Volume 96, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Human granulocytic anaplasmosis (HGA) is a tick-borne rickettsial zoonosis with fever, thrombocytopenia, and leukopenia. HGA has been reported in Korea in 2013 but it is uncertain how long it has existed. A retrospective study was conducted on patients who underwent bone marrow examination due to fever and cytopenia, with no clear hematologic or microbiologic causes, from 2003 through 2012. Laboratory diagnosis was made by detecting 16S rRNA genes of from the stored blood samples. Among the 70 patients, five (7.1%) HGA cases were found, and the earliest case dated back to 2006. Two cases met the diagnostic criteria of hemophagocytic lymphohistiocytosis (HLH) and were fatal. Although HGA has been prevalent in Korea since at least 2006, it is not always diagnosed and has posed a possible lethal health risk to the people in Korea. HGA should be considered as a cause of fever with cytopenia or HLH.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Raoult D, Roux V, , 1997. Rickettsioses as paradigms of new or emerging infectious diseases. Clin Microbiol Rev 10: 694719. [Google Scholar]
  2. Jensenius M, Davis X, von Sonnenburg F, Schwartz E, Keystone JS, Leder K, Lopez-Velez R, Caumes E, Cramer JP, Chen L, Parola P, GeoSentinel Surveillance Network; , 2009. Multicenter GeoSentinel analysis of rickettsial diseases in international travelers, 1996–2008. Emerg Infect Dis 15: 17911798.[Crossref] [Google Scholar]
  3. Botelho-Nevers E, Raoult D, , 2007. Fever of unknown origin due to rickettsioses. Infect Dis Clin North Am 21: 9971011, ix.[Crossref] [Google Scholar]
  4. Bleeker-Rovers CP, Vos FJ, de Kleijn EM, Mudde AH, Dofferhoff TS, Richter C, Smilde TJ, Krabbe PF, Oyen WJ, van der Meer JW, , 2007. A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol. Medicine (Baltimore) 86: 2638.[Crossref] [Google Scholar]
  5. Bakken JS, Dumler JS, , 2006. Clinical diagnosis and treatment of human granulocytotropic anaplasmosis. Ann N Y Acad Sci 1078: 236247.[Crossref] [Google Scholar]
  6. Dumler JS, Choi KS, Garcia-Garcia JC, Barat NS, Scorpio DG, Garyu JW, Grab DJ, Bakken JS, , 2005. Human granulocytic anaplasmosis and Anaplasma phagocytophilum . Emerg Infect Dis 11: 18281834.[Crossref] [Google Scholar]
  7. Dumler JS, Bakken JS, , 1998. Human ehrlichioses: newly recognized infections transmitted by ticks. Annu Rev Med 49: 201213.[Crossref] [Google Scholar]
  8. Dumler JS, Madigan JE, Pusterla N, Bakken JS, , 2007. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin Infect Dis 45 (Suppl 1): S45S51.[Crossref] [Google Scholar]
  9. Chen SM, Dumler JS, Bakken JS, Walker DH, , 1994. Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease. J Clin Microbiol 32: 589595. [Google Scholar]
  10. Petrovec M, Lotric Furlan S, Zupanc TA, Strle F, Brouqui P, Roux V, Dumler JS, , 1997. Human disease in Europe caused by a granulocytic Ehrlichia species. J Clin Microbiol 35: 15561559. [Google Scholar]
  11. Morais JD, Dawson JE, Greene C, Filipe AR, Galhardas LC, Bacellar F, , 1991. First European case of ehrlichiosis. Lancet 338: 633634.[Crossref] [Google Scholar]
  12. Centers for Disease Control and Prevention, 2013. Annual Cases of Anaplasmosis in the United States. Available at: http://www.cdc.gov/anaplasmosis/stats/index.html. Accessed December 23, 2014. [Google Scholar]
