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. 1996 Jan-Mar;2(1):18–29. doi: 10.3201/eid0201.960102

Emergence of the ehrlichioses as human health problems.

D H Walker 1, J S Dumler 1
PMCID: PMC2639805  PMID: 8903194

Abstract

Ehrlichiae are small, gram-negative, obligately intracellular bacteria that reside within a phagosome. The first human ehrlichial infection was recognized in the United States in 1987. It was later shown to be caused by a new species, Ehrlichia chaffeensis. In 1994, an ehrlichial pathogen within neutrophils that is closely related to the known veterinary pathogens E. equi and E. phagocytophila was found to infect humans. Molecular methods were required to detect, characterize, and identify these fastidious and uncultivated bacteria. Subsequently, E. chaffeensis infection was documented in more than 400 patients in 30 states, Europe, and Africa. Likewise, approximately 170 cases of human granulocytic ehrlichiosis have been diagnosed, most since 1994, predominantly in the upper midwestern and northeastern states, but also in northern California. The disease caused by ehrlichiae is generally undifferentiated but is often associated with leukopenia, thrombocytopenia, and elevated serum hepatic transaminase levels in tick-exposed patients. Infection ranges from subclinical to fatal; tetracycline appears to be an effective therapy. The emergence of these two newly recognized tickborne infections as threats to human health is probably due to increased clinical cognizance, but as in other emerging tickborne infections, it is likely that the rapid increase in identified cases signals a true emergence of disease associated with a changing vector-host ecology.

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Selected References

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  1. Anderson B. E., Dawson J. E., Jones D. C., Wilson K. H. Ehrlichia chaffeensis, a new species associated with human ehrlichiosis. J Clin Microbiol. 1991 Dec;29(12):2838–2842. doi: 10.1128/jcm.29.12.2838-2842.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson B. E., Greene C. E., Jones D. C., Dawson J. E. Ehrlichia ewingii sp. nov., the etiologic agent of canine granulocytic ehrlichiosis. Int J Syst Bacteriol. 1992 Apr;42(2):299–302. doi: 10.1099/00207713-42-2-299. [DOI] [PubMed] [Google Scholar]
  3. Anderson B. E., Sims K. G., Olson J. G., Childs J. E., Piesman J. F., Happ C. M., Maupin G. O., Johnson B. J. Amblyomma americanum: a potential vector of human ehrlichiosis. Am J Trop Med Hyg. 1993 Aug;49(2):239–244. doi: 10.4269/ajtmh.1993.49.239. [DOI] [PubMed] [Google Scholar]
  4. Anderson B. E., Sumner J. W., Dawson J. E., Tzianabos T., Greene C. R., Olson J. G., Fishbein D. B., Olsen-Rasmussen M., Holloway B. P., George E. H. Detection of the etiologic agent of human ehrlichiosis by polymerase chain reaction. J Clin Microbiol. 1992 Apr;30(4):775–780. doi: 10.1128/jcm.30.4.775-780.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bakken J. S., Dumler J. S., Chen S. M., Eckman M. R., Van Etta L. L., Walker D. H. Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging? JAMA. 1994 Jul 20;272(3):212–218. [PubMed] [Google Scholar]
  6. Bakken J. S., Krueth J., Wilson-Nordskog C., Tilden R. L., Asanovich K., Dumler J. S. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA. 1996 Jan 17;275(3):199–205. [PubMed] [Google Scholar]
  7. Barnewall R. E., Rikihisa Y. Abrogation of gamma interferon-induced inhibition of Ehrlichia chaffeensis infection in human monocytes with iron-transferrin. Infect Immun. 1994 Nov;62(11):4804–4810. doi: 10.1128/iai.62.11.4804-4810.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brouqui P., Dumler J. S., Lienhard R., Brossard M., Raoult D. Human granulocytic ehrlichiosis in Europe. Lancet. 1995 Sep 16;346(8977):782–783. doi: 10.1016/s0140-6736(95)91544-3. [DOI] [PubMed] [Google Scholar]
