Invasive Species Compendium

Detailed coverage of invasive species threatening livelihoods and the environment worldwide

Datasheet

tick-borne fever

Toolbox

Datasheet

tick-borne fever

Summary

  • Last modified
  • 21 November 2019
  • Datasheet Type(s)
  • Animal Disease
  • Preferred Scientific Name
  • tick-borne fever
  • Pathogens
  • Ehrlichia phagocytophila
  • There are no pictures available for this datasheet

    If you can supply pictures for this datasheet please contact:

    Compendia
    CAB International
    Wallingford
    Oxfordshire
    OX10 8DE
    UK
    compend@cabi.org
  • Distribution map More information

Don't need the entire report?

Generate a print friendly version containing only the sections you need.

Generate report

Identity

Top of page

Preferred Scientific Name

  • tick-borne fever

International Common Names

  • English: pasture fever; tickborne fever; tick-borne fever, anaplasma phagocytophila in ruminants; tick-borne fever, ehrlichia phagocytophila in ruminants

French acronym

  • TBF

Pathogen/s

Top of page Ehrlichia phagocytophila

Overview

Top of page

Tick-borne fever (TBF) is a rickettsial disease of sheep (Gordon et al., 1932; Foggie, 1951), goats (Miert et al., 1984; Gray et al., 1988) and cattle (Hudson, 1950; Venn and Woodford, 1956). It has been reported in wild ruminants such as feral goats and red, fallow and roe deer and rodents (McDiarmid, 1965; Foster and Greig, 1969; Ogden et al., 1998a; Alberdi et al., 2000). Studies have also revealed that the organism infects equines (Korbutiak and Schneiders, 1994) and canines (Clark et al., 1996; Pusterla et al., 1999).

Tick-borne fever was fortuitously discovered in 1932 (Macleod, 1932). After reproducing the disease in sheep by sub-inoculating blood from infected sheep and establishing that the agent was distinct from that which caused louping ill, Gordon and his co-workers (Gordon et al., 1932) gave the disease a provisional name ‘tick-borne fever’. The disease in cattle is also known as pasture fever, which was first described in 1950 by Hudson (1950). Tick-borne fever is a seasonal syndrome that occurs when dairy heifers and cows are returned to tick-infested pastures in the spring and early summer (Tuomi, 1966).

In the last decade, granulocytic ehrlichia similar to E. phagocytophila has also been detected in humans (Chen et al., 1994), dogs (Pusterla et al., 1997a), deer (Belongia et al., 1997), llamas (Barlough et al., 1997a) and rodents (Ogden et al., 1998a).

Host Animals

Top of page
Animal nameContextLife stageSystem
Bos indicus (zebu)Domesticated hostCattle & Buffaloes: All Stages
Bos taurus (cattle)Domesticated hostCattle & Buffaloes: All Stages
Canis familiaris (dogs)Domesticated hostOther: All Stages
Canis mesomelas (black-backed jackal)Wild hostOther: All Stages
Capra hircus (goats)
CervidaeWild hostOther: All Stages
Equus caballus (horses)Domesticated hostOther: All Stages
Ovis aries (sheep)Domesticated hostSheep & Goats: All Stages

Hosts/Species Affected

Top of page

The disease naturally affects sheep (Gordon et al., 1932) and cattle (Hudson, 1950). The organism has been isolated from red, fallow and roe deer (McDiarmid, 1965; Foster and Greig, 1969; Alberdi et al., 2000). Studies have also revealed that the organism infects equines (Korbutiak and Schneiders, 1994) and canines (Clark et al., 1996; Pusterla et al., 1999).

The presence of E. phagocytophila in wild ruminants and rodents (Ogden et al., 1998a) suggests that they may serve as natural reservoirs of infection (Mcdiarmid, 1965; Foster and Greig, 1969; Ogden et al., 1998a). Recently, a granulocytic ehrlichia has been isolated from humans (Chen et al., 1994), white-tailed deer (Belongia et al., 1997), dogs (Pusterla et al., 1997a) and from a llama (Lama glama) (Barlough et al., 1997a).

Systems Affected

Top of page blood and circulatory system diseases of large ruminants
blood and circulatory system diseases of small ruminants
digestive diseases of large ruminants
digestive diseases of small ruminants
mammary gland diseases of large ruminants
mammary gland diseases of small ruminants
nervous system diseases of large ruminants
nervous system diseases of small ruminants
reproductive diseases of large ruminants
reproductive diseases of small ruminants
respiratory diseases of large ruminants
respiratory diseases of small ruminants
urinary tract and renal diseases of large ruminants
urinary tract and renal diseases of small ruminants

Distribution

Top of page

Tick-borne fever was first recognized in tick-infested pastures of Scotland by Macleod in 1932 and later in other parts of the United Kingdom, (Hudson, 1950; Tutt and Loving, 1955; Webster and Mitchell, 1989; Ogdenet al., 1998b). It was also found in Israel (Waner et al., 1999) and in other parts of Europe such as Norway (Overas, 1959), The Netherlands (Siebinga and Jongejan, 2000), Finland (Tuomi, 1966), Austria (Hinaidy, 1973), Spain (Juste et al., 1989), Italy (Cinco et al., 1997; Cinco et al., 1998), Sweden (Engvall et al., 1996), Germany (Fingerle et al., 1999),Switzerland (Pfister et al., 1987) and Ireland (Collins et al., 1970). A similar organism was reported in the USA (Barlough et al., 1997a; Barlough et al., 1997b; Levin and Fish, 2000) India (Raghavachari and Reddy, 1959; Sreekumar et al., 1996) and in the Natal Region of South Africa (Retief et al., 1971).

Human granulocytic ehrlichiosis, a potentially fatal disease, was first recognized in the USA (Chen et al., 1994) and later on in mainland Europe (Petrovec et al., 1997; Dumler, 1997; Cinco et al., 1998; Corcaci, 1998; Parola et al., 1998; Pusterla et al., 1998a; Bjoersdorff et al., 1999; Fingerle et al., 1997; Oteo et al., 2000). Sumption et al. (1995) reported that the disease also occurs in the UK.

Distribution Table

Top of page

The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.

Last updated: 10 Jan 2020

Pathology

Top of page

Haematology and clinical pathology


Tick-borne fever is characterized by severe haematological changes which are dramatic and diagnostic in animals affected by the disease (Taylor et al., 1941; Tuomi, 1967; Foster and Cameron, 1968; Batungbacal et al., 1982a; Miert et al., 1984; Woldehiwet, 1987a; Brun-Hansen et al., 1998; Gokce and Woldehiwet, 1999a). In human granulocytic ehrlichiosis, haematological changes are reported to be similar to those observed in animals infected with E. phagocytophila (Bakken et al., 1996; Petrovec et al., 1997).


Leukocytes


Following infection with E. phagocytophila the total number of leukocytes decreases below pre-inoculation values at the onset of fever and remains low up to 14 to 16 days post-inoculation (Tuomi, 1967; Woldehiwet, 1987a; Campbell et al., 1994; Brun-Hansen et al., 1998). Leukopenia appears to be due to early lymphocytopenia and prolonged neutropenia (Tayloret al., 1941; Batungbacalet al., 1982; Woldehiwet, 1987a; Gokce and Woldehiwet, 1999a).


Neutrophils


Tick-borne fever is characterized by an early neutrophilia of 2 to 3 days duration (Woldehiwet, 1987a; Campbell et al., 1994). This is quickly followed by a progressive neutropenia (Tayloret al., 1941; Miert et al., 1984; Woldehiwet, 1987a; Campbell et al., 1994; Brun-Hansen et al., 1998). The number of neutrophils remains below the pre-inoculation levels until 14 to 18 days post-inoculation (Miert et al., 1984; Woldehiwet, 1987a; Campbell et al., 1994; Brun-Hansen et al., 1998; Gokce and Woldehiwet, 1999a).


Lymphocytes


The number of lymphocytes is significantly reduced 4 to 7 days post-inoculation and remains at significantly low levels until 14 to 16 days post-inoculation (Batungbacal et al., 1982b; Miertet al., 1984; Woldehiwet, 1987a; Campbell et al., 1994). Studies with monoclonal antibodies that recognize surface markers for lymphocyte subsets have revealed that the lymphocytopenia is associated with a significant reduction in the number of both B and T-lymphocytes. The reduction in the number of T-lymphocytes is characterized by a reduction in the number of circulating helper T-cells, cytotoxic/suppressor T-cells and gamma/delta T-cells. The various lymphocyte subsets return to pre-inoculation levels 13 to 16 days after experimental infection with E. phagocytophila. The circulating helper T-cells: cytotoxic/suppressor T-cells ratio has also been found to be reduced (Woldehiwet, 1991; Gokce and Woldehiwet, 1999c).


Eosinophils


A profound eosinopenia has been reported to occur at the beginning of fever, lasting up to 17 to 20 days post-inoculation with E. phagocytophila (Tuomi, 1967; Woldehiwet, 1983; Miert et al., 1984).


Monocytes


Following infection with E. phagocytophila, the number of monocytes in peripheral blood has been reported to increase on the 5th day post-inoculation, remaining at high levels for up to the 11th day post-inoculation (Woldehiwet, 1987a). Other workers have reported an initial reduction in the number of monocytes, followed by a significant increase in the number of monocytes (Campbell et al., 1994; Brun-Hansen et al., 1998).


Thrombocytes


A short period of thrombocytopenia has been reported in sheep and cattle experimentally infected with E. phagocytophila (Foster and Cameron, 1968; Brun-Hansen et al., 1998). Additionally, Gokce and Woldehiwet (1999a) reported that this short period of the reduction in thrombocyte numbers is followed by a significant increase for a longer period in animals experimentally infected with E. phagocytophila.


Erythrocytes


A significant reduction in the number of erythrocytes was observed in splenectomized calves (Purnell et al., 1977), cows (Brun-Hansen et al., 1998) and most recently in goats and sheep experimentally infected with E. phagocytophila (Gokce and Woldehiwet, 1999a). The reduction in the number of erythrocytes coincided with the onset of fever and lasted until approximately 20 days post-inoculation. The erythrocytopenia is thought to be due to increased destruction of erythrocytes (Brun-Hansen et al., 1998; Gokce and Woldehiwet, 1999a).


