ResearchPad - plagues https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Agent-based and continuous models of hopper bands for the Australian plague locust: How resource consumption mediates pulse formation and geometry]]> https://www.researchpad.co/article/elastic_article_14654 Locusts aggregate in swarms that threaten agriculture worldwide. Initially these aggregations form as aligned groups, known as hopper bands, whose individuals alternate between marching and paused (associated with feeding) states. The Australian plague locust (for which there are excellent field studies) forms wide crescent-shaped bands with a high density at the front where locusts slow in uneaten vegetation. The density of locusts rapidly decreases behind the front where the majority of food has been consumed. Most models of collective behavior focus on social interactions as the key organizing principle. We demonstrate that the formation of locust bands may be driven by resource consumption. Our first model treats each locust as an individual agent with probabilistic rules governing motion and feeding. Our second model describes locust density with deterministic differential equations. We use biological observations of individual behavior and collective band shape to identify numerical values for the model parameters and conduct a sensitivity analysis of outcomes to parameter changes. Our models are capable of reproducing the characteristics observed in the field. Moreover, they provide insight into how resource availability influences collective locust behavior that may eventually aid in disrupting the formation of locust bands, mitigating agricultural losses.

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<![CDATA[Human plague associated with Tibetan sheep originates in marmots]]> https://www.researchpad.co/article/5b8b29ea40307c405292ca55

The Qinghai-Tibet plateau is a natural plague focus and is the largest such focus in China. In this area, while Marmota himalayana is the primary host, a total of 18 human plague outbreaks associated with Tibetan sheep (78 cases with 47 deaths) have been reported on the Qinghai-Tibet plateau since 1956. All of the index infectious cases had an exposure history of slaughtering or skinning diseased or dead Tibetan sheep. In this study, we sequenced and compared 38 strains of Yersinia pestis isolated from different hosts, including humans, Tibetan sheep, and M. himalayana. Phylogenetic relationships were reconstructed based on genome-wide single-nucleotide polymorphisms identified from our isolates and reference strains. The phylogenetic relationships illustrated in our study, together with the finding that the Tibetan sheep plague clearly lagged behind the M. himalayana plague, and a previous study that identified the Tibetan sheep as a plague reservoir with high susceptibility and moderate sensitivity, indicated that the human plague was transmitted from Tibetan sheep, while the Tibetan sheep plague originated from marmots. Tibetan sheep may encounter this infection by contact with dead rodents or through being bitten by fleas originating from M. himalayana during local epizootics.

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<![CDATA[Two Isoforms of Yersinia pestis Plasminogen Activator Pla: Intraspecies Distribution, Intrinsic Disorder Propensity, and Contribution to Virulence]]> https://www.researchpad.co/article/5989db10ab0ee8fa60bcbebc

It has been shown previously that several endemic Y. pestis isolates with limited virulence contained the I259 isoform of the outer membrane protease Pla, while the epidemic highly virulent strains possessed only the T259 Pla isoform. Our sequence analysis of the pla gene from 118 Y. pestis subsp. microtus strains revealed that the I259 isoform was present exclusively in the endemic strains providing a convictive evidence of more ancestral origin of this isoform. Analysis of the effects of the I259T polymorphism on the intrinsic disorder propensity of Pla revealed that the I259T mutation slightly increases the intrinsic disorder propensity of the C-terminal tail of Pla and makes this protein slightly more prone for disorder-based protein-protein interactions, suggesting that the T259 Pla could be functionally more active than the I259 Pla. This assumption was proven experimentally by assessing the coagulase and fibrinolytic activities of the two Pla isoforms in human plasma, as well as in a direct fluorometric assay with the Pla peptide substrate. The virulence testing of Pla-negative or expressing the I259 and T259 Pla isoforms Y. pestis subsp. microtus and subsp. pestis strains did not reveal any significant difference in LD50 values and dose-dependent survival assays between them by using a subcutaneous route of challenge of mice and guinea pigs or intradermal challenge of mice. However, a significant decrease in time-to-death was observed in animals infected with the epidemic T259 Pla-producing strains as compared to the parent Pla-negative variants. Survival curves of the endemic I259 Pla+ strains fit between them, but significant difference in mean time to death post infection between the Plastrains and their I259 Pla+ variants could be seen only in the isogenic set of subsp. pestis strains. These findings suggest an essential role for the outer membrane protease Pla evolution in Y. pestis bubonic infection exacerbation that is necessary for intensification of epidemic process from endemic natural focality with sporadic cases in men to rapidly expanding epizootics followed by human epidemic outbreaks, local epidemics or even pandemics.

