Background
Diagnosing tuberculosis in children is challenging because specimens are difficult to obtain
and contain low tuberculosis concentrations, especially with HIV-coinfection. Few studies
included well-controls so test specificities are poorly defined. We studied tuberculosis diagnosis
in 525 children with and without HIV-infection.
Methods and Findings
‘Cases’ were children with suspected pulmonary tuberculosis (n = 209 HIV-negative; n = 81
HIV-positive) and asymptomatic ‘well-control’ children (n = 200 HIV-negative; n = 35 HIVpositive).
Specimens (n = 2422) were gastric aspirates, nasopharyngeal aspirates and
stools analyzed by a total of 9688 tests.
All specimens were tested with an in-house hemi-nested IS6110 PCR that took <24
hours. False-positive PCR in well-controls were more frequent in HIV-infection (P 0.01):
17% (6/35) HIV-positive well-controls versus 5.5% (11/200) HIV-negative well-controls;
caused by 6.7% (7/104) versus 1.8% (11/599) of their specimens, respectively. 6.7% (116/1719) specimens from 25% (72/290) cases were PCR-positive, similar (P>0.2) for HIV-positive
versus HIV-negative cases.
All specimens were also tested with auramine acid-fast microscopy, microscopic-observation
drug-susceptibility (MODS) liquid culture, and Lowenstein-Jensen solid culture that
took 6 weeks and had 100% specificity (all 2112 tests on 704 specimens from 235 wellcontrols
were negative). Microscopy-positivity was rare (0.21%, 5/2422 specimens) and all
microscopy-positive specimens were culture-positive. Culture-positivity was less frequent
(P 0.01) in HIV-infection: 1.2% (1/81) HIV-positive cases versus 11% (22/209) HIV-negative
cases; caused by 0.42% (2/481) versus 4.7% (58/1235) of their specimens,
respectively.
Conclusions
In HIV-positive children with suspected tuberculosis, diagnostic yield was so low that 1458
microscopy and culture tests were done per case confirmed and even in children with culture-proven
tuberculosis most tests and specimens were false-negative; whereas PCR was
so prone to false-positives that PCR-positivity was as likely in specimens from well-controls
as suspected-tuberculosis cases. This demonstrates the importance of control participants
in diagnostic test evaluation and that even extensive laboratory testing only rarely contributed
to the care of children with suspected TB.