Transmission shifts underlie variability in population responses to Yersinia pestis infection

Host populations for the plague bacterium, Yersinia pestis, are highly variable in their response to plague ranging from near deterministic extinction (i.e., epizootic dynamics) to a low probability of extinction despite persistent infection (i.e., enzootic dynamics). Much of the work to understand this variability has focused on specific host characteristics, such as population size and resistance, and their role in determining plague dynamics. Here, however, we advance the idea that the relative importance of alternative transmission routes may vary causing shifts from epizootic to enzootic dynamics. We present a model that incorporates host and flea ecology with multiple transmission hypotheses to study how transmission shifts determine population responses to plague. Our results suggest enzootic persistence relies on infection of an off-host flea reservoir and epizootics rely on transiently maintained flea infection loads through repeated infectious feeds by fleas. In either case, early-phase transmission by fleas (i.e., transmission immediately following an infected blood meal) has been observed in laboratory studies, and we show that it is capable of driving plague dynamics at the population level. Sensitivity analysis of model parameters revealed that host characteristics (e.g., population size and resistance) vary in importance depending on transmission dynamics, suggesting that host ecology may scale differently through different transmission routes enabling prediction of population responses in a more robust way than using either host characteristics or transmission shifts alone.     

Ecological characteristics of flea species relate to their suitability as plague vectors

The ability of vector-borne diseases to persist and spread is closely linked to the ecological characteristics of the vector species they use. Yet there have been no investigations of how species used as vectors by pathogens such as the plague bacterium differ from closely related species that are not used as vectors. The plague bacterium uses mammals as reservoir hosts and fleas as vectors. The ability of different fleas to serve as vectors is assumed to depend on how likely they are to experience gut blockage following bacterial multiplication; the blockage causes fleas to regurgitate blood into a wound and thus inject bacteria into new hosts. Beyond these physiological differences, it is unclear whether there exist fundamental ecological differences between fleas that are effective vectors and those that are not. Here, using a comparative analysis, we identify clear associations between the ability of flea species to transmit plague and their ecological characteristics. First, there is a positive relationship between the abundance of flea species on their hosts and their potential as vectors. Second, although the number of host species exploited by a flea is not associated with its potential as a vector, there is a negative relationship between the ability of fleas to transmit plague and the taxonomic diversity of their host spectrum. This suggests a correlation between some ecological characteristics of fleas and their ability to develop the plague blockage. The plague pathogen thus uses mainly abundant fleas specialized on a narrow taxonomic range of mammals, features that should maximize the persistence of the disease in the face of high flea mortality, and its transmission to suitable hosts only. This previously unrecognized pattern of vector use is of importance for the persistence and transmission of the disease.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .     

Seasonal patterns of rodents, fleas and plague status in the Western Usambara Mountains, Tanzania

Field and commensal rodents were live-trapped at three villages in an active focus of plague (Yersinia pseudotuberculosis pestis) in Lushoto District, Western Usambara Mountains, Tanga Region, Tanzania, from December 1983 to November 1984. Their flea ectoparasites were collected, identified and counted. The rodent carcasses were serologically examined for specific plague antibodies and antigens, and bacteriologically examined for bipolar staining bacilli. A total of 1758 traps were set during the 12-month period and 924 animals were caught. From these, 1037 fleas were collected. Rattus rattus (L.), Praomys natalensis (Smith) and Lophuromys flavopunctatus Thomas comprised the largest proportions of the rodent population, while Dinopsyllus lypusus Jordan & Rothschild, Ctenophthalmus calceatus Waterston and Xenopsylla brasiliensis (Baker) were the dominant flea species. Rodents were most abundantly trapped during December and January. Flea indices were highest from December to May. Human plague was most active from November to March. Rodents contained plague antibodies every month except May and July, with a peak in September. Plague antigens and bipolar bacilli were detected in rodent organs during January-April. From the product of abundance and infection rate, the most prevalent rodent hosts of plague appeared to be R. rattus, Otomys angoniensis Wroughton, P. natalensis and Pelomys fallax (Peters). Continuous integrated control of rodents and fleas was recommended, reinforced by quarantine and maintenance of a surveillance service for clinical detection, diagnosis and treatment of patients in the plague endemic area.     

