Paul Heyman

A clear and present danger tick borne diseases in Europe

Ticks can transmit a variety of viruses, bacteria or parasites that can cause serious infections or conditions in humans and animals. While tick-borne diseases are becoming an increasing and serious problem in Europe, tick-borne diseases are also responsible for major depressions in livestock production and mortality in sub-Saharan Africa, Latin America and Asia. This review will focus on the most important circulating tick-transmitted pathogens in Europe (Borrelia spp., Anaplasma phagocytophilum, Babesia spp., tick-borne encephalitis virus, Rickettsia spp. and Crimean-Congo hemorrhagic fever virus).

Determinants of the geographic distribution of Puumala virus and Lyme borreliosis infections in Belgium

BackgroundVector-borne and zoonotic diseases generally display clear spatial patterns due to different space-dependent factors. Land cover and land use influence disease transmission by controlling both the spatial distribution of vectors or hosts, and the probability of contact with susceptible human populations. The objective of this study was to combine environmental and socio-economic factors to explain the spatial distribution of two emerging human diseases in Belgium, Puumala virus (PUUV) and Lyme borreliosis. Municipalities were taken as units of analysis.ResultsNegative binomial regressions including a correction for spatial endogeneity show that the spatial distribution of PUUV and Lyme borreliosis infections are associated with a combination of factors linked to the vector and host populations, to human behaviours, and to landscape attributes. Both diseases are associated with the presence of forests, which are the preferred habitat for vector or host populations. The PUUV infection risk is higher in remote forest areas, where the level of urbanisation is low, and among low-income populations. The Lyme borreliosis transmission risk is higher in mixed landscapes with forests and spatially dispersed houses, mostly in wealthy peri-urban areas. The spatial dependence resulting from a combination of endogenous and exogenous processes could be accounted for in the model on PUUV but not for Lyme borreliosis.ConclusionA large part of the spatial variation in disease risk can be explained by environmental and socio-economic factors. The two diseases not only are most prevalent in different regions but also affect different groups of people. Combining these two criteria may increase the efficiency of information campaigns through appropriate targeting.

Prevalence of Neoehrlichia mikurensis in ticks and rodents from North-west Europe.

BackgroundNeoehrlichia mikurensis s an emerging and vector-borne zoonosis: The first human disease cases were reported in 2010. Limited information is available about the prevalence and distribution of Neoehrlichia mikurensis in Europe, its natural life cycle and reservoir hosts. An Ehrlichia-like schotti variant has been described in questing Ixodes ricinus ticks, which could be identical to Neoehrlichia mikurensis.MethodsThree genetic markers, 16S rDNA, gltA and GroEL, of Ehrlichia schotti-positive tick lysates were amplified, sequenced and compared to sequences from Neoehrlichia mikurensis. Based on these DNA sequences, a multiplex real-time PCR was developed to specifically detect Neoehrlichia mikurensis in combination with Anaplasma phagocytophilum in tick lysates. Various tick species from different life-stages, particularly Ixodes ricinus nymphs, were collected from the vegetation or wildlife. Tick lysates and DNA derived from organs of wild rodents were tested by PCR-based methods for the presence of Neoehrlichia mikurensis. Prevalence of Neoehrlichia mikurensis was calculated together with confidence intervals using Fishers exact test.ResultsThe three genetic markers of Ehrlichia schotti-positive field isolates were similar or identical to Neoehrlichia mikurensis. Neoehrlichia mikurensis was found to be ubiquitously spread in the Netherlands and Belgium, but was not detected in the 401 tick samples from the UK. Neoehrlichia mikurensis was found in nymphs and adult Ixodes ricinus ticks, but neither in their larvae, nor in any other tick species tested. Neoehrlichia mikurensis was detected in diverse organs of some rodent species. Engorging ticks from red deer, European mouflon, wild boar and sheep were found positive for Neoehrlichia mikurensis.ConclusionsEhrlichia schotti is similar, if not identical, to Neoehrlichia mikurensis. Neoehrlichia mikurensis is present in questing Ixodes ricinus ticks throughout the Netherlands and Belgium. We propose that Ixodes ricinus can transstadially, but not transovarially, transmit this microorganism, and that different rodent species may act as reservoir hosts. These data further imply that wildlife and humans are frequently exposed to Neoehrlichia mikurensis- infected ticks through tick bites. Future studies should aim to investigate to what extent Neoehrlichia mikurensis poses a risk to public health.

