Yersinia pestis factors,assuring circulation and maintenance of the plague pathogen in natural foci ecosystems. Report 1

Everlasting reproduction of Yersinia pestis, plague bacillus in natural pestholes needs virulent causative agent to invade into the host entity, be potent to overcome protection powers of the rodent organism and to pullulate to entail bacteriemia for subsequent conveyance the plague bacillus to the new host by fleas. All of legs of life cyclic patterns of Yersinia pestis are maintained by a number of plague bacillus factors acting jointly or separately, participating at the different stages of infectious process or conveyance. However these factors provide the perpetuation of the plague bacillus in the ecosystems of natural pestholes only acting in conjunction independently on their distinct contributions. Not only biomolecules, organellas and bacteria systems ensured the pursuance of virulent properties, but other factors, essential for survival of Yersinia pestis and the relationship between separate virulence factors and expression of the different genes of housekeeping and virulence of plague bacillus are considered in this review. The report I covers the problems concerned with adaptational plasticity of Yersinia pestis, it represents the classification of plague causative factors, securing its perpetuation in the environmental space, and discussion the factors promoting plague bacillus survival in the host entity. Not only wellknown publications, but papers in out-of-the-way or hard-to-reach, especially for English-reading experts, editions, also were used to compile this communication. The English version of this review may be requested from Alerton Press.     

Natural foci of diseases: the development of the concept at the close of the century

E. N. Pavlovski?'s concept of natural focality of diseases and the development of general knowledge about natural foci and their structural (components), functional (mechanisms of pathogen maintenance), and ecosystem-related organization (assortment and interrelations of ecosystems) are reviewed from principal (in authors' opinion) aspects. The 60-year history of this theory includes three stages at which its scope and contents differed. At the first stage, it concerned transmissible zoonoses. It had been assumed that structurally, natural foci necessarily include the pathogen-vector-host triad, and the functioning of the focus is provided for by only pathogen circulation in terrestrial ecosystems. At the second stage, it became clear that vector is not a necessary structural component of any focus (an example of nontransmissible diseases), although the functioning of foci remained to be unequivocally attributed to the continuous pathogen circulation among animals of terrestrial ecosystems. The third stage is characterized by an understanding that, in general, the presence of a warm-blooded host in the focus is also unnecessary for pathogen survival, and natural foci can be represented by soil and aquatic ecosystems. The only necessary and specific component of any natural focus is the pathogen population. In this context, modern views on natural focality of diseases are reviewed, and the essence of the terms "natural focus" and "epizootic process" is defined. It is proposed to distinguish the phases of pathogen reservation and epizootic spread (circulation) in ecosystems of any type. The current state of this concept provides evidence that, in general biological terms, studies on natural focality of diseases belong to one of the fields of symbiotology.     

The epidemiologic classification of plague morbidity

On the basis of the analysis of plague morbidity in the world in the XX century all epidemic foci are subdivided into 3 groups: primary, indirect primary and secondary. Each group is characterized by its specific type of morbidity in accordance with infective factors: factors connected with the natural foci of infection in group 1, economic and synanthropic factors, as well as laboratory infections, in group 2 and anthroponotic factors in group 3. In its turn, each type of morbidity differs in routes, sources, mechanisms and clinical forms of infection. In accordance with the conditions of infection, the natural foci of plague can be subdivided into mono-, oligo- and multifactor foci. The typing of plague morbidity facilitates more target-oriented organization of antiplague measures.     

The influence of the host on the frequency of block formation in males and females of Citellophilus tesquorum altaicus Ioff, 1936 (Siphonaptera: Ceratophyllidae) and transmission of the plague pathogen by these fleas

Data obtained during feeding of infested females and males of Citellophilus tesquorum altaicus Ioff, 1936 (Siphonaptera: Ceratophyllidae), the main vector of plague in Tuva natural plague focus, on the natural hosts and on laboratory animals were analyzed. Sexual differences in fleas were found to depend on the host. Females fed more actively on longtailed ground squirrels Spermophilus undulatus than on white mice. The feeding activity of males on the two hosts did not differ. A higher mortality of infested females and males was observed during feeding on mice. The frequency of block formation and pathogen transmission in males was higher during bloodsucking on the ground squirrel; in females, during feeding on mice. Thus, sex-related differences in the plague pathogen transmission revealed in laboratory white mice may be not the same in nature. This should be taken into account when extrapolating the experimental data on the natural relations between the plague pathogen and ectoparasites.     

