Sympatric Ixodes-tick species : pattern of distribution and pathogen transmission within wild rodent populations

The generalist tick Ixodes ricinus is the most important vector for tick-borne pathogens (TBP), including Borrelia burgdorferi sensu lato, in Europe. However, the involvement of other sympatric Ixodes ticks, such as the specialist vole tick I. trianguliceps, in the enzootic circulations of TBP remains unclear. We studied the distribution of I. ricinus and I. trianguliceps in Central Finland and estimated the TBP infection likelihood in the most common rodent host in relation with the abundance of the two tick species. Ixodes trianguliceps was encountered in all 16 study sites whereas I. ricinus was frequently observed only at a quarter of the study sites. The abundance of I. ricinus was positively associated with open water coverage and human population density around the study sites. Borrelia burgdorferi s. l.-infected rodents were found only in sites where I. ricinus was abundant, whereas the occurrence of other TBP was independent of I. ricinus presence. These results suggest that I. trianguliceps is not sufficient, at least alone, in maintaining the circulation of B. burgdorferi s. l. in wild hosts. In addition, anthropogenic factors might affect the distribution of I. ricinus ticks and, hence, their pathogens, thus shaping the landscape of tick-borne disease risk for humans.Peer reviewe

The effects of Borrelia infection on its wintering rodent host

In seasonal environments, appropriate adaptations are crucial for organisms to maximize their fitness. For instance, in many species, the immune function has been noticed to decrease during winter, which is assumed to be an adaptation to the season's limited food availability. Consequences of an infection on the health and survival of the host organism could thus be more severe in winter than in summer. Here, we experimentally investigated the effect of a zoonotic, endemic pathogen, Borrelia afzelii infection on the survival and body condition in its host, the bank vole (Myodes glareolus), during late autumn-early winter under semi-natural field conditions in 11 large outdoor enclosures. To test the interaction of Borrelia infection and energetic condition, four populations received supplementary nutrition, while remaining seven populations exploited only natural food sources. Supplementary food during winter increased the body mass independent of the infection status, however, Borrelia afzelii infection did not cause severe increase in the host mortality or affect the host body condition in the late autumn-early winter. While our study suggests that no severe effects are caused by B. afzelii infection on bank vole, further studies are warranted to identify any potentially smaller effects the pathogen may cause on the host fitness over the period of whole winter

Yersinia spp. in Wild Rodents and Shrews in Finland

Yersinia enterocolitica and Yersinia pseudotuberculosis are important zoonotic bacteria causing human enteric yersiniosis commonly reported in Europe. All Y. pseudotuberculosis strains are considered pathogenic, while Y. enterocolitica include both pathogenic and nonpathogenic strains which can be divided into six biotypes (1A, 1B, and 2-5) and about 30 serotypes. The most common types causing yersiniosis in Europe are Y. enterocolitica bioserotypes 4/O:3 and 2/O:9. Strains belonging to biotype 1A are considered as nonpathogenic because they are missing important virulence genes like the attachment-invasion-locus (ail) gene in the chromosome and the virulence plasmid. The role of wild small mammals as a reservoir of enteropathogenic Yersinia spp. is still obscure. In this study, the presence of Yersinia spp. was examined from 1840 wild small mammals, including voles, mice, and shrews, trapped in Finland during a 7-year period. We isolated seven Yersinia species. Y. enterocolitica was the most common species, isolated from 8% of the animals; while most of these isolates represented nonpathogenic biotype 1A, human pathogenic bioserotype 2/O:9 was also isolated from a field vole. Y. pseudotuberculosis of bioserotype 1/O:2 was isolated from two shrews. The ail gene, which is typically only found in the isolates of biotypes 1B and 2-5 associated with yersiniosis, was frequently (23%) detected in the nonpathogenic isolates of biotype 1A and sporadically (6%) in Yersinia kristensenii isolates. Our results suggest that wild small mammals, especially voles, may serve as carriers for ail-positive Y. enterocolitica 1A and Y. kristensenii. We also demonstrate that voles and shrews sporadically excrete pYV-positive Y. enterocolitica 2/O:9 and Y. pseudotuberculosis 1/O:2, respectively, in their feces and, thus, can serve as a contamination source for vegetables by contaminating the soil.Peer reviewe

