Tick-borne Fever Research Articles

HUMAN GRANULOCYTOTROPIC ANAPLASMOSIS

Natural focal tick-borne infections are widespread in the world and are characterized by a great etiologic diversity. Human granulocytotropic anaplasmosis (HGA), also transmitted by the bite of ticks became relevant in the last century of detection not only in animals but also in humans. The review provides an overview of the incidence of HGA in Russia and in the world, the prevalence of the habitat of mites, the diversity of reservoirs and sources of infection, mechanisms and pathways of transmission of the pathogen Anaplasma phagocytophilum and its biological features. The links and stages of the disease pathogenesis are considered in detail. Scientific data on the clinical course of the disease, the frequency and diversity of various symptoms of the disease, the issues of laboratory and differential diagnosis of anaplasmosis and its place in the nosological structure in patients with fever of unknown origin are discussed. At the same time, choosing a method of laboratory diagnostics it is necessary to take into account that molecular-genetic method (polymerase chain reaction PCR-diagnosis) allows to confirm the diagnosis quickly, while serological methods of research in a greater degree - to put a retrospective diagnosis. The article presents current data on the treatment of disease and methods of HGA prevention and also presents the results of the authors’ own observations based on the survey of 63 patients. The analysis of Moscow residents treatment about sucking mites is carried out and summarized the incidence of infections transmitted by ixode mites. For the diagnosis of HGA and other tick-borne fever used a technique called polymerase chain reaction. It has been revealed that in Moscow, lime borreliosis occupies a leading place among mites associated with infections 60%, and the share of granulocytic anaplasmosis of a person is only 5% of patients. However, the study of ticks for the presence of HGA pathogens and other natural focal tick infections is carried out in insufficient volume (less than 30%), which should be considered in clinical and laboratory differential diagnosis, as well as preventive measures.

Epidemiology of severe fever and thrombocytopenia syndrome virus infection and the need for therapeutics for the prevention.

Over the past ten years there has been a marked increase in cases of severe fever and thrombocytopenia syndrome in East Asia. This tick-borne hemorrhagic fever presents along with clinical signs including high fever and leukopenia. In addition to humans, the virus has also been detected with shared genetic homology in farm animals including goats, cattle, horses, and pigs. Furthermore, several genotypes of severe fever and thrombocytopenia syndrome virus (SFTSV) are currently co-circulating between humans and animals. In China, where the virus was first detected in rural areas in 2009, the SFTSV mortality rate has been reported to be as 6% and higher than 30%, especially in immuno-compromised patients. Moreover, this virus has been isolated in neighbor countries including Japan and South Korea where the fatality rates in 2015 were more than 30% in both countries. In this review, we comprehensively summarize the virology, genotypes, pathogenesis, and epidemiology of SFTSV infection in humans and animals. Currently, a collaborative global approach against SFTSV infection is being undertaken; however, the need for continuous disease surveillance and production of an effective vaccine is imperative as this virus may lead to an epidemic of irreversible status in both humans and animals.

Vaccinomics Approach to the Identification of Candidate Protective Antigens for the Control of Tick Vector Infestations and Anaplasma phagocytophilum Infection.

