Seroprevalence of Anaplasma phagocytophilum in patients with suspected Lyme borreliosis

Authors: M. Dvořáková Heroldová;  M. Dvořáčková
Authors‘ workplace: Mikrobiologický ústav LF MU a FN u sv. Anny
Published in: Epidemiol. Mikrobiol. Imunol. 63, 2014, č. 4, s. 297-302
Category: Review articles, original papers, case report


Human granulocytic anaplasmosis (HGA) is an emerging tick-borne zoonotic disease caused by an obligate intracellular bacterium, Anaplasma phagocytophilum. In Europe, A. phagocytophilum is transmitted by Ixodes ricinus ticks. After Lyme borreliosis and European tick-borne encephalitis, HGA is the third most common tick-borne infection in the USA and Europe. The clinical symptoms of anaplasmosis are non-specific and include malaise, fever, headache, myalgia, and arthralgia. In more severe cases, the gastrointestinal or respiratory tract may be affected. However, most infections are asymptomatic.

The aim of our study
was to determine the seroprevalence of A. phagocytophilum in patients with suspected Lyme borreliosis.

A total of 314 sera from patients with suspected Lyme borreliosis were screened for IgG and IgM antibodies against A. phagocytophilum. The immunoblot assay was used to detect the antibodies.

Anti-A. phagocytophilum antibodies were detected in 34 patients, i.e. in 10.82 %. IgM antibodies were positive in 19 cases and IgG antibodies in 10 cases. Positivity to both IgM and IgG antibodies was revealed in five patients.

Antibodies against Borrelia burgdorferi sensu lato were detected in 181 patients (57.64 %). Co-seroprevalence of Borrelia burgdorferi s. l. and A. phagocytophilum was found in 26 patients (8.3 %).

Positivity for anti-A. phagocytophilum antibodies was most often seen in samples from the age group 60–69 years.

Our results show that A. phagocytophilum infection is not uncommon in the Czech Republic and should be considered in patients with a history of a tick bite.

human granulocytic anaplasmosis – Anaplasma phagocytophilum – seroprevalence – immunoblot – Lyme disease


1. Dumler JS, Barbet AF, Broker CP, Dasch GA, et al. 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., 2001;51:2145–2165.

2. Dumler JS, Madigan JE, Pusterla N, Bakken JS. Ehrlichioses in Humans: Epidemiology, clinical presentation, diagnosis, and treatment. Clin Infect Dis, 2007;45:S45–51.

3. Infekce v ČR - EPIDAT. Vybrané infekční nemoci v ČR v letech 2004–2013 [on line]. [cit. 2014-03-13] Dostupné z

4. Blanco JR, Oteo JA. Human granulocytic ehrlichiosis in Europe. Clin Microb Infect Dis, 2002;8:763–772.

5. Chen SM, Dumler JS, Bakken JS, Walker DH. Identification of granulocytotropic Ehrlichia species as the etiologic agent of human disease, J Clin Microbiol, 1994;32:589–595.

6. Petrovec M, Lotric-Furlan S, Zupanc TA, Strle F, et al. Human disease in Europe caused by a granulocytic Ehrlichia species. J Clin Microbiol, 1997;35:1156–1159.

7. Brouqui P, Bacellar F, Baranton G, Birtles RJ, et al. Guidelines for the diagnosis of tick-borne bacterial diseases in Europe. Clin Microbiol Infect, 2005;10:1108–1132.

8. Mastrandrea S, Mura MS, Tola S, Patta C, et al. Two cases of human granulocytic ehrlichiosis in Sardinia, Italy confirmed by PCR. Ann N Y Acad Sci, 2006;1078:548–551.

9. Nováková M, Víchová B, Majláthová V, Lesňáková A, et al. First case of human granylocytic anaplasmosis from Slovakia. Ann Agric Environ Med, 2010;17:173–175.

10. Vogl UM, Presterl E, Stanek G, Ramharter M, et al. First described case of human granulocytic anaplasmosis in patient in Eastern Austria. Wien Med Wochenschr, 2010;160:91–93.

11. Melter O, Stehlík I, Kinská H, Volfová I, et al. Infection with Anaplasma phagocytophilum in a young dog: a case report. Veterinární medicína, 2007;52:207–212.

