Human ectoparasites and the spread of plague in Europe during the Second Pandemic.

Plague, caused by the bacterium Yersinia pestis, can spread through human populations by multiple transmission pathways. Today, most human plague cases are bubonic, caused by spillover of infected fleas from rodent epizootics, or pneumonic, caused by inhalation of infectious droplets. However, little is known about the historical spread of plague in Europe during the Second Pandemic (14-19th centuries), including the Black Death, which led to high mortality and recurrent epidemics for hundreds of years. Several studies have suggested that human ectoparasite vectors, such as human fleas (Pulex irritans) or body lice (Pediculus humanus humanus), caused the rapidly spreading epidemics. Here, we describe a compartmental model for plague transmission by a human ectoparasite vector. Using Bayesian inference, we found that this model fits mortality curves from nine outbreaks in Europe better than models for pneumonic or rodent transmission. Our results support that human ectoparasites were primary vectors for plague during the Second Pandemic, including the Black Death (1346-1353), ultimately challenging the assumption that plague in Europe was predominantly spread by rats.

The abundance threshold for plague as a critical percolation phenomenon.

Percolation theory is most commonly associated with the slow flow of liquid through a porous medium, with applications to the physical sciences. Epidemiological applications have been anticipated for disease systems where the host is a plant or volume of soil, and hence is fixed in space. However, no natural examples have been reported. The central question of interest in percolation theory, the possibility of an infinite connected cluster, corresponds in infectious disease to a positive probability of an epidemic. Archived records of plague (infection with Yersinia pestis) in populations of great gerbils (Rhombomys opimus) in Kazakhstan have been used to show that epizootics only occur when more than about 0.33 of the burrow systems built by the host are occupied by family groups. The underlying mechanism for this abundance threshold is unknown. Here we present evidence that it is a percolation threshold, which arises from the difference in scale between the movements that transport infectious fleas between family groups and the vast size of contiguous landscapes colonized by gerbils. Conventional theory predicts that abundance thresholds for the spread of infectious disease arise when transmission between hosts is density dependent such that the basic reproduction number (R(0)) increases with abundance, attaining 1 at the threshold. Percolation thresholds, however, are separate, spatially explicit thresholds that indicate long-range connectivity in a system and do not coincide with R(0) = 1. Abundance thresholds are the theoretical basis for attempts to manage infectious disease by reducing the abundance of susceptibles, including vaccination and the culling of wildlife. This first natural example of a percolation threshold in a disease system invites a re-appraisal of other invasion thresholds, such as those for epidemic viral infections in African lions (Panthera leo), and of other disease systems such as bovine tuberculosis (caused by Mycobacterium bovis) in badgers (Meles meles).

[The involvement of some flea species in the epizootic process in the Gorno-Altai natural plague focus: spatial and temporary characteristics].

The relative number of plague pathogen strains isolated from some flea species in different Gorno-Altai natural plague foci substantially varies; this indicator also varies with time. These patterns are due to the difference in the structure of multispecies communities of ectoparasites in these areas and their long-term transformation. As of now, the three species Paradoxopsyllus scorodumovi, Ctenophyllus hirticrus, and Amphalius runatus are widely involved in pathogen transmission in all three foci. These ectoparasites should be referred to as main plague vectors. In each focus, they are joined by other flea species, such as Rhadinopsylla dahurica and Amphipsylla primaris in the Ulandryk focus, Frontopsylla hetera, R. dahurica, Paradoxopsyllus kalabukhovi, and Paramonopsyllus scalodae in the Tarkhatin focus, and P. scalonae and P. kalabukhovi in the Kurai focus, which should be classified as an additional vector.

Induction of the Yersinia pestis PhoP-PhoQ regulatory system in the flea and its role in producing a transmissible infection.

Transmission of Yersinia pestis is greatly enhanced after it forms a bacterial biofilm in the foregut of the flea vector that interferes with normal blood feeding. Here we report that the ability to produce a normal foregut-blocking infection depends on induction of the Y. pestis PhoP-PhoQ two-component regulatory system in the flea. Y. pestis phoP-negative mutants achieved normal infection rates and bacterial loads in the flea midgut but produced a less cohesive biofilm both in vitro and in the flea and had a greatly reduced ability to localize to and block the flea foregut. Thus, not only is the PhoP-PhoQ system induced in the flea gut environment, but also this induction is required to produce a normal transmissible infection. The altered biofilm phenotype in the flea was not due to lack of PhoPQ-dependent or PmrAB-dependent addition of aminoarabinose to the Y. pestis lipid A, because an aminoarabinose-deficient mutant that is highly sensitive to cationic antimicrobial peptides had a normal phenotype in the flea digestive tract. In addition to enhancing transmissibility, induction of the PhoP-PhoQ system in the arthropod vector prior to transmission may preadapt Y. pestis to resist the initial encounter with the mammalian innate immune response.

