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Diagnostic TB tests performed accurately among adults, poorly in children
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Despite accuracy among adults, two diagnostic tests performed poorly when diagnosing tuberculosis in Tanzanian children, according to data published in Pediatrics.
Line Lindebo Holm, MD, of Copenhagen University Hospital Hvidovre in Denmark, and colleagues compared diagnostic accuracy of IP-10 and QuantiFERON-TB Gold In-tube (QFT-IT) among 203 children suspected to have tuberculosis with 102 adults confirmed to have tuberculosis. Children had at least one of the following tuberculosis symptoms: a cough lasting at least 14 days, fever lasting at least 7 days, or a weight-for-age z score of –2 or less. The median age of the children in the study was 3 years. This was a substudy of a prospective study conducted at Muheza District Hospital in Tanzania from 2008 to 2010.
Thirty-eight percent of children had HIV; 36% were aged younger than 2 years; and 58% had low weight-for-age.
Data indicated 72% of adults were positive responders to IP-10, and 75% were positive responders to QFT-IT.
Positive responder rates were significantly lower among children. When excluding indeterminate test results, the proportion of positive test responders was 33% among children with confirmed tuberculosis and 29% among children with probable tuberculosis for IP-10 and QFT-IT.
Overall agreement between IP-10 and QFT-IT results was 69% among children (P<.0001).
Twenty-nine percent of children had indeterminate IP-10 results, and 26% had indeterminate QTF-IT results.
Exposure to pulmonary tuberculosis was associated with positive IP-10 results (adjusted OR=3.6; 95% CI, 1.3-9.9). Previous exposure to pulmonary tuberculosis, however, was not associated with positive QFT-IT results.
Age younger than 2 years was associated with indeterminate results for both IP-10 (aOR=2.2; 95% CI, 1.12-4.34) and QFT-IT (aOR=2.4; 95% CI, 1.21-4.92). IP-10 and QFT-IT performed poorly when diagnosing active tuberculosis in severely ill Tanzanian children, according to the researchers.
“IP-10 and QFT-IT offer little diagnostic value in tuberculosis-suspect children from high-burden hospital settings,” the researchers wrote. “We emphasize the need for studies investigating other test modalities.”
Disclosure: One researcher reports financial ties with Qiagen. Hvidovre University Hospital, where Holm and Ruhwald were employed, holds issued and pending patents for IP-10.
Perspective
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Jeffrey R. Starke, MD
The creation of a new diagnostic tests that is sensitive and specific for determining the presence of Mycobacterium tuberculosis in a child has been an elusive goal.
Previous studies have shown poor performance of both the tuberculin skin test and the interferon-γ release assays (IGRAs) in children in high tuberculosis (TB) burden countries.
This study compared the results of the commercial product Quantiferon, an interferon-γ based test, with a “home-brew” assay for IP-10, a chemokine released by antigen-presenting cells upon T-cell stimulation, in diagnosing TB disease in adults and children in Tanzania. Both tests performed well in adults with TB disease. Although the IP-10 assay was more closely associated with TB exposure, neither test performed well in children, with low sensitivity and high rates of indeterminate results.
The major problem with this study and approach is that it attempted to use immunologically-based tests in a population of children that is largely immune compromised! Of the entire study population of children, 38% had HIV infection and 58% had low weight-for-age. An unknown number of children had helminthic infection which may affect the sensitivity of these tests. Finally, children in high burden countries tend to have more advanced TB at diagnosis and the disease itself can be immunosuppressing.
A further difficulty with this study is that the numbers were small: only 3 children had microbiologically confirmed tuberculosis; an additional 35 children had probable and 55 had possible tuberculosis using NIH consensus TB guidelines for pediatric research.
Accurately diagnosing TB disease in children in high burden settings likely will remain difficult until better, more sensitive methods of directly detecting the organism are developed.
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