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<![CDATA[The Fleas (Siphonaptera) in Iran: Diversity, Host Range, and Medical Importance]]> https://www.researchpad.co/article/5989db54ab0ee8fa60bdd03d

Background

Flea-borne diseases have a wide distribution in the world. Studies on the identity, abundance, distribution and seasonality of the potential vectors of pathogenic agents (e.g. Yersinia pestis, Francisella tularensis, and Rickettsia felis) are necessary tools for controlling and preventing such diseases outbreaks. The improvements of diagnostic tools are partly responsible for an easier detection of otherwise unnoticed agents in the ectoparasitic fauna and as such a good taxonomical knowledge of the potential vectors is crucial. The aims of this study were to make an exhaustive inventory of the literature on the fleas (Siphonaptera) and range of associated hosts in Iran, present their known distribution, and discuss their medical importance.

Methodology/Principal Findings

The data were obtained by an extensive literature review related to medically significant fleas in Iran published before 31st August 2016. The flea-host specificity was then determined using a family and subfamily-oriented criteria to further realize and quantify the shared and exclusive vertebrate hosts of fleas among Iran fleas. The locations sampled and reported in the literature were primarily from human habitation, livestock farms, poultry, and rodents’ burrows of the 31 provinces of the country. The flea fauna were dominated by seven families, namely the Ceratophyllidae, Leptopsyllidae, Pulicidae, Ctenophthalmidae, Coptopsyllidae, Ischnopsyllidae and Vermipsyllidae. The hosts associated with Iran fleas ranged from the small and large mammals to the birds. Pulicidae were associated with 73% (56/77) of identified host species. Flea-host association analysis indicates that rodents are the common hosts of 5 flea families but some sampling bias results in the reduced number of bird host sampled. Analyses of flea-host relationships at the subfamily level showed that most vertebrates hosted fleas belgonging to 3 subfamilies namely Xenopsyllinae (n = 43), Ctenophthalminae (n = 20) and Amphipsyllinae (n = 17). Meriones persicus was infested by 11 flea subfamilies in the arid, rocky, mountainous regions and Xenopsyllinae were hosted by at least 43 mammal species. These findings place the Persian jird (M. persicus) and the Xenopsyllinae as the major vertebrate and vector hosts of flea-borne diseases in Iran including Yersinia pestis, the etiological agent of plague. We found records of at least seven vector-borne pathogenic agents that can potentially be transmitted by the 117 flea species (or subspecies) of Iran.

Conclusions/Significance

Herein, we performed a thorough inventary of the flea species and their associated hosts, their medical importance and geographic distribution throughout Iran. This exercise allowed assessing the diversity of flea species with the potential flea-borne agents transmission risk in the country by arranging published data on flea-host associations. This information is a first step for issuing public health policies and rodent-flea control campaigns in Iran as well as those interested in the ecology/epidemiology of flea-borne disease.

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<![CDATA[Yersinia pestis Caf1 Protein: Effect of Sequence Polymorphism on Intrinsic Disorder Propensity, Serological Cross-Reactivity and Cross-Protectivity of Isoforms]]> https://www.researchpad.co/article/5989d9ddab0ee8fa60b68567