Prevalence of Yersinia pestis in rodents and fleas associated with black-tailed prairie dogs (Cynomys ludovicianus) at Thunder Basin National Grassland, Wyoming

Rodents (and their fleas) that are associated with prairie dogs are considered important for the maintenance and transmission of the bacterium (Yersinia pestis) that causes plague. Our goal was to identify rodent and flea species that were potentially involved in a plague epizootic in black-tailed prairie dogs at Thunder Basin National Grassland. We collected blood samples and ectoparasites from rodents trapped at off- and on-colony grids at Thunder Basin National Grassland between 2002 and 2004. Blood samples were tested for antibodies to Y. pestis F-1 antigen by a passive hemagglutination assay, and fleas were tested by a multiplex polymerase chain reaction, for the presence of the plague bacterium. Only one of 1,421 fleas, an Oropsylla hirsuta collected in 2002 from a deer mouse, Peromyscus maniculatus, tested positive for Y. pestis. Blood samples collected in summer 2004 from two northern grasshopper mice, Onychomys leucogaster, tested positive for Y. pestis antibodies. All three positive samples were collected from on-colony grids shortly after a plague epizootic occurred. This study confirms that plague is difficult to detect in rodents and fleas associated with prairie dog colonies, unless samples are collected immediately after a prairie dog die-off.     

准噶尔盆地荒漠景观不同地貌类型鼠、蚤多样性及分布特征

为揭示鼠、蚤空间分布特征与变化规律,本研究以准噶尔盆地鼠疫自然疫源地为靶区,基于鼠类和蚤类的样点采集数据,计算不同地貌的鼠、蚤生态学指标并分析其相关性。基于不同行政区生态学指标计算结果,借助Moran′s I指数、重心模型、标准差椭圆等分析方法探究不同行政区鼠、蚤生态学指标的聚类特征,开展鼠、蚤的空间分布特征及变化规律的相关研究。结果表明：(1)通过对不同地貌鼠、蚤生态指标的研究,可得出鼠、蚤的物种多样性和生态优势度呈负相关,表明在物种多样性较高的群落中,鼠、蚤生态优势度表现不明显。鼠类物种多样性较高的地貌类型与蚤类物种多样性呈正相关,证实鼠类(宿主)物种数量增加,蚤类(寄生)物种的数量也在增加。低海拔地区鼠、蚤群落的相似性总体上大于中海拔地区群落相似性,且相似性系数q值与Cody指数呈相反变化趋势;(2)不同鼠、蚤指标单变量Moran′s I指数表明,鼠类数量、子午沙鼠数量、蚤类均匀度的全局Moran′s I指数大于0,且P值小于0.05,表现出空间集聚现象。单变量局部空间自相关分析结果表明,部分鼠、蚤指标存在多种聚类模式,其中最为典型的聚类模式是高—高聚类模式。不同鼠、蚤指标双变量...     

Flea diversity as an element for persistence of plague bacteria in an East African plague focus

Plague is a flea-borne rodent-associated zoonotic disease that is caused by Yersinia pestis and characterized by long quiescent periods punctuated by rapidly spreading epidemics and epizootics. How plague bacteria persist during inter-epizootic periods is poorly understood, yet is important for predicting when and where epizootics are likely to occur and for designing interventions aimed at local elimination of the pathogen. Existing hypotheses of how Y. pestis is maintained within plague foci typically center on host abundance or diversity, but little attention has been paid to the importance of flea diversity in enzootic maintenance. Our study compares host and flea abundance and diversity along an elevation gradient that spans from low elevation sites outside of a plague focus in the West Nile region of Uganda (~725-1160 m) to higher elevation sites within the focus (~1380-1630 m). Based on a year of sampling, we showed that host abundance and diversity, as well as total flea abundance on hosts was similar between sites inside compared with outside the plague focus. By contrast, flea diversity was significantly higher inside the focus than outside. Our study highlights the importance of considering flea diversity in models of Y. pestis persistence.     

