National Institute of Health

KNIH (Korea National Institute of Health)

- 2025 Grant Program

Official Announcement on International Collaborative Research on Tuberculosis

(Sponsored by the Korea National Institute of Health, KDCA)

1. Background and Rationale

The Korea National Institute of Health (KNIH), a research institute of the Korea Disease Control and Prevention Agency (KDCA), is dedicated to promoting public health through research on both infectious and noninfectious diseases.

Tuberculosis (TB) remains a major global public health concern, with a continued high incidence in many high-burden countries. Close contacts of patients with active TB are classified as a high-risk group for developing the disease. Hence, providing preventive treatment to this population is considered one of the core strategies for TB elimination. However, the diagnostic indicators currently used for contact management are largely limited to identifying latent TB infection. There is insufficient scientific evidence to predict the actual progression to active disease at an early stage. Therefore, the discovery of early predictive biomarkers that can identify progression risk in advance is an essential task to improve the effectiveness of preventive therapy and establish more precise TB control strategies.

To shed light on this important area, this study aims to establish cohorts of active TB patients and their close contacts in high-burden countries for TB, and to systematically collect and analyze clinical data and biological specimens in order to identify predictive biomarkers of TB progression. Through this effort, the study seeks to provide scientific evidence for the development of effective TB prevention strategies. Furthermore, it aims to strengthen the foundation for international collaborative research and contribute to TB control and policy development at both national and global levels.

2. Project Details

  2.1. Title

    A study on predictive biomarkers for developing active TB in high-risk groups or close contacts

  2.2. Project Duration

    Within 26 months of the contract date:

      - Year 1: Contract date, 2025 – May 31, 2026

      - Year 2: June 1, 2026 – February 28, 2027

      - Year 3: March 1, 2027 – December 31, 2027

  2.3. Funding

    The annual funding will be 200,000,000 KRW.

  2.4 Countries

    Countries with a high TB burden in Asia (incidence > 100/100,000 people).

  2.5. Eligibility of Applicants

    Must have a Ph.D. or M.D.

  2.6. Research Areas of Focus

    2.6.1. Objective

To identify (clinical and/or biological) biomarkers predictive of active TB in a cohort of individuals exposed to active TB patients.

      Specific Objectives:

      a. Establish a prospective cohort of newly diagnosed active pulmonary TB patients (Cohort A) and their close contacts (Cohort B).

      b. Ensure the standardized collection of clinical data and biological specimens from cohort participants in accordance with the protocol-defined visit schedule.

      c. Analyze clinical data and specimens for biomarker development.

      d. Establish an international collaborative research platform (including long-term management of biospecimen collection, storage, and utilization).

    2.6.2. Study Design and Methodology

      ● Establishment of Single- or Multicenter Clinical Research Network:

         This prospective cohort study will be conducted in one or more clinical sites (e.g., national or regional hospitals, health centers) in TB high-burden countries. Participating sites will collaborate to recruit patients with TB and their close contacts; they will then implement harmonized standard operating procedures (SOPs) for participant enrollment, follow-up, biospecimen collection, and data management. A central coordinating center will oversee training, quality assurance, monitoring, and data integration to ensure consistency across sites and to establish a sustainable platform for future collaborative research.

      ● Subject Recruitment and Follow-up:

            ○ Cohort A (TB patients): Approximately 250 newly diagnosed pulmonary TB patients confirmed by sputum smear, culture, or molecular tests (e.g., Xpert MTB/RIF); all patients will be defined as adults according to the legal age of majority in each participating country. Patients will be followed during treatment and up to 6 months after the end of treatment (EOT+6M) to assess long-term outcomes.

            ○ Cohort B (Close contacts): Approximately 500 close contacts of Cohort A participants, with no evidence of active TB at baseline. These participants will be followed for up to 24 months to monitor TB progression.

            ○ Inclusion criteria: Individuals willing to participate and provide informed consent (or parental/guardian consent for minors).

            ○ Exclusion criteria: Individuals already on preventive therapy or with conditions precluding follow-up.