  9. Brouqui P., Raoult D. In vitro antibiotic susceptibility of the newly recognized agent of ehrlichiosis in humans, Ehrlichia chaffeensis. Antimicrob Agents Chemother. 1992 Dec;36(12):2799–2803. doi: 10.1128/aac.36.12.2799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Caldwell C. W., Everett E. D., McDonald G., Yesus Y. W., Roland W. E. Lymphocytosis of gamma/delta T cells in human ehrlichiosis. Am J Clin Pathol. 1995 Jun;103(6):761–766. doi: 10.1093/ajcp/103.6.761. [DOI] [PubMed] [Google Scholar]
  11. Centers for Disease Control and Prevention (CDC) Human granulocytic ehrlichiosis--New York, 1995. MMWR Morb Mortal Wkly Rep. 1995 Aug 18;44(32):593–595. [PubMed] [Google Scholar]
  12. Chen S. M., Dumler J. S., Bakken J. S., Walker D. H. Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease. J Clin Microbiol. 1994 Mar;32(3):589–595. doi: 10.1128/jcm.32.3.589-595.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chen S. M., Dumler J. S., Feng H. M., Walker D. H. Identification of the antigenic constituents of Ehrlichia chaffeensis. Am J Trop Med Hyg. 1994 Jan;50(1):52–58. [PubMed] [Google Scholar]
  14. Chen S. M., Popov V. L., Feng H. M., Wen J., Walker D. H. Cultivation of Ehrlichia chaffeensis in mouse embryo, Vero, BGM, and L929 cells and study of Ehrlichia-induced cytopathic effect and plaque formation. Infect Immun. 1995 Feb;63(2):647–655. doi: 10.1128/iai.63.2.647-655.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dawson J. E., Anderson B. E., Fishbein D. B., Sanchez J. L., Goldsmith C. S., Wilson K. H., Duntley C. W. Isolation and characterization of an Ehrlichia sp. from a patient diagnosed with human ehrlichiosis. J Clin Microbiol. 1991 Dec;29(12):2741–2745. doi: 10.1128/jcm.29.12.2741-2745.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dawson J. E., Ewing S. A. Susceptibility of dogs to infection with Ehrlichia chaffeensis, causative agent of human ehrlichiosis. Am J Vet Res. 1992 Aug;53(8):1322–1327. [PubMed] [Google Scholar]
  17. Dawson J. E., Stallknecht D. E., Howerth E. W., Warner C., Biggie K., Davidson W. R., Lockhart J. M., Nettles V. F., Olson J. G., Childs J. E. Susceptibility of white-tailed deer (Odocoileus virginianus) to infection with Ehrlichia chaffeensis, the etiologic agent of human ehrlichiosis. J Clin Microbiol. 1994 Nov;32(11):2725–2728. doi: 10.1128/jcm.32.11.2725-2728.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Dumler J. S., Asanovich K. M., Bakken J. S., Richter P., Kimsey R., Madigan J. E. Serologic cross-reactions among Ehrlichia equi, Ehrlichia phagocytophila, and human granulocytic Ehrlichia. J Clin Microbiol. 1995 May;33(5):1098–1103. doi: 10.1128/jcm.33.5.1098-1103.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Dumler J. S., Brouqui P., Aronson J., Taylor J. P., Walker D. H. Identification of Ehrlichia in human tissue. N Engl J Med. 1991 Oct 10;325(15):1109–1110. doi: 10.1056/NEJM199110103251517. [DOI] [PubMed] [Google Scholar]
  20. Dumler J. S., Chen S. M., Asanovich K., Trigiani E., Popov V. L., Walker D. H. Isolation and characterization of a new strain of Ehrlichia chaffeensis from a patient with nearly fatal monocytic ehrlichiosis. J Clin Microbiol. 1995 Jul;33(7):1704–1711. doi: 10.1128/jcm.33.7.1704-1711.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Dumler J. S., Dawson J. E., Walker D. H. Human ehrlichiosis: hematopathology and immunohistologic detection of Ehrlichia chaffeensis. Hum Pathol. 1993 Apr;24(4):391–396. doi: 10.1016/0046-8177(93)90087-w. [DOI] [PubMed] [Google Scholar]