12. Hulínská D, Votypka J, Plch J, Vlček E, et al. Molecular and microscopical evidence of Ehrlichia spp. and Borrelia burgdorferi sensu lato in patients, animals and ticks in the Czech republic. Microbiologica, 2002;25:437–448.

13. Stuen S, Granquist EG, Silaghi C. Anaplasma phagocytophilum – a widespread multi-host pathogen with highly adaptive strategie Frontiers in cellular and infection mikrobiology, 2013;3:1–33.

14. Ogden NH, Bown K, Horrocks BK, Woldehiwet Z, et al. Granulocytic Ehrlichia infection in ixodid ticks and mammals in woodlands and uplands of the U.K. Med Vet Entomol, 1998;12:423–429.

15. Ogden NH, Woldehiwet Z, Hart CA. Granulocytic ehrlichiosis: an emerging or rediscovered tick-borne disease? J Med Microbiol, 1998;47:475–482.

16. Scharf W, Schauer S, Freyburger F, Petrovec M, et al. Distinct host species correlate with Anaplasma phagocytophilum ankA gene clusters. J Clin Microbiol, 2011;49:790–796.

17. Parola P, Davoust B, Raoult D. Tick- and flea-borne rickettsial emerging zoonoses, Vet Res, 2005;36:469–492.

18. Bakken JS, Dumler JS. Human granulocytic ehrlichiosis. Clin Infect Dis, 2000;31:554–560.

19. Smrdel KS, Serdt M, Duh D, Knap N, et al. A. Anaplasma phagocytophilum in ticks in Slovenia. Parasit. Vectors, 2010;3: doi10.1186/1756-3305-3-102.

20. Šikutová S, Rudolf I, Golovchenko M, Rudenko N, et al. Detection of Anaplasma DNA in Ixodes ricinus ticks: Pitfalls. Folia Parasitologova, 2007;54:210–312.

21. Hulínská D, Votýpka JA, Holinková N, Kurzová Z, et al. Průkaz Borrelia, Anaplasma, Bartonella a Rickettsia sp. v klíšťatech Ixodes ricinus v roce 2007 a 2008 v pražských parcích. Zprávy CEM, 2009;18:167–171.

22. Venclíková K, Rudolf I, Mendel J, Betasova L, et al. Rickettsie in Ixodes ricinus ticks in the Czech Republic. Ticks Tick Borne Dis, 2014;5:135–138.

23. Dubská L, Literák I, Kverek P, Roubalová E, Kociánová E, Taragelová V. Tick-borne zoonotic pathogens in ticks feeding on the common ninghtingale including a novel strain of Rickettsia sp. Ticks Tick Borne Dis, 2012;3:265–268.

24. Thomas RJ, Dumler JS, Carlyon JA. Current managment of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis. Expert. Rev. Anti Infect Ther, 2009;7:709–722.

25. Dumler JS, Choi KS, Garcia-Garcia JC, Barat NS, et al. Human granulocytic anaplasmosis and Anapalsma phagocytophilum, Emerg Infect Dis, 2005;11(12):1828–1834.

26. Lotric-Furlan S, Strle F. Thrombocytopenia - a common finding in the initial phase of tick-borne encephalitis. Infection, 1995;23:203–206.

27. Lotric-Furlan S, Petrovec M, Avsic-Zupanc T, Strle F. Concomitant tick-borne encephalitis and human granulocytic ehrlichiosis. Emerg Infect Dis, 2005;11:485–488.

28. Bakken JS, Dumler JS. Clinical diagnosis and treatment of human granulocytotropic anaplasmosis. Ann NY Acad Sci, 2006;1078:236–247.

29. Dumler JS. The biological basis of severe outcomes in Anaplasma phagocytophilum infection. FEMS Immunol Med Microbiol, 2012;64:13–20.

30. Remy V, Hansmann Y, De Martino S, Christmann D, et al. Human anaplasmosis presenting as atypical pneumonitis in France. Clin Infect Dis, 2003;37:846–848.

31. Swanson SJ, Neitzel D, Reed KD, Belongia EA. Coinfections acquired from Ixodes ticks. Clin Microbiol Reviews, 2006;19:708–727.