Anaplasma phagocytophilum is an emerging tick-borne pathogen causing human granulocytic anaplasmosis (HGA), tick-borne fever (TBF) in small ruminants, and other forms of anaplasmosis in different domestic and wild animals. The main vectors of this pathogen are Ixodes tick species, particularly I. scapularis in the United States and I. ricinus in Europe. One of the main limitations for the development of effective vaccines for the prevention and control of A. phagocytophilum infection and transmission is the identification of effective tick protective antigens. The objective of this study was to apply a vaccinomics approach to I. scapularis-A. phagocytophilum interactions for the identification and characterization of candidate tick protective antigens for the control of vector infestations and A. phagocytophilum infection. The vaccinomics pipeline included the use of quantitative transcriptomics and proteomics data from uninfected and A. phagocytophilum-infected I. scapularis ticks for the selection of candidate protective antigens based on the variation in tick mRNA and protein levels in response to infection, their putative biological function, and the effect of antibodies against these proteins on tick cell apoptosis and pathogen infection. The characterization of selected candidate tick protective antigens included the identification and characterization of I. ricinus homologs, functional characterization by different methodologies including RNA interference, immunofluorescence, gene expression profiling, and artificial tick feeding on rabbit antibodies against the recombinant antigens to select the candidates for vaccination trials. The vaccinomics pipeline developed in this study resulted in the identification of two candidate tick protective antigens that could be selected for future vaccination trials. The results showed that I. scapularis lipocalin (ISCW005600) and lectin pathway inhibitor (AAY66632) and I. ricinus homologs constitute candidate protective antigens for the control of vector infestations and A. phagocytophilum infection. Both antigens are involved in the tick evasion of host defense response and pathogen infection and transmission, but targeting different immune response pathways. The vaccinomics pipeline proposed here could be used to continue the identification and characterization of candidate tick protective antigens for the development of effective vaccines for the prevention and control of HGA, TBF, and other forms of anaplasmosis caused by A. phagocytophilum.

Severe Fever with Thrombocytopenia Syndrome Virus Infection in Minks in China.

We analyzed the seroprevalence of tick-borne severe fever with thrombocytopenia syndrome virus (SFTSV) in farm-raised minks using double antigen ELISA (enzyme-linked immunosorbent assay) kit and indicated that 8.4% (15/178) of the minks had antibodies to the nucleoprotein of SFTSV and 72.7% (8/11) of mink farms had minks positive to SFTSV. The ELISA results were further confirmed by presence of neutralization to SFTSV in the mink sera. Our results suggested that minks were widely infected with SFTSV in China.

A comparison of nonlinear mixed models and response to selection of tick-infestation on lambs.

Tick-borne fever (TBF) is stated as one of the main disease challenges in Norwegian sheep farming during the grazing season. TBF is caused by the bacterium Anaplasma phagocytophilum that is transmitted by the tick Ixodes ricinus. A sustainable strategy to control tick-infestation is to breed for genetically robust animals. In order to use selection to genetically improve traits we need reliable estimates of genetic parameters. The standard procedures for estimating variance components assume a Gaussian distribution of the data. However, tick-count data is a discrete variable and, thus, standard procedures using linear models may not be appropriate. Thus, the objectives of this study were twofold: 1) to compare four alternative non-linear models: Poisson, negative binomial, zero-inflated Poisson and zero-inflated negative binomial based on their goodness of fit for quantifying genetic variation, as well as heritability for tick-count and 2) to investigate potential response to selection against tick-count based on truncation selection given the estimated genetic parameters from the best fit model. Our results showed that zero-inflated Poisson was the most parsimonious model for the analysis of tick count data. The resulting estimates of variance components and high heritability (0.32) led us to conclude that genetic determinism is relevant on tick count. A reduction of the breeding values for tick-count by one sire-dam genetic standard deviation on the liability scale will reduce the number of tick counts below an average of 1. An appropriate breeding scheme could control tick-count and, as a consequence, probably reduce TBF in sheep.

Anaplasma phagocytophilum Infection Subverts Carbohydrate Metabolic Pathways in the Tick Vector, Ixodes scapularis.

