Source: http://www.asmscience.org/content/book/10.1128/9781555816490.chap13
Timestamp: 2019-04-23 04:36:02+00:00

Document:
Life cycle of A. phagocytophilum in infected human (HL60) cells. (A) Binding to the cell surface; (B) internalization; (C) replication within the endosome with failure of fusion with lysosomal granules; (D) cell filled with multiple infected endosomes, near lysis ( 61 ).
Distribution of cases of HGA reported to the CDC in 2001 ( 37 ).
1. Adachi, J. A.,, E. M. Grimm,, P. Johnson,, M. Uthman,, B. Kaplan,, and R. M. Rakita. 1997. Human granulocytic ehrlichiosis in a renal transplant patient: case report and review of the literature. Transplantation 64: 1139– 1142.
2. Aguero-Rosenfeld, M. E. 2003. Laboratory aspects of tickborne diseases: Lyme, human granulocytic ehrlichiosis and babesiosis. Mt. Sinai J. Med. 70: 197– 206.
3. Aguero-Rosenfeld, M. E.,, H. W. Horowitz,, G. P. Wormser,, D. F. McKenna,, J. Nowakowski,, J. Munoz,, and J. S. Dumler. 1996. Human granulocytic ehrlichiosis: a case series from a medical center in New York State. Ann. Intern. Med. 125: 904– 908.
4. Akkoyunlu, M.,, and E. Fikrig. 2000. Gamma interferon dominates the murine cytokine response to the agent of human granulocytic ehrlichiosis and helps to control the degree of early rickettsemia. Infect. Immun. 68: 1827– 1833.
5. Akkoyunlu, M.,, S. E. Malawista,, J. Anguita,, and E. Fikrig. 2001. Exploitation of interleukin-8-induced neutrophil chemotaxis by the agent of human granulocytic ehrlichiosis. Infect. Immun. 69: 5577– 5588.
6. Arens, M. Q.,, A. M. Liddell,, G. Buening,, M. Gaudreault- Keener,, J. W. Sumner,, J. A. Comer,, R. S. Buller,, and G. A. Storch. 2003. Detection of Ehrlichia spp. in the blood of wild white-tailed deer in Missouri by PCR assay and serologic analysis. J. Clin. Microbiol. 41: 1263– 1265.
7. Arnez, M.,, T. Luznik-Bufon,, T. Avsic-Zupanc,, E. Ruzic- Sabljic,, M. Petrovec,, S. Lotric-Furlan,, and F. Strle. 2003. Causes of febrile illnesses after a tick bite in Slovenian children. Pediatr. Infect. Dis. J. 22: 1078– 1083.
8. Bakken, J. S.,, M. E. Aguero-Rosenfeld,, R. L. Tilden,, G. P. Wormser,, H. W. Horowitz,, J. T. Raffalli,, M. Baluch,, D. Riddell,, J. J. Walls,, and J. S. Dumler. 2001. Serial measurements of hematologic counts during the active phase of human granulocytic ehrlichiosis. Clin. Infect. Dis. 32: 862– 870.
9. Bakken, J. S.,, and J. S. Dumler. 2000. Human granulocytic ehrlichiosis. Clin. Infect. Dis. 31: 554– 560.
10. Bakken, J. S.,, J. S. Dumler,, S. M. Chen,, M. R. Eckman,, L. L. Van Etta,, and D. H. Walker. 1994. Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging? JAMA 272: 212– 218.
11. Bakken, J. S.,, S. A. Erlemeyer,, R. J. Kanoff,, T. C. Silvestrini,, D. D. Goodwin,, and J. S. Dumler. 1998. Demyelinating polyneuropathy associated with human granulocytic ehrlichiosis. Clin. Infect. Dis. 27: 1323– 1324.
12. Bakken, J. S.,, I. Haller,, D. Riddell,, J. J. Walls,, and J. S. Dumler. 2002. The serological response of patients infected with the agent of human granulocytic ehrlichiosis. Clin. Infect. Dis. 34: 22– 27.
13. Bakken, J. S.,, J. Krueth,, C. Wilson-Nordskog,, R. L. Tilden,, K. Asanovich,, and J. S. Dumler. 1996. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA 275: 199– 205.
14. Banerjee, R.,, J. Anguita,, and E. Fikrig. 2000. Granulocytic ehrlichiosis in mice deficient in phagocyte oxidase or inducible nitric oxide synthase. Infect. Immun. 68: 4361– 4362.
15. Banerjee, R.,, J. Anguita,, D. Roos,, and E. Fikrig. 2000. Cutting edge: infection by the agent of human granulocytic ehrlichiosis prevents the respiratory burst by down-regulating gp91phox. J. Immunol. 164: 3946– 3949.
16. Behl, R.,, M. B. Klein,, L. Dandelet,, R. R. Bach,, J. L. Goodman,, and N. S. Key. 2000. Induction of tissue factor procoagulant activity in myelomonocytic cells inoculated by the agent of human granulocytic ehrlichiosis. Thromb. Haemost. 83: 114– 118.
17. Belongia, E. A.,, K. D. Reed,, P. D. Mitchell,, P. H. Chyou,, N. Mueller-Rizner,, M. F. Finkel,, and M. E. Schriefer. 1999. Clinical and epidemiological features of early Lyme disease and human granulocytic ehrlichiosis in Wisconsin. Clin. Infect. Dis. 29: 1472– 1477.