32. Lin M, Rikihisa Y. Ehrlichia chaffeensis and Anaplasma phagocytophilum lack genes for lipid A biosynthesis and incorporate cholesterol for their survival. Infect Immun, 2003;71:5324–5331.

33. Bakken JS, Haller I, Riddell D, Walls JJ, et al. The serological response of patiens infected with the agent of human granulocytic ehrlichiosis. Clin Infect Dis, 2002;34:22–27.

34. Aureli S, Foley JE, Galuppi R, Rejmanek D, et al. Anaplasma phagocytophilum in ticks from parks in the Emilia-Romagna region of northern Italy. Veterinaria Italiana, 2012;48:413–423.

35. Alleman AR, Barbet AF, Sorenson HL, Strik NI, et al. Cloning and expression of the gene encoding the major surface protein 5 (MPSP5) of Anaplasma phagocytophilum and potential application for serodiagnosis. Vet Clin Pathol, 2006;35:418–425.

36. Magnarelli LA, Jdo JW, Ramakrishnan U, Henderson DW, Stafford III KC, Fikrig E. Use of recombinant antigens of Borrelia burgdorferi and Anaplasma phagocytophilum in enzyme-linked immunosorbent assay to detect antibodies in white-tailed deer. J Wildlife Dis, 2004;40:249–258.

37. Hansen MG, Christoffersen M, Thuesen LR, Petersen MR, et al. Seroprevalence of Borrelia burgdorferi and Anaplasma phagocytophilum in Danish horses. Acta Vet Scand, 2010;52:doi: 10.1186/1751-0147-52-3.

38. Woldehiwet Z, Yavari C. Evaluation of an indirect enzyme-linked immunosorbent assay (ELISA) for detection of antibodies against Anaplasma phagocytophilum in sheep. J Comp Pathol, 2012; 146:116–121.

39. Graf PCF, Chretien JP, Ung L, Gaydos JC, et al. Prevalence of seropositivity to spoted fever group rickettsiae and Anaplasma phagocytophilum in a large, demographically diverse US Sample. Clin Infect Dis, 2008;46:70–77.

40. Heo EJ, Park JH, Koo RJ, Park MS, et al. S. Serologic and molecular detection of Ehrlichia chaffeensis and Anaplasma phagocytophilum (human granulocytic ehrlichiosis agent) in Korean patiens. J Clin Microbiol, 2002;40:3082–3085.

41. Zeman P, Pazdiora P, Chmelík V, Januska J, et al. Epidemiological survey of tick-borne encephalitis virus and Anaplasma phagocytophilum co-infections in patiens from regions of the Czech republic endemic for tick-borne diseases. Wien Klin Wochenschr, 2007;119/17-18:538–543.

42. IJdo JW, Zhang Y, Hodzic E, Magnarelli LA, et al. The early hukotal response in human granuocytic ehrlichiosis. J Infect Dis, 1997;176:687–692.

43. Zhi N, Ohashi N, Rikihisa Y, Horowitz HW, et al. Cloning and expres-sion of the 44-kilodalton major outer membráně protein gene of the human granulocytic ehrlichiosis agent and application of the recombinant protein to serodiagnosis. J Clin Microbiol, 1998;36:1666–1673.

44. Magnarelli L, IJdo J, Wu C, Fikrig E. Recombinant protein-44-based class-specific enzyme-linked immunosorbent assay for serologic diagnosis of human granulocytic ehrlichiosis. Eur J Clin microbiol Infect Dis, 2001;20:482–485.

45. Strle F. Human granulocytic ehrlichiosis in Europe. Int J Med Microbiol, 2004;293 suppl. 37:27–35.

46. Oteo JA, Gil H, Barral M, Perez A, et al. Presence of granulocytic ehrlichia in ticks and serological evidence of human infection in La Rioja, Spain. Epidemiol Infect, 2001;127:353–358.

47. Tomasiewicz K, Modrzewska R, Buczek A, Stańczak J, et al. The risk of exposure to Anaplasma phagocytophilum infection in mid-eastern Poland. Ann Agric Environ Med, 2004;11:261–264.