The relationship between fleas and small mammals in households of the Western Yunnan Province, China.

The Yunnan province has one of the most serious outbreaks of the plague epidemic in China. Small mammals and fleas are risk factors for the occurrence of plague in commensal plague foci. Understanding the relationship between fleas and small mammals will help control fleas and prevent the onset of the plague. Four hundred and twenty-one small mammals, belonging to 9 species, were captured. Of these, 170 small mammals (40.4%) were found infested with fleas. A total of 992 parasitic fleas (including 5 species) were collected. The number of Leptopsylla segnis and Xenopsylla cheopis accounted for 91.03% (903/992). The final multiple hurdle negative binomial regression model showed that when compared with Rattus tanezumi, the probability of flea infestation with Mus musculus as well as other host species decreased by 58% and 99%, respectively, while the number of flea infestations of the other host species increased by 4.71 folds. The probability of flea prevalence in adult hosts increased by 74%, while the number of fleas decreased by 76%. The number of flea infestations in small male mammals increased by 62%. The number of fleas in small mammals weighing more than 59 g has been multiplied by about 4. R. tanezumi is the predominant species in households in the west Yunnan province, while L.segnis and X. cheopis were dominant parasitic fleas. There is a strong relationship between the abundance of fleas and the characteristics of small mammals (e.g. Species, age, sex, and body weight).

[Role of burrow microbiocenosis in plague enzootia].

The paper analyzes relationships of the plague bacilli to the representatives of different types of living organisms inhabiting the burrows. The authors give their own data on the qualitative and quantitative composition of indicoles of the burrow of little sousliks (Spermophillus pygmaeus). They assess the role of mutagenic agents in burrow microbiocenoses.

Climate-driven spatial dynamics of plague among prairie dog colonies.

We present a Bayesian hierarchical model for the joint spatial dynamics of a host-parasite system. The model was fitted to long-term data on regional plague dynamics and metapopulation dynamics of the black-tailed prairie dog, a declining keystone species of North American prairies. The rate of plague transmission between colonies increases with increasing precipitation, while the rate of infection from unknown sources decreases in response to hot weather. The mean annual dispersal distance of plague is about 10 km, and topographic relief reduces the transmission rate. Larger colonies are more likely to become infected, but colony area does not affect the infectiousness of colonies. The results suggest that prairie dog movements do not drive the spread of plague through the landscape. Instead, prairie dogs are useful sentinels of plague epizootics. Simulations suggest that this model can be used for predicting long-term colony and plague dynamics as well as for identifying which colonies are most likely to become infected in a specific year.

[Role of fleas, the principal and secondary plague vectors, in the circulation of the causative agent in Siberian natural foci].

The paper reviews data on the role of fleas as the principal and secondary vectors of infection in the Siberian natural foci of plague. The role of Citellophilus tesquorum as the principal plague vectors in the Transbaikalian and Tuvinian natural foci is shown to be determined by their ecological characteristics (the degree of specificity to the main host, numbers, and natural infection) to a greater extent and by the rate of block formation to a lesser extent. The significance of principal and secondary vectors is estimated in the circulation of the causative agent in the monovectoral (Transbaikalian and Tuvinian) and multivectoral (Gorno-Altai) foci of plagues. It is suggested that the "microfocal" form (phenotype) of the agent's existence is characteristic of the Siberian natural foci where the rate of block formation does not generally show high indices. This phenomenon might be a basis for the long circulation of the plague microbe in the mountain (Tuva and Gorno-Altai) foci where protracted interepizootic periods have not been registered.

The Eyam plague revisited: did the village isolation change transmission from fleas to pulmonary?

Back in the 17th century the Derbyshire village of Eyam fell victim to the Black Death, which is thought to have arrived from London in some old clothes brought by a travelling tailor. The village population was 350 at the commencement of plague, of which only 83 survived. Led by the church leaders, the village community realized that the whole surrounding region was at risk from the epidemic, and therefore decided to seal themselves off from the other surrounding villages. In the first 275 days of the outbreak, transmission was predominantly from infected fleas to susceptible humans. From then onward, mortality sharply increased, which indicates a changing in transmission pattern. We hypothesize that the confinement facilitated the spread of the infection by increasing the contact rate through direct transmission among humans. This would be more consistent with pulmonary plague, a deadlier form of the disease. In order to test the above hypothesis we designed a mathematical model for plague dynamics, incorporating both the indirect (fleas-rats-humans) and direct (human-to-human) transmissions of the infection. Our results show remarkable agreement between data and the model, lending support to our hypotheses. The Eyam plague episode is celebrated as a remarkable act of collective self-sacrifice. However, to the best of our knowledge, there were no evidence before that the confinement actually increased the burden payed by the commoners. In the light of our results, it can be said that the hypothesis that confinement facilitated the spread of the infection by increasing the contact rate through direct transmission is plausible.