18. Belongia, E. A.,, K. D. Reed,, P. D. Mitchell,, C. P. Kolbert,, D. H. Persing,, J. S. Gill,, and J. J. Kazmierczak. 1997. Prevalence of granulocytic Ehrlichia infection among white-tailed deer in Wisconsin. J. Clin. Microbiol. 35: 1465– 1468.
19. Belongia, E. A.,, K. D. Reed,, P. D. Mitchell,, N. Mueller- Rizner,, M. Vandermause,, M. F. Finkel,, and J. J. Kazmierczak. 2001. Tickborne infections as a cause of nonspecific febrile illness in Wisconsin. Clin. Infect. Dis. 32: 1434– 1439.
21. Bjoersdorff, A.,, B. Wittesjo,, J. Berglun,, R. F. Massung,, and I. Eliasson. 2002. Human granulocytic ehrlichiosis as a common cause of tick-associated fever in southeast Sweden: report from a prospective clinical study. Scand. J. Infect. Dis. 34: 187– 191.
22. Blanco, J. R.,, and J. A. Oteo. 2002. Human granulocytic ehrlichiosis in Europe. Clin. Microbiol. Infect. 8: 763– 772.
23. Borjesson, D. L.,, S. I. Simon,, E. Hodzic,, C. M. Ballantyne,, and S. W. Barthold. 2002. Kinetics of CD11b/CD18 up-regulation during infection with the agent of human granulocytic ehrlichiosis in mice. Lab. Investig. 82: 303– 311.
24. Brandsma, A. R.,, S. E. Little,, J. M. Lockhart,, W. R. Davidson,, D. E. Stallknecht,, and J. E. Dawson. 1999. Novel Ehrlichia organism (Rickettsiales: Ehrlichieae) in white-tailed deer associated with lone star tick (Acari: Ixodidae) parasitism. J. Med. Entomol. 36: 190– 194.
25. Brouqui, P.,, and J. S. Dumler. 2000. Serologic evidence of human monocytic and granulocytic ehrlichiosis in Israel. Emerg. Infect. Dis. 6: 314– 315.
26. Brouqui, P.,, and D. Raoult. 1992. In vitro antibiotic susceptibility of the newly recognized agent of ehrlichiosis in humans, Ehrlichia chaffeensis. Antimicrob. Agents Chemother. 36: 2799– 2803.
27. Brouqui, P.,, E. Salvo,, J. S. Dumler,, and D. Raoult. 2001. Diagnosis of granulocytic ehrlichiosis in humans by immunofluorescence assay. Clin. Diagn. Lab. Immunol. 8: 199– 202.
28. Brown, W. C.,, V. Shkap,, D. Zhu,, T. C. McGuire,, W. Tuo,, T. F. McElwain,, and G. H. Palmer. 1998. CD4 + T-lymphocyte and immunoglobulin G2 responses in calves immunized with Anaplasma marginale outer membranes and protected against homologous challenge. Infect. Immun. 66:5406- 5413.
29. Buitrago, M. I.,, J. W. Ijdo,, P. Rinaudo,, H. Simon,, J. Copel,, J. Gadbaw,, R. Heimer,, E. Fikrig,, and F. J. Bia. 1998. Human granulocytic ehrlichiosis during pregnancy treated successfully with rifampin. Clin. Infect. Dis. 27: 213– 215.
30. Bunnell, J. E.,, L. A. Magnarelli,, and J. S. Dumler. 1999. Infection of laboratory mice with the human granulocytic ehrlichiosis agent does not induce antibodies to diagnostically significant Borrelia burgdorferi antigens. J. Clin. Microbiol. 37: 2077– 2079.
31. Bunnell, J. E.,, E. R. Trigiani,, S. R. Srinivas,, and J. S. Dumler. 1999. Development and distribution of pathologic lesions are related to immune status and tissue deposition of human granulocytic ehrlichiosis agent-infected cells in a murine model system. J. Infect. Dis. 180: 546– 550.
32. Burkot, T. R.,, G. O. Maupin,, B. S. Schneider,, C. Denatale,, C. M. Happ,, J. S. Rutherford,, and N. S. Zeidner. 2001. Use of a sentinel host system to study the questing behavior of Ixodes spinipalpis and its role in the transmission of Borrelia bissettii, human granulocytic ehrlichiosis, and Babesia microti. Am. J. Trop. Med. Hyg. 65: 293– 299.
33. Carlyon, J. A.,, M. Akkoyunlu,, L. Xia,, T. Yago,, T. Wang,, R. D. Cummings,, R. P. McEver,, and E. Fikrig. 2003. Murine neutrophils require α1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophilum. Blood 102: 3387– 3395.
34. Carlyon, J. A.,, W. T. Chan,, J. Galan,, D. Roos,, and E. Fikrig. 2002. Repression of rac2 mRNA expression by Anaplasma phagocytophila is essential to the inhibition of superoxide production and bacterial proliferation. J. Immunol. 169: 7009– 7018.
35. Carlyon, J. A.,, D. A. Latif,, M. Pypaert,, P. Lacy,, and E. Fikrig. 2004. Anaplasma phagocytophilum utilizes multiple host evasion mechanisms to thwart NADPH oxidase-mediated killing during neutrophil infection. Infect. Immun. 72: 4772– 4783.
36. Carlyon, J. A. Centers for Disease Control and Prevention. 1995. Human granulocytic ehrlichiosis—New York, 1995. JAMA 274: 867.