Other haematological changes


A decrease in haematocrit and haemoglobin values has been reported in sheep, goats (Taylor et al., 1941, Van Miert et al., 1984; Gokce and Woldehiwet, 1999a) and in cattle (Brun-Hansen et al., 1998) infected with E. phagocytophila. Both parameters were reported to be reduced during the period of fever (Brun-Hansen et al., 1998). Reduction in haematocrit, haemoglobin and erythrocyte values indicates that animals infected with E. phagocytophila also develop anaemia (Gokce and Woldehiwet, 1999a). In addition, an increase in the fibrinogen levels of sheep infected with tick-borne fever (TBF) was also reported (Unruh, 1977).

The mechanism by which TBF causes leukopenia is not well-established. It was thought to be due to bone marrow aplasia (Taylor et al., 1941) or due to the destruction and sequestration of infected cells (Hudson, 1950; Foster and Cameron, 1970b). However, Woldehiwet and Scott (1982e) showed that when TBF-affected or E. phagocytophila-infected sheep were injected with betamethasone a significant influx of neutrophils from bone marrow reserve occurred, suggesting that there was no marrow aplasia.

Table: Haematological parameters of sheep infected with E. phagocytophila (Gokce and Woldehiwet, 1999a).


ParametersLowest value ((mean ± standard error)
Leukopenia (x 109 cell/l)4.25 ± 0.16
Lymphocytopenia (x 109 cell/l)3.25 ± 0.28
Neutropenia (x 109 cell/l)0.77 ± 0.07
Erythrocytopenia (x 1012 cell/l)6.71 ± 0.36
Thrombocytopenia (x 109 cell/l)95.16 ± 16.0
PCV (%)30.0± 01
Hypohaemoglobinaemia (g/dl)7.5 ± 0.23



Clinical chemistry


Experimental studies with TBF indicated that the disease is also characterized by a significant reduction in the activity of serum alkaline phosphatase. It is also characterized by reductions in plasma zinc, iron and albumin concentrations and significant increases in the concentrations of plasma total bilirubin, urea and creatinine (Miert et al, 1984; Campbell et al., 1994; Brun-Hansen et al., 1998; Gokce and Woldehiwet, 1999d). However, Brun-Hansen et al. (1998) reported that there was no change in the concentrations of glucose, phosphorus, calcium, magnesium, sodium and potassium and in the activity of aspartate aminotransferase, glutamyltransferase and creatine kinase in cattle infected with E. phagocytopila. Additionally, aspartate aminotransferase, lactate dehydrogenase, creatinine, C-reactive protein and erythrocyte sedimentation rate were found to be mildly elevated in patients infected with the agent of human granulocyte ehrlichiosis (Bakken et al., 1996; Petrovec et al., 1997).

TNF-a and IL-1a/ß are known to induce the production of acute phase proteins, which are thought to be responsible for reductions in the concentrations of zinc and iron and in the activity of alkaline phosphatase in the peripheral blood of sheep and goats during infection. They are also thought responsible for endotoxaemia (Schotman, 1982; Miert and Van Duin, 1982; Verheijden et al., 1982; Miert et al., 1983; Miert et al., 1990). The increase in the concentrations of serum TNF-a and IL-1a/ß may explain the reduction in the concentrations of biochemical parameters observed in goats and sheep experimentally infected with E. phagocytophila (Gokce, 1998; Gokce and Woldehiwet, 1999d). In addition, changes in the concentrations of total plasma bilirubin, urea and creatinine are thought to be associated with the febrile reaction, increased destruction of erythrocytes and the presence of mesangial glomerulitis observed in animals infected with E. phagocytophila (Campbell et al.,1994; Gokce and Woldehiwet, 1999d).

Table: Blood biochemical values of sheep infected with E. phagocytophila (Gokce and Woldehiwet, 1999d)


ParametersLowest/peak value (mean ± standard error)
Alkaline phosphotase (IU/l)41.6 ± 2.4
Zinc (µmol/l)7.1 ± 0.3
Iron (µmol/l)6.1 ± 0.6
Total bilirubin (µmol/l)9.9 ± 0.8
Urea (mmol/l)7.5 ± 0.8
Creatinine (µmol/l)93.3 ± 4.9


Gross pathology and histopathology


Early studies with tick-borne fever (TBF) have shown that the spleens of animals affected with E. phagocytophila become enlarged (Gordon et al., 1932; Hudson, 1950; Tuomi, 1966; Foster et al., 1968) and that there is mild liver damage (Foster et al., 1968). Histopathological examination of pulmonary lesions revealed that there is a diffuse large mononuclear cell infiltration in the alveolar septa within 24 h of experimental infection with E. phagocytophila (Munro et al., 1982). Foster et al. (1968) reported that a haemorrhage syndrome occurred in the large intestine of sheep 3 days after experimental infection with E. phagocytophila. The rectal wall appeared to be thickened and ulcerated, with apparent erosion of small vessels. The lesions were extensive and close to the rectum, but became progressively smaller and fewer towards the caeca. Histological examination of these lesions revealed that there were large areas of haemorrhage both in and on the mucosa (Foster et al., 1968). Other less common changes include petechiation of the thymus, serosal and subendocardial haemorrhages and hypopericarditis (McEben, 1947; Woldehiwet and Scott, 1993). Studies on the sequential pathology of TBF in sheep help to further explain the histopathology of the disease (Campbell et al., 1994; Lepidi et al., 2000). These studies revealed that pathological changes occurred between 2 and 21 days of the infection and were concentrated in the lungs, lymphoreticular system, liver, kidneys and the cranial neurovascular system. The main histopathological changes including pulmonary alveolitis with minimal shedding of cells, follicular and especially parafollicular lymphoreticular reactions in lymph nodes and spleen, messengial glomerulitis, and a marked choroiditis in the cranial nervous system, with minimal reaction in the brain (Campbell et al., 1994; Lepidi et al., 2000).

Microscopic examination of liver and lung sections revealed that rickettsial organisms were detected often in the neutrophils and occasionally in alveolar epithelial cells and macrophages and in Kupffer cells (Munro et al., 1982; Campbell et al., 1994). Campbell et al. (1994) showed that two types of rickettsial organisms were detected in the cytoplasm of macrophages and large lymphoid cells in the lung, lymph nodes, spleen, liver, kidney and brain. Type I consisted of granular, basophilic spherical particles, less than 1 µm in diameter, occurring in loose clumps; and Type 2 consisted of basophilic pleomorphic intravacuolar bodies, about 3-5 µm in diameter (Campbell et al., 1994).

Diagnosis

Top of page

Clinical signs


In natural infections, the incubation period in sheep and goats may vary from 4 to 8 days (Gordon et al., 1932; Woldehiwet and Scott, 1993), but this is shortened to 3 to 4 days when infected blood is inoculated intravenously (Foggie, 1951; Miert et al., 1984; Woldehiwet, 1987a; Campbell et al., 1994). The incubation period is reported to be longer in cattle than in sheep (Tuomi, 1967; Brun-Hansen et al., 1998; Pusterla and Braun, 1997). In sheep and goats, TBF is characterized by an abrupt rise in rectal temperatures that fluctuate between 40oC and 42oC for 4 to 22 days (Miert et al., 1984; Woldehiwet, 1987a; Campbell et al., 1994). The duration and magnitude of fever may vary according to the strain of E. phagocytophila and the type and immunological status of the host (Tuomi, 1967; Foster and Cameron, 1970a; Woldehiwet and Scott, 1982d; Woldehiwet and Scott, 1993). The highest point of thermal reaction usually occurs on the second day of rickettsaemia (Woldehiwet, 1983; Brun-Hansen et al., 1998; Pusterla and Braun, 1997). The febrile reaction is usually monophasic but secondary febrile reactions may occur (Foggie, 1951; Tuomi, 1967; Woldehiwet and Scott, 1993; Campbell et al., 1994; Brun-Hansen et al., 1998). In sheep and goats other signs are either absent or mild. Other symptoms include rapid and shallow respiration, occasional coughing, tachycardia, slight to moderate inhibition of rumen motility, dullness, low water and food intake and slight weight loss (Tuomi, 1967; Miert et al., 1984; Stuen et al., 1992; Campbell et al., 1994). In cattle, clinical signs are similar to those observed in sheep and goats. Additionally, dairy cattle may have a marked fall in milk yield and develop diffuse swellings in the hind limbs and a stiff gait (Hudson, 1950; Tutt and Loving, 1955; Tuomi, 1967; Pusterla and Braun, 1997; Brun-Hansen et al., 1998). The reaction in young animals is quite mild and manifested only by a moderate rise in rectal temperature (Stuen et al., 1992; Stuen, 1993). Stuen et al. (1992) showed that six-week-old lambs developed more pronounced febrile reaction and rickettsaemia than two-weeks-old lambs following infection with E. phagocytophila. It was also reported that a 13-days-old calf born from a cow infected with E. phagocytophila had a high temperature, swollen prescapular lymph nodes and rickettsaemia (Pusterla et al., 1997c).

Clinical symptoms in human granulocytic ehrlichiosis include fever, malasia, myalgias, headache, rigors, sweats, nausea, confusion, cough, arthralgias, anorexia, vomiting, prostration/weakness, diarrhoea, vertigo, pneumonia, pulmonary infiltrates, seizure, rash and upper gastrointestinal tract bleeding (Bakken et al., 1994; Bakken et al., 1996; Petrovec et al., 1997).


Diagnosis 


In sheep/goats, the presence of high fever, severe haematological changes and rickettsial inclusions within granulocytes and monocytes of animals grazing in tick-infested areas during spring and summer help to diagnose the disease (Woldehiwet and Scott, 1993).