The evolution of transmission mode

This article reviews research on the evolutionary mechanisms leading to different transmission modes. Such modes are often under genetic control of the host or the pathogen, and often in conflict with each other via trade-offs. Transmission modes may vary among pathogen strains and among host populations. Evolutionary changes in transmission mode have been inferred through experimental and phylogenetic studies, including changes in transmission associated with host-shifts and with evolution of the unusually complex life cycles of many parasites. Understanding the forces that determine the evolution of particular transmission modes presents a fascinating medley of problems for which there is a lack of good data and often a lack of conceptual understanding or appropriate methodologies. Our best information comes from studies that have been focused on the vertical vs. horizontal transmission dichotomy. With other kinds of transitions, theoretical approaches combining epidemiology and population genetics are providing guidelines for determining when and how rapidly new transmission modes may evolve, but these are still in need of empirical investigation and application to particular cases. Obtaining such knowledge is a matter of urgency in relation to extant disease threats

First report of Anaplasma phagocytophilum and Babesia microtiin rodents in Finland

Tick-borne diseases pose an increasingly important public health problem in Europe. Rodents are the reservoir host for many tick-transmitted pathogens, including Anaplasma phagocytophilum and Babesia microti, which can cause human granulocytic anaplasmosis and babesiosis, respectively. To estimate the presence of these pathogens in rodents in Finland, we examined blood samples from 151 bank voles (Myodes glareolus) and demonstrate, for the first time, that A. phagocytophilum and B. microti commonly infect bank voles (in 22% and 40% of animals, respectively) in Finland. Sequence analysis of a fragment of 18S rRNA showed that the B. microti strain isolated was identical to the Munich strain, which is considered to be nonzoonotic. The A. phagocytophilum strain (based on a fragment of the msp4 gene) was identical to one found earlier in rodents in the United Kingdom that is transmitted by the tick Ixodes trianguliceps, all the life stages of which feed on small mammals. The infection probability of B. microti in the bank voles was the greater the older the individual was, and males were more often infected than females. A. phagocytophilum infection probability first increased and then decreased with the age of individual without any difference between sexes. While these pathogens presumably pose a limited zoonotic risk to humans in Finland, they might have important interactions with other rodent pathogens and therefore affect infection dynamics of, for example, zoonotic pathogens

Conserved CDC20 Cell Cycle Functions Are Carried out by Two of the Five Isoforms in Arabidopsis thaliana

The CDC20 and Cdh1/CCS52 proteins are substrate determinants and activators of the Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligase and as such they control the mitotic cell cycle by targeting the degradation of various cell cycle regulators. In yeasts and animals the main CDC20 function is the destruction of securin and mitotic cyclins. Plants have multiple CDC20 gene copies whose functions have not been explored yet. In Arabidopsis thaliana there are five CDC20 isoforms and here we aimed at defining their contribution to cell cycle regulation, substrate selectivity and plant development.Studying the gene structure and phylogeny of plant CDC20s, the expression of the five AtCDC20 gene copies and their interactions with the APC/C subunit APC10, the CCS52 proteins, components of the mitotic checkpoint complex (MCC) and mitotic cyclin substrates, conserved CDC20 functions could be assigned for AtCDC20.1 and AtCDC20.2. The other three intron-less genes were silent and specific for Arabidopsis. We show that AtCDC20.1 and AtCDC20.2 are components of the MCC and interact with mitotic cyclins with unexpected specificity. AtCDC20.1 and AtCDC20.2 are expressed in meristems, organ primordia and AtCDC20.1 also in pollen grains and developing seeds. Knocking down both genes simultaneously by RNAi resulted in severe delay in plant development and male sterility. In these lines, the meristem size was reduced while the cell size and ploidy levels were unaffected indicating that the lower cell number and likely slowdown of the cell cycle are the cause of reduced plant growth.The intron-containing CDC20 gene copies provide conserved and redundant functions for cell cycle progression in plants and are required for meristem maintenance, plant growth and male gametophyte formation. The Arabidopsis-specific intron-less genes are possibly "retrogenes" and have hitherto undefined functions or are pseudogenes