Geographic variation in rodent-flea relationships in the presence of black-tailed prairie dog colonies

We characterized the relationship between fleas and their rodent hosts in the presence of prairie dog colonies and compared them to adjacent assemblages away from colonies. We evaluated the rodent-flea relationship by quantifying prevalence, probability of infestation, flea load, and intensity of fleas on rodents. As prairie dog burrows provide refugia for fleas, we hypothesized that prevalence, flea load, and intensity would be higher for rodents that are associated with black-tailed prairie dog colonies. Rodents were trapped at off- and on-colony grids, resulting in the collection of 4,509 fleas from 1,430 rodents in six study areas. The rodent community composition varied between these study areas. Flea species richness was not different between prairie dog colonies and the surrounding grasslands (p = 0.883) but was positively correlated with rodent species richness (p = 0.055). Prairie dog colonies did not increase the prevalence of fleas (p > 0.10). Flea loads on rodents did not vary between off- and on-colony grids at three of the study areas (p > 0.10). Based on the prevalence, infestation rates, and flea loads, we identified Peromyscus maniculatus, Onychomys leucogaster, and two Neotoma species as important rodent hosts for fleas and Aetheca wagneri, Orchopeus leucopus, Peromyscopsylla hesperomys, Pleochaetis exilis, and Thrassisfotus as the most important fleas associated with these rodents. Prairie dog colonies did not seem to facilitate transmission of fleas between rodent hosts, and the few rodent-flea associations exhibited significant differences between off- and on-colony grids.     

Plague and climate: scales matter

Plague is enzootic in wildlife populations of small mammals in central and eastern Asia, Africa, South and North America, and has been recognized recently as a reemerging threat to humans. Its causative agent Yersinia pestis relies on wild rodent hosts and flea vectors for its maintenance in nature. Climate influences all three components (i.e., bacteria, vectors, and hosts) of the plague system and is a likely factor to explain some of plague's variability from small and regional to large scales. Here, we review effects of climate variables on plague hosts and vectors from individual or population scales to studies on the whole plague system at a large scale. Upscaled versions of small-scale processes are often invoked to explain plague variability in time and space at larger scales, presumably because similar scale-independent mechanisms underlie these relationships. This linearity assumption is discussed in the light of recent research that suggests some of its limitations.     

Blood-feeding of the gerbil flea Nosopsyllus laeviceps kuzenkovi (Yagubyants), vector of plague in Inner Mongolia,China

Abstract. The gerbil flea Nosopsyllus laeviceps (Wagner) (Siphonaptera: Ceratophyllidae) is an important Palaearctic vector of enzootic plague among sylvan and campestral rodents. Laboratory blood-feeding experiments with the subspecies N.l.kuzenkovi (Yagubynts) from Inner Mongolia, China, using three rodent species including the natural host Meriones unguiculatus (Milne-Edwards), demonstrated a positive relationship between per cent feeding and time allowed for feeding, particularly for female fleas. Also the bloodmeal size was proportional to sucking time and was significantly greater in females, which are larger, than in males. However, on all four strains of host tested, there was no significant correlation between the feeding success rate of the fleas and the amount of blood they imbibed. Fleas fed better on active compared to confined M.unguiculatus. These findings agree with studies of other flea species.     

Field efficacy of deltamethrin for rodent flea control in San Bernardino County, California, USA.

A study was conducted to determine the initial and residual activity of deltamethrin (0.05% dust) applied to rodent burrows (at approximately 14 g/burrow) against fleas in the Silverwood Lake area of San Bernardino County. In initial toxicity (2-d post-treatment), deltamethrin provided 97% flea control and in residual toxicity it resulted in 68% control of the rodent fleas at 15-d post-treatment. The flea fauna consisted of Oropsylla montana (89.9%) and Hoplopsylls anomalus (10.1%). All rodents captured in this study were California ground squirrels, Spermophilus beecheyi. In mark-release-recapture trials, using the microchip identification implant method at the treatment site, the recapture rate of rodents was 29% from 2- to 58-d post-treatment, declining to 21% after 98 d. In the tail-clip method at the treatment site, the recapture rate of 40% at 15-d post-treatment rose to 87% and 73% at 56- and 58-d post-treatment, respectively. At the control site, the recapture rate of 100% at 15-d post-post-treatment dropped to 20% after 98 d. In another trial at Camp Cedar Crest in the Running Springs area, deltamethrin applied to rodent burrows resulted in 70% control of fleas infesting S. beecheyi. Based on the two trials, deltamethrin showed a good initial control of rodent fleas in enzootic or epizootic plague control.     