Host influence on the frequency of block formation in males and females of Citellophilus tesquorum altaicus Ioff, 1936 (Siphonaptera: Ceratophyllidae) and transmission the plague pathogen by these fleas

Data obtained during feeding of Citellophilus tesquorum aitaicus Ioff, 1936 infested females and males (Siphonaptera: Ceratophyllidae), the main vectors of plague in Tuva natural plague locus, on the natural host and laboratory animal was analyzed. It was found that sexual differences in fleas depended on the type of the host. Females fed more actively on the longtailed ground Citellus undulatus than on white mouse. Alimentary activity of males on these animals was similar. Higher mortality of fed females and males was noted during feeding on mice. Frequency of formation of the "block" and transmission of the pathogen in males was higher during bloodsucking on the ground squirrel; in females, during feeding on mice. Thus, differences in the transmission of the plague pathogen, revealed in laboratory on white mice, can be quite different in nature. So, extrapolation of experimental data on natural processes of interrelations between plague pathogen and ectoparasites must be performed taking into account revealed peculiarities.     

Development of views on natural focality of plague

The theory of natural focality of human diseases, basically formulated by Academician E.N. Pavlovsky in 1939, invigorated research on plague, the disease whose epidemics had taken millions of lives in the past. Numerous studies in Russia and abroad have provided a great amount of data on the pathogen, its carriers, and vectors, specific features of infection spread and dynamics of activity of natural plague foci. Over a long period, plague was considered to be an obligate transmissible zoonosis. However, recent laboratory experiments and direct observations in natural foci of this infection indicate that plague is probably a zoophilous sapronosis.     

Infectious disease dynamics: What characterizes a successful invader?

Against the background of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) and other potentially emerging (or re-emerging) infectious diseases, this review will focus on the properties which enable an infectious agent to establish and maintain itself within a specified host population. We shall emphasize that for a pathogen to cross a species barrier is one thing, but for it successfully to maintain itself in the new population is must have a 'basic reproductive number', R(0), which satisfies R(0) > 1. We shall further discuss how behavioural factors interweave with the basic biology of the production of transmission stages by the pathogen, all subject to possible secular changes, to determine the magnitude of R(0). Although primarily focusing on HIV and AIDS, we shall review wider aspects of these questions.     

A study of possible transovarial and transphase transmission of borreliae by the tick Dermacentor reticulatus (Ixodidae)

A study of possible transovarial and transphase transmission of borreliae by the tick Dermacentor reticulatus is carried out. The possibility of borreliae transmission by the ticks of this species being infected spontaneously as well as experimentally is shown in principle. Although borreliae are preserved in the organism of D. reticulatus, low values of the infestation are established in the different stages of D. reticulatus development and in all steps of the study. D. reticulatus may be involved in the process of borreliae circulation in natural foci of tick-born borreliosis, but this species has no a significant importance for the maintenance of it.     

Zecken als Krankheitsüberträger: Was tun bei einem Stich?

Because of its wide host‐range and capacity for transmission of multiple pathogens, Ixodes icinus poses a constant threat of human infection. Borrelia burgdorferi is the most prevalent tick‐borne pathogen affecting humans (Lyme Borreliosis), tick‐borne‐encephalitis (TBE) the most important viral tick‐borne disease in Europe. In natural foci the pathogens circulate between infected small mammals and ticks. Knowing the lifecycle of I.ricinus, their multistrategies for host finding, attachment and blood ingestion, we may understand, what makes the tick such an excellent vector. Instructions for individual behaviour in tick areas to avoid tick contact are given. Since transmission is closely related to the feeding period it is helpful to remove an attached tick as soon as possible. Protection against tick‐borne encephalitis by vaccination is possible.     

Crayfish population size under different routes of pathogen transmission

We present an epidemiological model for the crayfish plague, a disease caused by an invasive oomycete Aphanomyces astaci, and its general susceptible freshwater crayfish host. The pathogen shows high virulence with resulting high mortality rates in freshwater crayfishes native to Europe, Asia, Australia, and South America. The crayfish plague occurrence shows complicated dynamics due to the several types of possible infection routes, which include cannibalism and necrophagy. We explore this complexity by addressing the roles of host cannibalism and the multiple routes of transmission through (1) environment, (2) contact, (3) cannibalism, and (4) scavenging of infected carcasses. We describe a compartment model having six classes of crayfish and a pool of crayfish plague spores from a single nonevolving strain. We show that environmental transmission is the decisive factor in the development of epidemics. Compared with a pathogen-free crayfish population, the presence of the pathogen with a low environmental transmission rate, regardless of the contact transmission rate, decreases the crayfish population size with a low risk of extinction. Conversely, a high transmission rate could drive both the crayfish and pathogen populations to extinction. High contact transmission rate with a low but nonzero environmental transmission rate can have mixed outcomes from extinction to large healthy population, depending on the initial values. Scavenging and cannibalism have a relevant role only when the environmental transmission rate is low, but scavenging can destabilize the system by transmitting the pathogen from a dead to a susceptible host. To the contrary, cannibalism stabilizes the dynamics by decreasing the proportion of infected population. Our model provides a simple tool for further analysis of complex host parasite dynamics and for the general understanding of crayfish disease dynamics in the wild.     