  13. Zhang L, Cui F, Wang L, Zhang L, Zhang J, Yang S, Han J, , 2009. Anaplasma phagocytophilum and Ehrlichia chaffeensis in Yiyuan County, Shandong. Infectious Disease Information 1: 2125. [Google Scholar]
  14. Ohashi N, Gaowa W, Kawamori F, Wu D, Yoshikawa Y, Chiya S, Fukunaga K, Funato T, Shiojiri M, Nakajima H, Hamauzu Y, Takano A, Kawabata H, Ando S, Kishimoto T, , 2013. Human granulocytic anaplasmosis, Japan. Emerg Infect Dis 19: 289292.[Crossref] [Google Scholar]
  15. Chae JS, Yu DH, Shringi S, Klein TA, Kim HC, Chong ST, Lee IY, Foley J, , 2008. Microbial pathogens in ticks, rodents and a shrew in northern Gyeonggi-do near the DMZ, Korea. J Vet Sci 9: 285293.[Crossref] [Google Scholar]
  16. Kang JG, Ko S, Kim YJ, Yang HJ, Lee H, Shin NS, Choi KS, Chae JS, , 2011. New genetic variants of Anaplasma phagocytophilum and Anaplasma bovis from Korean water deer (Hydropotes inermis argyropus). Vector Borne Zoonotic Dis 11: 929938.[Crossref] [Google Scholar]
  17. Chae JS, Kim CM, Kim EH, Hur EJ, Klein TA, Kang TK, Lee HC, Song JW, , 2003. Molecular epidemiological study for tick-borne disease (Ehrlichia and Anaplasma spp.) surveillance at selected U.S. military training sites/installations in Korea. Ann N Y Acad Sci 990: 118125.[Crossref] [Google Scholar]
  18. Kim CM, Kim MS, Park MS, Park JH, Chae JS, , 2003. Identification of Ehrlichia chaffeensis, Anaplasma phagocytophilum, and A. bovis in Haemaphysalis longicornis and Ixodes persulcatus ticks from Korea. Vector Borne Zoonotic Dis 3: 1726.[Crossref] [Google Scholar]
  19. Kim CM, Yi YH, Yu DH, Lee MJ, Cho MR, Desai AR, Shringi S, Klein TA, Kim HC, Song JW, Baek LJ, Chong ST, O'Guinn ML, Lee JS, Lee IY, Park JH, Foley J, Chae JS, , 2006. Tick-borne rickettsial pathogens in ticks and small mammals in Korea. Appl Environ Microbiol 72: 57665776.[Crossref] [Google Scholar]
  20. Sachar DS, , 2000. Ehrlichia chaffeensis infection in an active duty soldier stationed in Korea. Med Surveill Mon Rep 6: 911. [Google Scholar]
  21. Kim KH, Yi J, Oh WS, Kim NH, Choi SJ, Choe PG, Kim NJ, Lee JK, Oh MD, , 2014. Human granulocytic anaplasmosis, South Korea, 2013. Emerg Infect Dis 20: 17081711.[Crossref] [Google Scholar]
  22. Arnow PM, Flaherty JP, , 1997. Fever of unknown origin. Lancet 350: 575580.[Crossref] [Google Scholar]
  23. Hot A, Jaisson I, Girard C, French M, Durand DV, Rousset H, Ninet J, , 2009. Yield of bone marrow examination in diagnosing the source of fever of unknown origin. Arch Intern Med 169: 20182023.[Crossref] [Google Scholar]
  24. Center for Surveillance, Epidemiology, and Laboratory Services, 2008. Ehrlichiosis and Anaplasmosis. Available at: http://wwwn.cdc.gov/NNDSS/script/casedef.aspx?CondYrID=667&DatePub=1/1/2008%2012:00:00%20AM. Accessed December 25, 2014. [Google Scholar]
  25. Oh JY, Moon B-C, Bae BK, Shin E-H, Ko YH, Kim Y-J, Park YH, Chae J-S, , 2009. Genetic identification and phylogenetic analysis of Anaplasma and Ehrlichia species in Haemaphysalis longicornis collected from Jeju Island, Korea. J Bacteriol Virol 39: 257267.[Crossref] [Google Scholar]
  26. Levin ML, Nicholson WL, Massung RF, Sumner JW, Fish D, , 2002. Comparison of the reservoir competence of medium-sized mammals and Peromyscus leucopus for Anaplasma phagocytophilum in Connecticut. Vector Borne Zoonotic Dis 2: 125136.[Crossref] [Google Scholar]