In dairy cattle, a febrile reaction together with a sudden drop in milk yield and respiratory symptoms following the introduction of cattle on to tick-infested pastures are highly indicative of tick-borne fever(TBF). Other clinical signs including abortions or respiratory illness are not diagnostic. Demonstration of a rise in E. phagocytophila-specific antibody titres by serological methods (Woldehiwet and Scott, 1982c; Paxton and Scott, 1989) and microscopic examination of infected cells in peripheral blood (Woldehiwet and Scott, 1993) are necessary for the conclusive diagnosis of the causative agent of TBF. Recently, polymerase chain reaction (PCR) has been widely used for epidemiological studies to detect E. phagocytophila and other granulocytic ehrlichia in domestic and wild animals (Chenet al., 1994; Belongia et al., 1997; Pusterla et al., 1997a, Pusterla et al., 1999; Sumneret al., 1997; Ogden et al., 1998a).

List of Symptoms/Signs

Top of page
SignLife StagesType
Cardiovascular Signs / Tachycardia, rapid pulse, high heart rate Cattle & Buffaloes:All Stages,Sheep & Goats:All Stages Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Diarrhoea Sheep & Goats:All Stages Sign
Digestive Signs / Grinding teeth, bruxism, odontoprisis Sheep & Goats:All Stages Sign
Digestive Signs / Hepatosplenomegaly, splenomegaly, hepatomegaly Sheep & Goats:All Stages Sign
Digestive Signs / Rumen hypomotility or atony, decreased rate, motility, strength Sheep & Goats:All Stages Sign
General Signs / Exercise intolerance, tires easily Cattle & Buffaloes:All Stages,Sheep & Goats:All Stages Sign
General Signs / Fever, pyrexia, hyperthermia Cattle & Buffaloes:All Stages,Sheep & Goats:All Stages Diagnosis
General Signs / Forelimb lameness, stiffness, limping fore leg Sign
General Signs / Generalized lameness or stiffness, limping Sign
General Signs / Haemorrhage of any body part or clotting failure, bleeding Cattle & Buffaloes:All Stages,Sheep & Goats:All Stages Sign
General Signs / Hindlimb lameness, stiffness, limping hind leg Sign
General Signs / Hindlimb swelling, mass in hind leg joint and / or non-joint area Sign
General Signs / Lack of growth or weight gain, retarded, stunted growth Cattle & Buffaloes:Calf,Sheep & Goats:Lamb Sign
General Signs / Lymphadenopathy, swelling, mass or enlarged lymph nodes Sign
General Signs / Pale mucous membranes or skin, anemia Cattle & Buffaloes:All Stages,Sheep & Goats:All Stages Sign
General Signs / Petechiae or ecchymoses, bruises, ecchymosis Cattle & Buffaloes:All Stages,Sheep & Goats:All Stages Sign
General Signs / Reluctant to move, refusal to move Sign
General Signs / Sudden death, found dead Sign
General Signs / Swelling of the limbs, legs, foot, feet, in birds Cattle & Buffaloes:All Stages,Cattle & Buffaloes:Calf Sign
General Signs / Trembling, shivering, fasciculations, chilling Cattle & Buffaloes:All Stages,Sheep & Goats:All Stages Sign
General Signs / Underweight, poor condition, thin, emaciated, unthriftiness, ill thrift Cattle & Buffaloes:All Stages,Sheep & Goats:All Stages Sign
General Signs / Weight loss Cattle & Buffaloes:All Stages,Cattle & Buffaloes:Calf,Sheep & Goats:All Stages,Sheep & Goats:Lamb Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sheep & Goats:All Stages Sign
Nervous Signs / Tremor Sheep & Goats:All Stages Sign
Ophthalmology Signs / Lacrimation, tearing, serous ocular discharge, watery eyes Sheep & Goats:All Stages Sign
Reproductive Signs / Abortion or weak newborns, stillbirth Cattle & Buffaloes:Cow,Sheep & Goats:Mature female Sign
Reproductive Signs / Agalactia, decreased, absent milk production Cattle & Buffaloes:Cow Diagnosis
Reproductive Signs / Female infertility, repeat breeder Sign
Reproductive Signs / Male infertility Cattle & Buffaloes:Bull,Sheep & Goats:Breeding male Sign
Respiratory Signs / Abnormal lung or pleural sounds, rales, crackles, wheezes, friction rubs Sign
Respiratory Signs / Coughing, coughs Sign
Respiratory Signs / Dyspnea, difficult, open mouth breathing, grunt, gasping Sign
Respiratory Signs / Increased respiratory rate, polypnea, tachypnea, hyperpnea Sign
Respiratory Signs / Mucoid nasal discharge, serous, watery Sign
Respiratory Signs / Purulent nasal discharge Sign
Skin / Integumentary Signs / Parasite visible, skin, hair, feathers Sign

Disease Course

Top of page

Transmission


The organism is transmitted to susceptible animals by the hard-tick Ixodes ricinus transstadially but not transovarially (Macleod and Gordon, 1933; Macleod, 1936, Webster and Mitchell, 1989). In other words, infected larvae or nymphs can transmit the organism but it can not be transmitted through to the tick eggs. Recently, E. phagocytophila was also detected in I. trianguliceps ticks, and in I. scapularis (Ogden et al., 1998a; Levin and Fish, 2000). The organism may also transmit to the susceptible animals by intravenous injection or oral administration of E. phagocytophila-infected blood (Pusterla et al., 1998b).

Additionally, the intrauterine transmission of E. phagocytophila to a foetus in a cow was also reported (Pusterla et al., 1997c). It was shown that when a cow was inoculated with E. phagocytophila after 270 days of gestation, it developed the clinical and haematological signs typical of tick-borne-fever (TBF) six days after inoculation, and 11 days later the cow gave birth to a live calf, which became ill at 13 days of age. The calf developed fever and the organisms were detected in peripheral blood neutrophils and eosinophils for seven days. The calf also developed antibodies against E. phagocytophila 14 days after it became ill (Pusterla et al., 1997c). Additionally, the agent of human granulocytic ehrlichiosis, genetically identical to E. phagocytophila, has been found to be transmitted to human by ticks I. ricinus (Petrovec et al., 1997), I. scapularis; (Vignes and Fish, 1997), I. pacificus (Bakken, et al., 1996) and I dammini (Barlough et al., 1997a). The survival of the organism in vector ticks for long periods (Macleod, 1936), the persistence of the organism in the blood of clinically recovered animals for a long period (Foggie, 1951), the possibility of its intrauterine transmission to the foetus (Pusterla et al., 1997c) and the presence of wildlife reservoirs (Mcdiarmid, 1965; Ogden et al., 1998a) ensure the continued maintenance of the disease.


Pathogenesis


The causative agent, E. phagocytophila, mainly invades granulocytes, monocytes and possibly lymphocytes (Gordon et al., 1940; Woldehiwet, 1987a; Campbell et al., 1994; see pictures). The organisms have also been demonstrated in Kupffer cells, alveolar macrophages, alveolar epithelial cells and large lymphoid cells of lymph nodes, spleen, liver, kidney and brain (Munro et al., 1982; Campbell et al., 1994; Lepidi et al., 2000). Additionally, E. phagocytophila has also been detected in leucocytes of milk samples obtained from lactating cows experimentally infected with E. phagocytophila (Pusterla et al., 1997d).

Following transmission of E. phagocytophila by infected ticks or by injection of infected blood by the intravenous route, the organisms were demonstrated in the lungs before they were present in the peripheral blood (Snodgrass, 1974). Three to seven days after experimental infection or infestation with infected ticks, cytoplasmic inclusions appear in the eosinophils, neutrophils, monocytes and basophils (Thrusfield et al., 1978; Woldehiwet, 1987a). The monocytes are reported to be predominantly infected during the later stages of rickettsaemia while the granulocytes are infected throughout the period of rickettsaemia (Woldehiwet, 1987a). The organism can be detected in granulocytes for 3-4 weeks (Woldehiwet, 1987a; Brun-Hansen et al., 1998). However, sheep which have recovered from clinical disease may harbour the organism for long periods (Foggie, 1951).

Other microorganisms are destroyed when they encounter phagocytic polymorphonuclear leukocytes and macrophages (Van der Valk and Herman, 1987). E. phagocytophila does not only survive but it preferentially multiplies within polymorphonuclear cells. The mechanism for this survival and multiplication is not well-known, but several bacterial pathogens are known to reside in phagosomes which neither fuse with lysosomes nor acidify (Wells and Rikihisa, 1988; Clemens and Horwitz, 1996; Heinzen et al., 1996; Rathman et al., 1997). Some other intracellular organisms can survive in an acidic environment (Fortier et al., 1995; Heinzen et al., 1996) or avoid the destructive effects of lysosomal enzymes by escaping from the phagosome before the occurrence of phagosome-lysosome fusion. Recently, a study revealed that E. phagocytophila does not affect the production of lysosomal enzymes, but actively inhibits fusion of lysosomes with phagosomes containing E. phagocytophila, suggesting that it establishes a suitable micro-environment within polymorphonuclear cells by avoiding the destructive effects of lysosomal enzymes (Gokce et al., 1999).

Other factors such as TNF-a , IFN-a /g and nitric oxide are also reported to inhibit multiplication of several rickettsiae (Manor and Sarov, 1990; Feng et al., 1994; Turco and Winkler, 1994). Gokce (1998) revealed that E. phagocytophila induces the production of TNF-a and nitric oxide by ovine monocytes/macrophages in vivo and in vitro. The peak concentrations of TNF-a and nitric oxide were reported to be produced during the peak period of rickettsaemia, suggesting that TNF-a and nitric oxide may act as anti-rickettsial agents (Gokce, 1998).

The febrile reaction that follows inoculation with E. phagocytophila is a characteristic feature of TBF. The mechanisms of pyrexia are not clearly understood, but it is generally believed to be mediated by endogenous pyrogens including TNF-a , IL-1a/ß, IL-6 and IFN-a (Dinerallo et al., 1988; Dinerallo, 1989; Rhotwell and Busbridge, 1990). It is known that TNF-a and IL-1a /ß induce the generation of fever which is mediated by increased synthesis of prostaglandins by cytokine-stimulated hypothalamic cells (Dinerallo et al., 1988; Dinerallo, 1989). Thus, TNF-a and IL-1a /ß observed in animals infected with E. phagocytophila (Gokce, 1998) may play a part in the mechanism of pyrexia.