[Level of parasitic contact in colonies of the little suslik in the semideserts of western Kazakhstan]. / Uroven' parazitarnogo kontakta v poseleniiakh malogo suslika v polupustyniakh zapadnogo Kazakhstana.

Field experiments were conducted during the settling of young animals of Citellus pygmaeus in four areas 4 to 13.6 hectares in size. From 3 to 6 animals were caught in each area and labeled by administering radioactive substance (0.5 micrograms of glycine 14C or methionine 35S) and colouring hair on the head. In a day or two labeled sousliks were caught again and in 6-7 days a total catching of animals and collection of ectoparasites from their hair and burrows done. In al, 942 sousliks were caught in the experimental areas and 2624 specimens of fleas of different species and 2305 ticks of R. schulzei collected. The average number of fleas which were labeled on one little souslik for a day was 0.1 to 2.3. The number of labeled fleas in the above areas coincided with the number of fleas infected with plague in the areas of epizootia. The level of parasitic contact in settlements of little souslik cannot provide the development of plague epizootia by transmission of the agent through fleas.

[Parasitic contacts between the great, red-tailed and midday gerbils in the Muyun-Kum]. / Parazitarnye kontakty mezhdu bol'shoi, krasnokhvostoi i poludennoi peschankami v Muiunkumakh.

Interspecies epizootic parasitic contacts between rodents, bearers of plague in Mujunkums, have been studied. Rhombomys opimus, Meriones meridianus and M. libicus were marked with different radioactive isotopes. A bilataral exchange with fleas between great gerbils and rodents of the genus Meriones has been established. The exchange proceeded in the direction from rodents of the genus Meriones to great gerbils. Theoretically each rodent of Meriones meridianus and M. libicus fallen ill with plague can transmit within 24 hours one "blocked" flea to a great gerbil. In autumn three of ten animals take part in such transmission.

[Faunistic analysis of the fleas on small mammals in the trans-Aral Sea area]. / Faunisticheskii analiz blokh melkikh mlekopitaiushchikh Zaaral'ia.

Materials on occurrence and abundance of 36 species of fleas on 17 species of small mammals are systematized. A great similarity between the faunas of ectoparasites of rodents and predators has been shown by means of special indices. The conception of parasitic field is formulated which implies the phenomenon of community of the fauna of plague vectors parasitic on its potential carriers. Some aspects of the formation of parasitic field and its possible effect the epizootic process are considered. It is established that the similarity between the faunas of fleas from different animals is ensured in this region first of all by a wide distribution of specific parasites of gerbils.

[Ecological aspects of evolution of the plague microbe Yersinia pestis and genesis of natural reservoirs]. / Ekologicheskie aspekty évoliutsii mikroba chumy Yersinia pestis i genezis prirodnykh ochagov.

A new hypothesis of the origin of the plague microbe in the Mongolian bobak (Marmota sibirica Radde, 1862) populations in Central Asia during the Pleistocene is based on the ideas of its relative phylogenetic recency. The Late Pleistocene cooling, which induced a deep freezing of the grounds in southern Siberia, Mongolia, and Manchuria, is considered as an inducer of speciation. The main ecological factors of the plague microbe evolution include the species specific behavior of the Mongolian bobak during preparation to hibernation related to its occurrence in arid petrophytic landscapes and the larval parasitism of the flea Oropsylla silantiewi Wagn., 1898 in winter. Genesis of the plague foci is divided into two periods: natural-historical and biosocial. During the first period, the primari natural foci in Eurasia were formed and, during the second period, synanthropic (rat) and secondary natural foci appeared, with the participation of humans, in Africa, The New World, and on some tropical islands.

[Blood digestion and the formation of a plague block in Ceratophyllus tesquorum fleas]. / Perevarivanie krovi i obrazovanie chumnogo bloka u blokh Ceratophyllus tesquorum.

The fleas of C. tesquorum are characterized by high protease activity in the epithelium and contents of the stomach, quick hemolysis of erythrocytes and low blood coagulation. Rare blockformation in C. tesquorum and its long terms under experimental conditions are apparently associated with changes in the quantity of plague microbes in the digestive tract depending on the stage of blood digestion: reduced during the hemolysis of erythrocytes and increased when it was over.

[Epizootiological importance of Frontopsylla hetera (Siphonaptera) fleas in the Gorno-Altai natural plague focus]. / Epizootologicheskoe znachenie blokh Frontopsylla hetera v Gorno-Altaiskom prirodnom ochage chumy (Siphonaptera).

