Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
PLoS Pathog. 2020 Dec 7;16(12):e1009092. doi: 10.1371/journal.ppat.1009092. eCollection 2020 Dec.
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.
鼠疫耶尔森菌可在感染性血餐后的第一周内通过跳蚤传播，称为早期或大量传播，并且在跳蚤前肠中形成阻止正常血液摄取的粘性生物膜后再次传播。我们比较了 Oropsylla montana 跳蚤在两个阶段通过感染性血液餐进行传播的效率和感染进展。在感染性血液餐后三天，跳蚤被允许吸食老鼠以评估早期传播，或者在它们已经完全阻塞前胃后进行。通过这两种方式传播的效率都很低，而且早期传播的可能性与进食的感染跳蚤数量呈正相关。通过感染生物发光菌株的跳蚤叮咬的个体小鼠的疾病进展进行了跟踪。在皮内跳蚤叮咬部位出现早期明显的感染焦点，并随后迅速扩散到引流淋巴结是常见特征，但与皮内注射模型观察到的不同，这并不总是导致进一步的全身扩散和终末疾病。这些小鼠中的一些没有进展为终末期败血症而解决了感染，并对鼠疫耶尔森菌产生了免疫反应，特别是那些接受中等数量早期传播的跳蚤叮咬的小鼠。此外，还注意到两种不同类型的终末期疾病：四天内典型的快速发作终末期疾病，或在最终全身扩散之前，淋巴结的延长、波动感染之前的延长发作。对于这两种传播方式，鼠疫而非原发性败血性鼠疫是主要的疾病结局。这些结果将有助于为用于预测两种传播方式对周期性爆发的疫源地爆发的相对贡献的跳蚤传播鼠疫动力学的数学模型提供信息。