Yersinia pestis Caf1 is a multifunctional protein responsible for antiphagocytic activity and is a key protective antigen. It is generally conserved between globally distributed Y. pestis strains, but Y. pestis subsp. microtus biovar caucasica strains circulating within populations of common voles in Georgia and Armenia were reported to carry a single substitution of alanine to serine. We investigated polymorphism of the Caf1 sequences among other Y. pestis subsp. microtus strains, which have a limited virulence in guinea pigs and in humans. Sequencing of caf1 genes from 119 Y. pestis strains belonging to different biovars within subsp. microtus showed that the Caf1 proteins exist in three isoforms, the global type Caf1NT1 (Ala48 Phe117), type Caf1NT2 (Ser48 Phe117) found in Transcaucasian-highland and Pre-Araks natural plague foci #4–7, and a novel Caf1NT3 type (Ala48 Val117) endemic in Dagestan-highland natural plague focus #39. Both minor types are the progenies of the global isoform. In this report, Caf1 polymorphism was analyzed by comparing predicted intrinsic disorder propensities and potential protein-protein interactivities of the three Caf1 isoforms. The analysis revealed that these properties of Caf1 protein are minimally affected by its polymorphism. All protein isoforms could be equally detected by an immunochromatography test for plague at the lowest protein concentration tested (1.0 ng/mL), which is the detection limit. When compared to the classic Caf1NT1 isoform, the endemic Caf1NT2 or Caf1NT3 had lower immunoreactivity in ELISA and lower indices of self- and cross-protection. Despite a visible reduction in cross-protection between all Caf1 isoforms, our data suggest that polymorphism in the caf1 gene may not allow the carriers of Caf1NT2 or Caf1NT3 variants escaping from the Caf1NT1-mediated immunity to plague in the case of a low-dose flea-borne infection.

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<![CDATA[Zoonoses As Ecological Entities: A Case Review of Plague]]> https://www.researchpad.co/article/5989daccab0ee8fa60bb4b11

As a zoonosis, Plague is also an ecological entity, a complex system of ecological interactions between the pathogen, the hosts, and the spatiotemporal variations of its ecosystems. Five reservoir system models have been proposed: (i) assemblages of small mammals with different levels of susceptibility and roles in the maintenance and amplification of the cycle; (ii) species-specific chronic infection models; (ii) flea vectors as the true reservoirs; (iii) Telluric Plague, and (iv) a metapopulation arrangement for species with a discrete spatial organization, following a source-sink dynamic of extinction and recolonization with naïve potential hosts. The diversity of the community that harbors the reservoir system affects the transmission cycle by predation, competition, and dilution effect. Plague has notable environmental constraints, depending on altitude (500+ meters), warm and dry climates, and conditions for high productivity events for expansion of the transmission cycle. Human impacts are altering Plague dynamics by altering landscape and the faunal composition of the foci and adjacent areas, usually increasing the presence and number of human cases and outbreaks. Climatic change is also affecting the range of its occurrence. In the current transitional state of zoonosis as a whole, Plague is at risk of becoming a public health problem in poor countries where ecosystem erosion, anthropic invasion of new areas, and climate change increase the contact of the population with reservoir systems, giving new urgency for ecologic research that further details its maintenance in the wild, the spillover events, and how it links to human cases.

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<![CDATA[Xenopsylla cheopis (Siphonaptera: Pulicidae) Susceptibility to Deltamethrin in Madagascar]]> https://www.researchpad.co/article/5989d9fbab0ee8fa60b71f38

The incidence of bubonic plague in Madagascar is high. This study reports the susceptibility of 32 different populations of a vector, the flea Xenopsylla cheopis (Siphonaptera: Pulicidae), to the insecticide Deltamethrin. Despite the use of Deltamethrin against fleas, plague epidemics have re-emerged in Madagascar. The majority of the study sites were located in the Malagasy highlands where most plague cases have occurred over the last 10 years. X. cheopis fleas were tested for susceptibility to Deltamethrin (0.05%): only two populations were susceptible to Deltamethrin, four populations were tolerant and 26 populations were resistant. KD50 (50% Knock-Down) and KD90 (90% Knock-Down) times were determined, and differed substantially from 9.4 to 592.4 minutes for KD50 and 10.4 min to 854.3 minutes for KD90. Susceptibility was correlated with latitude, but not with longitude, history of insecticide use nor date of sampling. Combined with the number of bubonic plague cases, our results suggest that an immediate switch to an insecticide other than Deltamethrin is required for plague vector control in Madagascar.