  27. Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G, , 2007. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48: 124131.[Crossref] [Google Scholar]
  28. Dhand A, Nadelman RB, Aguero-Rosenfeld M, Haddad FA, Stokes DP, Horowitz HW, , 2007. Human granulocytic anaplasmosis during pregnancy: case series and literature review. Clin Infect Dis 45: 589593.[Crossref] [Google Scholar]
  29. Horowitz HW, Kilchevsky E, Haber S, Aguero-Rosenfeld M, Kranwinkel R, James EK, Wong SJ, Chu F, Liveris D, Schwartz I, , 1998. Perinatal transmission of the agent of human granulocytic ehrlichiosis. N Engl J Med 339: 375378.[Crossref] [Google Scholar]
  30. Lepidi H, Bunnell JE, Martin ME, Madigan JE, Stuen S, Dumler JS, , 2000. Comparative pathology, and immunohistology associated with clinical illness after Ehrlichia phagocytophila-group infections. Am J Trop Med Hyg 62: 2937. [Google Scholar]
  31. Dumler JS, Barat NC, Barat CE, Bakken JS, , 2007. Human granulocytic anaplasmosis and macrophage activation. Clin Infect Dis 45: 199204.[Crossref] [Google Scholar]
  32. Otrock ZK, Eby CS, , 2015. Clinical characteristics, prognostic factors and outcomes of adult patients with hemophagocytic lymphohistiocytosis. Am J Hematol 90: 220224.[Crossref] [Google Scholar]
  33. Parikh SA, Kapoor P, Letendre L, Kumar S, Wolanskyj AP, , 2014. Prognostic factors and outcomes of adults with hemophagocytic lymphohistiocytosis. Mayo Clin Proc 89: 484492.[Crossref] [Google Scholar]
  34. George MR, , 2014. Hemophagocytic lymphohistiocytosis: review of etiologies and management. J Blood Med 5: 6986.[Crossref] [Google Scholar]
  35. Cascio A, Pernice LM, Barberi G, Delfino D, Biondo C, Beninati C, Mancuso G, Rodriguez-Morales AJ, Iaria C, , 2012. Secondary hemophagocytic lymphohistiocytosis in zoonoses. A systematic review. Eur Rev Med Pharmacol Sci 16: 13241337. [Google Scholar]
  36. Kim N, Kim KH, Lee SJ, Park SH, Kim IS, Lee EY, Yi J, , 2016. Bone marrow findings in severe fever with thrombocytopenia syndrome: prominent haemophagocytosis and its implication in haemophagocytic lymphohistiocytosis. J Clin Pathol 69: 537541.[Crossref] [Google Scholar]
  37. Li J, Wang Q, Zheng W, Ma J, Zhang W, Wang W, Tian X, , 2014. Hemophagocytic lymphohistiocytosis: clinical analysis of 103 adult patients. Medicine (Baltimore) 93: 100105.[Crossref] [Google Scholar]
  38. Shabbir M, Lucas J, Lazarchick J, Shirai K, , 2011. Secondary hemophagocytic syndrome in adults: a case series of 18 patients in a single institution and a review of literature. Hematol Oncol 29: 100106.[Crossref] [Google Scholar]
  39. Filipovich A, McClain K, Grom A, , 2010. Histiocytic disorders: recent insights into pathophysiology and practical guidelines. Biol Blood Marrow Transplant 16: S82S89.[Crossref] [Google Scholar]
  40. Korea Centers for Disease Control and Prevention, 2014. Infectious Diseases Surveillance Yearbook, 2013. Cheongwon-gun, Republic of Korea: Korea Centers for Disease Control and Prevention. [Google Scholar]

Data & Media loading...

Supplemental Tables

  • Received : 18 Apr 2016
  • Accepted : 04 Dec 2016
  • Published online : 16 Jan 2017

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error