Modeling Inhalational Tularemia: Deliberate Release and Public Health Response

Abstract

Two epidemic modeling studies of inhalational tularemia were identified in the published literature, both demonstrating the high number of potential casualties that could result from a deliberate aerosolized release of the causative agent in an urban setting. However, neither study analyzed the natural history of inhalational tularemia nor modeled the relative merits of different mitigation strategies. We first analyzed publicly available human/primate experimental data and reports of naturally acquired inhalational tularemia cases to better understand the epidemiology of the disease. We then simulated an aerosolized release of the causative agent, using airborne dispersion modeling to demonstrate the potential number of casualties and the extent of their spatial distribution. Finally, we developed a public health intervention model that compares 2 mitigation strategies: targeting antibiotics at symptomatic individuals with or without mass distribution of antibiotics to potentially infected individuals. An antibiotic stockpile that is sufficient to capture all areas where symptomatic individuals were infected is likely to save more lives than treating symptomatic individuals alone, providing antibiotics can be distributed rapidly and their uptake is high. However, with smaller stockpiles, a strategy of treating symptomatic individuals alone is likely to save many more lives than additional mass distribution of antibiotics to potentially infected individuals. The spatial distribution of symptomatic individuals is unlikely to coincide exactly with the path of the dispersion cloud if such individuals are infected near their work locations but then seek treatment close to their homes. The optimal mitigation strategy will depend critically on the size of the release relative to the stockpile level and the effectiveness of treatment relative to the speed at which antibiotics can be distributed.

A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application toFrancisella tularensis

“…For comparison, data from a number of relevant studies involving human infection with aerosolized Schu S4 [32,33,[41][42][43][44] are included within figure 5. Also included is the log-linear relation (equation (1.3)) obtained in [13] by fitting specifically to the data of [32,33]. This is equivalent to fitting the birth-death-survival deterministic solution (equation (2.3)) to these data (rather than using the parametrized solution), because when the decaying term in equation (2.1) is small the approximation given by equation (2.4) is also log-linear.…”

“…Arrows represent a range for studies in which an explicit result is not provided. [13] for comparison. Data from a number of relevant studies [32,33,41 -44] are also plotted (superscript numbers on points indicate number of subjects if greater than one).…”

“…Dose -response relation of the stochastic solution of the model (blue line) and others obtained in the literature[3,13] for comparison.…”

A review of back-calculation techniques and their potential to inform mitigation strategies with application to non-transmissible acute infectious diseases

“…In the first decade of the twenty-first century, back-calculation was then used in a variety of bioterrorism applications. The comparatively short incubation periods (of the order of days and weeks) of many of the diseases associated with bioterrorism make non-transmissible diseases, such as inhalational anthrax and tularaemia [88], particularly applicable to analysis via back-calculation. However, the prospective instantaneous exposure techniques of sections 3.2.1 and 4.1 could also be applied to acute transmissible diseases providing that the case data are based only on those persons who were exposed to the source of the outbreak and not via subsequent human-to-human transmission.…”

Generation and characterization of large-particle aerosols using a center flow tangential aerosol generator with a non-human-primate, head-only aerosol chamber

“…Naturally occurring aerosol particles containing pathogens are studied for prophylactic and therapeutic development. Additionally, aerosol particles containing pathogens can be created deliberately, for instance by rogue or bioterrorist organizations in attempts to destabilize governments and their associated economies (Leffel and Reed, 2004, Egan et al, 2011, Huang et al, 2007). When clinical trials of therapeutic agents against infections from hazardous pathogens are not ethical or feasible, well-characterized inhalational animal disease models are frequently required to develop medical countermeasures in lieu of human efficacy data (Food and Drug Administration, 2014b, Food and Drug Administration, 2014a).…”