The obligate intracellular pathogen, Anaplasma phagocytophilum, is the causative agent of human, equine, and canine granulocytic anaplasmosis and tick-borne fever (TBF) in ruminants. A. phagocytophilum has become an emerging tick-borne pathogen in the United States, Europe, Africa, and Asia, with increasing numbers of infected people and animals every year. It has been recognized that intracellular pathogens manipulate host cell metabolic pathways to increase infection and transmission in both vertebrate and invertebrate hosts. However, our current knowledge on how A. phagocytophilum affect these processes in the tick vector, Ixodes scapularis is limited. In this study, a genome-wide search for components of major carbohydrate metabolic pathways was performed in I. scapularis ticks for which the genome was recently published. The enzymes involved in the seven major carbohydrate metabolic pathways glycolysis, gluconeogenesis, pentose phosphate, tricarboxylic acid cycle (TCA), glyceroneogenesis, and mitochondrial oxidative phosphorylation and β-oxidation were identified. Then, the available transcriptomics and proteomics data was used to characterize the mRNA and protein levels of I. scapularis major carbohydrate metabolic pathway components in response to A. phagocytophilum infection of tick tissues and cultured cells. The results showed that major carbohydrate metabolic pathways are conserved in ticks. A. phagocytophilum infection inhibits gluconeogenesis and mitochondrial metabolism, but increases the expression of glycolytic genes. A model was proposed to explain how A. phagocytophilum could simultaneously control tick cell glucose metabolism and cytoskeleton organization, which may be achieved in part by up-regulating and stabilizing hypoxia inducible factor 1 alpha in a hypoxia-independent manner. The present work provides a more comprehensive view of the major carbohydrate metabolic pathways involved in the response to A. phagocytophilum infection in ticks, and provides the basis for further studies to develop novel strategies for the control of granulocytic anaplasmosis.

A Loop-Mediated Isothermal Amplification Assay Targeting 16S rRNA Gene for Rapid Detection of Anaplasma phagocytophilum Infection in Sheep and Goats.

Anaplasma phagocytophilum is a zoonotic pathogen and the causative agent of human granulocytic anaplasmosis in humans and tick-borne fever in various kinds of animals. In the present study, a loop-mediated isothermal amplification (LAMP) assay for rapid detection of A. phagocytophilum was developed using primers specific to 16S rRNA gene of this organism. The LAMP assay was performed at 65 C for 60 min and terminated at 80 C for 10 min. The optimal reaction conditions under which no cross-reaction was observed with other closely related tick-borne parasites ( Anaplasma bovis , Anaplasma ovis , Theileria luwenshuni, Babesia motasi, and Schistosoma japonicum ) were established. The assay exhibited much higher sensitivity compared with conventional polymerase chain reaction (PCR) (1 copy vs. 1,000 copies). To evaluate the applicability of the LAMP assay, 94 field samples of sheep blood were analyzed for A. phagocytophilum infection by using LAMP, nested PCR, and conventional PCR assays at the same time. A positive LAMP result was obtained from 53 (56.4%) of the 94 samples, whereas only 12 (12.8%) and 3 (3.2%) tested positive by nested and conventional PCR, respectively. In conclusion, this LAMP assay is a specific, sensitive, and rapid method for the detection of A. phagocytophilum in sheep/goats.