48. Chmielewska-Badora J, Moniuszko A, Żukiewicz-Sobczak W, Zwoliński J, et al. Serological survey in persons occupationally exposed to tick-borne pathogens in cases of co-infections with Borrelia burgdorferi, Anaplasma phagocytophilum, Bartonella spp. and Babesia microti. Ann Agric Environ Med, 2012;19:271–274.

49. Walder G, Tiwald G, Dietrich MP, Würzner R. Serological evidence for human granulocytic ehrlichiosis in Western Austria. Eur J Clin Microbiol Infect Dis, 2003;22:543–547.

50. Fingerle V, Goodman JL, Johnson RC, Kurtti TJ, et al. Human granulocytic ehrlichiosis in southern Germany: increased seroprevalence in high-risk groups. J Clin Microbiol, 1997;35:3244–3247.

51. Hunfeld KP, Brade V. Prevalence of antibodies against the human granulocytic ehrlichiosis agent in Lyme borreliosis patiens from Germany. Eur J Clin Microbiol Infect Dis, 1999;18:221–224.

52. Woessner R, Gaertner BC, Grauer MT, Weber K, et al. Incidence and prevalence of infection with human granulocytic ehrlichiosis agent in Germany. A prospective study in young healthy subjects. Infection, 2001;29:271–273.

53. Chochlakis D, Papaeustathious A, Minadakis G, Osaroulaki A, et al. A serosurvey of Anaplasma phagocytophilum in blood donors in Crete, Greece. Eur J Clin Microbiol Infect Dis, 2008;27:473–475.

54. Santino I, Cammarata E, Franco S, Galdiero F, et al. Multicentric study of seroprevalence of Borrelia burgdorferi and Anaplasma phagocytophilum in high-risk groups in regions of central and southern Italy. Int J Immunopathol Pharmacol, 2004;17:219–223.

55. Thomas DR, Sillis M, Coleman TJ, Kench SM, et al. Low rates of ehrlichiosis and Lyme borreliosis in English farmworkers. Epidemiol Infect, 1998;121:609–614.

56. Wittesjö B, Bjöersdorff A, Eliasson I, Berglund J. First long-term study of the seroresponse to the agent of human granulocytic ehrlichiosis aminy resident sof a tick-endemic area of Sweden. Eur J Clin Microbiol Infect Dis, 2001;20:173–178.

57. Kociánová E, Košťanová Z, Štefanidesová K, Špitálská E, Boldiš V, Hučková D, Stanek G. Serologic evidence of Anaplasma phgocytophilum infections in patiens with a history of tick bite in central Slovakia. Wien Klin Wochenschr, 2008;120/13-14:427–431.

58. Kalinová Z, Halánová M, Čisláková L, Sulinová Z, et al. Occurence of IgG antibodies to Anaplasma phagocytophilum in humans suspected of Lyme borreliosis in eastern Slovakia. Ann Agric Environ Med, 2009;16:285–288.

59. Balátová P, Kurzová Z, Hulínská D. Sérologie lymeské borreliózy a humánní granulocytární ehrlichiózy v letech 2005–2010. Epidemiol Mikrobiol Imunol, 2011;60:74–76.

60. Zeman P, Pazdiora P, Cintal J. HGE antibodies in sera of patiens with TBE in the Czech Republic. Int J Med Microbiol, 2002;291 Suppl. 33:190–193.

61. Hulínská D, Votýpka JA, Vaňousová D, Hercogová J, et al. Identification of Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato in Patiens with Erythema Migrans. Folia Microbiol, 2009;54:246–256.

62. Lásiková Š, Pícha D, Moravcová L. Sérové HGE (human granulocytic ehrlichiosis) protilátky u pacientů s lymeskou boréliózou v České republice. Klin Mikrobiol Inf Lék, 2000;6:112–115.

63. Horowitz HW, Aguero-Rosenfeld ME, Holmgren D, McKenna D, et al. Lyme disease and human granulocytic anaplasmosis coinfection: Impact of case definition on coinfection rates and illness severity. Clin Infect Dis, 2013;56:93–99.

Hygiene and epidemiology Medical virology Clinical microbiology
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account