  22. Dumler J. S., Sutker W. L., Walker D. H. Persistent infection with Ehrlichia chaffeensis. Clin Infect Dis. 1993 Nov;17(5):903–905. doi: 10.1093/clinids/17.5.903. [DOI] [PubMed] [Google Scholar]
  23. Dunn B. E., Monson T. P., Dumler J. S., Morris C. C., Westbrook A. B., Duncan J. L., Dawson J. E., Sims K. G., Anderson B. E. Identification of Ehrlichia chaffeensis morulae in cerebrospinal fluid mononuclear cells. J Clin Microbiol. 1992 Aug;30(8):2207–2210. doi: 10.1128/jcm.30.8.2207-2210.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Eng T. R., Harkess J. R., Fishbein D. B., Dawson J. E., Greene C. N., Redus M. A., Satalowich F. T. Epidemiologic, clinical, and laboratory findings of human ehrlichiosis in the United States, 1988. JAMA. 1990 Nov 7;264(17):2251–2258. [PubMed] [Google Scholar]
  25. Everett E. D., Evans K. A., Henry R. B., McDonald G. Human ehrlichiosis in adults after tick exposure. Diagnosis using polymerase chain reaction. Ann Intern Med. 1994 May 1;120(9):730–735. doi: 10.7326/0003-4819-120-9-199405010-00002. [DOI] [PubMed] [Google Scholar]
  26. Ewing S. A., Dawson J. E., Kocan A. A., Barker R. W., Warner C. K., Panciera R. J., Fox J. C., Kocan K. M., Blouin E. F. Experimental transmission of Ehrlichia chaffeensis (Rickettsiales: Ehrlichieae) among white-tailed deer by Amblyomma americanum (Acari: Ixodidae). J Med Entomol. 1995 May;32(3):368–374. doi: 10.1093/jmedent/32.3.368. [DOI] [PubMed] [Google Scholar]
  27. Fichtenbaum C. J., Peterson L. R., Weil G. J. Ehrlichiosis presenting as a life-threatening illness with features of the toxic shock syndrome. Am J Med. 1993 Oct;95(4):351–357. doi: 10.1016/0002-9343(93)90302-6. [DOI] [PubMed] [Google Scholar]
  28. Fishbein D. B., Dawson J. E., Robinson L. E. Human ehrlichiosis in the United States, 1985 to 1990. Ann Intern Med. 1994 May 1;120(9):736–743. doi: 10.7326/0003-4819-120-9-199405010-00003. [DOI] [PubMed] [Google Scholar]
  29. Fishbein D. B., Kemp A., Dawson J. E., Greene N. R., Redus M. A., Fields D. H. Human ehrlichiosis: prospective active surveillance in febrile hospitalized patients. J Infect Dis. 1989 Nov;160(5):803–809. doi: 10.1093/infdis/160.5.803. [DOI] [PubMed] [Google Scholar]
  30. Groves M. G., Dennis G. L., Amyx H. L., Huxsoll D. L. Transmission of Ehrlichia canis to dogs by ticks (Rhipicephalus sanguineus). Am J Vet Res. 1975 Jul;36(7):937–940. [PubMed] [Google Scholar]
  31. Hardalo C. J., Quagliarello V., Dumler J. S. Human granulocytic ehrlichiosis in Connecticut: report of a fatal case. Clin Infect Dis. 1995 Oct;21(4):910–914. doi: 10.1093/clinids/21.4.910. [DOI] [PubMed] [Google Scholar]
  32. Harkess J. R., Ewing S. A., Crutcher J. M., Kudlac J., McKee G., Istre G. R. Human ehrlichiosis in Oklahoma. J Infect Dis. 1989 Mar;159(3):576–579. doi: 10.1093/infdis/159.3.576. [DOI] [PubMed] [Google Scholar]
  33. Johansson K. E., Pettersson B., Uhlén M., Gunnarsson A., Malmqvist M., Olsson E. Identification of the causative agent of granulocytic ehrlichiosis in Swedish dogs and horses by direct solid phase sequencing of PCR products from the 16S rRNA gene. Res Vet Sci. 1995 Mar;58(2):109–112. doi: 10.1016/0034-5288(95)90061-6. [DOI] [PubMed] [Google Scholar]
  34. Larsen H. J., Overnes G., Waldeland H., Johansen G. M. Immunosuppression in sheep experimentally infected with Ehrlichia phagocytophila. Res Vet Sci. 1994 Mar;56(2):216–224. doi: 10.1016/0034-5288(94)90107-4. [DOI] [PubMed] [Google Scholar]
  35. Lewis G. E., Jr, Hill S. L., Ristic M. Effect of canine immune serum on the growth of Ehrlichia canis within nonimmune canine macrophages. Am J Vet Res. 1978 Jan;39(1):71–76. [PubMed] [Google Scholar]