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Experimental ecology on the interaction between the Puumala hantavirus and its host, the bank vole

Eva Kallio tutki väitöskirjatyössään ihmisissä myyräkuumetta aiheuttavan, Hantaviruksiin kuuluvan Puumala-viruksen ja sen isäntälajin metsämyyrän välistä vuorovaikutussuhdetta. Tutkimuksessa selvisi viruksen säilyvän infektiokykyisenä pitkään isännän ulkopuolellakin ja voivan tarttua myyrästä toiseen tai myyrästä ihmiseen ilman suoraa kontaktia. Kallio osoitti myös ensimmäisen kerran hantaviruksen olevan haitallinen isäntälajilleen.Kallion osoittaman Puumala-viruksen ja metsämyyrän välisen vuorovaikutussuhteen piirteet voivat osaltaan vaikuttaa ihmisten myyräkuume-epidemioiden ilmentymiseen. Uuden tiedon avulla pystytään myös yhä luotettavammin mallintamaan ja ennustamaan epidemioiden esiintymistä niin myyrillä kuin ihmisilläkin.Hantavirusten tartuntatapa myyrästä toiseen ja toisaalta ihmiseen on ollut vilkkaan tutkimuksen ja keskustelun kohde. Kallio tutki Puumala-viruksen infektiokyvyn säilymistä isännän ulkopuolella erilaisissa olosuhteissa. Huoneenlämmössä virus säilyi tartuntakykyisenä myyrille noin kahden viikon ajan, ja kylmässä ja kosteassa ympäristössä vielä kauemmin. Suorat kontaktit eivät myöskään ole edellytys viruksen leviämiseksi myyrien välillä tai myyristä ihmiseen. Puumala-viruksen tartuntakyvyn pitkä säilyminen isännän ulkopuolella tehostaa viruksen leviämistä ja edistää sen säilymistä alueellisesti metsämyyrätiheyden ollessa ajoittain alhainen.Metsämyyrän alttius infektoitua riippuu muun muassa perinnöllisistä tekijöistä, yksilön iästä, sukupuolesta ja lisääntymistilasta. Infektioalttiuteen vaikuttavat myös maternaaliset vasta-aineet. Suomessa on diagnosoitu viimeisen kymmenen vuoden aikana vuosittain 750–2600 Puumala-viruksen ihmiselle aiheuttamaa myyräkuumetapausta. Ihmisepidemioiden on katsottu riippuvan lähinnä myyräsyklin vaiheesta ja myyrätiheydestä. Metsämyyrien tiheys ei kuitenkaan yksin selitä myyräkuume-epidemioita. Kallion osoittama Puumala-viruksen pitkäaikainen säilyminen isännän ulkopuolella, etenkin kylmissä olosuhteissa, edistää viruksen yleisyyttä metsämyyräpopulaatioissa. Tämä voi osaltaan selittää usein loppusyksyyn ja alkutalveen ajoittuvia myyräkuume-epidemioita.More than half of the known human pathogens have their origins in various animal species in nature. To understand the zoonotic risks for humans, the biology and relationships between a specific pathogen and its carrier host species need to be well known. In this thesis, the relationship between Puumala hantavirus (PUUV), and its carrier, the bank vole (Myodes [Clethrionomys] glareolus) was investigated using an experimental approach. Laboratory experiments showed that PUUV remains infectious outside the host for a prolonged period of time. This is influenced by the environmental conditions. The maternal antibodies that infected females provide to their progeny postponed the PUUV infection and enhanced the breeding success of young bank voles. The role of the infection status of breeding females in the transmission dynamics of PUUV in bank vole populations was studied using two experiments in nature. Accordingly, the infection status of breeding females has substantial influence on the transmission of PUUV to and among the young bank voles during and soon after the breeding season. PUUV infection had a negative influence on the over-winter survival of bank voles, whereas the breeding success or survival during the breeding season was not affected by the infection. These studies suggest that PUUV transmission in the bank vole populations is influenced by the temporary immunity the maternal antibodies provide, by the prolonged survival of PUUV outside the host and by the decreased winter survival of PUUV infected bank voles