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<![CDATA[Caspase-3 Mediates the Pathogenic Effect of Yersinia pestis YopM in Liver of C57BL/6 Mice and Contributes to YopM's Function in Spleen]]> https://www.researchpad.co/article/5989dadbab0ee8fa60bb9f8b

The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found associated with myeloid cells in foci of inflammation and in liver sinusoids. A new in-vivo phenotype of YopM was revealed: death of inflammatory cells, evidenced by TUNEL staining beginning at d 1 of infection. Based on distributions of Ly6G+, F4/80+, and iNOS+ cells within foci, the cells that were killed could have included both PMNs and macrophages. By 2 d post-infection, YopM had no effect on distribution of these cells, but by 3 d cellular decomposition had outstripped acute inflammation in foci due to parent Y. pestis, while foci due to the ΔyopM-1 strain still contained many inflammatory cells. The destruction depended on the presence of both PMNs in the mice and YopM in the bacteria. In mice that lacked the apoptosis mediator caspase-3 the infection dynamics were novel: the parent Y. pestis was limited in growth comparably to the ΔyopM-1 strain in liver, and in spleen a partial growth limitation for parent Y. pestis was seen. This result identified caspase-3 as a co-factor or effector in YopM's action and supports the hypothesis that in liver YopM's main pathogenic effect is mediated by caspase-3 to cause apoptosis of PMNs.

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<![CDATA[Current Perspectives on Plague Vector Control in Madagascar: Susceptibility Status of Xenopsylla cheopis to 12 Insecticides]]> https://www.researchpad.co/article/5989da78ab0ee8fa60b974f5

Plague is a rodent disease transmissible to humans by infected flea bites, and Madagascar is one of the countries with the highest plague incidence in the world. This study reports the susceptibility of the main plague vector Xenopsylla cheopis to 12 different insecticides belonging to 4 insecticide families (carbamates, organophosphates, pyrethroids and organochlorines). Eight populations from different geographical regions of Madagascar previously resistant to deltamethrin were tested with a World Health Organization standard bioassay. Insecticide susceptibility varied amongst populations, but all of them were resistant to six insecticides belonging to pyrethroid and carbamate insecticides (alphacypermethrin, lambdacyhalothrin, etofenprox, deltamethrin, bendiocarb and propoxur). Only one insecticide (dieldrin) was an efficient pulicide for all flea populations. Cross resistances were suspected. This study proposes at least three alternative insecticides (malathion, fenitrothion and cyfluthrin) to replace deltamethrin during plague epidemic responses, but the most efficient insecticide may be different for each population studied. We highlight the importance of continuous insecticide susceptibility surveillance in the areas of high plague risk in Madagascar.

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<![CDATA[High Throughput, Multiplexed Pathogen Detection Authenticates Plague Waves in Medieval Venice, Italy]]> https://www.researchpad.co/article/5989dae2ab0ee8fa60bbc273

Background

Historical records suggest that multiple burial sites from the 14th–16th centuries in Venice, Italy, were used during the Black Death and subsequent plague epidemics.

Methodology/Principal Findings

High throughput, multiplexed real-time PCR detected DNA of seven highly transmissible pathogens in 173 dental pulp specimens collected from 46 graves. Bartonella quintana DNA was identified in five (2.9%) samples, including three from the 16th century and two from the 15th century, and Yersinia pestis DNA was detected in three (1.7%) samples, including two from the 14th century and one from the 16th century. Partial glpD gene sequencing indicated that the detected Y. pestis was the Orientalis biotype.

Conclusions

These data document for the first time successive plague epidemics in the medieval European city where quarantine was first instituted in the 14th century.

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<![CDATA[PLoS Neglected Tropical Diseases Issue Image | Vol. 12(7) July 2018]]> https://www.researchpad.co/article/5b6d8c51463d7e2ccdcccfef

Photo of a great gerbil (Rhombomys opimus) exiting a burrow system in southeastern Kazkhstan

Great gerbils are the primary host of plague and cutaneous leismaniasis in most natural foci in Central Asia. The colonies built by these rodents are extensive, sometimes 50 meters in diameter, with the total length of the burrow systems occasionally reaching up to one kilometer. Great gerbil burrows systems play an important role in desert ecosystems, with several animal species utilizing them. Poché et al. (2018)

Image Credit: Richard M. Poché

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<![CDATA[Mechanism study on a plague outbreak driven by the construction of a large reservoir in southwest china (surveillance from 2000-2015)]]> https://www.researchpad.co/article/5989db54ab0ee8fa60bdd10b

Background

Plague, a Yersinia pestis infection, is a fatal disease with tremendous transmission capacity. However, the mechanism of how the pathogen stays in a reservoir, circulates and then re-emerges is an enigma.