Exposure of small rodents to plague during epizootics in black-tailed prairie dogs

Plague, caused by the bacterium Yersinia pestis, causes die-offs of colonies of prairie dogs (Cynomys ludovicianus). It has been argued that other small rodents are reservoirs for plague, spreading disease during epizootics and maintaining the pathogen in the absence of prairie dogs; yet there is little empirical support for distinct enzootic and epizootic cycles. Between 2004 and 2006, we collected blood from small rodents captured in colonies in northern Colorado before, during, and for up to 2 yr after prairie dog epizootics. We screened 1,603 blood samples for antibodies to Y. pestis, using passive hemagglutination and inhibition tests, and for a subset of samples we cultured blood for the bacterium itself. Of the four species of rodents that were common in colonies, the northern grasshopper mouse (Onychomys leucogaster) was the only species with consistent evidence of plague infection during epizootics, with 11.1-23.1% of mice seropositive for antibody to Y. pestis during these events. Seropositive grasshopper mice, thirteen-lined ground squirrels (Spermophilus tridecemlineatus), and deer mice (Peromyscus maniculatus) were captured the year following epizootics. The appearance of antibodies to Y. pestis in grasshopper mice coincided with periods of high prairie dog mortality; subsequently, antibody prevalence rates declined, with no seropositive individuals captured 2 yr after epizootics. We did not detect plague in any rodents off of colonies, or on colonies prior to epizootics, and found no evidence of persistent Y. pestis infection in blood cultures. Our results suggest that grasshopper mice could be involved in epizootic spread of Y. pestis, and possibly, serve as a short-term reservoir for plague, but provide no evidence that the grasshopper mouse or any small rodent acts as a long-term, enzootic host for Y. pestis in prairie dog colonies.     

Plague studies in California: a review of long‐term disease activity,flea‐host relationships and plague ecology in the coniferous forests of the Southern Cascades and northern Sierra Nevada mountains

We review 28 years of long‐term surveillance (1970–1997) for plague activity among wild rodents from ten locations within three coniferous forest habitat types in the northern Sierra Nevada and the Southern Cascade mountains of northeastern California. We identify rodent hosts and their fleas and document long‐term plague activity in each habitat type. The highest seroprevalence for Yersinia pestis occurred in the chipmunks, Tamias senex and T. quadrimaculatus, and the pine squirrel, Tamiasciurus douglasii. The most commonly infected fleas were Ceratophyllus ciliatus and Eumolpianus eumolpi from chipmunks and Oropsylla montana and O. idahoensis from ground squirrels. Serological surveillance demonstrated that populations of T. senex, T. quadrimaculatus and T. douglasii are moderately resistant to plague, survive infection, and are, therefore, good sentinels for plague activity. Recaptured T. senex and T. quadrimaculatus showed persistence of plague antibodies and evidence of re‐infection over a two year period. These rodent species, their fleas, and the ecological factors common to the coniferous forest habitats likely promote the maintenance of plague foci in northeastern California.     

Host range and distribution of small mammal fleas in South Africa,with a focus on species of medical and veterinary importance

The host range and distribution of flea species on rodents and insectivores across multiple vegetation types in South Africa were investigated. Habitat suitability for flea species considered as important vectors of disease in humans and domestic animals was modelled. Data originated from fleas that were recovered from small mammals captured at 29 localities during 2009–2013 and published literature searched for flea records. Climate‐based predictor variables, widely used in arthropod vector distribution, were selected and habitat suitability modelled for 10 flea vector species. A total of 2469 flea individuals representing 33 species and subspecies were collected from 1185 small mammals. Ten of each of the flea and rodent species are plague vectors and reservoirs, respectively. Multiple novel flea–host associations and locality records were noted. Three vector species were recorded from insectivores. Geographic distributions of flea species ranged from broad, across‐biome distributions to narrower distributions within one or two biomes. Habitat suitability models performed excellently for the majority of flea vectors and identified regions of summer and all‐year rainfall as representing suitable habitats for most vector species. Current knowledge of vector and disease ecology can benefit from similar sampling approaches that will be important not only for South Africa, but also for the sub‐region.     

