title: Intensified specimen collection to improve tuberculosis diagnosis in children from Rural South Africa, an observational study.
abstract: BACKGROUND
  In drug-resistant TB settings, specimen collection is critical for drug-susceptibility testing (DST). This observational study included multiple specimen types collected from pediatric TB suspects with the aim to determine diagnostic yield and inform clinical practice in children with drug-resistant and drug-susceptible TB.
  
  
  METHODS
  From 03/2009-07/2010, TB suspects aged ≥6 months and ≤12 years were recruited among outpatient and inpatient settings. Subjects were new TB suspects or had persistent symptoms despite ≥2 months of TB treatment. The protocol included collection of a single blood and urine specimen, a single sputum induction and, if inpatients and <5 years of age, collection of 3 gastric aspirates (GA). Samples were cultured on solid and/or liquid media. DST was by 1% proportion method.
  
  
  RESULTS
  Among 118 children with possible, probable or confirmed TB, the mean age was 4.9 years [SD 3.2] and 64 (62%) of those tested were HIV-positive. Eight (7%) subjects were culture-positive from at least one specimen; yield did not differ by HIV status or TB treatment history. Among those with positive cultures, 7/8 (88%) were from induced sputum, 5/6 (83%) from GA, 3/8 (38%) from blood, and 3/7 (43%) from urine. In subjects with both induced sputum and GA collection, sputum provided one additional case compared to GA. Multidrug resistant (MDR)-TB was detected by urine culture alone in one child >5 years old. Pan-resistant extensively drug resistant (XDR)-TB was identified by cultures from all sites in one subject.
  
  
  CONCLUSIONS
  TB was cultured from HIV-positive and -negative children, and allowed for identification of MDR and XDR-TB cases. Urine and induced sputum each provided an additional TB diagnosis and, when compared to GA, may be considered a less invasive, same-day method of specimen collection for childhood TB suspects. This study illustrates the continued challenges and limitations of available strategies for pediatric TB diagnostics.
authors.affiliation: Division of Infectious Diseases & International Health, University of Virginia, PO Box 801337, Charlottesville, VA 22908-1337, USA. tthomasheysell@gmail.com.
authors.forename: Tania A
authors.initials: TA
authors.lastname: Thomas
authors.forename: Scott K
authors.initials: SK
authors.lastname: Heysell
authors.forename: Prashini
authors.initials: P
authors.lastname: Moodley
authors.forename: Romualde
authors.initials: R
authors.lastname: Montreuil
authors.forename: Xia
authors.initials: X
authors.lastname: Ha
authors.forename: Gerald
authors.initials: G
authors.lastname: Friedland
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Bamber
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Moll
authors.forename: Neel
authors.initials: N
authors.lastname: Gandhi
authors.forename: William E
authors.initials: WE
authors.lastname: Brant
authors.forename: Willem
authors.initials: W
authors.lastname: Sturm
authors.forename: Sarita
authors.initials: S
authors.lastname: Shah
mesh_terms: D002648:Child; D002675:Child, Preschool; D054908:Extensively Drug-Resistant Tuberculosis / Q000175:diagnosis; D005260:Female; D005766:Gastrointestinal Contents / Q000382:microbiology; D006679:HIV Seropositivity; D006801:Humans; D007223:Infant; D008297:Male; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D012424:Rural Population; D013019:South Africa; D013048:Specimen Handling; D013183:Sputum / Q000382:microbiology*; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000652:urine