查看文章

Tuberculosis has been a major cause of morbidity and mortality globally for hundreds of years and remains so today. In spite of evidence pointing to significant burdens of asymptomatic but infectious (subclinical) disease, there is very little knowledge on the rates and directions of progression. Models reflect this lack of information by simplifying the structure of disease, with very little data informing the direct transitions between states. This thesis seeks to understand the natural history of tuberculosis from first infection to death or recovery with a focus on accurately representing the spectrum of disease through pathology, bacteriology, and symptom presentation in order to better parameterise models. A systematic review of TB research following untreated cohorts found research from the first half of the 1900s describing both progression and regression of disease in terms of bacteriology, radiology, and symptoms. I used this data to construct and parameterise a model of pulmonary TB disease, extending the commonly used “active disease” compartment into three stages of disease: minimal, subclinical, and clinical. I then simulated cohorts through disease to discover that 50% of people with subclinical disease may never present symptomatically, and that, despite finding a median duration of infectious disease of 12 months, after 5 years up to 20% of people starting with infectious disease could still be living with infectious TB. I then used the new model structure to compare the impact different screening tests could provide. With the current limited data on test performance for minimal and subclinical disease, mass x-ray screenings, as used in the first …