title: Evaluation of Xpert® MTB/RIF Assay in Induced Sputum and Gastric Lavage Samples from Young Children with Suspected Tuberculosis from the MVA85A TB Vaccine Trial.
abstract: OBJECTIVE
  Diagnosis of childhood tuberculosis is limited by the paucibacillary respiratory samples obtained from young children with pulmonary disease. We aimed to compare accuracy of the Xpert® MTB/RIF assay, an automated nucleic acid amplification test, between induced sputum and gastric lavage samples from young children in a tuberculosis endemic setting.
  
  
  METHODS
  We analyzed standardized diagnostic data from HIV negative children younger than four years of age who were investigated for tuberculosis disease near Cape Town, South Africa [2009-2012]. Two paired, consecutive induced sputa and early morning gastric lavage samples were obtained from children with suspected tuberculosis. Samples underwent Mycobacterial Growth Indicator Tube [MGIT] culture and Xpert MTB/RIF assay. We compared diagnostic yield across samples using the two-sample test of proportions and McNemar's χ2 test; and Wilson's score method to calculate sensitivity and specificity.
  
  
  RESULTS
  1,020 children were evaluated for tuberculosis during 1,214 admission episodes. Not all children had 4 samples collected. 57 of 4,463[1.3%] and 26 of 4,606[0.6%] samples tested positive for Mycobacterium tuberculosis on MGIT culture and Xpert MTB/RIF assay respectively. 27 of 2,198[1.2%] and 40 of 2,183[1.8%] samples tested positive [on either Xpert MTB/RIF assay or MGIT culture] on induced sputum and gastric lavage samples, respectively. 19/1,028[1.8%] and 33/1,017[3.2%] admission episodes yielded a positive MGIT culture or Xpert MTB/RIF assay from induced sputum and gastric lavage, respectively. Sensitivity of Xpert MTB/RIF assay was 8/30[26.7%; 95% CI: 14.2-44.4] for two induced sputum samples and 7/31[22.6%; 11.4-39.8] [p = 0.711] for two gastric lavage samples. Corresponding specificity was 893/893[100%;99.6-100] and 885/890[99.4%;98.7-99.8] respectively [p = 0.025].
  
  
  CONCLUSIONS
  Sensitivity of Xpert MTB/RIF assay was low, compared to MGIT culture, but diagnostic performance of Xpert MTB/RIF did not differ sufficiently between induced sputum and gastric lavage to justify selection of one sampling method over the other, in young children with suspected pulmonary TB.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00953927.
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Erick Wekesa
authors.initials: EW
authors.lastname: Bunyasi
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Michele
authors.initials: M
authors.lastname: Tameris
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Hennie
authors.initials: H
authors.lastname: Geldenhuys
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Bey-Marrie
authors.initials: BM
authors.lastname: Schmidt
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Angelique Kany Kany
authors.initials: AK
authors.lastname: Luabeya
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Humphrey
authors.initials: H
authors.lastname: Mulenga
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.affiliation: Department of Health, Western Cape Province and Division of Community Health, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahomed
authors.affiliation: Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
mesh_terms: D001431:Bacteriological Techniques; D002675:Child, Preschool; D004311:Double-Blind Method; D019353:Endemic Diseases; D005260:Female; D005766:Gastrointestinal Contents / Q000382:microbiology*; D018023:HIV Seronegativity; D006801:Humans; D007223:Infant; D008297:Male; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D021141:Nucleic Acid Amplification Techniques; D009928:Organ Specificity; D012680:Sensitivity and Specificity; D013019:South Africa / Q000453:epidemiology; D013183:Sputum / Q000382:microbiology*; D007507:Therapeutic Irrigation; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology / Q000382:microbiology; D032581:Tuberculosis Vaccines
chemical_list: D032581:Tuberculosis Vaccines