Table:Clinical parameters of sheep infected with E. phagocytophila (Gokce and Woldehiwet, 1999a)


ParametersValue (mean ± standard error)
Incubation period (days)3.14 ± 0.13
Peak fever (oC)41.62 ± 0.04
Febrile period (days)6.42 ± 0.27
Prepatent period (days)3.0 ± 0.00
Peak rickettsaemia (x 109 cell/l)1.85 ± 0.31
Duration of rickettsaemia (days)13.37 ± 0.96


The mechanisms of immunosuppression


E. phagocytophila is regarded as an immunosuppressive and pathogen-potentiating agent (Batungbacal and Scott, 1982a; Larsen et al, 1994). Perhaps the most important aspect of tick-borne fever (TBF) is its implication as a predisposing factor to other secondary bacterial or viral infections (Foggie, 1956; Foggie, 1957; Batungbacal and Scott, 1982a). In natural infections, TBF is often followed by other infections such as tick pyraemia (Taylor et al., 1941), purulent pneumonias (Foggie, 1951), listeric septicaemia (Gronstol and Ulvand, 1977) and septicaemic pasteurellosis (Overas et al., 1993). Experimental studies with E. phagocytophila and other bacterial or viral pathogens also revealed that dual infections of lambs with E. phagocytophila and S. aureus (Foggie, 1956; Foggie, 1957), P. haemolytica (Gilmour et al., 1982), C. psittaci (Munro et al., 1982), louping-ill virus (Reid et al., 1986), parainfluenza type-3 (PI-3) virus (Batungbacal and Scott, 1982a; Larsen et al., 1994) or orf virus (Gokce and Woldehiwet, 1999c) resulted in more severe clinical disease than infections caused by a single agent.

The mechanisms by which E. phagocytophila causes immunosuppression in animals are not clearly understood. It is thought to be related to the reduction in the number of circulating polymorphonuclear cells and lymphocytes and to the down-regulation of their functions (Foggie, 1956; Foster and Cameron, 1970b; Batungbacal and Scott, 1982a, Batungbacal and Scott, 1982b; Woldehiwet, 1987a). Leukocytes obtained from sheep experimentally infected with E. phagocytophila were shown to be less capable of phagocytosing and killing S. aureus (Woldehiwet, 1987a). PMN cells infected with the organism showed less diapedesis than normal PMN cells in vivo and a reduced capacity to adhere to glass or plastic surfaces in vitro (Foster and Cameron, 1970b; Woldehiwet, 1987a). PMN cells were also reported to be more susceptible to the cytotoxin of P. haemolytica (Woldehiwet et al., 1993). It has also been demonstrated that lymphocytes obtained from sheep experimentally infected with E. phagocytophila were less responsive to mitogens in vitro (Woldehiwet, 1987b; Larsen et al., 1994, Gokce and Woldehiwet, 1999e).

It has been reported that some soluble factors may also affect the immunity of animals infected with E. phagocytophila (Woldehiwet and Scott, 1982f; Larsen et al., 1994). For example, Woldehiwet and Scott (1982f) showed that leukocytes infected with E. phagocytophila produced soluble factors that inhibited the in vitro migration of normal ovine leukocytes. Larsen et al.(1994) and Gokce (1998) reported some inhibitory substances in the serum of sheep infected with E. phagocytophila. When this serum sample was added to cultures the proliferative responses of normal ovine lymphocytes to PHA, Con A and PWM were significantly reduced (Gokce, 1998). Recently, Gokce (1998) indicated that E. phagocytophila induce the production of TNF-a, Nitric oxide and IL-1ß but not IL-2-like factors. Additionally, purified E. phagocytophila were also found to reduce the capability of producing IL-2-like factors by Con A-induced ovine peripheral blood lymphocytes in vitro. These authors suggested that unknown serum factors or inhibition of IL-2 production were, at least in part, responsible for the immunosuppression associated with TBF (Larsen et al., 1994; Gokce, 1998).

Infection with E. phagocytophila also appears to affect the humoral immune responses of animals to bacterial or viral antigens (Batungbacal and Scott, 1982a; Batungbacal and Scott, 1982b; Reid et al., 1986; Larsen et al., 1994). For example, antibody titres to Clostridium chauvoei and anti-toxins to Cl. tetani were found to be lower in sheep previously or concurrently infected with E. phagocytophila compared to those of control sheep inoculated with the vaccine only (Batungbacal and Scott, 1982b; Larsen et al., 1994). Similarly, sheep experimentally infected with PI-3 virus or orf virus developed significantly lower levels of antibodies than sheep infected with the virus alone and, these animals shed significantly longer and higher titres of virus than animals infected with the virus alone. In these studies, the increased severity of the viral infections was attributed to the suppressive effects of E. phagocytophila on the production of antiviral antibodies (Batungbacal and Scott, 1982a, Gokce and Woldehiwet, 1999c). In contrast, the organism was reported to have no effect on the virus-specific lymphocyte proliferation (Gokce and Woldehiwet, 1999c).

Impact: Economic

Top of page

Tick-borne fever causes important economic losses, despite the relative mildness of the clinical disease. TBF is often followed by other complications including abortion in pregnant ewes and cows (Stamp and Watt, 1950; Venn and Woodford, 1956; Wilsonet al., 1964; Jones and Davies, 1995), infertility in rams and bulls (Watson, 1964; Retief et al., 1971) and respiratory diseases (Overas, 1972; Overas et al., 1993). Generally death is rare but it may occur when the infection is complicated by other agents (Batungbacal and Scott, 1982a; Reid et al., 1986; Overas et al., 1993; Larsen et al., 1994). Additionally, lambs infected with E. phagocytophila gain less weight than normal lambs.

Zoonoses and Food Safety

Top of page

E. phagocytophila is transmitted by Ixodid ticks. The disease occurs only in domestic and wild animals. However, granulocytic ehrlichiosis, a zoonose, is known to occur in humans and animals and is also transmitted by ticks. E. phagocytophila is closely related to the agent of human granulocytic ehrlichiosis (Anderson et al., 1991; Dumler et al., 1995). It is still not clear whether the agent of human granulocytic ehrlichiosis is a new species or a strain of E. phagocytophila or E. equi.

E. phagocytophila has been detected in beripheral blood, macrophages of the body organs (Campbell et al., 1994) and in milk samples of lactating infected-cows (Pusterla et al., 1997d). Experimental transmission of E. phagocytophila to susceptible animals by oral route has been reported (Pusterla et al., 1998b) but there is no information about food safety.

Disease Treatment

Top of page

Sensitivity to drugs


The organism, Ehrlichia phagocytophila, which is reposible for tick-borne fever,is sensitive to oxytetracycline, sulphamethazine, sulphadimidine, doxycycline and a combination of trimethoprim, sulphadimidine and sulphamethylphenazole (Tuomi, 1967; Evans, 1972; Anika et al., 1986; Brodie et al., 1988). It is also relatively sensitive to chloramphenicol and tylosin but not sensitive to ampicillin and streptomycin (Tuomi, 1967; Evans, 1972; Anika et al., 1986).


Treatment and control


Short-acting oxytetracyclines are regarded as the most effective drugs at a dose of 10 mg/kg body weight when given three hours before inoculation of E. phagocytophila with the therapy continuing for the following two days (Anika et al., 1986; Brodie et al., 1986). Alternatively, long-acting tetracyclines may be used as a prophylactive measure against tick-borne fever (TBF). A dose of 20 mg/kg of a long-acting tetracycline is reported to be sufficient to prevent the development of TBF when given as early as 5 days before experimental infection with E. phagocytophila (Evans, 1972; Brodie et al., 1988). Treatment of TBF-infected animals with long-acting or short-acting oxytetracyclines resulted in the rapid suppression of fever and rickettsaemia. However, animals treated with long-acting tetracyclines were reported to be non-immune to subsequent challenge (Brodie et al., 1988). When susceptible animals are moved to from tick-free to tick-infested areas, a combination of dipping and administration of long-acting tetracyclines before the onset of fever may help to the animals to adapt to the area without contracting from the disease. Unfortunately, a vaccine has not been developed, but susceptible animals may have deliberately infected and treated with long acting oxytetracyclines before the onset of fever which allows the stimulation of the animal’s immune system by the organisms (Woldehiwet and Scott, 1993).

Prevention and Control

Top of page

Innate resistance


Some degree of innate resistance related to age and breed has been reported (Tuomi, 1966; Stuen et al., 1992; Pusterla and Braun, 1997). Stuen et al. (1992) found that lambs are more resistant to experimental infection than adult sheep.

Tuomi (1966) reported that tick-borne fever (TBF) was more common in some breeds of Finnish cattle than in other breeds. Experimental infection with the feral goat isolate resulted in more severe clinical disease in Anglo-Nubian goats than in other goat breeds (Ramsden and Scott,1985). Pusterla and Braun (1997) also showed that lactating cows developed more severe clinical disease than dry cows.


Acquired immunity


Animals exposed to the organism develop a degree of protective immunity. The degree of protection has been reported as variable and depending on the strain of the organism, the type and age of the host and the time and frequency of challenge (Tuomi, 1966; Snodgrass and Ramachandran, 1971; Woldehiwet and Scott, 1982d; Webster and Mitchell, 1988).

The duration of immunity is a matter of controversy. While some workers reported that, under field conditions, a primary infection with E. phagocytophila invariably fails to protect sheep and cattle against challenge 3 months after primary infection (Hudson, 1950; Jamieson, 1947), other workers reported solid immunity which may last for more than one year (LittleJohn, 1950). Woldehiwet and Scott (1982d) found that some animals are immune for a few months while others are immune for over 12 months. The duration of immunity is reported to be related to the carrier state and the level of humoral antibodies (Woldehiwet and Scott, 1982d). For example, sheep challenged with E. phagocytophila when their reciprocal complement fixing (CF) antibody titres were above 4 log2 did not react clinically irrespective of the time between first exposure and challenge (Woldehiwet and Scott, 1982d). When they were challenged after the reciprocal CF antibody titres had dropped below 4 log2 they reacted with rickettsaemia with or without fever (Woldehiwet and Scott, 1982d).