  36. Lewis G. E., Jr, Huxsoll D. L., Ristic M., Johnson A. J. Experimentally induced infection of dogs, cats, and nonhuman primates with Ehrlichia equi, etiologic agent of equine ehrlichiosis. Am J Vet Res. 1975 Jan;36(1):85–88. [PubMed] [Google Scholar]
  37. Lockhart J. M., Davidson W. R., Dawson J. E., Stallknecht D. E. Temporal association of Amblyomma americanum with the presence of Ehrlichia chaffeensis reactive antibodies in white-tailed deer. J Wildl Dis. 1995 Apr;31(2):119–124. doi: 10.7589/0090-3558-31.2.119. [DOI] [PubMed] [Google Scholar]
  38. Madewell B. R., Gribble D. H. Infection in two dogs with an agent resembling Ehrlichia equi. J Am Vet Med Assoc. 1982 Mar 1;180(5):512–514. [PubMed] [Google Scholar]
  39. Madigan J. E., Richter P. J., Jr, Kimsey R. B., Barlough J. E., Bakken J. S., Dumler J. S. Transmission and passage in horses of the agent of human granulocytic ehrlichiosis. J Infect Dis. 1995 Oct;172(4):1141–1144. doi: 10.1093/infdis/172.4.1141. [DOI] [PubMed] [Google Scholar]
  40. Maeda K., Markowitz N., Hawley R. C., Ristic M., Cox D., McDade J. E. Human infection with Ehrlichia canis, a leukocytic rickettsia. N Engl J Med. 1987 Apr 2;316(14):853–856. doi: 10.1056/NEJM198704023161406. [DOI] [PubMed] [Google Scholar]
  41. Magnarelli L. A., Stafford K. C., 3rd, Mather T. N., Yeh M. T., Horn K. D., Dumler J. S. 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. 1995 Oct;33(10):2710–2714. doi: 10.1128/jcm.33.10.2710-2714.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Morais J. D., Dawson J. E., Greene C., Filipe A. R., Galhardas L. C., Bacellar F. First European case of ehrlichiosis. Lancet. 1991 Sep 7;338(8767):633–634. doi: 10.1016/0140-6736(91)90644-5. [DOI] [PubMed] [Google Scholar]
  43. Moskovitz M., Fadden R., Min T. Human ehrlichiosis: a rickettsial disease associated with severe cholestasis and multisystemic disease. J Clin Gastroenterol. 1991 Feb;13(1):86–90. [PubMed] [Google Scholar]
  44. Ohashi N., Fukuhara M., Shimada M., Tamura A. Phylogenetic position of Rickettsia tsutsugamushi and the relationship among its antigenic variants by analyses of 16S rRNA gene sequences. FEMS Microbiol Lett. 1995 Jan 15;125(2-3):299–304. doi: 10.1111/j.1574-6968.1995.tb07372.x. [DOI] [PubMed] [Google Scholar]
  45. Paddock C. D., Suchard D. P., Grumbach K. L., Hadley W. K., Kerschmann R. L., Abbey N. W., Dawson J. E., Anderson B. E., Sims K. G., Dumler J. S. Brief report: fatal seronegative ehrlichiosis in a patient with HIV infection. N Engl J Med. 1993 Oct 14;329(16):1164–1167. doi: 10.1056/NEJM199310143291605. [DOI] [PubMed] [Google Scholar]
  46. Pancholi P., Kolbert C. P., Mitchell P. D., Reed K. D., Jr, Dumler J. S., Bakken J. S., Telford S. R., 3rd, Persing D. H. Ixodes dammini as a potential vector of human granulocytic ehrlichiosis. J Infect Dis. 1995 Oct;172(4):1007–1012. doi: 10.1093/infdis/172.4.1007. [DOI] [PubMed] [Google Scholar]
  47. Pretzman C., Ralph D., Stothard D. R., Fuerst P. A., Rikihisa Y. 16S rRNA gene sequence of Neorickettsia helminthoeca and its phylogenetic alignment with members of the genus Ehrlichia. Int J Syst Bacteriol. 1995 Apr;45(2):207–211. doi: 10.1099/00207713-45-2-207. [DOI] [PubMed] [Google Scholar]
  48. Relman D. A., Loutit J. S., Schmidt T. M., Falkow S., Tompkins L. S. The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens. N Engl J Med. 1990 Dec 6;323(23):1573–1580. doi: 10.1056/NEJM199012063232301. [DOI] [PubMed] [Google Scholar]
  49. Richter P. J., Jr, Kimsey R. B., Madigan J. E., Barlough J. E., Dumler J. S., Brooks D. L. Ixodes pacificus (Acari: Ixodidae) as a vector of Ehrlichia equi (Rickettsiales: Ehrlichieae). J Med Entomol. 1996 Jan;33(1):1–5. doi: 10.1093/jmedent/33.1.1. [DOI] [PubMed] [Google Scholar]
