Improved methods are urgently needed for pediatric tuberculosis (TB) diagnosis. We evaluated the performance of a blood-based assay (NanoDisk-MS), which utilizes immunoenrichment and mass spectrometry to quantify a TB-specific CFP-10 peptide, for TB diagnosis in HIV-exposed South African infants enrolled in an isoniazid TB prevention trial (IMPAACT P1041).
Cryopreserved sera from 519 infants (284 HIV-exposed infected [HEI], 235 HIV-exposed uninfected [HEU]) were evaluated for CFP-10 peptide expression by NanoDisk-MS. At entry, all subjects were BCG-immunized, 90-120 days of age, and TB-disease-negative. They were randomized 1:1 to isoniazid or placebo and followed for up to 192 weeks for TB disease or infection. For this analysis, all children were classified as Confirmed, Unconfirmed or Unlikely TB cases using 2015 NIH TB diagnostic criteria and clinical, laboratory, histopathological, and radiological data.
NanoDisk-MS exhibited sensitivity for Confirmed (5/5, 100%; 95% CI: 47.8–100) and Unconfirmed (36/43, 83.7%; 69.3–93.2) TB cases in HEI, with 93.1% (203/218, 88.9–96.1) specificity. In the HEU group, NanoDisk-MS detected the single Confirmed TB case and most of the Unconfirmed TB cases (15/20, 75.0%; 50.9–91.3), and had 96.2% (177/184, 92.3–98.5) specificity. Most (72.7%) CFP-10-positive subjects with Unlikely TB diagnoses also exhibited at least one criterion for TB diagnosis (11/15; 73.3% HEI and 5/7; 71.4% HEU). For TB cases, CFP-10 peptide could be detected in serum drawn ≤ 60 weeks before TB diagnosis, and its diagnostic sensitivity reached 83.3% (5/6, 35.9–99.6) at ≤ 12 weeks before diagnosis. CFP-10 peptide positivity and expression levels declined following anti-TB therapy initiation.
NanoDisk-MS detection of a TB-specific CFP-10 peptide in sera revealed sensitivity and specificity for TB diagnosis in HEI and HEU infants and displayed results suggesting its potential for early TB detection and the monitoring of anti-TB treatment responses.