Persistent Infection with Ehrlichia chaffeensis

Dumler, J. Stephen; Sutker, William L.; Walker, David H.

doi:10.1093/clinids/17.5.903

Cited by 116 publications

(58 citation statements)

References 13 publications

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“…21,22 We have identified one horse with severe hyperadrenocorticism and possible chronic granulocytic ehrlichiosis based on two positive E. equi-specific PCR test results at a six-month interval (Madigan JE, unpublished data). Infection with E. canis in dogs can persist in the spleen for years.…”

Section: Discussionmentioning

confidence: 99%

A simian model of human granulocytic ehrlichiosis.

Foley

Lerche²,

Dumler

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Following intravenous inoculation with horse blood-infected with the agent of human granulocytic ehrlichiosis (HGE) from a human fatality, two rhesus macaques (Macaca mulatta) exhibited pyrexia and lethargy on days 4-12 postinfection (PI). Hematology revealed neutropenia, thrombocytopenia, and anemia, with ehrlichial morulae in monocytes and neutrophils on days 4-12. Blood was polymerase chain reaction (PCR)-positive on days 4-12 and bone marrow was PCR-positive on day 11. There was a minor increase in gamma-glutamyl transpeptidase on day 12 and serum interferon-␥ levels increased by day 18. Seroconversion occurred on day 20 PI to a titer of 100 by day 22. Western blot bands characteristic of HGE included 25-, 44-, 80-, 94-, 105-, and 125-kD 10 The development of clinical signs appears to be largely host-species dependent. An early attempt to infect non-human primates with Ehrlichia equi was successful based on visualization of ehrlichial inclusions within the cytoplasm of neutrophils.3 However, that study was hampered by the lack of some diagnostic procedures such as the polymerase chain reaction (PCR) and DNA sequencing, cytokine assays, and other immunologic assays. Moreover, the investigators did not know at that time that E. equi or its close relative, the agent of human granulocytic ehrlichiosis (HGE), was capable of producing life-threatening disease in humans. 1 In the present study, we report successful experimental infection of rhesus macaques with the HGE agent from a severely ill human case. This animal model of human disease is important for further studies of HGE diagnosis, management, and pathogenesis. MATERIALS AND METHODS Animals and inoculation.Three rhesus macaques were pre-screened for ehrlichiosis by serology and E. equi-specific PCR. Monkey 312 was a 16-year-old reproductively intact female who had been used previously for breeding and a teratogenesis study (zinc deprivation). Monkey 121 was a 17-year-old intact female with a history of use for breeding and anti-progestin drug studies. Monkey 324 was a 14-yearold intact female from the breeding colony. Monkeys 121 and 312 were inoculated intravenously with fresh horse blood containing 2 ϫ 10 6 neutrophils of which 15% contained HGE agent strain BDS inclusions (morulae); monkey 324 was control-inoculated with 2 ϫ 10 6 uninfected horse neutrophils. All monkeys were monitored twice a day for clinical signs of disease, including lethargy, inappetance, and depression. Rectal temperature was assessed at the time of each blood sample collection. Blood samples were collected every two days into tubes containing EDTA for Wright-Giemsa staining and PCR and without anticoagulant for serology and serum chemistry. Bone marrow aspirates were performed on days 3, 11, and 14 postinfection (PI) and submitted for cytology and PCR. On day 21 PI, monkeys 121 and 324 were killed with an intravenous overdose of barbiturate and necropsied. Samples from tissues were either snap-frozen in liquid nitrogen for PCR or fixed overnight in 10% buffered forma...

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Section: Discussionmentioning

confidence: 99%

A simian model of human granulocytic ehrlichiosis.

Foley

Lerche²,

Dumler

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…Anaplasma and most Ehrlichia species usually cause persistent infection in their natural animal hosts (Andrew & Norval, 1989;Telford et al, 1996;Breitschwerdt et al, 1998;Harrus et al, 1998). Persistent ehrlichial infection in humans has also been documented (Dumler et al, 1993;Roland et al, 1995;Dumler & Bakken, 1996;Horowitz et al, 1998). Experimentally infected whitetailed deer (Odocoileus virginianus) carry E. chaffeensis for up to 3 months (Davidson et al, 2001).…”

Section: Introductionmentioning

confidence: 97%

Experimental Ehrlichia chaffeensis infection in beagles

Zhang

Long

et al. 2003

Journal of Medical Microbiology

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A canine model for human monocytic ehrlichiosis was used to assess persistent infection and antigenic variation of Ehrlichia chaffeensis. Two beagle dogs were infected subcutaneously with E. chaffeensis Arkansas strain. The dogs were observed for 6 months after inoculation for clinical signs, blood chemistry changes, antibodies to E. chaffeensis and presence of E. chaffeensis in the blood. Both dogs developed thrombocytopenia, but exhibited normal body temperatures during the entire course of infection. In one dog, E. chaffeensis was cultivated for up to 74 days post-inoculation and E. chaffeensis DNA was detected in the dog's blood for up to 81 days. In the other dog, E. chaffeensis was cultured for up to 102 days and E. chaffeensis DNA was detected in the blood for up to 117 days. PCR amplification and DNA sequence analysis indicated that there was no genetic variation in the 120 kDa outer-membrane glycoprotein gene of E. chaffeensis during infection of the dogs. The dogs developed antibodies to the immunodominant proteins of E. chaffeensis, including the 175, 140, 120, 80, 50 and 28 kDa proteins, starting in the fifth week post-inoculation. The dogs maintained high antibody titres throughout the 6-month study period. These results indicate that dogs become carriers of E. chaffeensis for 2-4 months after infection without exhibiting signs of clinical disease, suggesting that dogs may serve as a natural host for E. chaffeensis.

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“…Anaplasma and Ehrlichia species can cause persistent infection in their natural mammalian hosts (1,3,6,11,14,28,29,38). Persistent or prolonged ehrlichial infection in humans has been reported for both E. chaffeensis (10,25) and A. phagocytophilum (8,15).…”

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Expression of Members of the 28-Kilodalton Major Outer Membrane Protein Family of Ehrlichia chaffeensis during Persistent Infection

et al. 2004

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The 28-kDa immunodominant outer membrane proteins (P28 OMPs) of Ehrlichia chaffeensis are encoded by a multigene family. As an indirect measure of the in vivo expression of the members of the p28 multigene family of E. chaffeensis, sera from two beagle dogs experimentally infected with E. chaffeensis were evaluated for the presence of specific antibodies to P28 OMPs by enzyme-linked immunosorbent assay. Antigenic peptides unique to each of the P28s were identified within the first hypervariable region of each P28 OMP. Serological responses to peptides derived from all P28 OMPs were detected from day 30 postinoculation to day 468 and from day 46 until day 159 in the two beagles. Although antibody titers to the peptides fluctuated, the peak response to all of the peptides appeared simultaneously in each dog. The antibody responses to another outer membrane protein of E. chaffeensis (GP120) showed similar temporal and quantitative changes. These data suggest that the P28 OMPs are expressed concurrently during persistent Ehrlichia infection.

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Persistent Infection with Ehrlichia chaffeensis

Cited by 116 publications

References 13 publications

A simian model of human granulocytic ehrlichiosis.

A simian model of human granulocytic ehrlichiosis.

Experimental Ehrlichia chaffeensis infection in beagles

Expression of Members of the 28-Kilodalton Major Outer Membrane Protein Family of Ehrlichia chaffeensis during Persistent Infection

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