Methodology/Principal findings

We studied a plague outbreak caused by the construction of a large reservoir in southwest China followed 16-years’ surveillance.

Conclusions/Significance

The results show the prevalence of plague within the natural plague focus is closely related to the stability of local ecology. Before and during the decade of construction the reservoir on the Nanpan River, no confirmed plague has ever emerged. With the impoundment of reservoir and destruction of drowned farmland and vegetation, the infected rodent population previously dispersed was concentrated together in a flood-free area and turned a rest focus alive. Human plague broke out after the enzootic plague via the flea bite. With the construction completed and ecology gradually of human residential environment, animal population and type of vegetation settling down to a new balance, the natural plague foci returned to a rest period. With the rodent density decreased as some of them died, the flea density increased as the rodents lived near or in local farm houses where had more domestic animals, and human has a more concentrated population. In contrast, in the Himalayan marmot foci of the Qinghai-Tibet Plateau in the Qilian Mountains. There are few human inhabitants and the local ecology is relatively stable; plague is prevalence, showing no rest period. Thus the plague can be significantly affected by ecological shifts.

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<![CDATA[Feeding Behavior Modulates Biofilm-Mediated Transmission of Yersinia pestis by the Cat Flea, Ctenocephalides felis]]> https://www.researchpad.co/article/5989da7eab0ee8fa60b99b99

Background

The cat flea, Ctenocephalides felis, is prevalent worldwide, will parasitize animal reservoirs of plague, and is associated with human habitations in known plague foci. Despite its pervasiveness, limited information is available about the cat flea’s competence as a vector for Yersinia pestis. It is generally considered to be a poor vector, based on studies examining early-phase transmission during the first week after infection, but transmission potential by the biofilm-dependent proventricular-blocking mechanism has never been systematically evaluated. In this study, we assessed the vector competence of cat fleas by both mechanisms. Because the feeding behavior of cat fleas differs markedly from important rat flea vectors, we also examined the influence of feeding behavior on transmission dynamics.

Methodology/Principal Findings

Groups of cat fleas were infected with Y. pestis and subsequently provided access to sterile blood meals twice-weekly, 5 times per week, or daily for 4 weeks and monitored for infection, the development of proventricular biofilm and blockage, mortality, and the ability to transmit. In cat fleas allowed prolonged, daily access to blood meals, mimicking their natural feeding behavior, Y. pestis did not efficiently colonize the digestive tract and could only be transmitted during the first week after infection. In contrast, cat fleas that were fed intermittently, mimicking the feeding behavior of the efficient vector Xenopsylla cheopis, could become blocked and regularly transmitted Y. pestis for 3–4 weeks by the biofilm-mediated mechanism, but early-phase transmission was not detected.

Conclusions

The normal feeding behavior of C. felis, more than an intrinsic resistance to infection or blockage by Y. pestis, limits its vector competence. Rapid turnover of midgut contents results in bacterial clearance and disruption of biofilm accumulation in the proventriculus. Anatomical features of the cat flea foregut may also restrict transmission by both early-phase and proventricular biofilm-dependent mechanisms.

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<![CDATA[Flea Diversity as an Element for Persistence of Plague Bacteria in an East African Plague Focus]]> https://www.researchpad.co/article/5989db0bab0ee8fa60bca30e

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.

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<![CDATA[Disruption of Fas-Fas Ligand Signaling, Apoptosis, and Innate Immunity by Bacterial Pathogens]]> https://www.researchpad.co/article/5989da26ab0ee8fa60b80b82 ]]> <![CDATA[Two Distinct Yersinia pestis Populations Causing Plague among Humans in the West Nile Region of Uganda]]> https://www.researchpad.co/article/5989da8eab0ee8fa60b9ee40

Background

Plague is a life-threatening disease caused by the bacterium, Yersinia pestis. Since the 1990s, Africa has accounted for the majority of reported human cases. In Uganda, plague cases occur in the West Nile region, near the border with Democratic Republic of Congo. Despite the ongoing risk of contracting plague in this region, little is known about Y. pestis genotypes causing human disease.