Prevalence and abundance of fleas in black-tailed prairie dog burrows: implications for the transmission of plague (Yersinia pestis)

Plague, the disease caused by the bacterium Yersinia pestis, can have devastating impacts on North American wildlife. Epizootics, or die-offs, in prairie dogs (Cynomys ludovicianus) occur sporadically and fleas (Siphonaptera) are probably important in the disease's transmission and possibly as maintenance hosts of Y. pestis between epizootics. We monitored changes in flea abundance in prairie dog burrows in response to precipitation, temperature, and plague activity in shortgrass steppe in northern Colorado. Oropsylla hirsuta was the most commonly found flea, and it increased in abundance with temperature. In contrast, Oropsylla tuberculata cynomuris declined with rising temperature. During plague epizootics, flea abundance in burrows increased and then subsequently declined after the extirpation of their prairie dog hosts.     

Molecular and physiological insights into plague transmission, virulence and etiology

Plague is caused by Yersinia pestis, which evolved from the enteric pathogen Y. pseudotuberculosis, which normally causes a chronic and relatively mild disease. Y. pestis is not only able to parasitize the flea but also highly virulent to rodents and humans, causing epidemics of a systemic and often fatal disease. Y. pestis could be used as a bio-weapon and for bio-terrorism. It uses a number of strategies that allow the pathogen to change its lifestyle rapidly to survive in fleas and to grow in the mammalian hosts. Extensive studies reviewed here give an overall picture of the determinants responsible for plague pathogenesis in mammalians and the transmission by fleas. The availability of multiple genomic sequences and more extensive use of genomics and proteomics technologies should allow a comprehensive dissection of the complex of host-adaptation and virulence in Y. pestis.     

Polymerase chain reaction (PCR) identification of rodent blood meals confirms host sharing by flea vectors of plague

Elucidating feeding relationships between hosts and parasites remains a significant challenge in studies of the ecology of infectious diseases, especially those involving small or cryptic vectors. Black‐tailed prairie dogs (Cynomys ludovicianus) are a species of conservation importance in the North American Great Plains whose populations are extirpated by plague, a flea‐vectored, bacterial disease. Using polymerase chain reaction (PCR) assays, we determined that fleas (Oropsylla hirsuta) associated with prairie dogs feed upon northern grasshopper mice (Onychomys leucogaster), a rodent that has been implicated in the transmission and maintenance of plague in prairie‐dog colonies. Our results definitively show that grasshopper mice not only share fleas with prairie dogs during plague epizootics, but also provide them with blood meals, offering a mechanism by which the pathogen, Yersinia pestis, may be transmitted between host species and maintained between epizootics. The lack of identifiable host DNA in a significant fraction of engorged Oropsylla hirsuta collected from animals (47%) and prairie‐dog burrows (100%) suggests a rapid rate of digestion and feeding that may facilitate disease transmission during epizootics but also complicate efforts to detect feeding on alternative hosts. Combined with other analytical approaches, e.g., stable isotope analysis, molecular genetic techniques can provide novel insights into host‐parasite feeding relationships and improve our understanding of the role of alternative hosts in the transmission and maintenance of disease.     

Prairie dog presence affects occurrence patterns of disease vectors on small mammals

Wildlife disease is recognized as a burgeoning threat to imperiled species and aspects of host and vector community ecology have been shown to have significant effects on disease dynamics. The black‐tailed prairie dog is a species of conservation concern that is highly susceptible to plague, a flea‐transmitted disease. Prairie dogs (Cynomys) alter the grassland communities in which they exist and have been shown to affect populations of small rodents, which are purported disease reservoirs. To explore potential ecological effects of black‐tailed prairie dogs on plague dynamics, we quantified flea occurrence patterns on small mammals in the presence and absence of prairie dogs at 8 study areas across their geographic range. Small mammals sampled from prairie dog colonies showed significantly higher flea prevalence, flea abundance, and relative flea species richness than those sampled from off‐colony sites. Successful plague transmission likely is dependent on high prevalence and abundance of fleas that can serve as competent vectors. Prairie dogs may therefore facilitate the maintenance of plague by increasing flea occurrence on potential plague reservoir species. Our data demonstrate the previously unreported ecological influence of prairie dogs on vector species assemblages, which could influence disease dynamics.     