Introduction: Invasive Ecologies

Introduction:Invasive Ecologies Rafi Youatt (bio) during a recent collective research effort at the us-mexico border in Texas, some members of the group went to see a section of the border fence at a place called the Hidalgo Pumphouse. The Pumphouse itself is now a museum about early agriculture in Texas. The site is also visited because it is a World Birding Center, home to hundreds of species of migrating birds. Thousands of people come to watch the bird migrations that pass through each year. While we were there to interview a local activist about the border fence, we also were part of a disturbing moment in which two individuals, who had managed to climb over the border fence from the Mexican side to the American side and were hiding in the tall grass, were pointed out to US Border Patrol by some of the birdwatchers. Within minutes, the full force of the Border Patrol descended, and the two individuals were pulled up, handcuffed, put in a van with tinted windows, and taken away. Not far from the Pumphouse, a century-old, tick-eradication quarantine line runs for hundreds of miles, roughly parallel to the border. Staffed by dozens of US government-funded horse-mounted cowboys, the purpose of the quarantine line is to keep tick-borne cattle fever out of the United States, largely by keeping stray cattle from Mexico from wandering north. The region also has a thriving population of wild Nilgai antelope. Along with the native white-tailed deer, Nilgai are sometimes a vector for the cattle-fever-carrying ticks, particularly when they cross the Rio Grande into Mexico and come back into the United States. Nilgai were brought to the region in the 1930s from India, and have since flourished in the wild spaces of dry Texan [End Page 167] landscapes. Unlike the white-tailed deer with whom they compete for rangeland, the Nilgai must face an open-hunting season. Increasingly, there are also government efforts to control their movements through the quarantine line, in an effort to ensure that the damaging cattle-fever disease does not affect local livestock populations. I am wondering, still, how to think about the stark but swirling differences in that space, and about the ostensible invasiveness of migrants who, perhaps, were not from that far away; the abiding hospitality for migratory birds in protected natural spaces that also make border patrolling easier; the "invasive" label as attached to a species (Nilgai) that in no plausible way invaded local ecologies but was introduced and encouraged; and the many ways that invasiveness attaches to both human and nonhuman life. The three papers gathered here highlight for me some of the ways that we might want to think about the politics of invasiveness, and the practices both beyond the human and in intersection with various figurations of it. One way we might think about invasiveness is in relation to a series of oppositions. Some of those oppositions can be politically generative in troubling ways, in particular in the opposition of invasiveness to nativeness and purity. This sense is frequently invoked, especially when invasiveness is discussed in an ecological setting, partly in debt to ecology's own language and history of thinking in terms of invasive species and native species, and with an eye to the troubling ways that this has sometimes been read from or back onto political projects of nativeness and purity. But each of the authors, in their contributions here and elsewhere, also raise other oppositions, or antonyms, of "invade" that open a wider range of possibilities: to aid or assist; to help or protect; or to leave alone. Eleana Kim does this through an engagement with cosmopolitanism and hospitality; Hugh Raffles does so by starting with native plants and nativist politics but also via a "thoughtful and inclusive response" to invasive species in a basic condition of cosmopolitan impurity; and Fabio Parasecoli does it by considering ways to affiliate with small-scale bacteria, to create "pluralities, interdependence, [End Page 168] and innovation." These other oppositions to "invasive" raise a powerful series of alternative ways we might start to understand invasiveness. This leads to a second general point about invasiveness...

Environmental risk factors for Ixodes ricinus ticks and their infestation on lambs in a changing ecosystem: Implications for tick control and the impact of woodland encroachment on tick-borne disease in livestock

Despite global deforestation some regions, such as Europe, are currently experiencing rapid reforestation. Some of this is unintended woodland encroachment onto farmland as a result of reduced livestock pasture management. Our aim was to determine the likely impacts of this on exposure to ticks and tick-borne disease risk for sheep in Norway, a country experiencing ecosystem changes through rapid woodland encroachment as well as increases in abundance and distribution of Ixodes ricinus ticks and tick-borne disease incidence. We conducted surveys of I. ricinus ticks on ground vegetation using cloth lure transects and counts of ticks biting lambs on spring pastures, where lambs are exposed to infection with Anaplasma phagocytophilum, the causative agent of tick-borne fever in livestock. Pastures had higher densities of I. ricinus ticks on the ground vegetation and more ticks biting lambs if there was more tree cover in or adjacent to pastures. Importantly, there was a close correlation between questing tick density on pastures and counts of ticks biting lambs on the same pasture, indicating that cloth lure transects are a good proxy of risk to livestock of tick exposure and tick-borne disease. These findings can inform policy on environmental tick control measures such as habitat management, choice of livestock grazing area and off-host application of tick control agents.

Multiple-locus variable-number tandem repeat analysis potentially reveals the existence of two groups of Anaplasma phagocytophilum circulating in cattle in France with different wild reservoirs.

