The probability of severe disease in zoonotic and commensal infections

Cross-species transfers of pathogens (zoonoses) cause some of the most viru lent diseases, including anthrax, hantavirus and Q fever. Zoonotic infectio ns occur when a pathogen moves from its reservoir host species into a secon dary host species. Similarly, commensal infections often have a primary res ervoir location within their hosts' bodies from which they rarely cause dis ease symptoms, but commensals such as Neisseria meningitidis cause severe d isease when they cross into a different body compartment from their normal location. Both zoonotic and commensal infections cause either mild symptoms or severe disease, but rarely intermediate symptoms. We develop a mathemat ical model for studying three factors that affect the probability of severe disease: the size of the inoculum, the route of inoculation and the freque ncy of naturally occurring infections that do not cause symptoms but do ind uce protective immunity (vaccinating inoculations). With a single route of infection, increasing pathogen density causes inoculations to develop more often into disease rather than asymptomatic vaccinations that provide prote ctive immunity. With two routes of infection, it may happen that a lower de nsity of a pathogen or of a particular antigenic variant leads to a relativ ely higher frequency of disease-inducing versus vaccinating inoculations. T his reversal occurs when one route of infection tends to vaccinate against relatively common pathogens but less often vaccinates against relatively ra re pathogens, whereas the other route of infection is susceptible to diseas e-inducing inoculation even at relatively low pathogen density.