37. Carlyon, J. A. Centers for Disease Control and Prevention. 2004. Summary of notifiable diseases—United States 2002. Morb. Mortal. Wkly. Rep. 51: 1– 84.
38. Chang, Y. F.,, V. Novosel,, C. F. Chang,, J. B. Kim,, S. J. Shin,, and D. H. Lein. 1998. Detection of human granulocytic ehrlichiosis agent and Borrelia burgdorferi in ticks by polymerase chain reaction. J. Vet. Diagn. Investig. 10: 56– 59.
39. Chaput, E. K.,, J. I. Meek,, and R. Heimer. 2002. Spatial analysis of human granulocytic ehrlichiosis near Lyme, Connecticut. Emerg. Infect. Dis. 8: 943– 948.
40. Chen, S. M.,, J. S. Dumler,, J. S. Bakken,, and D. H. Walker. 1994. Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease. J. Clin. Microbiol. 32: 589– 595.
41. Choi, K. S.,, D. G. Scorpio,, and J. S. Dumler. 2004. Anaplasma phagocytophilum ligation to toll-like receptor (TLR) 2, but not to TLR4, activates macrophages for nuclear factor-kappa B nuclear translocation. J. Infect. Dis. 189: 1921– 1925.
42. Christova, I. S.,, and J. S. Dumler. 1999. Human granulocytic ehrlichiosis in Bulgaria. Am. J. Trop. Med. Hyg. 60: 58– 61.
43. Cinco, M.,, D. Padovan,, R. Murgia,, M. Heldtander,, and E. O. Engvall. 1998. Detection of HGE agent-like Ehrlichia in Ixodes ricinus ticks in northern Italy by PCR. Wien. Klin. Wochenschr. 110: 898– 900.
44. Daniel, S. A.,, K. Manika,, M. Arvanitidou,, E. Diza,, N. Symeonidis,, and A. Antoniadis. 2002. Serologic evidence of human granulocytic ehrlichiosis, Greece. Emerg. Infect. Dis. 8: 643– 644.
45. Daniels, T. J.,, G. R. Battaly,, D. Liveris,, R. C. Falco,, and I. Schwartz. 2002. Avian reservoirs of the agent of human granulocytic ehrlichiosis? Emerg. Infect. Dis. 8: 1524– 1525.
46. des Vignes, F.,, and D. Fish. 1997. Transmission of the agent of human granulocytic ehrlichiosis by host-seeking Ixodus scapularis (Acari: Ixodidae) in southern New York state. J. Med. Entomol. 34: 379– 382.
47. des Vignes, F.,, J. Piesman,, R. Heffernan,, T. L. Schulze,, K. C. Stafford III,, and D. Fish. 2001. Effect of tick removal on transmission of Borrelia burgdorferi and Ehrlichia phagocytophila by Ixodes scapularis nymphs. J. Infect. Dis. 183: 773– 778.
48. Dumler, J. S.,, and J. S. Bakken. 1996. Human granulocytic ehrlichiosis in Wisconsin and Minnesota: a frequent infection with the potential for persistence. J. Infect. Dis. 173: 1027– 1030.
49. Dumler, J. S.,, A. F. Barbet,, C. P. Bekker,, G. A. Dasch,, G. H. Palmer,, S. C. Ray,, Y. Rikihisa,, and F. R. Rurangirwa. 2001. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and ‘HGE agent’ as subjective synonyms of Ehrlichia phagocytophila. Int. J. Syst. Evol. Microbiol. 51: 2145– 2165.
50. Dumler, J. S.,, E. R. Trigiani,, J. S. Bakken,, M. E. Aguero- Rosenfeld,, and G. P. Wormser. 2000. Serum cytokine responses during acute human granulocytic ehrlichiosis. Clin. Diagn. Lab. Immunol. 7: 6– 8.
51. Edelman, D. C.,, and J. S. Dumler. 1996. Evaluation of an improved PCR diagnostic assay for human granulocytic ehrlichiosis. Mol. Diagn. 1: 41– 49.
52. Edelson, B. T.,, and E. R. Unanue. 2001. Intracellular antibody neutralizes Listeria growth. Immunity 14: 503– 512.
53. Fingerle, V.,, J. L. Goodman,, R. C. Johnson,, T. J. Kurtti,, U. G. Munderloh,, and B. Wilske. 1997. Human granulocytic ehrlichiosis in southern Germany: increased seroprevalence in high-risk groups. J. Clin. Microbiol. 35: 3244– 3247.
54. Fingerle, V.,, U. G. Munderloh,, G. Liegl,, and B. Wilske. 1999. Coexistence of ehrlichiae of the phagocytophila group with Borrelia burgdorferi in Ixodes ricinus from southern Germany. Med. Microbiol. Immunol. (Berlin) 188: 145– 149.
55. Gardner, S. L.,, R. C. Holman,, J. W. Krebs,, R. Berkelman,, and J. E. Childs. 2003. National surveillance for the human ehrlichioses in the United States, 1997-2001, and proposed methods for evaluation of data quality. Ann. N. Y. Acad. Sci. 990: 80– 89.
56. Goodman, J. L.,, and Herron, M. J. Unpublished data.
57. Goodman, J. L.,, C. Nelson,, B. Vitale,, J. E. Madigan,, J. S. Dumler,, T. J. Kurtti,, and U. G. Munderloh. 1996. Direct cultivation of the causative agent of human granulocytic ehrlichiosis. N. Engl. J. Med. 334: 209– 215.
