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Understanding tuberculosis transmission and progression: A prospective cohort study of index cases and close contacts
Rehan R Syed1, Donald G Catanzaro2, Naomi Hillery3
1Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
Objectives:
This study aims to determine the progression rate, risk factors and timeline for the progression from exposure to active tuberculosis (TB) in a high-risk population. Using a prospective cohort in the Republic of Moldova, we investigated pulmonary TB disease progression among close contacts of patients with TB in a low-burden country with high rates of drug-resistant TB.
Methods:
Close contacts of patients with newly diagnosed TB were recruited and monitored to evaluate for progression rates to active TB. Data collected included demographic information, medical and exposure history, and clinical samples. Follow-up clinical evaluations of close contacts were conducted at regular intervals over at least 24 months to monitor for progression to TB disease.
Results:
The overall incidence rate of TB disease among close contacts was 3.7%. Among the close contacts, 2.3% were identified as progressor cases, developing TB disease more than 30 days after index case treatment initiation. Thirteen (1.3%) were co-prevalent cases, diagnosed within 30 days of index case treatment initiation. Identified risk factors for progression included male sex, active tobacco use, prior TB infection, and frequent, prolonged exposure to index cases. Close contacts with daily exposure of more than eight hours had a significantly higher risk of disease progression (adjusted OR: 4.28, 95% CI: 1.79-10.23).
Conclusion:
The incidence of TB disease among close contacts was consistent with global findings, highlighting the need for enhanced diagnostic tools and targeted interventions to manage TB transmission and progression. These results underscore the importance of contact tracing and progression monitoring in low-burden, high drug-resistant TB settings. Future research should focus on developing a better understanding of factors contributing to the risk for and timeline of TB disease progression, and more precise methods, including biomarkers, to identify individuals at the highest risk for progression from TB exposure to active disease.
Insights
Tuberculosis (TB) progression occurred in 2.3% of close contacts, with male sex, tobacco use, and prolonged exposure being key risk factors. Enhanced monitoring and diagnostics are crucial for managing TB transmission in high-risk populations.
Area of Science:
- Epidemiology
- Infectious Diseases
- Public Health
Background:
- Tuberculosis (TB) remains a global health challenge, particularly in low-burden countries with high rates of drug-resistant strains.
- Close contacts of individuals with active TB are at an elevated risk of developing the disease.
- Understanding TB progression dynamics in high-risk groups is essential for effective control strategies.
Purpose of the Study:
- To determine the incidence rate, risk factors, and timeline of progression from TB exposure to active disease among close contacts.
- To investigate TB disease progression in a prospective cohort within the Republic of Moldova, a low-burden country with significant drug-resistant TB.
- To identify specific risk factors associated with increased likelihood of TB progression in this population.
Main Methods:
- Prospective cohort study involving close contacts of newly diagnosed TB patients.
- Regular clinical evaluations and sample collection over a minimum of 24 months.
- Data collection included demographics, medical history, exposure details, and clinical assessments.
Main Results:
- The overall incidence of TB disease among close contacts was 3.7%.
- Progressor cases (TB diagnosed >30 days after index case treatment) accounted for 2.3% of contacts.
- Significant risk factors for progression included male sex, active tobacco use, prior TB infection, and prolonged daily exposure (>8 hours) to index cases (adjusted OR: 4.28).
Conclusions:
- The observed TB incidence in close contacts aligns with global data, emphasizing the need for improved diagnostics and interventions.
- Contact tracing and monitoring for progression are vital in settings with low TB incidence but high drug resistance.
- Further research is recommended to elucidate risk factors and develop biomarkers for identifying individuals at highest risk of TB progression.
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