Blood-based diagnosis of pediatric tuberculosis: a prospective cohort study in South Africa and Dominican Republic

Lin Li; Liyan Mao; Marieke M van der Zalm; Juan Olivo; Shan Liu; Carlos Vergara; Megan Palmer; Qingbo Shu; Anne-Marie Demers; Christopher J Lyon; Pierre Goussard; H Simon Schaaf; Anneke C Hesseling; Sharon Nachman; Eddy Pérez-Then; Charles D Mitchell; Elisabetta Ghimenton; Tony Y Hu

doi:10.1016/j.jinf.2024.106404

Blood-based diagnosis of pediatric tuberculosis: a prospective cohort study in South Africa and Dominican Republic

J Infect. 2025 Jan 2:106404. doi: 10.1016/j.jinf.2024.106404. Online ahead of print.

Authors

Lin Li¹, Liyan Mao², Marieke M van der Zalm³, Juan Olivo⁴, Shan Liu¹, Carlos Vergara⁴, Megan Palmer³, Qingbo Shu⁵, Anne-Marie Demers³, Christopher J Lyon⁵, Pierre Goussard³, H Simon Schaaf³, Anneke C Hesseling³, Sharon Nachman⁶, Eddy Pérez-Then⁴, Charles D Mitchell⁷, Elisabetta Ghimenton⁸, Tony Y Hu⁹

Affiliations

¹ Center for Cellular and Molecular Diagnostics, Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA; Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.
² Center for Cellular and Molecular Diagnostics, Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA; Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁴ O&M Medical School (O&Med), Santo Domingo, Dominican Republic.
⁵ Center for Cellular and Molecular Diagnostics, Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA.
⁶ Department of Pediatrics, Stony Brook Children's, SUNY Stony Brook University, Stony Brook, NY, USA.
⁷ Department of Pediatrics, Division of Infectious Diseases and Immunology, University of Miami Miller School of Medicine, Batchelor Children's Research Institute, Miami, FL, USA. Electronic address: cmitchel@miami.edu.
⁸ North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees, UK. Electronic address: elisabetta.ghimenton@nhs.net.
⁹ Center for Cellular and Molecular Diagnostics, Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA. Electronic address: tonyhu@tulane.edu.

PMID: 39755278
DOI: 10.1016/j.jinf.2024.106404

Abstract

Objectives: Pediatric tuberculosis (TB) diagnosis is complicated by challenges in obtaining invasive respiratory specimens that frequently contain few Mycobacterium tuberculosis (Mtb) bacilli. We report the diagnostic performance of an Mtb antigen-derived peptide (MAP-TB) assay and its ability to monitor TB treatment response.

Methods: Study cohorts enrolled children who presented with presumptive TB at two hospitals in South Africa from 2012 to 2017 (157 children aged <13 years) and at community-based clinics in the Dominican Republic from 2019 to 2023 (101 children aged <18 years). Children were evaluated for TB at enrollment and six months post-enrollment and assigned confirmed, unconfirmed, or unlikely TB diagnoses using the 2015 NIH diagnostic criteria for pediatric TB. MAP-TB assay performance was evaluated using serum collected at baseline and at regular intervals post-enrollment following STARD guidelines.

Results: MAP-TB sensitivity for confirmed and unconfirmed TB was comparable to culture and Xpert sensitivity for confirmed TB, but MAP-TB specificity revealed age-dependence, decreasing from 98·1% to 78·4%, when including children aged <1 year. MAP-TB values decreased by six months post-treatment initiation in children with symptom improvement.

Conclusions: Serum MAP-TB results can effectively diagnose pediatric TB, including unconfirmed and extrapulmonary TB missed by current methods, and correspond to effective treatment.

Keywords: Extrapulmonary tuberculosis; Immuno-affinity liquid chromatography-tandem mass spectrometry; Mycobacterium tuberculosis antigen-derived peptide; Non-sputum diagnostics; Paucibacillary tuberculosis; Pediatric tuberculosis.