Abstract

BackgroundIn current epidemiology of tuberculosis (TB), heterogeneity in infectiousness among TB patients is a challenge, which is not well studied. We aimed to quantify this heterogeneity and the presence of “super-spreading” events that can assist in designing optimal public health interventions.MethodsTB epidemiologic investigation data notified between 1 January 2005 and 31 December 2015 from Victoria, Australia were used to quantify TB patients’ heterogeneity in infectiousness and super-spreading events. We fitted a negative binomial offspring distribution (NBD) for the number of secondary infections and secondary active TB disease each TB patient produced. The dispersion parameter, k, of the NBD measures the level of heterogeneity, where low values of k (e.g. k < 1) indicate over-dispersion. Super-spreading was defined as patients causing as many or more secondary infections as the 99th centile of an equivalent homogeneous distribution. Contact infection was determined based on a tuberculin skin test (TST) result of ≥10 mm. A NBD model was fitted to identify index characteristics that were associated with the number of contacts infected and risk ratios (RRs) were used to quantify the strength of this association.ResultsThere were 4190 (2312 pulmonary and 1878 extrapulmonary) index TB patients and 18,030 contacts. A total of 15,522 contacts were tested with TST, of whom 3213 had a result of ≥10 mm. The dispersion parameter, k for secondary infections was estimated at 0.16 (95%CI 0.14–0.17) and there were 414 (9.9%) super-spreading events. From the 3213 secondary infections, 2415 (75.2%) were due to super-spreading events. There were 226 contacts who developed active TB disease and a higher level of heterogeneity was found for this outcome than for secondary infection, with k estimated at 0.036 (95%CI 0.025–0.046). In regression analyses, we found that infectiousness was greater among index patients found by clinical presentation and those with bacteriological confirmation.ConclusionTB transmission is highly over dispersed and super-spreading events are responsible for a substantial majority of secondary infections. Heterogeneity of transmission and super-spreading are critical issues to consider in the design of interventions and models of TB transmission dynamics.

Highlights

  • In current epidemiology of tuberculosis (TB), heterogeneity in infectiousness among TB patients is a challenge, which is not well studied

  • Testing of contacts is conducted by either tuberculin skin testing (TST) using the Mantoux procedure or an interferon gamma release assay (IGRA), during the study period the large majority of testing was undertaken with TST

  • The Victorian TB program data had a total of 4190 confirmed TB index patients and 18,030 contacts within the period from 1 January 2005 to 31 December 2015

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Summary

Introduction

In current epidemiology of tuberculosis (TB), heterogeneity in infectiousness among TB patients is a challenge, which is not well studied. The existence of heterogeneity in transmission has the potential to disrupt elimination strategies, many of which assume broadly similar transmission potential of infectious people. Several studies have reported heterogeneity in the capacity of individual source patients to transmit various pathogens to their contacts [4,5,6,7]. Variation between infectious individuals in their capacity to transmit infectious agents is well described, with some super-spreaders infecting large number of contacts while others may only infect very few or none [4, 5, 7,8,9,10]. The contribution of super-spreading has previously been quantified for directly transmitted infections such as SARS, measles, smallpox, monkey-pox and pneumonic plague [4]

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