Chain of Emergence Approach

Viruses and bacteria from animals are not all at the same ‘level of emergence’. Some have been able to sporadically transmit from animals to humans yet cannot transmit from human to human (e.g., Influenza A/H5N1 (bird flu) or Coxiella burnetii). Others sporadically cause human-to-human infectious outbreaks, but (currently) lack the ability and opportunity to establish prolonged outbreaks in humans. Examples include Ebola virus, Lassa virus, Crimean Congo Hemorrhagic Fever virus and Nipah virus. Others, such as seasonal or pandemic influenza and HIV have been able to make the full transition from zoonotic pathogens into exclusively human pathogens. For any zoonotic virus or bacterium to emerge from its original animal reservoir(s) and develop into a pathogen with human pandemic potential, it must successfully cross various consecutive and interdependent barriers, commonly referred to as the species barrier. Conceptually, this species barrier can be divided into three main barriers as depicted below (click to enlarge):



The interspecies barriers encompass those that determine the level and nature of exposure of humans to viruses and bacteria in animals . Among these are geographical barriers (e.g., oceans, rivers, and mountain ranges), environmental or ecological barriers (e.g., temperature and humidity gradients and habitat differences) and anthropological and behavioural barriers (e.g., meat consumption, livestock management practices).

The intrahuman barriers determine the ability of a zoonotic pathogen to (1) gain access to the appropriate tissue (2) replicate in the appropriate cell type, (3) deal appropriately with the human immune response, and (4) be excreted from the infected human host. As such, these intrahuman barriers are a key decision point in the process of pathogen emergence. Given that exposure is sufficient, it is the ability of a zoonotic pathogen to overcome the intrahuman barriers that determines its ability to replicate within a human host.

The interhuman barriers are the final set of barriers at the human-to-human level that a zoonotic pathogen must overcome in order to acquire the ability and opportunity to transmit efficiently among humans and cause human epidemics or pandemics.

These three main conceptual barriers form the basis of ANTIGONE’s Chain of Emergence approach. At the core of ANTIGONE are a series of primary ‘factor finding’ research studies and interlinked Dahlem studies, aimed at identifying the key factors that promote the ability of zoonotic viruses and bacteria to cross the consecutive barriers in the chain of emergence. Both feed into translational risk assessment and modelling exercises and an international cross-disciplinary One Health training programme. Click the image below to enlarge.