58. Goodman, J. L.,, C. M. Nelson,, M. B. Klein,, S. F. Hayes,, and B. W. Weston. 1999. Leukocyte infection by the granulocytic ehrlichiosis agent is linked to expression of a selectin ligand. J. Clin. Investig. 103: 407– 412.
59. Greig, B.,, K. M. Asanovich,, P. J. Armstrong,, and J. S. Dumler. 1996. Geographic, clinical, serologic, and molecular evidence of granulocytic ehrlichiosis, a likely zoonotic disease, in Minnesota and Wisconsin dogs. J. Clin. Microbiol. 34: 44– 48.
60. Gribble, D. H. 1969. Equine ehrlichiosis. J. Am. Vet. Med. Assoc. 155: 462– 469.
61. Hayes, S. F.,, C. M. Nelson,, and J. L. Goodman. The life cycle of A. phagocytophilum in human cells. Unpublished data.
62. Herron, M. J.,, and J. L. Goodman. 2001. Proceedings, 16 th American Society for Rickettsiology Annual Meeting.
63. Herron, M. J.,, C. M. Nelson,, J. Larson,, K. R. Snapp,, G. S. Kansas,, and J. L. Goodman. 2000. Intracellular parasitism by the human granulocytic ehrlichiosis bacterium through the P-selectin ligand, PSGL-1. Science 288: 1653– 1656.
65. Hodzic, E.,, D. Fish,, C. M. Maretzki,, A. M. De Silva,, S. Feng,, and S. W. Barthold. 1998. Acquisition and transmission of the agent of human granulocytic ehrlichiosis by Ixodes scapularis ticks. J. Clin. Microbiol. 36: 3574– 3578.
66. Horowitz, H. W.,, M. Aguero-Rosenfeld,, J. S. Dumler,, D. F. McKenna,, T. C. Hsieh,, J. Wu,, I. Schwartz,, and G. P. Wormser. 1998. Reinfection with the agent of human granulocytic ehrlichiosis. Ann. Intern. Med. 129: 461– 463.
67. Horowitz, H. W.,, M. E. Aguero-Rosenfeld,, D. F. McKenna,, D. Holmgren,, T. C. Hsieh,, S. A. Varde,, S. J. Dumler,, J. M. Wu,, I. Schwartz,, Y. Rikihisa,, and G. P. Wormser. 1998. Clinical and laboratory spectrum of culture-proven human granulocytic ehrlichiosis: comparison with culture-negative cases. Clin. Infect. Dis. 27: 1314– 1317.
68. Horowitz, H. W.,, T. C. Hsieh,, M. E. Aguero-Rosenfeld,, F. Kalantarpour,, I. Chowdhury,, G. P. Wormser,, and J. M. Wu. 2001. Antimicrobial susceptibility of Ehrlichia phagocytophila. Antimicrob. Agents Chemother. 45: 786– 788.
69. Horowitz, H. W.,, E. Kilchevsky,, S. Haber,, M. Aguero- Rosenfeld,, R. Kranwinkel,, E. K. James,, S. J. Wong,, F. Chu,, D. Liveris,, and I. Schwartz. 1998. Perinatal transmission of the agent of human granulocytic ehrlichiosis. N. Engl. J. Med. 339: 375– 378.
70. Horowitz, H. W.,, S. J. Marks,, M. Weintraub,, and J. S. Dumler. 1996. Brachial plexopathy associated with human granulocytic ehrlichiosis. Neurology 46: 1026– 1029.
71. Ijdo, J. W.,, C. Wu,, L. A. Magnarelli,, and E. Fikrig. 1999. Serodiagnosis of human granulocytic ehrlichiosis by a recombinant HGE-44-based enzyme-linked immunosorbent assay. J. Clin. Microbiol. 37: 3540– 3544.
72. Jahangir, A.,, C. Kolbert,, W. Edwards,, P. Mitchell,, J. S. Dumler,, and D. H. Persing. 1998. Fatal pancarditis associated with human granulocytic ehrlichiosis in a 44-year-old man. Clin. Infect. Dis. 27: 1424– 1427.
73. Jauron, S. D.,, C. M. Nelson,, V. Fingerle,, M. D. Ravyn,, J. L. Goodman,, R. C. Johnson,, R. Lobentanzer,, B. Wilske,, and U. G. Munderloh. 2001. Host cell-specific expression of a p44 epitope by the human granulocytic ehrlichiosis agent. J. Infect. Dis. 184: 1445– 1450.
74. Kalantarpour, F.,, I. Chowdhury,, G. P. Wormser,, and M. E. Aguero-Rosenfeld. 2000. Survival of the human granulocytic ehrlichiosis agent under refrigeration conditions. J. Clin. Microbiol. 38: 2398– 2399.
75. Katavolos, P.,, P. M. Armstrong,, J. E. Dawson,, and S. R. Telford III. 1998. Duration of tick attachment required for transmission of granulocytic ehrlichiosis. J. Infect. Dis. 177: 1422– 1425.
76. Kim, H. Y.,, and Y. Rikihisa. 2000. Expression of interleukin- 1β, tumor necrosis factor alpha, and interleukin-6 in human peripheral blood leukocytes exposed to human granulocytic ehrlichiosis agent or recombinant major surface protein P44. Infect. Immun. 68: 3394– 3402.
77. Klein, M. B.,, S. F. Hayes,, and J. L. Goodman. 1998. Monocytic differentiation inhibits infection and granulocytic differentiation potentiates infection by the agent of human granulocytic ehrlichiosis. Infect. Immun. 66: 3410– 3415.