Background Anaplasma phagocytophilum is the causative agent of tick-borne fever, a disease with high economic impact for domestic ruminants in Europe. Epidemiological cycles of this species are complex, and involve different ecotypes circulating in various host species. To date, these epidemiological cycles are poorly understood, especially in Europe, as European reservoir hosts (i.e. vertebrate hosts enabling long-term maintenance of the bacterium in the ecosystem), of the bacterium have not yet been clearly identified. In this study, our objective was to explore the presence, the prevalence, and the genetic diversity of A. phagocytophilum in wild animals, in order to better understand their implications as reservoir hosts of this pathogen.MethodsThe spleens of 101 wild animals were collected from central France and tested for the presence of A. phagocytophilum DNA by msp2 qPCR. Positive samples were then typed by multi-locus variable-number tandem repeat (VNTR) analysis (MLVA), and compared to 179 previously typed A. phagocytophilum samples.Results Anaplasma phagocytophilum DNA was detected in 82/101 (81.2%) animals including 48/49 red deer (98%), 20/21 roe deer (95.2%), 13/29 wild boars (44.8%), and 1/1 red fox. MLVA enabled the discrimination of two A. phagocytophilum groups: group A contained the majority of A. phagocytophilum from red deer and two thirds of those from cattle, while group B included a human strain and variants from diverse animal species, i.e. sheep, dogs, a horse, the majority of variants from roe deer, and the remaining variants from cattle and red deer.ConclusionsOur results suggest that red deer and roe deer are promising A. phagocytophilum reservoir host candidates. Moreover, we also showed that A. phagocytophilum potentially circulates in at least two epidemiological cycles in French cattle. The first cycle may involve red deer as reservoir hosts and cattle as accidental hosts for Group A strains, whereas the second cycle could involve roe deer as reservoir hosts and at least domestic ruminants, dogs, horses, and humans as accidental hosts for Group B strains.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1888-4) contains supplementary material, which is available to authorized users.

Pathological observations of tick-borne fever and intercurrent bacterial infections in lambs

Eighteen lamb deaths were recorded in a group of 250 ewes and lambs, following turnout onto newly rented upland pasture, in the spring of 2016. Three lambs were presented for...

Transstadial Transmission and Long-term Association of Crimean-Congo Hemorrhagic Fever Virus in Ticks Shapes Genome Plasticity.

The trade-off hypothesis, the current paradigm of arbovirus evolution, proposes that cycling between vertebrate and invertebrate hosts presents significant constraints on genetic change of arboviruses. Studying these constraints in mosquito-borne viruses has led to a new understanding of epizootics. The trade-off hypothesis is assumed to be applicable to tick-borne viruses too, although studies are lacking. Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the family Bunyaviridae, is a major cause of severe human disease worldwide and shows an extraordinary amount of genetic diversity compared to other arboviruses, which has been linked to increased virulence and emergence in new environments. Using a transmission model for CCHFV, utilizing the main vector tick species and mice plus next generation sequencing, we detected a substantial number of consensus-level mutations in CCHFV recovered from ticks after only a single transstadial transmission, whereas none were detected in CCHFV obtained from the mammalian host. Furthermore, greater viral intra-host diversity was detected in the tick compared to the vertebrate host. Long-term association of CCHFV with its tick host for 1 year demonstrated mutations in the viral genome become fixed over time. These findings suggest that the trade-off hypothesis may not be accurate for all arboviruses.

Crimean–Congo Hemorrhagic Fever Virus in Bulgaria and Turkey

Infections of humans with the tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) can cause a severe hemorrhagic fever with case fatality rates of up to 80%. Most humans are infected by tick bite, crushing infected ticks by hand or by unprotected contact with blood of viremic mammals. Next to the notified human CCHF cases, the real distribution and the situation in animals in Southeastern Europe are nearly unknown. Since domestic ruminants play a crucial role in the life cycle of the vector ticks and the transmission and amplification of the virus, the antibody prevalence in those animals is a good indicator for the presence of CCHFV in a region. Therefore, the prevalence of CCHFV-specific antibodies was investigated in domestic ruminants of different regions of Bulgaria and Turkey. Sera of 1165 ruminants were tested and a prevalence of up to 90% was identified. The overall prevalence for Bulgaria was 26% and for Turkey 57%. The results highlight the risk of human infections in those regions and the importance of the investigation of the prevalence in animals for identification of risk areas. This article provides a unique overview about published CCHFV antibody prevalence in animals in comparison to human incidences in different areas of Bulgaria and Turkey. Although it will help to complete the understanding of the CCHFV situation in these countries, it also demonstrates the lack of unpublished and published data even in these highly endemic areas.

Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection.

Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human and animal granulocytic anaplasmosis and tick-borne fever of ruminants. This obligate intracellular bacterium evolved to use common strategies to establish infection in both vertebrate hosts and tick vectors. Herein, we discuss the different strategies used by the pathogen to modulate cell apoptosis and establish infection in host cells. In vertebrate neutrophils and human promyelocytic cells HL-60, both pro-apoptotic and anti-apoptotic factors have been reported. Tissue-specific differences in tick response to infection and differential regulation of apoptosis pathways have been observed in adult female midguts and salivary glands in response to infection with A. phagocytophilum. In tick midguts, pathogen inhibits apoptosis through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, while in salivary glands, the intrinsic apoptosis pathways is inhibited but tick cells respond with the activation of the extrinsic apoptosis pathway. In Ixodes scapularis ISE6 cells, bacterial infection down-regulates mitochondrial porin and manipulates protein processing in the endoplasmic reticulum and cell glucose metabolism to inhibit apoptosis and facilitate infection, whereas in IRE/CTVM20 tick cells, inhibition of apoptosis appears to be regulated by lower caspase levels. These results suggest that A. phagocytophilum uses different mechanisms to inhibit apoptosis for infection of both vertebrate and invertebrate hosts.

ACTUAL TICK-BORNE INFECTIONS IN CRIMEA

The Crimean Peninsula is located in the Northern part of the Black sea, from the East it is washed by the Sea of Azov, to the South and West by the Black Sea. The unique geographical and climatic conditions facilitate leptospirosis, tularemia, tick-borne encephalitis, Lyme disease, intestinal yersiniosis, pseudotuberculosis, hemorrhagic fever with renal syndrome, Crimean-Congo hemorrhagic fever, Mediterranean fever, Q-fever and other infectious diseases natural foci formation on the territory of Crimea Republic. Tick-borne natural focal infections have the most significance due to favorable epidemiologic conditions especially on the background of high raid ticks attacks on people. A leading role in the epizootology and epidemiology of tick-borne natural-focal infections of the Crimea are playing Ixodidae that occur in different landscape-climatic zones, with the greatest their species diversity is observed in mountain-foothill, forest and forest-steppe regions. There are about 30 species in Ixodidae fauna of the Crimean Peninsula. Ticks species composition identification shows that over 50% of people attacks episodes in the Crimea on recent years is caused by Ixodes ricinus ticks species, the remaining are associated with Haemophisalis punctata, Rhipicephalus sanguineus, Hyalomma marginatum, Dermacentor marginatus and other. Refusal of treatment in medical institutions of the people affected by tick bites, and the possibility of an attack on people subtle phases of mites are lubricates the real picture of the frequency of contacts of the population with ticks and complicates the forecasting of the epidemiological situation. This review summarizes the available information about spreading of tick-borne encephalitis, Lyme disease, Mediterranean and Crimean-Congo haemorrhagic fevers on the territory of Crimea Republic and demonstrates the modern trends and manifestations of epidemic process of these nosological forms. The results obtained in the analysis of our investigations and literature data, showed that the conditions of globalization lead to an increase in the frequency of contacts of the population with natural foci, and one of the most common tick-borne natural focal infections on the territory of the Peninsula are Lyme disease and the Mediterranean fever. Epidemiological analysis of the prevalence of tick-borne encephalitis and Crimean-Congo haemorrhagic fever in Crimea revealed a decrease in the activity of natural foci of these infections at the present stage. The problem of tick-borne natural focal infections in Crimea Republic requires further careful study.