      ● Clinical Data and Sample Collection:

            ○ Clinical data: Baseline and follow-up data will include demographics, medical history, TB symptoms, radiological findings (CXR), comorbidities (e.g., diabetes), and treatment outcomes.

            ○ Biospecimens: Blood (for transcriptomic, metabolomic, and immunological assays), sputum (for microbiological confirmation and molecular diagnostics), and other specimens as feasible.

            ○ Schedule:

          - Cohort A: Baseline, 2 months, 6 months (EOT), and 12 months (EOT+6M).

          - Cohort B: Baseline, 2, 6, 12, and 24 months.

* All biospecimen collection, processing, and storage will follow harmonized SOPs across institutions. The detailed visit schedule and clinical/laboratory procedures are summarized in the Schedule of Events (Appendix), which should be referenced when finalizing the study plan.

      ● Biomarker Discovery and Analysis:

            ○ Biomarker categories:

          - KNIH-identified candidates: Blood-based metabolite biomarkers (≥10 species) primarily related to amino acid and lipid metabolism, identified through previous research undertaken by KNIH and prioritized for validation.

          - Internationally recognized candidates: Transcriptomic signatures (≥5 mRNA markers) and immunological markers (≥9, e.g., IP-10, IL-6).

            ○ Analytical Approach:

          - Comparative multivariate analysis between progressors (contacts who develop TB) and non-progressors.

          - Stepwise evaluation including univariate screening, multivariable regression, and time-to-event (Cox) models.

          - Predictive performance will be assessed using sensitivity, specificity, receiver operating characteristic (ROC), area under the ROC curve (AUC), and cross-validation.

            ○ Implementation Consideration:

          - Final selection of biomarker panels and analytical methods will be made in consultation with partner institutions, reflecting their technical capacity and infrastructure.

          - Biomarker candidates already identified by KNIH (blood-based metabolite markers) will be validated using standardized KNIH protocols to ensure reproducibility.

          - Advanced analyses requiring specialized equipment (e.g., metabolomics) will be conducted in collaboration with KNIH laboratories.

    2.6.3. Sample Collection and Data Management

      ● Samples will be collected, processed, and stored according to SOPs established by participating institutions.

      ● Samples will be stored in a central biobank designated by the host country for up to 10 years.

      ● Sample (DNA from Mtb isolates, sputum, and blood) and data transfer, including secure transfer of collected biospecimens to the KNIH for advanced biomarker analyses, will comply with ethical and legal regulations in both countries (with separate informed consent forms).

        - RCA, MOA, MTA, DTA

      ● Encrypted unique identifiers will be used to protect personal information.

      ● Quality assurance will include staff training, routine monitoring, and periodic audits to ensure compliance with protocols.

    2.6.4. Ethical Considerations

      ● The study will be conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and the Good Clinical Practice guidelines.

      ● Institutional Review Board approvals will be obtained from each participating institution prior to study initiation.

      ● Written informed consent will be obtained from all study participants after the objective, procedures, potential risks, and benefits of the study are explained. Participation will be entirely voluntary, and patients will be able to withdraw from the study at any time without affecting their routine care.

3. Affiliation

  Government institutes, universities, hospitals, etc.

4. Reporting System

  The application should be submitted in English via email before November 6, 2025.

  Pl http:// ease use MS Word format (important).

5. Key Dates

  - Application opens on October 22, 2025.

  - Application due by November 5, 2025

   * Letter of intent and project proposal should be submitted via email (jia88@korea.kr)

  Confirmation of your submission will be sent via email within three days.

  - Review due November 12, 2025

  - Result notification (via email) November 14, 2025.

6. Contact

  Jia88@korea.kr

(28159)

187, Osongsaengmyeong2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, Division of Bacterial Disease Research, Center for Infectious Disease Research, National Institute of Health, Korea Disease Control and Prevention Agency, South Korea

TEL: +82-43-719-8311

Download

• KNIH Program Proposal(Form)
• Appendix. Schedule of events