78. Klein, M. B.,, S. Hu,, C. C. Chao,, and J. L. Goodman. 2000. The agent of human granulocytic ehrlichiosis induces the production of myelosuppressing chemokines without induction of proinflammatory cytokines. J. Infect. Dis. 182: 200– 205.
79. Klein, M. B.,, J. S. Miller,, C. M. Nelson,, and J. L. Goodman. 1997. Primary bone marrow progenitors of both granulocytic and monocytic lineages are susceptible to infection with the agent of human granulocytic ehrlichiosis. J. Infect. Dis. 176: 1405– 1409.
80. Klein, M. B.,, C. M. Nelson,, and J. L. Goodman. 1997. Antibiotic susceptibility of the newly cultivated agent of human granulocytic ehrlichiosis: promising activity of quinolones and rifamycins. Antimicrob. Agents Chemother. 41: 76– 79.
81. Kocan, K. M.,, J. delaFuente,, A. A. Guglielmone,, and R. D. Melendez. 2003. Antigens and alternatives for control of Anaplasma marginale infection in cattle. Clin. Microbiol. Rev. 16: 698– 712.
82. Kocan, K. M.,, T. Halbur,, E. F. Blouin,, V. Onet,, J. de la Fuente,, J. C. Garcia-Garcia,, and J. T. Saliki. 2001. Immunization of cattle with Anaplasma marginale derived from tick cell culture. Vet. Parasitol. 102: 151– 161.
83. Kramer, V. L.,, M. P. Randolph,, L. T. Hui,, W. E. Irwin,, A. G. Gutierrez,, and D. J. Vugia. 1999. Detection of the agents of human ehrlichioses in ixodid ticks from California. Am. J. Trop. Med. Hyg. 60: 62– 65.
84. Krause, P. J.,, C. L. Corrow,, and J. S. Bakken. 2003. Successful treatment of human granulocytic ehrlichiosis in children using rifampin. Pediatrics 112: e252– e253.
85. Layfield, D.,, and P. Guilfoile. 2002. The prevalence of Borrelia burgdorfieri (Spirochaetales: spirochaetaceae) and the agent of human granulocytic ehrlichiosis (Rickettsiaceae: Ehrlichieae) in Ixodes scapularis (Acari: Ixodidae) collected during 1998 and 1999 from Minnesota. J. Med. Entomol. 39: 218– 220.
86. Lee, H. C.,, J. Han,, R. K. Purr,, and J. L. Goodman. 2004. Anaplasma phagocytophilum inhibits human neutrophil apoptosis through multiple molecular pathways: genomic studies. FDA 2004 Science Forum.
86. Lepidi, H.,, J. E. Bunnell,, M. E. Martin,, J. E. Madigan,, S. Stuen,, and J. S. Dumler. 2000. Comparative pathology, and immunohistology associated with clinical illness after Ehrlichia phagocytophila-group infections. Am. J. Trop. Med. Hyg. 62: 29– 37.
87. Levin, M. L.,, F. des Vignes,, and D. Fish. 1999. Disparity in the natural cycles of Borrelia burgdorferi and the agent of human granulocytic ehrlichiosis. Emerg. Infect. Dis. 5: 204– 208.
88. Levin, M. L.,, W. L. Nicholson,, R. F. Massung,, J. W. Sumner,, and D. Fish. 2002. Comparison of the reservoir competence of medium-sized mammals and Peromyscus leucopus for Anaplasma phagocytophilum in Connecticut . Vector Borne Zoonotic Dis. 2: 125– 136.
89. Little, S. E.,, D. E. Stallknecht,, J. M. Lockhart,, J. E. Dawson,, and W. R. Davidson. 1998. Natural coinfection of a whitetailed deer ( Odocoileus virginianus) population with three Ehrlichia spp. J. Parasitol. 84: 897– 901.
90. Liz, J. S.,, J. W. Sumner,, K. Pfister,, and M. Brossard. 2002. PCR detection and serological evidence of granulocytic ehrlichial infection in roe deer ( Capreolus capreolus) and chamois ( Rupicapra rupicapra). J. Clin. Microbiol. 40: 892– 897.
91. Lodes, M. J.,, R. Mohamath,, L. D. Reynolds,, P. McNeill,, C. P. Kolbert,, E. S. Bruinsma,, D. R. Benson,, E. Hofmeister,, S. G. Reed,, R. L. Houghton,, and D. H. Persing. 2001. Serodiagnosis of human granulocytic ehrlichiosis by using novel combinations of immunoreactive recombinant proteins. J. Clin. Microbiol. 39: 2466– 2476.
92. Lotric-Furlan, S.,, M. Petrovec,, T. Avsic-Zupanc,, and F. Strle. 2003. Comparison of patients fulfilling criteria for confirmed and probable human granulocytic ehrlichiosis. Ann. N. Y. Acad. Sci. 990: 344– 345.
93. Lotric-Furlan, S.,, M. Petrovec,, T. Avsic-Zupanc,, and F. Strle. 2003. Human granulocytic ehrlichiosis in Slovenia. Ann. N. Y. Acad. Sci. 990: 279– 284.
94. Lotric-Furlan, S.,, M. Petrovec,, T. A. Zupanc,, W. L. Nicholson,, J. W. Sumner,, J. E. Childs,, and F. Strle. 1998. Human granulocytic ehrlichiosis in Europe: clinical and laboratory findings for four patients from Slovenia. Clin. Infect. Dis. 27: 424– 428.
