Representing Tuberculosis Transmission with Complex Contagion: An Agent-Based Simulation Modeling Approach.

OBJECTIVE: A recent study reported a tuberculosis (TB) outbreak in which, among newly infected individuals, exposure to additional active infections was associated with a higher probability of developing active disease. Referred to as complex contagion, multiple reexposures to TB within a short period after initial infection is hypothesized to confer a greater likelihood of developing active infection in 1 y. The purpose of this article is to develop and validate an agent-based simulation model (ABM) to study the effect of complex contagion on population-level TB transmission dynamics. METHODS: We built an ABM of a TB epidemic using data from a series of outbreaks recorded in the 20th century in Saskatchewan, Canada. We fit 3 dynamical schemes: base, with no complex contagion; additive, in which each reexposure confers an independent risk of activated infection; and threshold, in which a small number of reexposures confers a low risk and a high number of reexposures confers a high risk of activation. RESULTS: We find that the base model fits the mortality and incidence output targets best, followed by the threshold and then the additive models. The threshold model fits the incidence better than the base model does but overestimates mortality. All 3 models produce qualitatively realistic epidemic curves. CONCLUSION: We find that complex contagion qualitatively changes the trajectory of a TB epidemic, although data from a high-incidence setting are reproduced better with the base model. Results from this model demonstrate the feasibility of using ABM to capture nuances in TB transmission.

Tuberculosis sanatorium treatment at the advent of the chemotherapy era.

BACKGROUND: The discovery of antibiotics in the mid-twentieth century marked a major transition in tuberculosis (TB) treatment and control. There are few studies describing the duration of TB disease and its treatment from the pre-chemotherapy era and little data on how these treatments changed in response to the development of effective antibiotics. The goal of this research is to understand how inpatient treatment for high incidence populations, the First Nations peoples of Saskatchewan, Canada, changed in response to increasing availability of antibiotics effective against TB. We expected that as treatment regimens transitioned from convalescence-only to triple antibiotic therapy, the length of inpatient treatment would shorten. METHODS: Analyses were performed on records of sanatoria admissions and discharges occurring between 1933 and 1959 in Saskatchewan, Canada. Year of antibiotic discovery was taken as a proxy for treatment regimen: no chemotherapy (pre-1944), mono-therapy (Streptomycin, 1944-1946), dual-therapy (Streptomycin and PAS, 1946-1952), and triple-therapy (Streptomycin, PAS, and INH 1952-). A pooled linear regression of log-transformed length of first admission as predicted by year of admission was modeled to assess the relationship between admission length and year of admission, corrected for clinical and demographic variables. RESULTS: First admission length increased 19% in the triple-therapy era as compared to the pre-chemotherapy era, from 316 days (10.4 months) to 377 days (12.4 months). After the discovery of INH (1952), we find statistically significant increases in the proportion of successfully completed therapies (0.55 versus 0.60, p = 0.035), but also in patients who left hospital against medical advice (0.19 versus 0.29, p < 0.0001), indicating that as hospitalizations lengthened, more patients chose to discharge without the sanction of their physician. The readmission rate increased from 10 to 50% of all admissions while the province-level TB-specific death rate fell from 63.1 per 10,000 in 1933 to 4.7 per 10,000 in 1958. CONCLUSION: Counterintuitively, we find that the length of first admissions increased with the discovery of TB-treating antibiotics. Increasing admission volume and readmission rate indicate an intensification of inpatient TB treatment during this era. These analyses provide a novel estimate of the effect of changing treatment policy on sanatorium admissions in this population.