Humoral immune responses


Several serological methods such as the indirect immunofluorescent test (IFAT) (Paxton and Scott, 1989; Hardeng, 1991), the complement fixation test (CFT) (Snodgrass and Ramachandran, 1971; Woldehiwet and Scott, 1982d) and counter immunoelectrophoresis (CIEP) (Webster and Mitchell, 1988) have been used to detect antibodies against E. phagocytophila.

Experimental studies revealed that humoral antibodies against E. phagocytophila appear in ovine serum as early as 7 to 11 days after experimental infection with the organism and persist for 6 to 10 weeks after inoculation (Woldehiwet and Scott, 1982d; Webster and Mitchell, 1988; Paxton and Scott, 1989; Larsen et al., 1994). Woldehiwet and Scott (1982d) reported that both IgM and IgG antibodies appear in the sera of sheep within two weeks of experimental infection with E. phagocytophila (Woldehiwet and Scott, 1982d). The IgM antibodies are predominant for the first three weeks, the IgG antibodies being predominant thereafter. High levels of IgM-antibodies persist in carriers (Woldehiwet and Scott, 1982d).


Cellular immune responses



The humoral immune responses of E. phagocytophila-infected animals are relatively well-established. However, studies on the cell-mediated immunity of E. phagocytophila-infected animals are very limited. Recently, antigen-specific lymphocyte proliferation was detected in ovine lymphocyte samples obtained 11 to 21 days post-inoculation with E. phagocytophila (Gokce and Woldehiwet, 1999e). Gokce (1998) revealed that E. phagocytophila also induce the production of TNF-a, IL-1ß and nitric oxide in vivo and in vitro. However, the organism did not induce the production of IL-2 in vivo and in vitro. Additionally, E. phagocytophila even inhibits the production of IL-2 by Con A-induced ovine lymphocytes in vitro(Gokce, 1998). It is suggested that TNF-a and nitric oxide play a role on the killing of E. phagocytophila as these substances are known to kill several rickettsiae (Manor and Sarov, 1990; Feng et al., 1994, Turco and Winkler, 1994). The inhibitory effect of the organism on the production of IL-2 in vivo and in vitro may explain poor proliferative lymphocyte responses to E. phagocytophila or mitogens observed in E. phagocytophila infected animals (Woldehiwet 1987b; Gokce and Woldehiwet, 1999e).

References

Top of page

Alberdi MP; Walker AR; Urquhart KA, 2000. Field evidence that roe deer (Capreolus capreolus) are a natural host for Ehrlichia phagocytophila. Epidemiology and Infection, 124(2):315-323; 40 ref.

Anderson BE; Dawson JE; Jones DC; Wilson KH, 1991. Ehrlichia chaffeensis, a new species associated with human ehrlichiosis. Journal of Clinical Microbiology, 29(12):2838-2842; 20 ref.

Anika SM; Nouws JFM; Gogh Hvan; Nieuwenhuijs J; Vree TB; Miert ASJPAMvan, 1986. Chemotherapy and pharmacokinetics of some antimicrobial agents in healthy dwarf goats and those infected with Ehrlichia phagocytophila (tick-borne fever). Research in Veterinary Science, 41(3):386-390; 20 ref.

Bakken JS, Dumler JS et al. , 1994. Human granulocytic ehrlichiosis in the upper Midwest United States; A new species emerging? Journal of American Medical Association, 272(3):212-218.

Bakken JS; Krueth J; Tilden RL; Dumler JS; Kristiansen BE, 1996. Serological evidence of human granulocytic ehrlichiosis in Norway. European Journal of Clinical Microbiology & Infectious Diseases, 15(10):829-832; 12 ref.

Barlough JE, Madigan JE et al. , 1997. An Ehrlichia strain from llama (Lama glama) and llama-associated ticks (Ixodes pacificus). Journal of Clinical Microbiology, 35(4):1005.1007.

Barlough JE; Madigan JE; Kramer VL; Clover JR; Hui LT; Webb JP; Vredevoe LK, 1997. Ehrlichia phagocytophila genogroup rickettsiae in ixodid ticks from California collected in 1995 and 1996. Journal of Clinical Microbiology, 35(8):2018-2021; 35 ref.

Batungbacal MR; Scott GR, 1982. Suppression of the immune response to clostridial vaccine by tick-borne fever. Journal Comparative Pathology, 92:409-413.

Batungbacal MR; Scott GR, 1982. Tick-borne fever and concurrent parainfluenza-3 virus infection in sheep. Journal Comparative Pathology, 92:415-428.

Batungbacal MR; Scott GR; Burrels C, 1982. The lymphocytopenia in tick-borne fever. Journal Comparative Pathology, 92:403-407.

Beisel WR, 1977. Zinc metabolism in infection. In: Alan R, ed. Zinc Metabolism: Current Aspects in Health and Diseases. New York, USA: Willey-Liss, 155-176.

Belongia EA; Reed KD; Mitchell PD; Kolbert CP; Persing DH; Gill JS; Kazmierczak JJ, 1997. Prevalence of granulocytic Ehrlichia infection among white-tailed deer in Wisconsin. Journal of Clinical Microbiology, 35(6):1465-1468; 24 ref.

Bjoersdorff A, Berglund J et al. , 1999. Varying clinical picture and course of human granulocytic ehrlichiosis. Twelve Scandinavian cases of the new tick-borne zoonosis are presented. Lakartidningen, 96(39):4200-4204.

Bovarnick MN; Miller JC; Synder JC, 1950. The influence of certain salts, amino acids, sugars and proteins on the stability of rickettsiae. Journal of Bacteriology, 59:509-522.

Brodie TA; Holmes PH; Urquhart GM, 1986. Some aspects of tick-borne diseases of British sheep. Veterinary Record, 118(15):415-418; 32 ref.

Brodie TA; Holmes PH; Urquhart GM, 1988. Prophylactic use of long-acting tetracycline against tick-borne fever (Cytoecetes phagocytophila) in sheep. Veterinary Record, 122(2):43-44; 11 ref.

Brun-Hansen H; GrOnstol H; Hardeng F, 1998. Experimental infection with Ehrlichia phagocytophila in cattle. Journal of Veterinary Medicine. Series B, 45(4):193-203; 42 ref.

Campbell RSF; Rowland AC; Scott GR, 1994. Sequential pathology of tick-borne fever. Journal of Comparative Pathology, 111(3):303-313; 13 ref.

Chen ShengMin; Dumler JS; Bakken JS; Walker DH, 1994. Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease. Journal of Clinical Microbiology, 32(3):589-595; 27 ref.

Cinco M; Padovan D; Murgia R; Heldtander M; Engvall EO, 1998. Detection of HGE agent-like Ehrlichia in Ixodes ricinus ticks in northern Italy by PCR. Wiener Klinische Wochenschrift, 110(24):898-900; 10 ref.

Cinco M; Padovan D; Murgia R; Maroli M; Frusteri L; Heldtander M; Johansson KE; Engvall EO, 1997. Coexistence of Ehrlichia phagocytophila and Borrelia burgdorferi sensu lato in Ixodes ricinus ticks from Italy as determined by 16S rRNA gene sequencing. Journal of Clinical Microbiology, 35(12):3365-3366; 13 ref.

Clark AM; Hopkins GF; MacLean IA, 1996. Tick-borne fever in dogs. Veterinary Record, 139(11):268; 2 ref.

Clemens DL; Horwitz MA, 1996. The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accesible to exogenously administered transferrin. Journal of Experimental Medicine, 184:1349-1355.

Collins JO; Hanna J; Ferguson AR; Wilson JO, 1970. Tick-borne fever in Ireland. Irish Veterinary Journal, 24:162-166.

Corcaci DC, 1998. An update on human ehrlichiosis. Revista Medico-Chirurgicala a societatii de Medici Si Naturalisti Din Iasi, 102(3-4):65-68.

Dinerallo CA, 1989. Interleukin and its biologically related cytokines. Advances in Immunology, 44:153-205.

Dinerallo CA; Cannon JG; Wolff SM, 1988. New concepts on the pathogenesis of fever. Reviews of Infectious Diseases, 10:168-189.

Dubinina EV; Alekseev AN, 1999. The biodiversity dynamics of the causative agents of diseases transmitted by tick in the genus Ixodes; an analysis of multiyear data. Journal of Medical Parasitology, 2:13-9.

Dumler JS, 1997. Is human granulocytic ehrlichiosis a new Lyme disease? Review and comparison of clinical, laboratory, epidemiological, and some biological features. Clinical Infectious Diseases, 25(Suppl. 1):S43-S47; 54 ref.

Dumler JS; Asanovich KM; Bakken JS; Richter P; Kimsey R; Madigan JE, 1995. Serologic cross-reactions among Ehrlichia equi, Ehrlichia phagocytophila, and human granulocytic ehrlichia. Journal of Clinical Microbiology, 33(5):1098-1103; 25 ref.

Engvall EO; Pettersson B; Persson M; Artursson K; Johansson KE, 1996. A 16S rRNA-based PCR assay for detection and identification of granulocytic Ehrlichia species in dogs, horses, and cattle. Journal of Clinical Microbiology, 34(9):2170-2174; 27 ref.

Evans AT, 1972. Preliminary observations on the chemotherapy of tick-borne fever of sheep and cattle. Transaction of the Royal Society of Tropical Medicine and Hygiene, 66:547.

Feng HM; Popov VL; Walker DH, 1994. Depletion of gamma interferon and tumor necrosis factor alpha in mice with Rickettsia conorii-infected endothelium: impairment of rickettsicidal nitric oxide production resulting in fatal, overwhelming rickettsial disease. Infection and Immunity, 62(5):1952-1960; 41 ref.

Fingerle V; Goodman JL; Johnson RC; Kurtti TJ; Munderloh UG; Wilske B, 1997. Human granulocytic ehrlichiosis in southern Germany: increased seroprevalence in high-risk groups. Journal of Clinical Microbiology, 35(12):3244-3247; 31 ref.