95. Madigan, J. E.,, and D. Gribble. 1987. Equine ehrlichiosis in northern California: 49 cases (1968-1981). J. Am. Vet. Med. Assoc. 190: 445– 448.
96. Magnarelli, L.,, J. Ijdo,, C. Wu,, and E. Fikrig. 2001. Recombinant protein-44-based class-specific enzyme-linked immunosorbent assays for serologic diagnosis of human granulocytic ehrlichiosis. Eur. J. Clin. Microbiol. Infect. Dis. 20: 482– 485.
97. Magnarelli, L. A.,, J. W. Ijdo,, S. J. Padula,, R. A. Flavell,, and E. Fikrig. 2000. Serologic diagnosis of Lyme borreliosis by using enzyme-linked immunosorbent assays with recombinant antigens. J. Clin. Microbiol. 38: 1735– 1739.
98. Magnarelli, L. A.,, K. C. Stafford III,, T. N. Mather,, M. T. Yeh,, K. D. Horn,, and J. S. Dumler. 1995. Hemocytic rickettsialike organisms in ticks: serologic reactivity with antisera to ehrlichiae and detection of DNA of agent of human granulocytic ehrlichiosis by PCR. J. Clin. Microbiol. 33: 2710– 2714.
99. Magnarelli, L. A.,, K. C. Stafford III,, T. N. Mather,, M. T. Yeh,, K. D. Horn,, and J. S. Dumler. 1995. Hemocytic rickettsia- like organisms in ticks: serologic reactivity with antisera to ehrlichiae and detection of DNA of agent of human granulocytic ehrlichiosis by PCR. J. Clin. Microbiol. 33: 2710– 2714.
100. Martin, M. E.,, K. Caspersen,, and J. S. Dumler. 2001. Immunopathology and ehrlichial propagation are regulated by interferon-gamma and interleukin-10 in a murine model of human granulocytic ehrlichiosis. Am. J. Pathol. 158: 1881– 1888.
101. Massung, R. F.,, K. Slater,, J. H. Owens,, W. L. Nicholson,, T. N. Mather,, V. B. Solberg,, and J. G. Olson. 1998. Nested PCR assay for detection of granulocytic ehrlichiae. J. Clin. Microbiol. 36: 1090– 1095.
102. Massung, R. F.,, and K. G. Slater. 2003. Comparison of PCR assays for detection of the agent of human granulocytic ehrlichiosis, Anaplasma phagocytophilum. J. Clin. Microbiol. 41: 717– 722.
103. Maurin, M.,, J. S. Bakken,, and J. S. Dumler. 2003. Antibiotic susceptibilities of Anaplasma ( Ehrlichia) phagocytophilum strains from various geographic areas in the United States. Antimicrob. Agents Chemother. 47: 413– 415.
104. McGarey, D. J.,, A. F. Barbet,, G. H. Palmer,, T. C. McGuire,, and D. R. Allred. 1994. Putative adhesins of Anaplasma marginale: major surface polypeptides 1a and 1b. Infect. Immun. 62: 4594– 4601.
105. McQuiston, J. H.,, C. D. Paddock,, R. C. Holman,, and J. E. Childs. 1999. The human ehrlichioses in the United States. Emerg. Infect. Dis. 5: 635– 642.
106. Morozova, O. V.,, A. K. Dobrotvorsky,, N. N. Livanova,, S. E. Tkachev,, V. N. Bakhvalova,, A. B. Beklemishev,, and F. C. Cabello. 2002. PCR detection of Borrelia burgdorferi sensu lato, tick-borne encephalitis virus, and the human granulocytic ehrlichiosis agent in Ixodes persulcatus ticks from western Siberia, Russia. J. Clin. Microbiol. 40: 3802– 3804.
107. Mott, J.,, R. E. Barnewall,, and Y. Rikihisa. 1999. Human granulocytic ehrlichiosis agent and Ehrlichia chaffeensis reside in different cytoplasmic compartments in HL-60 cells. Infect. Immun. 67: 1368– 1378.
108. Munderloh, U. G.,, S. D. Jauron,, V. Fingerle,, L. Leitritz,, S. F. Hayes,, J. M. Hautman,, C. M. Nelson,, B. W. Huberty,, T. J. Kurtti,, G. G. Ahlstrand,, B. Greig,, M. A. Mellencamp,, and J. L. Goodman. 1999. Invasion and intracellular development of the human granulocytic ehrlichiosis agent in tick cell culture. J. Clin. Microbiol. 37: 2518– 2524.
109. Munderloh, U. G.,, M. J. Lynch,, M. J. Herron,, A. T. Palmer,, T. J. Kurtti,, R. D. Nelson,, and J. L. Goodman. 2004. Infection of endothelial cells with Anaplasma marginale and A. phagocytophilum. Vet. Microbiol. 101: 53– 64.
110. Nadelman, R. B.,, J. Nowakowski,, D. Fish,, R. C. Falco,, K. Freeman,, D. McKenna,, P. Welch,, R. Marcus,, M. E. Aguero-Rosenfeld,, D. T. Dennis,, and G. P. Wormser. 2001. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N. Engl. J. Med. 345: 79– 84.
111. Nicholson, W. L.,, M. B. Castro,, V. L. Kramer,, J. W. Sumner,, and J. E. Childs. 1999. Dusky-footed wood rats ( Neotoma fuscipes) as reservoirs of granulocytic ehrlichiae ( Rickettsiales: Ehrlichieae) in northern California. J. Clin. Microbiol. 37: 3323– 3327.
