Current Advice on Parasite Control:
Vector-Borne Diseases - Ehrlichia spp. and Anaplasma spp.
Ehrlichia muris-like agent
Anaplasma phagocytophilum (=Ehrlichia equi, Ehrlichia phagocytophila, human granulocytic ehrlichiosis [HGE] agent)
*Although Ehrlichia spp. and Anaplasma spp. have been reported to cause disease in cats, little is known about the prevalence of infection, disease manifestations, and treatment recommendations for feline infections with these agents.
Overview of Life Cycles
- Dogs and cats become infected with Ehrlichia spp. and Anaplasma spp. when feeding ticks inoculate the organisms. The rickettsiae enter mononuclear leukocytes(E. canis, E. chaffeensis, E. muris), granulocytes (A. phagocytophilum, E. ewingii), or presumably, platelets (A. platys), where they survive, multiply, and disseminate throughout the host.
All Ehrlichia spp. and Anaplasma spp. common to dogs and cats in the United States are maintained in a tick vector/vertebrate reservoir host system in nature.
- Ehrlichia canis is thought to cycle primarily between domestic dogs and Rhipicephalus sanguineus, the brown dog tick. However, Dermacentor variabilis, the American dog tick, has also been shown to be a competent vector. Both E. ewingii and E. chaffeensis are thought to be maintained primarily in a cycle between white-tailed deer and Amblyomma americanum, the lone star tick; D. variabilis is also a potential vector of E. chaffeensis.
- Rodents are considered the main reservoir host of A. phagocytophilum although a wide variety of mammals are susceptible to infection. Infection with A. phagocytophilum is transmitted by Ixodes scapularis in the northeastern and upper Midwest and by Ixodes pacificus in the western United States. An E. muris-like pathogen was recently detected in people, a dog, and ticks from the upper Midwestern U.S.; this monocytotropic pathogen appears to use the same reservoir and vector and as A. phagocytophilum. The maintenance cycle of A. platys has not been fully confirmed, but dogs are the likely reservoir host, and transmission is thought to occur via feeding of R. sanguineus.
- Morulae of Ehrlichia spp. and Anaplasma spp. occasionally can be found on Giemsa-stained blood smears inside monocytes or lymphocytes (E. canis, E. chaffeensis, E. muris-like agent), granulocytes (A. phagocytophilum, E. ewingii), or platelets (A. platys).
- Organisms are usually rare and can be found on blood smears only during acute infection; therefore, other diagnostic methods are recommended for identifying infection in dogs and cats (see Diagnosis).
- Subclinical infections with Ehrlichia spp. and Anaplasma spp. are common among dogs.
- Dogs with disease caused by infection with Ehrlichia spp. or Anaplasma spp. commonly present with fever, lethargy, depression, anorexia, and weight loss. Lymphadenopathy is occasionally seen, and petechial to ecchymotic hemorrhages or epistaxis related to thrombocytopenia may be evident. Occasionally dogs may present with neurologic disease, vomiting, or diarrhea. Ocular lesions including uveitis, chorioretinitis, and retinal detachment have been reported.
- Dogs with E. ewingii and A. phagocytophilum have been reported to develop polyarthritis and may present with stiffness, swollen joints, or reluctance to move.
- Coinfection with multiple Ehrlichia spp., Anaplasma spp., and additional tick-borne pathogens has been documented and when present, may complicate interpretation of the clinical presentation and diagnostic assays.
- Disease caused by infection with Ehrlichia spp. and Anaplasma spp. is less well characterized in cats, but fever, lethargy, anorexia, weight loss, petechiae, joint pain, dyspnea, vomiting, and diarrhea have all been described.
- Although infections with A. platys and E. chaffeensis have not commonly been associated with clinical disease in small animals, these agents may occasionally cause disease in pets. When infection is identified, treatment is warranted, particularly in light of the zoonotic threat associated with E. chaffeensis.
- Canine infection with Ehrlichia spp. and Anaplasma spp. is common throughout the world. Infection is more common in areas where tick infestation pressure is high and when routine acaricide use is not practiced. Although E. canis is perhaps the most well known of these canine pathogens, infection with E. ewingii occurs more commonly in some areas.