  50. Rikihisa Y. The tribe Ehrlichieae and ehrlichial diseases. Clin Microbiol Rev. 1991 Jul;4(3):286–308. doi: 10.1128/cmr.4.3.286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Roland W. E., McDonald G., Caldwell C. W., Everett E. D. Ehrlichiosis--a cause of prolonged fever. Clin Infect Dis. 1995 Apr;20(4):821–825. doi: 10.1093/clinids/20.4.821. [DOI] [PubMed] [Google Scholar]
  52. Smith R. D., Sells D. M., Stephenson E. H., Ristic M. R., Huxsoll D. L. Development of Ehrlichia canis, causative agent of canine ehrlichiosis, in the tick Rhipicephalus sanguineus and its differentiation from a symbiotic Rickettsia. Am J Vet Res. 1976 Feb;37(2):119–126. [PubMed] [Google Scholar]
  53. Standaert S. M., Dawson J. E., Schaffner W., Childs J. E., Biggie K. L., Singleton J., Jr, Gerhardt R. R., Knight M. L., Hutcheson R. H. Ehrlichiosis in a golf-oriented retirement community. N Engl J Med. 1995 Aug 17;333(7):420–425. doi: 10.1056/NEJM199508173330704. [DOI] [PubMed] [Google Scholar]
  54. Sumner J. W., Sims K. G., Jones D. C., Anderson B. E. Ehrlichia chaffeensis expresses an immunoreactive protein homologous to the Escherichia coli GroEL protein. Infect Immun. 1993 Aug;61(8):3536–3539. doi: 10.1128/iai.61.8.3536-3539.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Tamura A., Ohashi N., Urakami H., Miyamura S. Classification of Rickettsia tsutsugamushi in a new genus, Orientia gen. nov., as Orientia tsutsugamushi comb. nov. Int J Syst Bacteriol. 1995 Jul;45(3):589–591. doi: 10.1099/00207713-45-3-589. [DOI] [PubMed] [Google Scholar]
  56. Telford S. R., 3rd, Lepore T. J., Snow P., Warner C. K., Dawson J. E. Human granulocytic ehrlichiosis in Massachusetts. Ann Intern Med. 1995 Aug 15;123(4):277–279. doi: 10.7326/0003-4819-123-4-199508150-00006. [DOI] [PubMed] [Google Scholar]
  57. Tuomi J. Experimental studies on bovine tick-borne fever. 2. Differences in virulence of strains in cattle and sheep. Acta Pathol Microbiol Scand. 1967;70(4):577–589. [PubMed] [Google Scholar]
  58. Wen B., Rikihisa Y., Mott J., Fuerst P. A., Kawahara M., Suto C. Ehrlichia muris sp. nov., identified on the basis of 16S rRNA base sequences and serological, morphological, and biological characteristics. Int J Syst Bacteriol. 1995 Apr;45(2):250–254. doi: 10.1099/00207713-45-2-250. [DOI] [PubMed] [Google Scholar]
  59. Williams J. D., Snow R. M., Arciniegas J. G. Myocardial involvement in a patient with human ehrlichiosis. Am J Med. 1995 Apr;98(4):414–415. doi: 10.1016/S0002-9343(99)80324-6. [DOI] [PubMed] [Google Scholar]
  60. Wilson K. H., Blitchington R. B., Greene R. C. Amplification of bacterial 16S ribosomal DNA with polymerase chain reaction. J Clin Microbiol. 1990 Sep;28(9):1942–1946. doi: 10.1128/jcm.28.9.1942-1946.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Woldehiwet Z. The effects of tick-borne fever on some functions of polymorphonuclear cells of sheep. J Comp Pathol. 1987 Jul;97(4):481–485. doi: 10.1016/0021-9975(87)90026-0. [DOI] [PubMed] [Google Scholar]
  62. Yevich S. J., Sánchez J. L., DeFraites R. F., Rives C. C., Dawson J. E., Uhaa I. J., Johnson B. J., Fishbein D. B. Seroepidemiology of infections due to spotted fever group rickettsiae and Ehrlichia species in military personnel exposed in areas of the United States where such infections are endemic. J Infect Dis. 1995 May;171(5):1266–1273. doi: 10.1093/infdis/171.5.1266. [DOI] [PubMed] [Google Scholar]
  63. Yu X., Brouqui P., Dumler J. S., Raoult D. Detection of Ehrlichia chaffeensis in human tissue by using a species-specific monoclonal antibody. J Clin Microbiol. 1993 Dec;31(12):3284–3288. doi: 10.1128/jcm.31.12.3284-3288.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

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