Open questions and recent advances in the control of a multi-host infectious disease: animal tuberculosis : Recent advances in animal tuberculosis control

Many infectious agents, especially those that cause emerging diseases, infect more than one host species. Managing reservoirs of multihost pathogens often plays a crucial role in effective disease control. However, reservoirs remain variously and loosely defined. We propose that reservoirs can only be understood with reference to defined target populations. Therefore, we define a reservoir as one or more epidemiologically connected populations or environments in which the pathogen can be permanently maintained and from which infection is transmitted to the defined target population. Existence of a reservoir is confirmed when infection within the target population cannot be sustained after all transmission between target and nontarget populations has been eliminated. When disease can be controlled solely by interventions within target populations, little knowledge of potentially complex reservoir infection dynamics is necessary for effective control. We discuss the practical value of different approaches that may be used to identify reservoirs in the field.

Bovine tuberculosis (TB) is one of the most complex, persistent and controversial problems facing the British cattle industry, costing the country an estimated £100 million per year. The low sensitivity of the standard diagnostic test leads to considerable ambiguity in determining the main transmission routes of infection, which exacerbates the continuing scientific debate. In turn this uncertainty fuels the fierce public and political disputes on the necessity of controlling badgers to limit the spread of infection. Here we present a dynamic stochastic spatial model for bovine TB in Great Britain that combines within-farm and between-farm transmission. At the farm scale the model incorporates stochastic transmission of infection, maintenance of infection in the environment and a testing protocol that mimics historical government policy. Between-farm transmission has a short-range environmental component and is explicitly driven by movements of individual cattle between farms, as recorded in the Cattle Tracing System. The resultant model replicates the observed annual increase of infection over time as well as the spread of infection into new areas. Given that our model is mechanistic, it can ascribe transmission pathways to each new case; the majority of newly detected cases involve several transmission routes with moving infected cattle, reinfection from an environmental reservoir and poor sensitivity of the diagnostic test all having substantive roles. This underpins our findings on the implications of control measures. Very few of the control options tested have the potential to reverse the observed annual increase, with only intensive strategies such as whole-herd culling or additional national testing proving highly effective, whereas controls focused on a single transmission route are unlikely to be highly effective.

The emergence of wildlife reservoirs of Mycobacterium bovis infection in cattle as well as increased inter-regional trade with associated spread of M. bovis has led to renewed interest in the use of vaccines for the control of bovine tuberculosis (TB). Field efficacy trials performed in the early 20th century demonstrated the partial effectiveness of bacilli Calmette-Guerin (BCG) for the control of bovine TB. Recent experimental trials with cattle have demonstrated that: (1) subunit vaccines may boost immunity elicited by BCG in cattle, (2) T cell central memory immune responses evoked by protective vaccines correlate with protection upon subsequent M. bovis challenge, (3) BCG is particularly protective when administered to neonates, and (4) differentiation of infected from vaccinated animals (DIVA) is feasible in cattle using in vitro or in vivo methods. In regards to wildlife reservoirs, the efficacy of BCG delivered orally has been demonstrated for brushtail possums (in field trials) as well as Eurasian badgers, wild boar, and white-tailed deer (each in experimental challenge studies). Vaccine delivery to wildlife reservoirs will primarily be oral, although a parenteral route is being deployed for badgers in England. Vaccine efficacy trials, both experimental challenge and field studies, with cattle and their wildlife reservoirs represent a primary example of the one health approach, with outcomes relevant for both veterinary and medical applications. Published by Elsevier Ltd.