Experiments conducted during all seasons have established that F. hetera, one of the mass species of fleas in Mountain Altai, can be infected both by the strain of selective virulence typical to this nidus and by the non-typical non-virulent mountain-altai strain of plague agent. The non-virulent strain does not form in fleas the block of proventriculus and within 1.5-2 months they become free from the microbe. At the infection with the typical strain of the altai subspecies rare transmissions of the agent to Pallas' pika can take place as well as its long preservation in fleas.

[Notes on fleas (Siphonaptera) in plague foci on the Tay Nguyen plateau (Vietnam)]. / Zamechaniia o blokhakh (Siphonaptera) v ochagakh chumy na plato Tainguen (V'etnam).

The fleas of wild and commensal small mammals, domestic animals (dogs, cats) and free-living flea forms in houses have been collected in plague nidi of Tay Nguyen plate, Dak-Lak province, Vietnam. Pulex irritans, Ctenocephalides felis felis, Ct. felis orientis were found in the houses on dogs, cats and on the ground floor. Commensal rats in populated areas were infested by Xenopsylla cheopis and rarely by Lentistivalius klossi. The agricultural zone was inhabited by both home and wild animals such as commensal, savannah and forest-dwelling small mammals. The flea fauna of this zone is presented by X. cheopis and L. klossi. In the tropical forest surrounding villages four of the flea species were found: X. vexabilis, a specific parasite of the forest-dwelling rat Berylmys berdmorei, L. klossi found on six species of forest small mammals, Acropsylla girshami from Berylmys bowersii and Pariodontis subjugis from Hystrix brachyura. The agricultural zone is the most possible place of commensal and forest-dwelling small mammals contact, where the latter can get plague microbe.

[The effect of the vole subspecies of the plague microbe on the viability of Callopsylla caspia fleas]. / Vliianie chumnogo mikroba polevoch'ego podvida na zhizhnesposobnost' blokh Callopsylla caspia.

When infected with cultures of plague microbe reared at 28 C the experimental fleas showed no reliable differences in the mortality as compared to control ones. By contrast, the infection with agent cultures reared at 37 C as well as the infection on agonizing white mice caused a statistically reliable increase in the mortality in insects of both sexes. In the groups of fleas infected on white mice the most intensive mortality was observed during the first 24 hours after the infectious feeding that, apparently, is connected with the effect of toxins present in the blood of agonizing animals.

[An attempt to search for the correlations between the indices of plague infectivity in small mammals and fleas]. / Opyt poiska korreliatsionnykh sviazei mezhdu pokazateliami zarazhennosti melkikh mlekopitaiushchikh chumoi i blokhami.

On the basis of faunal analysis of 1.2 mln fleas collected from about 300,000 individuals belonging to 30 species of small mammals were obtained average indices of abundance and similarity between faunas of ectoparasites of different animals in a number of autonomous plague nidi of the Aral sea area. Their comparison with published earlier average data on the infection of mammals with plague has revealed notable statistical connections between these indices in all nidi under study. Thus, has been shown a leading role of transmission of plague microbe by fleas in the maintenance of natural nidality of this zoonosis. At the same time a new confirmation of the multiple-host nature of Middle Asian natural nidus of plague has been obtained.

[The epizootiological significance of flea accumulation in aggregations of the female long-tailed suslik in the Tuva plague focus]. / Epizootologicheskoe znachenie nakopleniia blokh v agregatsiiakh samok dlinnokhvostogo suslika v Yuvinskom ochage chumy.

The formation of aggregations of related females is a peculiarity of the intrapopulational organization of long-tailed suslik that results in the accumulation of Citellophilus tesquorum, the main vector and keeper of the plague microbe in the Tuva plague nidus. The plague agent is adapted to the existence on the territory occupied by aggregations of females that manifests itself in the delay of the beginning and prolixity of block-formation periods in fleas. The transfer of the agent from one place to another takes place only at the high abundance of long-tailed suslik. When the number of the suslik is low the plague microbe circulates in the ranges of one or several neighbouring aggregations of females having no possibility for successful transfer to a new place.

[The seasonal dynamics of blocking in the flea Citellophorus tesquorum altaicus from the Tuva natural plague focus]. / Sezonnaia dinamika blokoobrazovaniia u blokhi Citellophorus tesquorum altaicus iz Tuvinskogo prirodnogo ochaga chumy.

Seasonal changes in the frequency of block formation have been established in C. tesquorum altaicus from the Tuva natural plague [correction of plaque] focus. Distinctions have been observed in the blocking of fleas born in different calendar years. "Young" fleas born the current year block more frequently than old ones born the previous year.