- The geographic distribution of Ehrlichia spp. and Anaplasma spp. closely follows that of the vector ticks responsible for transmitting the infections. Ehrlichia canis and A. platys are reported throughout the United States, much like their vector tick R. sanguineus. Ehrlichia ewingii and E. chaffeensis infections are more common in the southern United States, where dense populations of A. americanum ticks are found. However, this tick species and these agents may be present up the mid-Atlantic seaboard as far north as New England. Anaplasma phagocytophilum is most commonly found in dogs in the northeastern, upper Midwestern, and West Coast foci where populations of I. scapularis and I. pacificus, respectively, maintain infection pressure on dogs.
Host Associations and Transmission Between Hosts
- Dogs and cats become infected with Ehrlichia spp. and Anaplasma spp. upon inoculation of organisms by tick feeding. Ticks are not able to transmit infection immediately upon first attachment to a host but instead require a period of approximately 24 to 48 hours of initial feeding before organisms are able to pass across the salivary glands and into the vertebrate host.
- Direct transmission from an infected to a naïve animal is considered rare but could occur following blood transfusion or iatrogenic inoculation with contaminated needles or surgical instruments.
- Ticks acquire these infections by feeding on infected hosts, and these infections remain in ticks as they molt to different stages (i.e., through transstadial passage of the pathogens). In this way, immature tick stages that acquire infections and can transmit them when they feed during a subsequent stage. In addition, male metastriate ticks have been shown capable of both acquisition and subsequent transmission (i.e., via intrastadial pathogen passage) of some Anaplasma and Ehrlichia spp., including E. canis and E. chaffeensis. Passage of Anaplasma or Ehrlichia spp. to tick offspring (e.g., transovarian passage) has not been conclusively demonstrated with Ehrlichia or Anaplasma spp. in any of the tick species that commonly feed on dogs and cats.
Prepatent Period and Environmental Factors
- Morulae appear in circulating blood within a few weeks after the organisms are introduced by tick feeding.
- Some Ehrlichia spp. and Anaplasma spp. set up persistent infections in dogs. For example, E. canis infections have been reported to last over 10 years and, in the absence of treatment, infection may persist for the life of the dog. Although less studied, A. phagocytophilum and A. platys infections in dogs may be equally long-lived.
- Infection with E. ewingii and E. chaffeensis appears to have a more self-limiting nature in pets, persisting for several months before infections are naturally cleared. However, reinfections may commonly occur when infected ticks from the environment are able to again feed on pets.
Site of Infection and Pathogenesis
- Ticks inoculate infectious Ehrlichia spp. and Anaplasma spp. directly into the tick feeding lesion. Organisms invade circulating blood cells and disseminate via the bloodstream to peripheral tissues.
- Inflammatory processes induced by the infection result in the development of hematologic abnormalities, most notably thrombocytopenia. The thrombocytopenia associated with infection may be consistent or cyclic in nature and is thought to be associated with immune-mediated destruction of platelets as well as decreased platelet production. The low platelet counts contribute to the petechial and ecchymotic hemorrhages and other bleeding diatheses associated with disease due to infection with these pathogens.
- Classical microscopic diagnosis of Ehrlichia spp. and Anaplasma spp. infection relies on identification of morulae in circulating monocytes, neutrophils, or platelets in Giemsa-stained blood smears. However, morulae are usually difficult to find in blood smears, even during the acute stage of the disease. Cell culture isolation, which some consider a gold standard for confirming these infections, is laborious, expensive, time-consuming and available only in specialized research laboratories. Experimental cultivation from host blood has only been achieved for E. canis, E. chaffeensis, and A. phagocytophilum; E. ewingii and A. platys have yet to be isolated in cell culture.
- Serology may be helpful in identifying the presence of antibodies to Ehrlichia spp. and Anaplasma spp., but may not detect early infections during the acute phase of disease.
- Indirect fluorescent antibody (IFA) assays to determine IgM and IgG titers are available through diagnostic laboratories for those organisms that have been cultured, namely E. canis, E. chaffeensis, and A. phagocytophilum. Cross-reaction among the Ehrlichia spp. and Anaplasma spp. is commonly recognized, and nonspecific IFA titers may develop due to infection with related agents.
- A patient-side enzyme-linked immunosorbent assay (ELISA) (IDEXX 4Dx Plus SNAP) is available for identifying antibodies to E. canis, E. ewingii, A. phagocytophilum and A. platys.
