Sputum Microscopy With Fluorescein Diacetate Predicts Tuberculosis Infectiousness

Area of Science:

• Microbiology
• Infectious Diseases
• Public Health

Background:

• Tuberculosis (TB) diagnosis relies on detecting Mycobacterium tuberculosis (Mtb) in sputum.
• Sputum contains metabolically active and inactive Mtb subpopulations with unknown infectiousness implications.

Purpose of the Study:

• To assess sputum microscopy with fluorescein diacetate (FDA) for predicting Mtb infectiousness.
• To quantify Mtb in pretreatment sputum using FDA microscopy, culture, and acid-fast microscopy.

Main Methods:

• 35 pulmonary TB patients' sputum Mtb quantified via FDA microscopy, culture, and acid-fast microscopy.
• 209 household contacts followed for TB diagnosis over 6 years.
• Statistical analysis adjusted for disease severity, chemoprophylaxis, drug resistance, and social determinants.

Main Results:

• FDA microscopy detected fewer bacteria than acid-fast microscopy (median 119 vs 2069 bacteria/µL).
• Contacts of patients with low FDA-positive Mtb had higher TB incidence (10% vs 2.7%).
• Low FDA-positive Mtb was significantly associated with increased TB transmission (adjusted HR, 3.9; P = .02).

Conclusions:

• FDA microscopy-negative Mtb in pretreatment sputum was paradoxically associated with greater infectiousness.
• This suggests a nonstaining, slowly metabolizing Mtb phenotype may be better adapted for airborne transmission.
• FDA microscopy may offer insights into Mtb transmission dynamics beyond simple bacterial load.