112. Ogden, N. H.,, Z. Woldehiwet,, and C. A. Hart. 1998. Granulocytic ehrlichiosis: an emerging or rediscovered tick-borne disease? J. Med. Microbiol. 47: 475– 482.
113. Oteo, J. A.,, H. Gil,, M. Barral,, A. Perez,, S. Jimenez,, J. R. Blanco,, V. MartinezdeArtola,, V. A. Garcia-Perez,, and R. A. Juste. 2001. Presence of granulocytic ehrlichia in ticks and serological evidence of human infection in La Rioja, Spain. Epidemiol. Infect. 127: 353– 358.
114. Pancholi, P.,, C. P. Kolbert,, P. D. Mitchell,, K. D. Reed,, Jr., J. S. Dumler,, J. S. Bakken,, S. R. Telford III,, and D. H. Persing. 1995. Ixodes dammini as a potential vector of human granulocytic ehrlichiosis. J. Infect. Dis. 172: 1007– 1012.
115. Prukk, T.,, K. Ainsalu,, E. Laja,, and A. Aigro. 2003. Human granulocytic ehrlichiosis in Estonia. Emerg. Infect. Dis. 9: 1499– 1500.
116. Rabinstein, A.,, V. Tikhomirov,, A. Kaluta,, N. Gelfmann,, P. Iannini,, and L. Edwards. 2000. Recurrent and prolonged fever in asplenic patients with human granulocytic ehrlichiosis. QJM 93: 198– 201.
117. Ramsey, A. H.,, E. A. Belongia,, C. M. Gale,, and J. P. Davis. 2002. Outcomes of treated human granulocytic ehrlichiosis cases. Emerg. Infect. Dis. 8: 398– 401.
118. Ravyn, M. D.,, J. L. Goodman,, C. B. Kodner,, D. K. Westad,, L. A. Coleman,, S. M. Engstrom,, C. M. Nelson,, and R. C. Johnson. 1998. Immunodiagnosis of human granulocytic ehrlichiosis by using culture-derived human isolates. J. Clin. Microbiol. 36: 1480– 1488.
119. Reubel, G. H.,, R. B. Kimsey,, J. E. Barlough,, and J. E. Madigan. 1998. Experimental transmission of Ehrlichia equi to horses through naturally infected ticks ( Ixodes pacificus) from northern California. J. Clin. Microbiol. 36: 2131– 2134.
120. Richter, P. J., Jr.,, R. B. Kimsey,, J. E. Madigan,, J. E. Barlough,, J. S. Dumler,, and D. L. Brooks. 1996. Ixodes pacificus (Acari: Ixodidae) as a vector of Ehrlichia equi (Rickettsiales: Ehrlichieae). J. Med. Entomol. 33: 1– 5.
121. Ruscio, M.,, and M. Cinco. 2003. Human granulocytic ehrlichiosis in Italy: first report on two confirmed cases. Ann. N. Y. Acad. Sci. 990: 350– 352.
122. Saint, A. A.,, N. M. Blackwell,, L. R. Hall,, A. Hoerauf,, N. W. Brattig,, L. Volkmann,, M. J. Taylor,, L. Ford,, A. G. Hise,, J. H. Lass,, E. Diaconu,, and E. Pearlman. 2002. The role of endosymbiotic Wolbachia bacteria in the pathogenesis of river blindness. Science 295: 1892– 1895.
123. Schwartz, I.,, D. Fish,, and T. J. Daniels. 1997. Prevalence of the rickettsial agent of human granulocytic ehrlichiosis in ticks from a hyperendemic focus of Lyme disease. N. Engl. J. Med. 337: 49– 50.
124. Skarphedinsson, S.,, P. Sogaard,, and C. Pedersen. 2001. Seroprevalence of human granulocytic ehrlichiosis in high-risk groups in Denmark. Scand. J. Infect. Dis. 33: 206– 210.
125. Strle, F. 2004. Human granulocytic ehrlichiosis in Europe. Int. J. Med. Microbiol(Suppl. 37). 293: 27– 35.
126. Sumner, J. W.,, W. L. Nicholson,, and R. F. Massung. 1997. PCR amplification and comparison of nucleotide sequences from the groESL heat shock operon of Ehrlichia species. J. Clin. Microbiol. 35: 2087– 2092.
127. Sun, W.,, J. W. Ijdo,, S. R. IIITelford,, E. Hodzic,, Y. Zhang,, S. W. Barthold,, and E. Fikrig. 1997. Immunization against the agent of human granulocytic ehrlichiosis in a murine model. J. Clin. Investig. 100: 3014– 3018.
128. Sun, W., Task Force on Consensus Approach for Ehrlichiosis (CAFE). 2000. Diagnosing human ehrlichioses: current status and recommendations. ASM News 66: 277– 280.
129. Taylor, G. A.,, C. G. Feng,, and A. Sher. 2004. p47 GTPases: regulators of immunity to intracellular pathogens. Nat. Rev. Immunol. 4: 100– 109.
130. Telford, S. R.,, III ,J. E. Dawson,, P. Katavolos,, C. K. Warner,, C. P. Kolbert,, and D. H. Persing. 1996. Perpetuation of the agent of human granulocytic ehrlichiosis in a deer tick-rodent cycle. Proc. Natl. Acad. Sci. USA 93: 6209– 6214.