鼠疫的发病机制研究进展

鼠疫是由鼠疫耶尔森菌(Yersinia pestis，Y. pestis)感染引起的一种人畜共患病。鼠疫在世界范围内出现过3次大流行，均引起致命的瘟疫。由于自然疫源面积不断扩大和人口流动愈加频繁，我国的鼠疫防治形势依旧严峻。本文就鼠疫耶尔森菌的毒力因子、对宿主细胞的黏附和侵袭、胞内繁殖、宿主内播散等机制的研究进展进行总结，有助于揭示鼠疫独特的致病和传播机制，为精准防治鼠疫提供工作基础。     

HOST-SPECIFICITY AND HOST-SELECTION OF FLEAS IN FOCI OF HUMAN PLAGUE IN YUNNAN CHINA*

Abstract The host-specificity and the host-selection of 11 species of fleas collected from 47 species of small mammals in foci of human plague in Yunnan, China, were studied by using methods in the evaluation of ecological niche breadth and overlap. Levins' niche breadth was used for the host-specificity. while clip angle niche overlap and a fuzzy clustering analysis were used for host-selection. Of the 11 species of fleas, the host-specificity of Nosopsyllus elongatus puerensis and Xenopsylla cheopis are the highest (narrow niche breadth), and those of Aviostivalis klossi bispiniformis and Neopsylla stevensi sichuanyunnana the lowest (wide niche breadth). Of 11 species of fleas, the dominant host of X. cheopis (a very high effective vector of plague in the foci of human plague in Yunnan Province. China) is Rattw flavipectus (the main animal host and infectious source of plague in the foci). A high host-specificity of X. cheopis implies that X. cheopis mainly maintains or transmits the pathogen of plague among the individuals of its dominant species of host, R. flavipectus. The result of niche overlap analysis reveals that Ctenophthalrnus In-evipre jiciens and Ctenophthaltnus parcus have a similar host-selection while other species of fleas are quite different in their host selection.     

DNA microarray analysis of genome dynamics in Yersinia pestis: insights into bacterial genome microevolution and niche adaptation

Genomics research provides an unprecedented opportunity for us to probe into the pathogenicity and evolution of the world's most deadly pathogenic bacterium, Yersinia pestis, in minute detail. In our present work, extensive microarray analysis in conjunction with PCR validation revealed that there are considerable genome dynamics, due to gene acquisition and loss, in natural populations of Y. pestis. We established a genomotyping system to group homologous isolates of Y. pestis, based on profiling or gene acquisition and loss in their genomes, and then drew an outline of parallel microevolution of the Y. pestis genome. The acquisition of a number of genomic islands and plasmids most likely induced Y. pestis to evolve rapidly from Yersinia pseudotuberculosis to a new, deadly pathogen. Horizontal gene acquisition also plays a key role in the dramatic evolutionary segregation of Y. pestis lineages (biovars and genomovars). In contrast to selective genome expansion by gene acquisition, genome reduction occurs in Y. pestis through the loss of DNA regions. We also theorized about the links between niche adaptation and genome microevolution. The transmission, colonization, and expansion of Y. pestis in the natural foci of endemic plague are parallel and directional and involve gradual adaptation to the complex of interactions between the environment, the hosts, and the pathogen itself. These adaptations are based on the natural selections against the accumulation of genetic changes within genome. Our data strongly support that the modern plague originated from Yunnan Province in China, due to the arising of biovar orientalis from biovar antiqua rather than mediaevalis.     

云南省剑川县鼠疫自然疫源地宿主媒介情况分析

了解鼠疫自然疫源地的宿主、媒介群落结构及其种群动态,为提出针对性的鼠疫防控策略与机制提供依据.云南省剑川县属于齐氏姬鼠和大绒鼠鼠疫自然疫源地的核心区,该区域小型兽类种类丰富,存在2种类型鼠疫菌,为进一步研究疫源地的演变提供了重要的现场模型.本文对剑川县1976-2019年鼠疫监测资料进行整理和分析,发现该疫源地室内共捕...     

An additional step in the transmission of Yersinia pestis?