Short Report: Identification of a Potential Marker of Anaplasma Phagocytophilum Associated with Cattle Abortion.

Anaplasma phagocytophilum is a tick-borne pathogen that causes tick-borne fever in domestic ruminants. Tick-borne fever is characterized by diverse symptoms and occasionally causes abortions in domestic ruminants, resulting in significant economic impact. However, in France, the potential frequency of A.phagocytophilum-related abortions is unknown, and thus, it remains difficult to estimate the full extent of its economic impact. This gap in our knowledge is likely explained, at least in part, by the absence of suitable and specific tools capable of detecting A.phagocytophilum associated with abortion. Our objective was to identify a genetic marker able to differentiate A.phagocytophilum strains isolated from domestic ruminants that had aborted compared to those that had not. Thus, we typed a total of 123 A.phagocytophilum obtained from cattle, of which 25 originated from cows that had aborted, via multiple-locus variable-number tandem repeat (VNTR) analysis. These included 56 new A.phagocytophilum samples and 67 previously published A.phagocytophilum samples. A multivariate logistic model demonstrated that the triple-repeat allele of the APV-A VNTR was statistically more frequent in A.phagocytophilum from cattle that had aborted, compared to A.phagocytophilum from cattle that had not aborted (P=0.03), while controlling for any regional effects (P<0.0001). For four other VNTR, there were no statistical associations between specific alleles and abortion. The APV-A triple-repeat VNTR allele could thus act as a marker of A.phagocytophilum involved in abortions. If this hypothesis is confirmed in additional samples from other regions, this marker could then be utilized in the development of A.phagocytophilum abortive strain surveillance measures.

Alpha proteobacteria of genus Anaplasma (Rickettsiales: Anaplasmataceae): Epidemiology and characteristics of Anaplasma species related to veterinary and public health importance.

The Anaplasma species are important globally distributed tick-transmitted bacteria of veterinary and public health importance. These pathogens, cause anaplasmosis in domestic and wild animal species including humans. Rhipicephalus, Ixodes, Dermacentor and Amblyomma genera of ticks are the important vectors of Anaplasma. Acute anaplasmosis is usually diagnosed upon blood smear examination followed by antibodies and nucleic acid detection. All age groups are susceptible but prevalence increases with age. Serological cross-reactivity is one of the important issues among Anaplasma species. They co-exist and concurrent infections occur in animals and ticks in same geographic area. These are closely related bacteria and share various common attributes which should be considered while developing vaccines and diagnostic assays. Movement of susceptible animals from non-endemic to endemic regions is the major risk factor of bovine/ovine anaplasmosis and tick-borne fever. Tetracyclines are currently available drugs for clearance of infection and treatment in humans and animals. Worldwide vaccine is not yet available. Identification, elimination of reservoirs, vector control (chemical and biological), endemic stability, habitat modification, rearing of tick resistant breeds, chemotherapy and tick vaccination are major control measures of animal anaplasmosis. Identification of reservoirs and minimizing the high-risk tick exposure activities are important control strategies for human granulocytic anaplasmosis.

Anaplasma marginale and Anaplasma phagocytophilum: Rickettsiales pathogens of veterinary and public health significance.