131. Trofe, J.,, K. S. Reddy,, R. J. Stratta,, S. D. Flax,, K. T. Somerville,, R. R. Alloway,, M. F. Egidi,, M. H. Shokouh- Amiri,, and A. O. Gaber. 2001. Human granulocytic ehrlichiosis in pancreas transplant recipients. Transpl. Infect. Dis. 3: 34– 39.
132. Unver, A.,, S. Felek,, C. D. Paddock,, N. Zhi,, H. W. Horowitz,, G. P. Wormser,, L. C. Cullman,, and Y. Rikihisa. 2001. Western blot analysis of sera reactive to human monocytic ehrlichiosis and human granulocytic ehrlichiosis agents. J. Clin. Microbiol. 39: 3982– 3986.
133. Vannorsdall, M. D.,, S. Thomas,, R. P. Smith,, R. Zimmerman,, R. Christman,, and J. P. Vella. 2002. Human granulocytic ehrlichiosis in a renal allograft recipient: review of the clinical spectrum of disease in solid organ transplant patients. Transpl. Infect. Dis. 4: 97– 101.
134. Varde, S.,, J. Beckley,, and I. Schwartz. 1998. Prevalence of tick-borne pathogens in Ixodes scapularis in a rural New Jersey county. Emerg. Infect. Dis. 4: 97– 99.
135. Von Loewenich, F. D.,, D. G. Scorpio,, U. Reischl,, J. S. Dumler,, and C. Bogdan. 2004. Frontline: control of Anaplasma phagocytophilum, an obligate intracellular pathogen, in the absence of inducible nitric oxide synthase, phagocyte NADPH oxidase, tumor necrosis factor, Toll-like receptor (TLR) 2 and TLR4, or the TLR adaptor molecule MyD88. Eur. J. Immunol. 34: 1789– 1797.
136. Walls, J. J.,, P. Caturegli,, J. S. Bakken,, K. M. Asanovich,, and J. S. Dumler. 2000. Improved sensitivity of PCR for diagnosis of human granulocytic ehrlichiosis using epank1 genes of Ehrlichia phagocytophila-group ehrlichiae. J. Clin. Microbiol. 38: 354– 356.
137. Walls, J. J.,, B. Greig,, D. F. Neitzel,, and J. S. Dumler. 1997. Natural infection of small mammal species in Minnesota with the agent of human granulocytic ehrlichiosis. J. Clin. Microbiol. 35: 853– 855.
138. Webster, P.,, J. W. Ijdo,, L. M. Chicoine,, and E. Fikrig. 1998. The agent of human granulocytic ehrlichiosis resides in an endosomal compartment. J. Clin. Investig. 101: 1932– 1941.
139. Whist, S. K.,, A. K. Storset,, G. M. Johansen,, and H. J. Larsen. 2003. Modulation of leukocyte populations and immune responses in sheep experimentally infected with Anaplasma (formerly Ehrlichia) phagocytophilum. Vet. Immunol. Immunopathol. 94: 163– 175.
140. Woldehiwet, Z. 1983. Tick-borne fever: a review. Vet. Res. Commun. 6: 163– 175.
141. Wormser, G. P.,, H. W. Horowitz,, J. Nowakowski,, D. McKenna,, J. S. Dumler,, S. Varde,, I. Schwartz,, C. Carbonaro,, and M. Aguero-Rosenfeld. 1997. Positive Lyme disease serology in patients with clinical and laboratory evidence of human granulocytic ehrlichiosis. Am. J. Clin. Pathol. 107: 142– 147.
142. Wormser, G. P.,, R. B. Nadelman,, R. J. Dattwyler,, D. T. Dennis,, E. D. Shapiro,, A. C. Steere,, T. J. Rush,, D. W. Rahn,, P. K. Coyle,, D. H. Persing,, D. Fish,, and B. J. Luft. 2000. Practice guidelines for the treatment of Lyme disease. Guideline from the Infectious Diseases Society of America. Clin. Infect. Dis. 31( Suppl. 1): 1– 14.
143. Yago, T.,, A. Leppanen,, J. A. Carlyon,, M. Akkoyunlu,, S. Karmakar,, E. Fikrig,, R. D. Cummings,, and R. P. McEver. 2003. Structurally distinct requirements for binding of P-selectin glycoprotein ligand-1 and sialyl Lewis x to Anaplasma phagocytophilum and P-selectin. J. Biol. Chem. 278: 37987– 37997.
144. Yoshiie, K.,, H. Y. Kim,, J. Mott,, and Y. Rikihisa. 2000. Intracellular infection by the human granulocytic ehrlichiosis agent inhibits human neutrophil apoptosis. Infect. Immun. 68: 1125– 1133.
145. Zeidner, N. S.,, T. R. Burkot,, R. Massung,, W. L. Nicholson,, M. C. Dolan,, J. S. Rutherford,, B. J. Biggerstaff,, and G. O. Maupin. 2000. Transmission of the agent of human granulocytic ehrlichiosis by Ixodes spinipalpis ticks: evidence of an enzootic cycle of dual infection with Borrelia burgdorferi in northern Colorado. J. Infect. Dis. 182: 616– 619.
146. Zhi, N.,, N. Ohashi,, Y. Rikihisa,, H. W. Horowitz,, G. P. Wormser,, and K. Hechemy. 1998. Cloning and expression of the 44-kilodalton major outer membrane protein gene of the human granulocytic ehrlichiosis agent and application of the recombinant protein to serodiagnosis. J. Clin. Microbiol. 36: 1666– 1673.

References: V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V.