Blood Tuberculosis DNA Levels to Monitor Tuberculosis Treatment

Mycobacterium Tuberculosis Complex Cell-free DNA (Mtb-cfDNA) for the Pharmacometric Assessment of Anti-tuberculosis Treatment: a Proof-of-concept Study

Tuberculosis (TB) is a leading infectious cause of death worldwide. Current strategies for monitoring TB treatment response are culture dependent and insensitive. New methods of assessing treatment response in vivo could inform new drug development and other treatment strategies. Cell-free DNA (cfDNA) - small circulating fragments of DNA - is widely used in maternofetal medicine and oncology for diagnosis and assessment of treatment response. This study aims to investigate whether pathogen derived Mycobacterium tuberculosis-specific cfDNA (Mtb-cfDNA) can be used to monitor TB treatment response.

This feasibility study will take place at Mae RaMat TB Center in Thailand and includes two study groups:

1. Assay Development and Validation
2. Longitudinal Assessment of Mtb-cfDNA levels

This study is funded by the Wellcome Trust; grant reference number: 223099/Z/21/Z

Inclusion Criteria:

Participants with a new diagnosis of tuberculosis

• Aged ≥ 18 years old
• Newly microbiologically confirmed (culture or nucleic acid amplification test) diagnosis of Mycobacterium tuberculosis (Mtb.) infection (of any site)
• Has not yet commenced antituberculosis therapy
• Able to understand study procedures and requirements and is able to give informed consent

For healthy volunteers:

• Aged ≥ 18 years old
• Healthy as judged by a responsible physician
• Able to understand study procedures and requirements and is able to give informed consent

Exclusion Criteria:

Participants with a new diagnosis of tuberculosis

• Exposure to antituberculosis treatment in the last 8 weeks (or Mycobacterium tuberculosis (Mtb.) active fluoroquinolone)
• Known history of underlying malignancy
• Pregnancy
• Transfusion dependent anaemia

For healthy volunteers:

• History of tuberculosis infection or latent tuberculosis infection
• Household, or other close contact, of a person living with tuberculosis disease
• Chest radiograph (CXR) changes suggestive of pulmonary tuberculosis
• Presence of symptoms which would otherwise indicate screening for tuberculosis (cough > 2 weeks duration, fever, weight loss, night sweats)
• Other major medical comorbidity
• Pregnancy
• Known malignancy