Methodology/Principal Findings

During January 2004–December 2012, 1,092 suspect human plague cases were recorded in the West Nile region of Uganda. Sixty-one cases were culture-confirmed. Recovered Y. pestis isolates were analyzed using three typing methods, single nucleotide polymorphisms (SNPs), pulsed field gel electrophoresis (PFGE), and multiple variable number of tandem repeat analysis (MLVA) and subpopulations analyzed in the context of associated geographic, temporal, and clinical data for source patients. All three methods separated the 61 isolates into two distinct 1.ANT lineages, which persisted throughout the 9 year period and were associated with differences in elevation and geographic distribution.

Conclusions/Significance

We demonstrate that human cases of plague in the West Nile region of Uganda are caused by two distinct 1.ANT genetic subpopulations. Notably, all three typing methods used, SNPs, PFGE, and MLVA, identified the two genetic subpopulations, despite recognizing different mutation types in the Y. pestis genome. The geographic and elevation differences between the two subpopulations is suggestive of their maintenance in highly localized enzootic cycles, potentially with differing vector-host community composition. This improved understanding of Y. pestis subpopulations in the West Nile region will be useful for identifying ecologic and environmental factors associated with elevated plague risk.

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<![CDATA[Identification of Small-Molecule Inhibitors of Yersinia pestis Type III Secretion System YscN ATPase]]> https://www.researchpad.co/article/5989dabfab0ee8fa60bb01a5

Yersinia pestis is a Gram negative zoonotic pathogen responsible for causing bubonic and pneumonic plague in humans. The pathogen uses a type III secretion system (T3SS) to deliver virulence factors directly from bacterium into host mammalian cells. The system contains a single ATPase, YscN, necessary for delivery of virulence factors. In this work, we show that deletion of the catalytic domain of the yscN gene in Y. pestis CO92 attenuated the strain over three million-fold in the Swiss-Webster mouse model of bubonic plague. The result validates the YscN protein as a therapeutic target for plague. The catalytic domain of the YscN protein was made using recombinant methods and its ATPase activity was characterized in vitro. To identify candidate therapeutics, we tested computationally selected small molecules for inhibition of YscN ATPase activity. The best inhibitors had measured IC50 values below 20 µM in an in vitro ATPase assay and were also found to inhibit the homologous BsaS protein from Burkholderia mallei animal-like T3SS at similar concentrations. Moreover, the compounds fully inhibited YopE secretion by attenuated Y. pestis in a bacterial cell culture and mammalian cells at µM concentrations. The data demonstrate the feasibility of targeting and inhibiting a critical protein transport ATPase of a bacterial virulence system. It is likely the same strategy could be applied to many other common human pathogens using type III secretion system, including enteropathogenic E. coli, Shigella flexneri, Salmonella typhimurium, and Burkholderia mallei/pseudomallei species.

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<![CDATA[Comparative Ability of Oropsylla montana and Xenopsylla cheopis Fleas to Transmit Yersinia pestis by Two Different Mechanisms]]> https://www.researchpad.co/article/5989db54ab0ee8fa60bdd12d

Background

Transmission of Yersinia pestis by flea bite can occur by two mechanisms. After taking a blood meal from a bacteremic mammal, fleas have the potential to transmit the very next time they feed. This early-phase transmission resembles mechanical transmission in some respects, but the mechanism is unknown. Thereafter, transmission occurs after Yersinia pestis forms a biofilm in the proventricular valve in the flea foregut. The biofilm can impede and sometimes completely block the ingestion of blood, resulting in regurgitative transmission of bacteria into the bite site. In this study, we compared the relative efficiency of the two modes of transmission for Xenopsylla cheopis, a flea known to become completely blocked at a high rate, and Oropsylla montana, a flea that has been considered to rarely develop proventricular blockage.