Possible vector dissemination by swift foxes following a plague epizootic in black-tailed prairie dogs in northwestern Texas

To determine whether swift foxes (Vulpes velox) could facilitate transmission of Yersinia pestis to uninfected black-tailed prairie dog (Cynomys ludovicianus) colonies by acquiring infected fleas, ectoparasite and serologic samples were collected from swift foxes living adjacent to prairie dog towns during a 2004 plague epizootic in northwestern Texas, USA. A previous study (1999-2001) indicated that these swift foxes were infested almost exclusively with the flea Pulex irritans. Black-tailed prairie dogs examined from the study area harbored only Pulex simulans and Oropsylla hirsuta. Although P. irritans was most common, P. simulans and O. hirsuta were collected from six swift foxes and a single coyote (Canis latrans) following the plague epizootic. Thus, both of these canids could act as transport hosts (at least temporarily) of prairie dog fleas following the loss of their normal hosts during a plague die-off. All six adult swift foxes tested positive for antibodies to Y. pestis. All 107 fleas from swift foxes tested negative for Y. pestis by mouse inoculation. Although swift foxes could potentially carry Y. pestis to un-infected prairie dog colonies, we believe they play only a minor role in plague epidemiology, considering that they harbored just a few uninfected prairie dog fleas (P. simulans and O. hirsuta).     

Flea-Associated Bacterial Communities across an Environmental Transect in a Plague-Endemic Region of Uganda

The vast majority of human plague cases currently occur in sub-Saharan Africa. The primary route of transmission of Yersinia pestis, the causative agent of plague, is via flea bites. Non-pathogenic flea-associated bacteria may interact with Y. pestis within fleas and it is important to understand what factors govern flea-associated bacterial assemblages. Six species of fleas were collected from nine rodent species from ten Ugandan villages between October 2010 and March 2011. A total of 660,345 16S rRNA gene DNA sequences were used to characterize bacterial communities of 332 individual fleas. The DNA sequences were binned into 421 Operational Taxonomic Units (OTUs) based on 97% sequence similarity. We used beta diversity metrics to assess the effects of flea species, flea sex, rodent host species, site (i.e. village), collection date, elevation, mean annual precipitation, average monthly precipitation, and average monthly temperature on bacterial community structure. Flea species had the greatest effect on bacterial community structure with each flea species harboring unique bacterial lineages. The site (i.e. village), rodent host, flea sex, elevation, precipitation, and temperature also significantly affected bacterial community composition. Some bacterial lineages were widespread among flea species (e.g. Bartonella spp. and Wolbachia spp.), but each flea species also harbored unique bacterial lineages. Some of these lineages are not closely related to known bacterial diversity and likely represent newly discovered lineages of insect symbionts. Our finding that flea species has the greatest effect on bacterial community composition may help future investigations between Yersinia pestis and non-pathogenic flea-associated bacteria. Characterizing bacterial communities of fleas during a plague epizootic event in the future would be helpful.     

The Deer Mouse (<Emphasis Type="Italic">Peromyscus maniculatus</Emphasis>) as an Enzootic Reservoir of Plague in California

It has long been theorized that deer mice (Peromyscus maniculatus) are a primary reservoir of Yersinia pestis in California. However, recent research from other parts of the western USA has implicated deer mice as spillover hosts during epizootic plague transmission. This retrospective study analyzed deer mouse data collected for plague surveillance by public health agencies in California from 1971 to 2016 to help elucidate the role of deer mice in plague transmission. The fleas most commonly found on deer mice were poor vectors of Y. pestis and occurred in insufficient numbers to maintain transmission of the pathogen, while fleas whose natural hosts are deer mice were rarely observed and even more rarely found infected with Y. pestis on other rodent hosts. Seroprevalence of Y. pestis antibodies in deer mice was significantly lower than that of several chipmunk and squirrel species. These analyses suggest that it is unlikely that deer mice play an important role in maintaining plague transmission in California. While they may not be primary reservoirs, results supported the premise that deer mice are occasionally exposed to and infected by Y. pestis and instead may be spillover hosts.