Abstract
Diagnosis of pediatric tuberculosis (TB) is often complicated by its nonspecific symptoms, paucibacillary nature, and the need for invasive specimen collection techniques. However, a recently reported assay that detects Mycobacterium tuberculosis virulence factors in serum can diagnose various TB manifestations, including paucibacillary TB cases, in adults with good sensitivity and specificity. The current study examined the ability of this M. tuberculosis biomarker assay to diagnose pediatric TB using archived cryopreserved serum samples drawn from children ≤18 years of age who were screened for suspected TB as part of a prospective population-based active surveillance study. In this analysis, any detectable level of either of the M. tuberculosis virulence factors CFP-10 and ESAT-6 was considered direct evidence of TB. Serum samples from 105 children evaluated for TB (55 TB cases and 50 close contacts without TB) were analyzed. The results of this analysis yielded sensitivity of 85.5% (95% confidence interval [CI], 73.3 to 93.5). Similar diagnostic sensitivities were observed for culture-positive (87.5%; 95% CI, 67.6 to 97.3) and culture-negative (83.9%; 95% CI, 66.3 to 94.5) TB cases and for culture negative pulmonary (77.8%; 95% CI, 40.0 to 97.2) and extrapulmonary (86.4%; 95% CI, 65.1 to 97.1) TB cases. These results suggest that serum biomarker analysis holds significant promise for rapid and sensitive diagnosis of pediatric TB cases, including extrapulmonary or paucibacillary TB cases. The ability to use frozen samples for this analysis should also permit assays to be performed at central sites, without a requirement for strict timelines for sample analysis.
Highlights
Diagnosis of pediatric tuberculosis (TB) is often complicated by its nonspecific symptoms, paucibacillary nature, and the need for invasive specimen collection techniques
Serum CFP-10 and ESAT-6 (SCE) levels detected by this approach can serve as evidence of active TB and can accurately diagnose active TB cases in adults, independently of disease site or M. tuberculosis culture status [6,7,8], but the diagnostic performance of this method has not been rigorously evaluated in a pediatric population
Results of this study indicated that serum detection of two M. tuberculosis virulence factors had strong diagnostic performance for pediatric TB and exhibited similar levels of performance regardless of M. tuberculosis culture status or the M. tuberculosis infection site
Summary
The study protocol was approved by the biomedical research ethics committees of the City of Houston Department of Health and Human Services, Harris County Public Health and Environmental Services, and the Houston Methodist Research Institute. Samples and clinical data analyzed in this study were obtained from archived study data and clinical specimens provided by investigators who conducted the Houston Tuberculosis Initiative (HTI) study [9], a retrospective population-based active surveillance and molecular epidemiology project that enrolled patients with suspected TB cases who were reported to the City of Houston Department of Health and Human Services and Harris County Public Health and Environmental Services from 20 October 1995 through 19 September 2002. All sample preparation and handling steps were conducted in a designated biosafety hood, following standard biosafety protocols for unfixed human blood samples
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