Circulation of four Anaplasma phagocytophilum ecotypes in Europe

BackgroundAnaplasma phagocytophilum is the etiological agent of granulocytic anaplasmosis in humans and animals. Wild animals and ticks play key roles in the enzootic cycles of the pathogen. Potential ecotypes of A. phagocytophilum have been characterized genetically, but their host range, zoonotic potential and transmission dynamics has only incompletely been resolved.MethodsThe presence of A. phagocytophilum DNA was determined in more than 6000 ixodid ticks collected from the vegetation and wildlife, in 289 tissue samples from wild and domestic animals, and 69 keds collected from deer, originating from various geographic locations in The Netherlands and Belgium. From the qPCR-positive lysates, a fragment of the groEL-gene was amplified and sequenced. Additional groEL sequences from ticks and animals from Europe were obtained from GenBank, and sequences from human cases were obtained through literature searches. Statistical analyses were performed to identify A. phagocytophilum ecotypes, to assess their host range and their zoonotic potential. The population dynamics of A. phagocytophilum ecotypes was investigated using population genetic analyses.ResultsDNA of A. phagocytophilum was present in all stages of questing and feeding Ixodes ricinus, feeding I. hexagonus, I. frontalis, I. trianguliceps, and deer keds, but was absent in questing I. arboricola and Dermacentor reticulatus. DNA of A. phagocytophilum was present in feeding ticks and tissues from many vertebrates, including roe deer, mouflon, red foxes, wild boar, sheep and hedgehogs but was rarely found in rodents and birds and was absent in badgers and lizards. Four geographically dispersed A. phagocytophilum ecotypes were identified, that had significantly different host ranges. All sequences from human cases belonged to only one of these ecotypes. Based on population genetic parameters, the potentially zoonotic ecotype showed significant expansion.ConclusionFour ecotypes of A. phagocytophilum with differential enzootic cycles were identified. So far, all human cases clustered in only one of these ecotypes. The zoonotic ecotype has the broadest range of wildlife hosts. The expansion of the zoonotic A. phagocytophilum ecotype indicates a recent increase of the acarological risk of exposure of humans and animals.

Ticks and associated pathogens collected from dogs and cats in Belgium

BackgroundAlthough Ixodes spp. are the most common ticks in North-Western Europe, recent reports indicated an expanding geographical distribution of Dermacentor reticulatus in Western Europe. Recently, the establishment of a D. reticulatus population in Belgium was described. D. reticulatus is an important vector of canine and equine babesiosis and can transmit several Rickettsia species, Coxiella burnetii and tick-borne encephalitis virus (TBEV), whilst Ixodes spp. are vectors of pathogens causing babesiosis, borreliosis, anaplasmosis, rickettsiosis and TBEV.MethodsA survey was conducted in 2008-2009 to investigate the presence of different tick species and associated pathogens on dogs and cats in Belgium. Ticks were collected from dogs and cats in 75 veterinary practices, selected by stratified randomization. All collected ticks were morphologically determined and analysed for the presence of Babesia spp., Borrelia spp., Anaplasma phagocytophilum and Rickettsia DNA.ResultsIn total 2373 ticks were collected from 647 dogs and 506 cats. Ixodes ricinus (76.4%) and I. hexagonus (22.6%) were the predominant species. Rhipicephalus sanguineus (0.3%) and D. reticulatus (0.8%) were found in low numbers on dogs only. All dogs infested with R. sanguineus had a recent travel history, but D. reticulatus were collected from a dog without a history of travelling abroad. Of the collected Ixodes ticks, 19.5% were positive for A. phagocytophilum and 10.1% for Borrelia spp. (B. afzelii, B. garinii, B. burgdorferi s.s., B. lusitaniae, B. valaisiana and B. spielmanii). Rickettsia helvetica was found in 14.1% of Ixodes ticks. All Dermacentor ticks were negative for all the investigated pathogens, but one R. sanguineus tick was positive for Rickettsia massiliae.ConclusionD. reticulatus was confirmed to be present as an indigenous parasite in Belgium. B. lusitaniae and R. helvetica were detected in ticks in Belgium for the first time.

Hantavirus infections in Europe: from virus carriers to a major public-health problem

In Europe, hantavirus disease or hemorrhagic fever with renal syndrome is an endemic zoonosis that affects tens of thousands of individuals each year. The causative agents are viruses of the genus Hantavirus, family Bunyaviridae, rodents and insectivores act as carriers. In all European countries there is a seroprevalence for hantaviruses in the general population but not all countries report cases. Here, we give an overview of the hantavirus situation in Europe.