Methodology/Principal findings

Fleas that took an infectious blood meal containing Y. pestis were maintained and monitored for four weeks for infection and proventricular blockage. The number of Y. pestis transmitted by groups of fleas by the two modes of transmission was also determined. O. montana readily developed complete proventricular blockage, and large numbers of Y. pestis were transmitted by that mechanism both by it and by X. cheopis, a flea known to block at a high rate. In contrast, few bacteria were transmitted in the early phase by either species.

Conclusions

A model system incorporating standardized experimental conditions and viability controls was developed to more reliably compare the infection, proventricular blockage and transmission dynamics of different flea vectors, and was used to resolve a long-standing uncertainty concerning the vector competence of O. montana. Both X. cheopis and O. montana are fully capable of transmitting Y. pestis by the proventricular biofilm-dependent mechanism.

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<![CDATA[Systematic Review and Meta-Analysis on the Association between Outpatient Statins Use and Infectious Disease-Related Mortality]]> https://www.researchpad.co/article/5989da28ab0ee8fa60b8155b

Background

To update and refine systematic literature review on the association between outpatient statins use and mortality in patients with infectious disease.

Materials and Methods

We searched articles published before September 31, 2012, on the association between statins and infectious disease-related mortality through electronic databases. Eligible articles were analyzed in Review Manager 5.1. We conducted stratification analysis by study design, infection types, clinical outcomes and study locations.

Results

The pooled odds ratio (OR) for death (statins use vs. no use) across the 41 included studies was 0.71 (95% confidence interval: 0.64, 0.78). The corresponding pooled ORs were 0.58 (0.38, 0.90), 0.66 (0.57, 0.75), 0.71 (0.57, 0.89) and 0.83 (0.67, 1.04) for the case-control study, retrospective cohort studies, prospective cohort studies and RCTs; 0.40 (0.20, 0.78), 0.61 (0.41, 0.90), 0.69 (0.62, 0.78) and 0.86 (0.68, 1.09) for bacteremia, sepsis, pneumonia and other infections; 0.62 (0.534, 0.72), 0.68 (0.53, 0.89), 0.71 (0.61, 0.83) and 0.86 (0.70, 1.07) for 30-day, 90-day, in-hospital and long-term (>1 year) mortality, respectively.

Conclusions

Outpatient statins use is associated with a lower risk of death in patients with infectious disease in observational studies, but in a less extent in clinical trials. This association also varies considerably by infection types and clinical outcomes.

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<![CDATA[Imaging of Bubonic Plague Dynamics by In Vivo Tracking of Bioluminescent Yersinia pestis]]> https://www.researchpad.co/article/5989dac6ab0ee8fa60bb2880

Yersinia pestis dissemination in a host is usually studied by enumerating bacteria in the tissues of animals sacrificed at different times. This laborious methodology gives only snapshots of the infection, as the infectious process is not synchronized. In this work we used in vivo bioluminescence imaging (BLI) to follow Y. pestis dissemination during bubonic plague. We first demonstrated that Y. pestis CO92 transformed with pGEN-luxCDABE stably emitted bioluminescence in vitro and in vivo, while retaining full virulence. The light produced from live animals allowed to delineate the infected organs and correlated with bacterial loads, thus validating the BLI tool. We then showed that the first step of the infectious process is a bacterial multiplication at the injection site (linea alba), followed by a colonization of the draining inguinal lymph node(s), and subsequently of the ipsilateral axillary lymph node through a direct connection between the two nodes. A mild bacteremia and an effective filtering of the blood stream by the liver and spleen probably accounted for the early bacterial blood clearance and the simultaneous development of bacterial foci within these organs. The saturation of the filtering capacity of the spleen and liver subsequently led to terminal septicemia. Our results also indicate that secondary lymphoid tissues are the main targets of Y. pestis multiplication and that colonization of other organs occurs essentially at the terminal phase of the disease. Finally, our analysis reveals that the high variability in the kinetics of infection is attributable to the time the bacteria remain confined at the injection site. However, once Y. pestis has reached the draining lymph nodes, the disease progresses extremely rapidly, leading to the invasion of the entire body within two days and to death of the animals. This highlights the extraordinary capacity of Y. pestis to annihilate the host innate immune response.

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