Fingerle V; Munderloh UG; Liegl G; Wilske B, 1999. Coexistense of ehrlichiae of phagocytophila group with Borelia burgdorferi in Ixodes ricinus from south Germany. Journal of Medical Microbiology and Immunology, 188(3):145-149.

Foggie A, 1951. Studies on the infectious agent of tick-borne fever in sheep. Journal of Pathology and Bacteriology, 63:343-347.

Foggie A, 1956. The effects of tick-borne fever on the resistance of lambs to staphylococci. Journal of Comparative Pathology, 66:278-285.

Foggie A, 1957. Further experiments on the effects of tick-borne fever infection on the susceptibility of lambs to staphylococci. Journal of Comparative Pathology, 67:369-377.

Foggie A, 1962. Studies on tick pyaemia and tick-borne fever. Symposium of the Zoological Society of London, 6:51-58.

Foggie A; Allison CJ, 1960. A note on the occurrence of tick-borne fever in cattle in Scotland with comparative studies of bovine and ovine strains of the organism. Veterinary Record, 72:767-770.

Foggie A; Lumsden WHR; Mcneillage GJC, 1966. Preservation of the infectious agent of tick-borne fever in a frozen state. Journal of Comparative Patholology, 76:413-416.

Fortier AH, Leiby DA et al. , 1995. Growth of Francisella tularensis LVS in macrophages: the acidic intracellular compartment provides essential iron required for growth. Infection and Immunity, 63:1478-1483.

Foster WNM; Cameron AE, 1968. Thrombocytopenia in sheep associated with experimental tick-borne fever infection. Journal of Comparative Pathology, 78:251-254.

Foster WNM; Cameron AE, 1970. Observations on ovine strains of tick-borne fever. Journal of Comparative Pathology, 80:429-436.

Foster WNM; Cameron AE, 1970. Observations on the functional integrity of neutrophil leucocytes infected with tick-borne fever. Journal of Comparative Pathology, 80:487-491.

Foster WNM; Cameron AE; Nisbet DI, 1968. Haemorrhagic enteritis in sheep experimentally infected with tick-borne fever. Journal of Comparative Pathology, 78:255-258.

Foster WNM; Greig JC, 1969. Isolation of tick-borne fever from feral goats in New Galloway. Veterinary Record, 85:585-586.

Gilmour NJL; Brodie TA; Holmes PH, 1982. Tick-borne fever and pasteurellosis in sheep. Veterinary Record, 111:512.

Gilot B; Perez-Eid C, 1998. Bioecology of ticks causing the most important pathology in France. Médecine et Maladies Infectieuses, 28(5, Special):325-334; 83 ref.

Gokce HI, 1998. Studies on the effect Ehrlichia (Cytoecetes) phagocytophila on some cellular immune responses in sheep. PhD Thesis, University of Liverpool, UK.

Gokce HI; Ross G; Woldehiwet Z, 1999. Inhibition of phagosome-lysosome fusion in ovine polymorphonuclear leucocytes by Ehrlichia (Cytoecetes) phagocytophila. Journal of Comparative Pathology, 120(4):369-381; 36 ref.

Gokce HI; Woldehiwet Z, 1999. Differential haematological effects of tick-borne fever in sheep and goats. Journal of Veterinary Medicine. Series B, 46(2):105-115; 42 ref.

Gokce HI; Woldehiwet Z, 1999. Ehrlichia (Cytoecetes) phagocytophila predisposes to severe contagious ecthyma (orf) in lambs. Journal of Comparative Pathology, 121(3):227-240; 31 ref.

Gokce HI; Woldehiwet Z, 1999. Lymphocyte responses to mitogens and rickettsial antigens in sheep experimentally infected with Ehrlichia (Cytoecetes) phagocytophila. Veterinary Parasitology, 83(1):55-64; 27 ref.

Gokce HI; Woldehiwet Z, 1999. The effects of Ehrlichia (Cytoecetes) phagocytophila on the clinical chemistry of sheep and goats. Journal of Veterinary Medicine. Series B, 46(2):93-103; 53 ref.

Goodman JL, Curtis Nelson BA et al. , 1996. Direct cultivation of the causative agent of human granulocytic ehrlichiosis. New England Journal of Medicine, 334(4):209-215.

Gordon WS; Brovnlee A; Wilson DR; Macleod J, 1932. Tick-borne fever (a hitherto undescribed disease of sheep). Journal of Comparative Pathology, 45:301-312.

Gordon WS; Brownlee A; Wilson DR, 1940. Studies in louping ill, tick-borne fever and scrapie. Proceedings of the Third International Congress of Microbiology, New York, pp 362-363.

Gordon WS; Brownlee A; Wilson DR; Macleod J, 1962. The epizootology of louping ill and tick-borne fever with observations on the control of these sheep diseases. Symposium of the Zoological Society of London, 6:1-27.

Gray D; Webster K; Berry JE, 1988. Evidence of louping ill and tick-borne fever in goats. Veterinary Record, 122(3):66; 9 ref.

Gronstol H; Ulvand MJ, 1977. Listeric septicemia in sheep associated with tick-borne fever. Acta Veterinary Scandinavia, 18: 575-577.

Hardeng F, 1991. A modification of the indirect immunofluorescence test for detection of Ehrlichia phagocytophila antibodies. Acta Veterinaria Scandinavica, 32(4):499-502; 8 ref.

Heinzen RA; Scidmore MA; Rockey DD; Hackstadt T, 1996. Differential interaction with endocytic and exocytic pathways distinguish parasitophorous vacuoles of Coxiella burnetii and Chlamydia trachomatis. Infection and Immunity, 64(3):796-809; 45 ref.

Hinaidy; HK, 1973. Wiener Tierarzliche Monatsschrift, Abstracted in The Veterinary Journal, 44:292-364-366.

Hudson JR, 1950. The recognition of tick-borne fever as a disease of cattle. British Veterinary Journal, 106:3-17.

Jamieson S, 1947. Some aspects of immunty to tick-borne fever in hogg. Veterinary Record, 59:201- 202.

Jones GL; Davies IH, 1995. An ovine abortion storm caused by infection with Cytoecetes phagocytophila. Veterinary Record, 136(5):127; 4 ref.

Jongejan F, Wassix LA et al. , 1989. Serotype of Cowdria ruminantium and relationship with Ehrlichia phagocytophila determined by immunofluorescence. Veterinary Microbiology, 21(1):31-40.

Juste RA; Scott GR; Paxton EA; Gelabert JL; Jiménez S, 1989. Presence of Cytoecetes phagocytophila in an atypical disease of cattle in Spain. Veterinary Record, 124(24):636; 8 ref.

Korbutiak E; Schneiders DH, 1994. First confirmed case of equine ehrlichiosis in Great Britain. Equine Veterinary Education, 6(6):303-304; 13 ref.

Larsen HJS; Overnes G; Waldeland H; Johansen GM, 1994. Immunosuppression in sheep experimentally infected with Ehrlichia phagocytophila. Research in Veterinary Science, 56(2):216-224; 39 ref.

Lepidi H, Bunnell JE et al. , 2000. Comparative pathology and immunohistology associated with clinical illness of Ehrlichia phagocytophila-group infections. American Journal of Tropical Medicine and Hygiene, 62(1):29-37.

Levin ML; Fish D, 2000. Acquisition of coinfection and simultaneous transmission of Borelia burgdorferi and Ehrlichia phagocytophila by Ixodes scapularis ticks. Journal of Infection and Immunity, 68(4):2183-2186.

Littlejohn AI, 1950. Tick-borne fever as a cause of abortion in sheep. Veterinary Record, 62:577-579.

Macleod J, 1932. Preliminary studies in tick transmission of louping ill. II. A study of the reaction of sheep to tick infestation. Veterinary Journal, 88:276-284.

Macleod J, 1936. Studies on tick-borne fever of sheep. II Experiment on transmission and distribution of the disease. Parasitology, 28:320-329.

Macleod J; Gordon WS, 1933. Studies on tick borne fever of sheep.1. Transmission by the tick-Ixodes ricinus with a description of the disease produced. Parasitology, 25:273-283.

Manor E; Sarov I, 1990. Inhibition of Rickettsia conorii growth by recombinant tumor necrosis factor alpha: Enhancement of inhibition by gamma interferon. Infection and Immunity, 58:1886-1890.

Mcdiarmid A, 1965. Modern trends in animal health and husbandry. Some infectioun diseases of free-living wild-life. British Veterinary Journal, 121:245-257.

Mceben AD, 1947. Tick-borne fever in young lambs. Veterinary Record, 59:198-201.

Miert ASJPAMvan; Duin CTMvan; Schotman AJH; Franssen FF, 1984. Clinical, haematological and blood biochemical changes in goats after experimental infection with tick-borne fever. Veterinary Parasitology, 16(3/4):225-233; 29 ref.

Miert ASJPAMvan; Duin CTMvan; Wensing T, 1990. Fever and changes in plasma zinc and iron concentrations in the goat. The effects of interferon inducers and recombinant IFN-. Journal of Comparative Pathology, 103(3):289-300; 43 ref.

Munderloh UG; Madigan JE; Dumler JS; Goodman JL; Hayes SF; Barlough JE; Nelson CM; Kurtti TJ, 1996. Isolation of the equine granulocytic ehrlichiosis agent, Ehrlichia equi, in tick cell culture. Journal of Clinical Microbiology, 34(3):664-670; 48 ref.

Munro R; Hunter AR; Mackenzie G; Mcmartin DA, 1982. Pulmonary lesion in sheep following experimental infection by Ehrlichia phagocytophila and Chlamydia psittaci. Journal of Comparative Pathology, 92:117-129.

Ogden NH; Bown K; Horrocks BK; Woldehiwet Z; Bennett M, 1998. Granulocytic Ehrlichia infection in ixodid ticks and mammals in woodlands and uplands of the UK. Medical and Veterinary Entomology, 12(4):423-429; 32 ref.

