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Observational Study
. 2025 Aug 25;25(1):647.
doi: 10.1186/s12887-025-05554-3.

Novel and optimized diagnostics for pediatric TB in endemic countries: NOD-pedFEND study protocol

Rinn Song #  1 , Else Margreet Bijker #  2   3 , Grace Kisitu #  4 , Emily Douglass #  5 , Emmanuel Nasinghe  6   7 , Francesca Wanda Basile  2 , Nisreen Khambati  2 , Adam Penn-Nicholson  8 , Morten Ruhwald  8 , Soyeon Kim  9 , Nathan Mudrak  2 , Nandini Dendukuri  10 , César Ugarte-Gil  11 , Padmini Salgame #  5 , David Alland #  12 , Susan E Dorman #  13 , Jerrold Ellner #  5 , Moses Joloba #  6   7 , Adeodata Kekitiinwa #  4 ; NOD-pedFEND consortium
Collaborators, Affiliations
Observational Study

Novel and optimized diagnostics for pediatric TB in endemic countries: NOD-pedFEND study protocol

Rinn Song et al. BMC Pediatr. .

Abstract

Background: Pediatric tuberculosis is a major global public health challenge, with reliable diagnosis being a main obstacle to identifying and treating affected children. New and improved diagnostics, ideally on non-sputum samples, are urgently required, especially in the most vulnerable group of children under five years of age. Studies to date have been limited by small sample sizes and few bacteriologically-confirmed cases. Here, we describe the study protocol of the NIH-funded NOD-pedFEND study, which will be one of the largest diagnostic studies to date of children at greatest risk of tuberculosis.

Methods: In this prospective observational cohort study, we aim to evaluate existing and novel diagnostic assays, including pathogen- and host-based tests and combinations of tests. A consecutive cohort of children under five years of age with signs and symptoms of tuberculosis is enrolled in Uganda and Peru. All children undergo an extensive baseline workup with signs- and symptoms recording, microbiological reference tests, chest X-ray and tuberculin skin test for rigorous classification according to internationally recognized microbiological, composite reference and strict standards. An array of samples is collected for investigational tests. Follow-up visits are conducted at 2 weeks, 2 months and 6 months. A small cohort of healthy controls is enrolled to evaluate the specificity of selected diagnostics. The study has been approved by the relevant institutional review boards.

Discussion: With this large cohort study of children under five years of age, we aim to make an important contribution to the evaluation of new diagnostics for pediatric tuberculosis. By establishing a comprehensive biorepository, the study will also enable the assessment of novel tests as they become available during and after the study.

Keywords: Assays; Children; Cohort; Diagnosis; Tests; Tuberculosis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Local ethical approval has been obtained in Uganda from School of Biomedical Sciences Research Ethics Committee (SBSREC) and Uganda National Counsel for Science and Technology (UNCST) and in Peru from Universidad Peruana Cayetano Heredia Research Ethics Committee (Comité Institucional de Ética en Investigación – Humanos) and the Research Ethics Committees from Hospital Nacional Cayetano Heredia and Hospital Nacional Docente Madre Niño San Bartolomé, and local approval from the National TB program and local registration in PRISA repository (Nº: EI00003204) following local regulations before study commencement. Ethical approval has also been obtained from Rutgers University IRB and the Oxford Tropical Research Ethics Committee. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Clinical classification definitions and reference standards. SRS = Strict Reference Standard, MRS = Microbiological Reference Standard, CRS = Composite Reference Standard, GA = gastric aspirate, NPA = nasopharyngeal aspirate. Participants MRS-positive meet the case definition of Confirmed TB. Participants MRS-negative meet the case definition of either Unconfirmed TB or Unlikely TB AND must have 6 negative tests for Mtb. Participants CRS-positive meet either case definitions of Confirmed TB or Unconfirmed TB. Participants CRS-negative meet the case definition of Unlikely TB. Participants SRS-positive meet the case definition of Confirmed TB (identical to MRS-positive). Participants SRS-negative meet the Clinical Case Definition of Unlikely TB AND must have 6 negative tests for Mtb. Immunological evidence of Mtb infection was defined by a positive TST
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