Plague, caused by the bacterium Yersinia pestis, is a mammalian vector-borne disease, transmitted by fleas that serve as the vector between rodent hosts. For many pathogens, including Y. pestis, there are strong evolutionary pressures that lead to a reduction in ‘useless genes'', with only those retained that reflect function in the specific environment inhabited by the pathogen. Genetic traits critical for survival and transmission between two environments, the rodent and the flea, are conserved in epizootic/epidemic plague strains. However, there are genes that remain conserved for which no function in the flea–rodent cycle has yet been observed, indicating an additional environment may exist in the transmission cycle of plague. Here, we present evidence for highly conserved genes that suggests a role in the persistence of Y. pestis after death of its host. Furthermore, maintenance of these genes points to Y. pestis traversing a post-mortem path between, and possibly within, epizootic periods and offering insight into mechanisms that may allow Y. pestis an alternative route of transmission in the natural environment.     

Spread of plague among black-tailed prairie dogs is associated with colony spatial characteristics

Sylvatic plague (Yersinia pestis) is an exotic pathogen that is highly virulent in black-tailed prairie dogs (Cynomys ludovicianus) and causes widespread colony losses and individual mortality rates >95%. We investigated colony spatial characteristics that may influence inter-colony transmission of plague at 3 prairie dog colony complexes in the Great Plains. The 4 spatial characteristics we considered include: colony size, Euclidean distance to nearest neighboring colony, colony proximity index, and distance to nearest drainage (dispersal) corridor. We used multi-state mark–recapture models to determine the relationship between these colony characteristics and probability of plague transmission among prairie dog colonies. Annual mapping of colonies and mark–recapture analyses of disease dynamics in natural colonies led to 4 main results: 1) plague outbreaks exhibited high spatial and temporal variation, 2) the site of initiation of epizootic plague may have substantially influenced the subsequent inter-colony spread of plague, 3) the long-term effect of plague on individual colonies differed among sites because of how individuals and colonies were distributed, and 4) colony spatial characteristics were related to the probability of infection at all sites although the relative importance and direction of relationships varied among sites. Our findings suggest that conventional prairie dog conservation management strategies, including promoting large, highly connected colonies, may need to be altered in the presence of plague. © 2011 The Wildlife Society     

Testing the Generality of a Trophic-cascade Model for Plague

Climate may affect the dynamics of infectious diseases by shifting pathogen, vector, or host species abundance, population dynamics, or community interactions. Black-tailed prairie dogs (Cynomys ludovicianus) are highly susceptible to plague, yet little is known about factors that influence the dynamics of plague epizootics in prairie dogs. We investigated temporal patterns of plague occurrence in black-tailed prairie dogs to assess the generality of links between climate and plague occurrence found in previous analyses of human plague cases. We examined long-term data on climate and plague occurrence in prairie dog colonies within two study areas. Multiple regression analyses revealed that plague occurrence in prairie dogs was not associated with climatic variables in our Colorado study area. In contrast, plague occurrence was strongly associated with climatic variables in our Montana study area. The models with most support included a positive association with precipitation in April–July of the previous year, in addition to a positive association with the number of “warm” days and a negative association with the number of “hot” days in the same year as reported plague events. We conclude that the timing and magnitude of precipitation and temperature may affect plague occurrence in some geographic areas. The best climatic predictors of plague occurrence in prairie dogs within our Montana study area are quite similar to the best climatic predictors of human plague cases in the southwestern United States. This correspondence across regions and species suggests support for a (temperature-modulated) trophic-cascade model for plague, including climatic effects on rodent abundance, flea abundance, and pathogen transmission, at least in regions that experience strong climatic signals.     

The Scaling of Host Density with Richness Affects the Direction,Shape, and Detectability of Diversity-Disease Relationships

Pathogen transmission responds differently to host richness and abundance, two unique components of host diversity. However, the heated debate around whether biodiversity generally increases or decreases disease has not considered the relationships between host richness and abundance that may exist in natural systems. Here we use a multi-species model to study how the scaling of total host community abundance with species richness mediates diversity-disease relationships. For pathogens with density-dependent transmission, non-monotonic trends emerge between pathogen transmission and host richness when host community abundance saturates with richness. Further, host species identity drives high variability in pathogen transmission in depauperate communities, but this effect diminishes as host richness accumulates. Using simulation we show that high variability in low richness communities and the non-monotonic relationship observed with host community saturation may reduce the detectability of trends in empirical data. Our study emphasizes that understanding the patterns and predictability of host community composition and pathogen transmission mode will be crucial for predicting where and when specific diversity-disease relationships should occur in natural systems.     

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.