Ogden NH; Woldehiwet Z; Hart CA, 1998b. Granulocytic ehrlichiosis: an emerging or rediscovered tick-borne disease?. Journal of Medical Microbiology, 47(6):475-482; 61 ref.

Oteo JA; Blanco JR; Martinez de Artala V; Ibarra V, 2000. First report of human granulocytic ehrlichiosis from southern Europe (Spain). Emerging Infectious Diseases, 6(4):430-432.

Overas J, 1959. Tick-borne fever. Some arsak til abort hos. Nordisk. Veterinaer Medicin, 11:475-482.

Overas J, 1972. Studies on immunity to tick-borne fever. Disease in sheep kept on Ixodes ricinus infected pastures. Nordisk Veterinaer Medicin, 83:561-567.

OverÅs J; Lund A; Ulvund MJ; Waldeland H, 1993. Tick-borne fever as a possible predisposing factor in septicaemic pasteurellosis in lambs. Veterinary Record, 133(16):398; 9 ref.

Parola P; Beati L; Cambon M; Brouqui P; Raoult D, 1998. Ehrlichial DNA amplified from Ixodes ricinus (Acari: Ixodidae) in France. Journal of Medical Entomology, 35(2):180-183; 14 ref.

Paxton EA; Scott GR, 1989. Detection of antibodies to the agent of tick-borne fever by indirect immunofluorescence. Veterinary Microbiology, 21(2):133-138; 8 ref.

Petrovec M; Furlan SL; Zupanc TA; Strle F; Brouqui P; Roux V; Dumler JS, 1997. Human disease in Europe caused by a granulocytic Ehrlichia species. Journal of Clinical Microbiology, 35(6):1556-1559; 22 ref.

Pfister K; Roesti A; Boss PH; Balsiger B, 1987. Ehrlichia phagocytophila as the cause of "pasture fever", a tickborne fever of cattle in the Bernese Oberland of Switzerland. Schweizer Archiv für Tierheilkunde, 129(7):343-347; 13 ref.

Purnell RE; Young ER; Brocklesby DW; Henry DJ, 1977. The haematology of experimentally-induced B. divergens and E. phagocytophila infections in splenectomized calves. Veterinary Record, 99:415-417.

Pusterla N; Braun U, 1997. Clinical findings in cows after experimental infection with Ehrlichia phagocytophila. Journal of Veterinary Medicine. Series A, 44(7):385-390; 17 ref.

Pusterla N; Braun U; Wolfensberger C; Lutz H, 1997. Intrauterine infection with Ehrlichia phagocytophila in a cow. Veterinary Record, 141(4):101-102; 24 ref.

Pusterla N; Deplazes P; Braun U; Lutz H, 1999. Serological evidence of infection with Ehrlichia spp. in red foxes (Vulpes vulpes) in Switzerland. Journal of Clinical Microbiology, 37(4):1168-1169; 15 ref.

Pusterla N; Huder J; Wolfensberger C; Braun U; Lutz H, 1997. Laboratory findings in cows after experimental infection with Ehrlichia phagocytophila. Clinical and Diagnostic Laboratory Immunology, 4(6):643-647; 28 ref.

Pusterla N; Huder J; Wolfensberger C; Litschi B; Parvis A; Lutz H, 1997. Granulocytic ehrlichiosis in two dogs in Switzerland. Journal of Clinical Microbiology, 35(9):2307-2309; 15 ref.

Pusterla N; Huder J; Wolfensberger C; Lutz H; Braun U, 1998. Experimental oral transmission of Ehrlichia phagocytophila to calves. Veterinary Record, 143(9):250-251; 12 ref.

Pusterla N; Weber R; Wolfensberger C; Schär G; Zbinden R; Fierz W; Madigan JE; Dumler JS; Lutz H, 1998. Serological evidence of human granulocytic ehrlichiosis in Switzerland. European Journal of Clinical Microbiology & Infectious Diseases, 17(3):207-209; 12 ref.

Pusterla N; Wolfensberger C; Gerber-Bretscher R; Lutz H, 1997. Comparison of indirect immunofluorescence for Ehrlichia phagocytophila and Ehrlichia equi in horses. Equine Veterinary Journal, 29(6):490-492; 18 ref.

Raghavachari K; Reddy AMK, 1959. Cytoecetes ovis var deccani (nsp.) as the cause of tick-borne fever in sheep in India. Indian Journal of Veterinary Science, 29:69-86.

Ramsden EK; Scott GR, 1985. Tick-borne fever in goats. In Newsletter, Centre for Tropical Veterinary Medicine, Royal (Dick) School of Veterinary Studies, Edinburgh, UK, 40:10.

Rathman M; Barker LC; Falkow S, 1997. The unique trafficking pattern of Salmonella typhimurium-containing phagosomes in murine macrophages is independent of the mechanism of bacterial entry. Infection and Immunity, 65:1475-1485.

Reid HW; Buxton D; Pow I; Brodie TA; Holmes PH; Urquhart GM, 1986. Response of sheep to experimental concurrent infection with tick-borne fever (Cytoecetes phagocytophila) and louping-ill virus. Research in Veterinary Science, 41(1):56-62; 24 ref.

Retief GP; Neitz WO; Mcfarlane IS, 1971. Observations on the effect of tick-borne fever (Cytoecetes phagocytophila, Foggie, 1949) on the spermatogenesis of bulls. Journal of the South African Veterinary Medical Association, 42(4):321-325.

Rhotwell NJ; Busbridge NJ, 1990. Central actions of interleukin-1ß on fever and thermogenesis. In: Dinerallo CA, Kluger MJ, Powanda MC, Oppenheim JJ, eds. The physiological and pathological effects of cytokines. New York, USA: Willey-liss, 307-311.

Ristic M; Huxsoll DL, 1984. Tribe Ehrlichieae (Philip 1954). In: Kreig NR, Holt JG, eds. Bergey's Manual of Systematic Bacteriology, Baltimore USA: Williams and Wilkins, 704-710.

Schotman AJH, 1982. Endotoxin-induced fever and associated haematological and blood biochemical changes in the goat: The effect of repeated administration and the influence of flurbiprofen. Research in Veterinary Science, 33:248-255.

Scott GR; Horsburgh D, 1983. New rickettsial isolates. In: Newsletter, Centre for Tropical Veterinary Medicine, Royal (Dick) School of Veterinary Studies. 34:9.

Siebinga JT; Jongejan F, 2000. Tick-borne fever (Ehrlichia phagocytophila infection) on a dairy farm in Friesland. Tijdschr Diergeneeskd, 125(3):74-80.

Snodgrass DR, 1974. Studies on bovine petechial fever and ovine tick-borne fever. PhD. Thesis, University of Edinburgh.

Snodgrass DR; Ramachandran S, 1971. A complement fixation test for tick-borne fever in sheep. British Veterinary Journal, 127:xliv-xlvi.

Sreekumar C; Anandan R; Balasundaram S; Rajavelu G, 1996. Morphology and staining characteristics of Ehrlichia bovis. Comparative Immunology, Microbiology and Infectious Diseases, 19(1):79-83; 17 ref.

Stamp JT; Watt JA, 1950. Tick-borne fever as a cause of abortion in sheep-Part I. Veterinary Record, 62:465-468.

Stuen S, 1993. Tick-borne fever in lambs of different ages. Acta Veterinaria Scandinavica, 34(1):45-52; 23 ref.

Stuen S; Hardeng F; Larsen HJ, 1992. Resistance to tick-borne fever in young lambs. Research in Veterinary Science, 52(2):211-216; 16 ref.

Sumner JW; Nicholson WL; Massung RF, 1997. PCR amplification and comparison of nucleotide sequences from the groESL heat shock operon of Ehrlichia species. Journal of Clinical Microbiology, 35(8):2087-2092; 49 ref.

Sumption KJ; Wright DJM; Cutler SJ; DaleBAS, 1995. Human ehrlichiosis in the UK. Lancet (British edition), 346(8988):1487-1488; 5 ref.

Synge BA, 1976. Chemotherapeutic studies on tick-borne fever and heart-water. Master of Philosophy Thesis, University of Edinburgh.

Taylor AW; Holman HH; Gordon WS, 1941. Attempts to reproduce the pyemia associated with tick-bite. Veterinary Record, 24:337-344.

Thrusfield MV; Synge BA; Scott GR, 1978. Attempts to cultivate Cytoecetes phagocytophila in vitro. Veterinary Microbiology, 2:257-260.

Tuomi J, 1966. Studies on the epidemiology of bovine tick-borne fever in Finland and clinical description of field cases. Annales Medicinal Experimentalis et Biologiae Fenniae, 44:61-62.

Tuomi J, 1967. Experimental studies on bovine tick-borne fever(1) clinical and haematological data, some properties of the causative agent and homologous immunity. Acta Pathologica et Microbiologica Scandinavica, 70:429-445.

Tuomi J; Von Bonsdorff CH, 1966. Electron microscopy of tick-borne fever agent in bovine and ovine phagocytozing leucocytes. Journal of Bacteriology, 92:1478-1492.

Turco J; Winkler HH, 1994. Relationship of tumor necrosis factor alpha, the nitric oxide synthase pathway, and lipopolysaccharide to the killing of gamma interferon-treated macrophagelike RAW264.7 cells by Rickettsia prowazekii. Infection and Immunity, 62(6):2568-2574; 40 ref.

Tutt JB; Loving C, 1955. Tick-borne fever in dairy cattle. Veterinary Record, 67:866.

Unruh DHA, 1977. Disseminated intravenous coagulation, a study into the possible pathogenesis of tick-borne fever. MSc. Thesis, University of Edinburgh.

Van der Valk P; Herman CJ, 1987. Biology of disease. Leucocyte functions. Laboratory Investigations, 56:127-137.

Van Miert ASJPAM, Van Duin CTM et al. , 1983. Staphylococcal enterotoxin B and Escherichia coli endotoxin: Comparative observations in goats on fever and associated clinical haematologic and blood biochemical changes after intravenous and intramammary administration. American Journal of Veterinary Research, 44:955-963.

