Comparison of the transmission efficiency and plague progression dynamics associated with two mechanisms by which fleas transmit Yersinia pestis.

Author summary Yersinia pestis can be transmitted by fleas within a few days after taking a blood meal from a highly bacteremic host, termed early-phase or mass transmission; and again after it forms a dense biofilm in the foregut of its vector that can eventually block blood feeding. The relative importance of the two transmission modes in the ecology of plague is a matter of current debate, but estimates of transmission rate, efficiency, and other parameters are limited. We compared transmission and disease progression dynamics in mice bitten by groups of fleas three days after their infectious blood meal (early-phase or mass transmission mode) and in mice bitten by individual blocked fleas. In general, a higher percentage of transmissions by blocked fleas led to terminal disease, whereas early-phase transmissions more often led to survival and an immune response, which are nonproductive infections in the sense that the bacteremia required to continue the Y. pestis life cycle did not develop and these animals would be removed from the pool of susceptibles in the host population. The data will be useful in mathematical models of plague dynamics in wild rodent populations. Yersinia pestis can be transmitted by fleas during the first week after an infectious blood meal, termed early-phase or mass transmission, and again after Y. pestis forms a cohesive biofilm in the flea foregut that blocks normal blood feeding. We compared the transmission efficiency and the progression of infection after transmission by Oropsylla montana fleas at both stages. Fleas were allowed to feed on mice three days after an infectious blood meal to evaluate early-phase transmission, or after they had developed complete proventricular blockage. Transmission was variable and rather inefficient by both modes, and the odds of early-phase transmission was positively associated with the number of infected fleas that fed. Disease progression in individual mice bitten by fleas infected with a bioluminescent strain of Y. pestis was tracked. An early prominent focus of infection at the intradermal flea bite site and dissemination to the draining lymph node(s) soon thereafter were common features, but unlike what has been observed in intradermal injection models, this did not invariably lead to further systemic spread and terminal disease. Several of these mice resolved the infection without progression to terminal sepsis and developed an immune response to Y. pestis, particularly those that received an intermediate number of early-phase flea bites. Furthermore, two distinct types of terminal disease were noted: the stereotypical rapid onset terminal disease within four days, or a prolonged onset preceded by an extended, fluctuating infection of the lymph nodes before eventual systemic dissemination. For both modes of transmission, bubonic plague rather than primary septicemic plague was the predominant disease outcome. The results will help to inform mathematical models of flea-borne plague dynamics used to predict the relative contribution of the two transmission modes to epizootic outbreaks that erupt periodically from the normal enzootic background state.