Anaplasma marginale and Anaplasma phagocytophilum are the most important tick-borne bacteria of veterinary and public health significance in the family Anaplasmataceae. The objective of current review is to provide knowledge on ecology and epidemiology of A. phagocytophilum and compare major similarities and differences of A. marginale and A. phagocytophilum. Bovine anaplasmosis is globally distributed tick-borne disease of livestock with great economic importance in cattle industry. A. phagocytophilum, a cosmopolitan zoonotic tick transmitted pathogen of wide mammalian hosts. The infection in domestic animals is generally referred as tick-borne fever. Concurrent infections exist in ticks, domestic and wild animals in same geographic area. All age groups are susceptible, but the prevalence increases with age. Movement of susceptible domestic animals from tick free non-endemic regions to disease endemic regions is the major risk factor of bovine anaplasmosis and tick-borne fever. Recreational activities or any other high-risk tick exposure habits as well as blood transfusion are important risk factors of human granulocytic anaplasmosis. After infection, individuals remain life-long carriers. Clinical anaplasmosis is usually diagnosed upon examination of stained blood smears. Generally, detection of serum antibodies followed by molecular diagnosis is usually recommended. There are problems of sensitivity and cross-reactivity with both the Anaplasma species during serological tests. Tetracyclines are the drugs of choice for treatment and elimination of anaplasmosis in animals and humans. Universal vaccine is not available for either A. marginale or A. phagocytophilum, effective against geographically diverse strains. Major control measures for bovine anaplasmosis and tick-borne fever include rearing of tick-resistant breeds, endemic stability, breeding Anaplasma-free herds, identification of regional vectors, domestic/wild reservoirs and control, habitat modification, biological control, chemotherapy, and vaccinations (anaplasmosis and/or tick vaccination). Minimizing the tick exposure activities, identification and control of reservoirs are important control measures for human granulocytic anaplasmosis.

Opening the black box of Anaplasma phagocytophilum diversity: current situation and future perspectives.

Anaplasma phagocytophilum is a zoonotic obligate intracellular bacterium known to be transmitted by ticks belonging to the Ixodes persulcatus complex. This bacterium can infect several mammalian species, and is known to cause diseases with variable symptoms in many domestic animals. Specifically, it is the causative agent of tick-borne fever (TBF), a disease of important economic impact in European domestic ruminants, and human granulocytic anaplasmosis (HGA), an emerging zoonotic disease in Asia, USA and Europe. A. phagocytophilum epidemiological cycles are complex and involve different ecotypes, vectors, and mammalian host species. Moreover, the epidemiology of A. phagocytophilum infection differs greatly between Europe and the USA. These different epidemiological contexts are associated with considerable variations in bacterial strains. Until recently, few A. phagocytophilum molecular typing tools were available, generating difficulties in completely elucidating the epidemiological cycles of this bacterium. Over the last few years, many A. phagocytophilum typing techniques have been developed, permitting in-depth epidemiological exploration. Here, we review the current knowledge and future perspectives regarding A. phagocytophilum epidemiology and phylogeny, and then focus on the molecular typing tools available for studying A. phagocytophilum genetic diversity.

The genus Anaplasma: new challenges after reclassification.

Summary The genus Anaplasmais one of four distinct genera in the family Anaplasmataceae, which are obligate intracellular pathogens vectored by ticks and found exclusively within parasitophorous vacuoles in the host cell cytoplasm. The 2001 reclassification of the order Rickettsiales expanded the genus Anaplasma, which previously contained pathogens that were host specific for ruminants (A. marginale, A. centrale and A. bovis), by adding A. phagocytophilum, a unification of three organisms previously classified as Ehrlichia (E. equi, E. phagocytophila and the unnamed agent of human granulocytic ehrlichiosis). Also included in the genus Anaplasma were A. bovis (formerly E. bovis), A. platys (formerly E. platys) and Aegyptianella pullorum. Despite the genomic relatedness of the regrouped organisms, many aspects of their biology are diverse, including their host specificity, host cell preferences, major surface proteins (MSPs) and tick vectors. This review focuses on the two most important pathogens: A. marginale, which causes bovine anaplasmosis, and A. phagocytophilum, the aetiologic agent of tick-borne fever in sheep and human granulocytic anaplasmosis, an emerging tick-borne disease of humans. For both pathogens, strain diversity is much greater than previously recognised. While MSPs were found to be useful in phylogenetic studies and strain identification, highly conserved MSPs were found to affect the specificity of serologic tests. Comparison of these two important pathogens highlights the challenges and insight derived from reclassification and molecular analysis, both of which have implications for the development and evaluation of diagnosis and control strategies.