administrative, clinical, and data teams for their dedication and support.

We thank members of the Kizazi Working Group, UW Global Center for Integrated Health of Women, Adolescents and Children (Global WACh), Dr. Grace John–Stewart’s pre/postdoctoral mentorship group, and Kenya Research & Training Center (KRTC) for their support during the preparation of this article.

The authors report no conflicts of interest.

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Research Funding:

This work was supported by the National Institute of Child Health and Human Development (NICHD), National Institute of Allergy and Infectious Diseases (NIAID), Fogarty International Center, and National Center For Advancing Translational Sciences at the National Institutes of Health (NIH) (R01 HD023412 and K24 HD054314-06 to GJS, K23 AI 120793-01 to SML, T32 AI007140 to PBP, K12 HD000850 to LMC, D43TW009783 to IN, and UL1TR000423 for REDCap), Firland Foundation (pilot award to JLW), University of Washington Center for AIDS Research (P30 AI027757), UW Global Center for Integrated Heath of Women, Adolescents and Children (Global WACh), and the Pediatric Scientist Development Program (PSDP) through grants from the American Pediatric Society and American Academy of Pediatrics (LMC).

Alere Determine™ TB LAM Ag kits were donated by Alere©.

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

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

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Journal Title:

AIDS

Volume:

Volume 32, Number 1

Publisher:

, Pages 69-78

Type of Work:

Article | Post-print: After Peer Review

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.

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