Seoul hantavirus in Europe: first demonstration of the virus genome in wild Rattus norvegicus captured in France.

Although rats (Rattus rattus or Rattus norvegicus) worldwide have been found to carry Seoul hantavirus, there are at present only a very few reports of confirmed human Seoul hantavirus infections outside Asia, where the virus, in certain areas, is responsible for approximately 25% of the human hantavirus infections. In Europe, no confirmed human infections outside laboratories have been described, and although rats occasionally have been found to be antibody positive, the viral genome has not been demonstrated in these animals. The present report describes the first confirmed finding of Seoul hantavirus in R. norvegicus captured in Europe.

Factors driving hantavirus emergence in Europe.

Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. In Europe both the amplitude and the magnitude of outbreaks of HFRS have increased. The mechanisms that drive the incidences are complex and multi-factorial and only partially due to increased awareness and improved diagnostic tools. Risk determinants include reservoir ecology, virus ecology and anthropogenic factors. The dogma of one specific rodent species as primordial reservoir for a specific hantavirus is increasingly challenged. New hantaviruses have been discovered in shrews, moles and bats and increasing evidence points at host-switching events and co-circulation in multiple, sympatric reservoir species, challenging the strict rodent-virus co-evolution theory. Changing landscape attributes and climatic parameters determine fluctuations in hantavirus epidemiology, for instance through increased food availability, prolonged virus survival and decreased biodiversity.

A multi-level analysis of the relationship between environmental factors and questing Ixodes ricinus dynamics in Belgium

BackgroundTicks are the most important pathogen vectors in Europe. They are known to be influenced by environmental factors, but these links are usually studied at specific temporal or spatial scales. Focusing on Ixodes ricinus in Belgium, we attempt to bridge the gap between current “single-sided” studies that focus on temporal or spatial variation only. Here, spatial and temporal patterns of ticks are modelled together.MethodsA multi-level analysis of the Ixodes ricinus patterns in Belgium was performed. Joint effects of weather, habitat quality and hunting on field sampled tick abundance were examined at two levels, namely, sampling level, which is associated with temporal dynamics, and site level, which is related to spatial dynamics. Independent variables were collected from standard weather station records, game management data and remote sensing-based land cover data.ResultsAt sampling level, only a marginally significant effect of daily relative humidity and temperature on the abundance of questing nymphs was identified. Average wind speed of seven days prior to the sampling day was found important to both questing nymphs and adults. At site level, a group of landscape-level forest fragmentation indices were highlighted for both questing nymph and adult abundance, including the nearest-neighbour distance, the shape and the aggregation level of forest patches. No cross-level effects or spatial autocorrelation were found.ConclusionsNymphal and adult ticks responded differently to environmental variables at different spatial and temporal scales. Our results can advise spatio-temporal extents of environment data collection for continuing empirical investigations and potential parameters for biological tick models.

In Search for Factors that Drive Hantavirus Epidemics

In Europe, hantaviruses (Bunyaviridae) are small mammal-associated zoonotic and emerging pathogens that can cause hemorrhagic fever with renal syndrome (HFRS). Puumala virus, the main etiological agent carried by the bank vole Myodes glareolus is responsible for a mild form of HFRS while Dobrava virus induces less frequent but more severe cases of HFRS. Since 2000 in Europe, more than 3000 cases of HFRS have been recorded, in average, each year, which is nearly double compared to the previous decade. In addition to this upside long-term trend, significant oscillations occur. Epidemic years appear, usually every 2–4 years, with an increased incidence, generally in localized hot spots. Moreover, the virus has been identified in new areas in the recent years. A great number of surveys have been carried out in order to assess the prevalence of the infection in the reservoir host and to identify links with different biotic and abiotic factors. The factors that drive the infections are related to the density and diversity of bank vole populations, prevalence of infection in the reservoir host, viral excretion in the environment, survival of the virus outside its host, and human behavior, which affect the main transmission virus route through inhalation of infected rodent excreta. At the scale of a rodent population, the prevalence of the infection increases with the age of the individuals but also other parameters, such as sex and genetic variability, interfere. The contamination of the environment may be correlated to the number of newly infected rodents, which heavily excrete the virus. The interactions between these different parameters add to the complexity of the situation and explain the absence of reliable tools to predict epidemics. In this review, the factors that drive the epidemics of hantaviruses in Middle Europe are discussed through a panorama of the epidemiological situation in Belgium, France, and Germany.