Van Miert ASJPAM; Van Duin CTM, 1982. Endotoxin-induced fever and associated haematological and blood biochemical changes in the goat: the effect of repeated administration and the influence of flurbiprofen. Research in Veterinary Science. 33:248-255.

Venn JAJ; Woodford MH, 1956. An outbreak of tick-borne fever in ovines. Veterinary Record, 68:132-133.

Verheijden JHM, Van Miert ASJPAM et al. , 1982. Plasma zinc and iron concentrations as measurements for evaluating the influence of endotoxin-neutralizing agents in Escherichia coli endotoxin-induced mastitis. American Journal of Veterinary Research, 43:724-728.

Vignes Fdes; Fish D, 1997. Transmission of the agent of human granulocytic ehrlichiosis by host-seeking Ixodes scapularis (Acari: Ixodidae) in southern New York State. Journal of Medical Entomology, 34(4):379-382; 10 ref.

Waner T; Baneth G; Strenger C; Keysary A; King R; Harrus S, 1999. Antibodies reactive with Ehrlichia canis, Ehrlichia phagocytophila genogroup antigens and the spotted fever group rickettsial antigens, in free-ranging jackals (Canis aureus syriacus) from Israel. Veterinary Parasitology, 82(2):121-128; 28 ref.

Watson WA, 1964. Infertility in the ram associated with tick-borne fever. Veterinary Record, 7:1131-1136.

Webster KA; Mitchell GBB, 1988. Use of counter immunoelectrophoresis in detection of antibodies to tickborne fever. Research in Veterinary Science, 45(1):28-30; 16 ref.

Webster KA; Mitchell GBB, 1989. An electron microscopic study of Cytoecetes phagocytophila infection in Ixodes ricinus.. Research in Veterinary Science, 47(1):30-33; 19 ref.

Wells MY; Rikihisa Y, 1988. Lack of lysosomal fusion with phagosomes containing Ehrlichia risticii in P388D cells: abrogation of inhibition with oxytetracycline. Infection and Immunity, 56(12):3209-3215; 11 ref.

Wilson JE; Foggie A; Carmichael MA, 1964. Tick-borne fever as a cause of abortion and still-births in cattle. Veterinary Record, 76:1081-1084.

Woldehiwet Z, 1981. Observations on the immune responses of sheep infected with Cytoecetes phagocytophila. PhD. Thesis, University of Edinburgh, UK.

Woldehiwet Z, 1983. Tick-borne fever: a review. Veterinary Research Communications, 6(3):163-175.

Woldehiwet Z, 1987. Depression of lymphocyte response to mitogens in sheep infected with tick-borne fever. Journal of Comparative Pathology, 97(6):637-643; 16 ref.

Woldehiwet Z, 1987. The effects of tick-borne fever on some functions of polymorphonuclear cells of sheep. Journal of Comparative Pathology, 97(4):481-485; 15 ref.

Woldehiwet Z, 1991. Lymphocyte subpopulations in peripheral blood of sheep experimentally infected with tick-borne fever. Research in Veterinary Science, 51(1):40-43; 11 ref.

Woldehiwet Z; Dare C; Carter SD, 1993. The effects of tick-borne fever on the susceptibility of ovine polymorphonuclear cells to P. haemolytica cytotoxin. Journal of Comparative Pathology, 109(3):303-307; 20 ref.

Woldehiwet Z; Scott GR, 1982. Corticosteroid therapy of tick-borne fever. Veterinary Record, 110:151-152.

Woldehiwet Z; Scott GR, 1982. Differentiation of strains of Cytoecetes phagocytophila, the causative agent of tick-borne fever, by complement fixation. Journal of Comparative Patholology, 92(3):475-478.

Woldehiwet Z; Scott GR, 1982. Immunological studies on tick-borne fever in sheep. Journal of Comparative Pathology, 92:457-467.

Woldehiwet Z; Scott GR, 1982. In vitro propagation of Cytoecetes phagocytophila, The causative agent of tick-borne fever. Veterinary Microbiology, 7(2):127-133.

Woldehiwet Z; Scott GR, 1982. Stages in development of Cytoecetes phagocytophila, the causative agent of tick-borne fever. Veterinary Microbiology, 92(3):469-474.

Woldehiwet Z; Scott GR, 1982. Tick-borne fever: Leucocyte migration inhibition. Veterinary Microbiology, 7(5):437-455.

Woldehiwet Z; Scott GR, 1993. Tick-borne (Pasture) fever. In: Woldehiwet Z, Ristic M, eds. Rickettsial and Chlamydial diseases of domestic animals. Oxford, UK: Peramon Press, pp 233-254.

Distribution References

Barlough J E, Madigan J E, Kramer V L, Clover J R, Hui L T, Webb J P, Vredevoe L K, 1997. Ehrlichia phagocytophila genogroup rickettsiae in ixodid ticks from California collected in 1995 and 1996. Journal of Clinical Microbiology. 35 (8), 2018-2021.

CABI, Undated. Compendium record. Wallingford, UK: CABI

CABI, Undated a. CABI Compendium: Status inferred from regional distribution. Wallingford, UK: CABI

CABI, Undated b. CABI Compendium: Status as determined by CABI editor. Wallingford, UK: CABI

Cinco M, Padovan D, Murgia R, Heldtander M, Engvall E O, 1998. Detection of HGE agent-like Ehrlichia in Ixodes ricinus ticks in northern Italy by PCR. In: Wiener Klinische Wochenschrift [Lyme borreliosis. Papers from "Pathogenesis and management of tick-borne diseases" held in Vienna, Austria, 28-30 September, 1998.], 110 (24) 898-900.

Cinco M, Padovan D, Murgia R, Maroli M, Frusteri L, Heldtander M, Johansson K E, Engvall E O, 1997. Coexistence of Ehrlichia phagocytophila and Borrelia burgdorferi sensu lato in Ixodes ricinus ticks from Italy as determined by 16S rRNA gene sequencing. Journal of Clinical Microbiology. 35 (12), 3365-3366.

Collins J D, Hannan J, Ferguson A R, Wilson J O, 1970. Tick-borne fever in Ireland. Irish Veterinary Journal. 162-166.

Dubinina EV, Alekseev AN, 1999. The biodiversity dynamics of the causative agents of diseases transmitted by tick in the genus Ixodes; an analysis of multiyear data. In: Journal of Medical Parasitology, 2 13-9.

Engvall E O, Pettersson B, Persson M, Artursson K, Johansson K E, 1996. A 16S rRNA-based PCR assay for detection and identification of granulocytic Ehrlichia species in dogs, horses, and cattle. Journal of Clinical Microbiology. 34 (9), 2170-2174.

Fingerle V, Munderloh UG, Liegl G, Wilske B, 1999. Coexistense of ehrlichiae of phagocytophila group with Borelia burgdorferi in Ixodes ricinus from south Germany. In: Journal of Medical Microbiology and Immunology, 188 (3) 145-149.

Gilot B, Perez-Eid C, 1998. Bioecology of ticks causing the most important pathology in France. (Bio-écologie des tiques induisant les pathologies les plus importantes en France.). In: Médecine et Maladies Infectieuses [7e Colloque sur le Contrôle Epidémiologique des Maladies Infectieuses. Institut Pasteur de Paris, France, 29 mai 1998.], 28 (5, Special) 325-334. DOI:10.1016/S0399-077X(98)70217-3

HUDSON J R, 1950. The recognition off tick-borne fever as a disease of cattle. British Veterinary Journal. 3-17.

Juste R A, Scott G R, Paxton E A, Gelabert J L, Jiménez S, 1989. Presence of Cytoecetes phagocytophila in an atypical disease of cattle in Spain. Veterinary Record. 124 (24), 636.

Ogden N H, Bown K, Horrocks B K, Woldehiwet Z, Bennett M, 1998. Granulocytic Ehrlichia infection in ixodid ticks and mammals in woodlands and uplands of the UK. Medical and Veterinary Entomology. 12 (4), 423-429. DOI:10.1046/j.1365-2915.1998.00133.x

Overas J, 1959. Tick-borne fever as the cause of abortion in ewes. (Tick-Borne Fever (sjodogg) som arsak til abort hos sau.). Nordisk Veterinaermedicin. 475-482.

Pfister K, Roesti A, Boss P H, Balsiger B, 1987. Ehrlichia phagocytophila as the cause of "pasture fever", a tickborne fever of cattle in the Bernese Oberland of Switzerland. (Ehrlichia phagocytophila als Erreger des "Weidefiebers" im Berner Oberland.). Schweizer Archiv für Tierheilkunde. 129 (7), 343-347.

Raghavachari K, Reddy A M K, 1959. Cytoecetes ovis var. deccani (n. sp.) as the cause of tick-borne fever in sheep in India. Indian Journal of Veterinary Science. 29 (2 & 3), 69-86 pp.

Retief G P, Neitz W O, McFarlane I S, 1971. Observations on the effect of tick-borne fever (Cytoecetes phagocytophila Foggie, 1949) on the spermatogenesis of bulls. Journal of the South African Veterinary Medical Association. 42 (No.4), 321-325.

Siebinga JT, Jongejan F, 2000. Tick-borne fever (Ehrlichia phagocytophila infection) on a dairy farm in Friesland. In: Tijdschr Diergeneeskd, 125 (3) 74-80.

Tuomi J, 1966. Studies on the epidemiology of bovine tick-borne fever in Finland and clinical description of field cases. In: Annales Medicinal Experimentalis et Biologiae Fenniae, 44 61-62.

Tutt JB, Loving C, 1955. Tick-borne fever in dairy cattle. In: Veterinary Record, 67 866.

Waner T, Baneth G, Strenger C, Keysary A, King R, Harrus S, 1999. Antibodies reactive with Ehrlichia canis, Ehrlichia phagocytophila genogroup antigens and the spotted fever group rickettsial antigens, in free-ranging jackals (Canis aureus syriacus) from Israel. Veterinary Parasitology. 82 (2), 121-128. DOI:10.1016/S0304-4017(99)00002-3

Distribution Maps

Top of page
You can pan and zoom the map
Save map