- Antibody titers may persist months to years after treatment and resolution of clinical signs, suggesting either persistent infection or reinfection; this persistence has been noted particularly in E. canis infections. However, the presence of antibodies alone does not indicate a need for treatment in the absence of any evidence of clinical disease.
- In recent years, molecular diagnosis of Ehrlichia and Anaplasma infection in dogs and cats via polymerase chain reaction (PCR) of whole blood has become readily available. However, results should be interpreted with caution because the techniques used in different diagnostic laboratories vary. Amplification of related organisms by nonspecific primers has been shown to result in false-positive reactions. Conversely, apparent false-negatives may occur if extraction procedures fail to remove PCR inhibitors present in a blood sample or if the level of circulating rickettsemia falls below the level of assay detection due to a normal decrease in circulating organisms or temporary suppression of infection following antibiotic treatment. To maximize the utility of molecular diagnostics, blood samples should be collected as early as possible in the course of clinical disease, before the initiation of antimicrobial therapy, and should be submitted to experienced diagnostic laboratories with stringent quality control measures in place.
- All Ehrlichia spp. and Anaplasma spp. infections in dogs and cats respond to treatment with doxycycline. A treatment regimen of 10 mg/kg for 28 days is currently recommended. Some studies have documented failure to clear infections in dogs, expecially with shorter courses of therapy.
- Protective immunity does not appear to develop, and reinfection may occur following treatment, requiring additional courses of therapy.
- Some recent data suggest that treatment may not be entirely effective at clearing the organisms and that recrudescence of infection is possible. Although additional research into this area is needed, retreatment may be indicated in cases of relapse of clinical disease or reinfection from ticks.
Control and Prevention
- Vaccines are not available to prevent infection of pets by Ehrlichia spp. and Anaplasma spp. pathogens. Stringent adherence to routine application of effective acaricides is critical for preventing infection and disease caused by these organisms.
- Various stages and species of ticks are active at different times of the year in different parts of the country. Because tick activity may occur year-round and pets may travel to areas where ticks are active, CAPC recommends that all pets be maintained on tick-control products year-round.
- Attached ticks found on pets should be removed promptly to prevent transmission of any pathogens they may harbor. To avoid both zoonotic infection and accidental inoculation of agents into the pet during the removal process, ticks should be retracted using forceps or a commercial tick-removal device, and care should be taken to avoid contact with tick contents, ideally by wearing gloves. Careful attention to handwashing following tick removal is also recommended.
- Tick infestations and resultant infection with Ehrlichia spp. and Anaplasma spp. can be prevented by avoiding tick-infested areas whenever possible and by modifying the habitat around the home through such basic measures as keeping shrubbery and grass closely clipped to discourage both tick populations and the wildlife species that often harbor them from flourishing. In some areas, immature ticks on rodents may be controlled through the use of pyrethrin-treated cotton baits.
Public Health Considerations
- Most of the Ehrlichia spp. and Anaplasma spp. that infect and cause disease in pets are well-established zoonotic agents that also infect and cause disease in people.
- Ehrlichia chaffeensis and A. phagocytophilum are primarily known as human disease agents, and infections with these organisms are responsible for human monocytic ehrlichiosis and human anaplasmosis (formerly known as human granulocytic ehrlichiosis, or HGE), respectively.
- Ehrlichia ewingii is also an etiologic agent of human granulocytic ehrlichiosis.
- Human infection with E. canis was reported in Venezuela, but further research is needed to determine if E. canis strains enzootic to other countries are also infectious to people.
- People contract these infections the same way that pets do: via the bite of an infected tick. Although direct transmission from an infected animal is possible through inoculation of contaminated blood or tissue, pets are not an considered a direct source of infection to people.
- Prevention of human infection with Ehrlichia spp. and Anaplasma spp. relies on preventing tick bites of people through many of the same measures that prevent tick bites of animals. Stringent adherence to the routine use of acaricides on pets to limit infestations and thus prevent family pets from bringing ticks into the home. People should also take basic precautions when in tick-infested areas. Such precautions include wearing light-colored, protective clothing; performing frequent tick checks and promptly removing any ticks found; and using repellent products specifically labeled as effective at preventing tick attachment. More information about preventing transmission can be found at the CAPC web page about ticks (http://www.capcvet.org/capc-recommendations/ticks).