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Vol 10, No 3 (2017)
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Published online: 2017-10-25
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Babesiosis — a new challenge in transfusion medicine?

Joanna Szymczak, Adrian Syta, Katarzyna Tołkacz, Małgorzata Bednarska, Maria Joanna Doligalska
Journal of Transfusion Medicine 2017;10(3):90-98.

open access

Vol 10, No 3 (2017)
REVIEWS
Published online: 2017-10-25

Abstract

Babesiosis is a tick-transmitted human blood disease caused by protozoan parasite Babesia
microti. Recently, an increasing incidence of babesiosis has been observed outside endemic
areas. The source of a growing number of human infections are blood transfusions and organ
transplantations in the condition of therapeutic immunosuppression. Under such circumstances,
a latent babesiosis may develop into acute blood-stage disease accompanied by severe complications
and often fatal outcome. Unfortunately, currently available antimalarial drugs are
not effective against piroplasms. This may be due to different developmental strategies used by
both parasites inside infected erythrocytes. To establish new therapies, drugs that inhibit protozoa
divisions or damage nucleic acids are searched. To prevent Babesia transmission through
blood transfusion, parasite-inactivation technologies, which weaken protozoa viability and
reduce its infectivity, are used to purify blood. Additionally, there is a need to identify the mechanism
that is responsible for babesiosis relapse upon immunotherapy, in which lymphocytes
with regulatory functions play a key role.

Abstract

Babesiosis is a tick-transmitted human blood disease caused by protozoan parasite Babesia
microti. Recently, an increasing incidence of babesiosis has been observed outside endemic
areas. The source of a growing number of human infections are blood transfusions and organ
transplantations in the condition of therapeutic immunosuppression. Under such circumstances,
a latent babesiosis may develop into acute blood-stage disease accompanied by severe complications
and often fatal outcome. Unfortunately, currently available antimalarial drugs are
not effective against piroplasms. This may be due to different developmental strategies used by
both parasites inside infected erythrocytes. To establish new therapies, drugs that inhibit protozoa
divisions or damage nucleic acids are searched. To prevent Babesia transmission through
blood transfusion, parasite-inactivation technologies, which weaken protozoa viability and
reduce its infectivity, are used to purify blood. Additionally, there is a need to identify the mechanism
that is responsible for babesiosis relapse upon immunotherapy, in which lymphocytes
with regulatory functions play a key role.

Get Citation

Keywords

Babesia microti; blood transfusion; infection relapse; immunosuppression

About this article
Title

Babesiosis — a new challenge in transfusion medicine?

Journal

Journal of Transfusion Medicine

Issue

Vol 10, No 3 (2017)

Pages

90-98

Published online

2017-10-25

Bibliographic record

Journal of Transfusion Medicine 2017;10(3):90-98.

Keywords

Babesia microti
blood transfusion
infection relapse
immunosuppression

Authors

Joanna Szymczak
Adrian Syta
Katarzyna Tołkacz
Małgorzata Bednarska
Maria Joanna Doligalska

References (97)
  1. Paparini A, Senanayake SN, Ryan UM, et al. Molecular confirmation of the first autochthonous case of human babesiosis in Australia using a novel primer set for the beta-tubulin gene. Exp Parasitol. 2014; 141: 93–97.
  2. Hunfeld KP, Hildebrandt A, Gray JS. Babesiosis: recent insights into an ancient disease. Int J Parasitol. 2008; 38(11): 1219–1237.
  3. Herwaldt BL, Linden JV, Bosserman E, et al. Transfusion-associated babesiosis in the United States: a description of cases. Ann Intern Med. 2011; 155(8): 509–519.
  4. C R. Szczepiorkowski, Z. M. and Dunbar, N. Babesia parasitemia rebound after red blood cell exchange. J Clin Apheresis. ; 2016.
  5. Homer MJ, Aguilar-Delfin I, Telford SR, et al. Babesiosis. Clinical Microbiology Reviews. 2000; 13(3): 451–469.
  6. Leiby DA. Transfusion-associated babesiosis: shouldn't we be ticked off? Ann Intern Med. 2011; 155(8): 556–557.
  7. Herwaldt BL, McGovern PC, Gerwel MP, et al. Endemic babesiosis in another eastern state: New Jersey. Emerg Infect Dis. 2003; 9(2): 184–188.
  8. Holman MS, Caporale DA, Goldberg J, et al. Anaplasma phagocytophilum, Babesia microti, and Borrelia burgdorferi in Ixodes scapularis, southern coastal Maine. Emerg Infect Dis. 2004; 10(4): 744–746.
  9. Joseph JT, Roy SS, Shams N, et al. Babesiosis in Lower Hudson Valley, New York, USA. Emerg Infect Dis. 2011; 17(5): 843–847.
  10. Weld ED, Eimer KM, Saharia K, et al. Transfusion medicine illustrated. The expanding range and severity of babesiosis. Transfusion. 2010; 50(2): 290–291.
  11. Meldrum SC, Birkhead GS, White DJ, et al. Human babesiosis in New York State: an epidemiological description of 136 cases. Clin Infect Dis. 1992; 15(6): 1019–1023.
  12. White DJ, Talarico J, Chang HG, et al. Human babesiosis in New York State: Review of 139 hospitalized cases and analysis of prognostic factors. Arch Intern Med. 1998; 158(19): 2149–2154.
  13. Poisnel E, Ebbo M, Berda-Haddad Y, et al. Babesia microti: an unusual travel-related disease. BMC Infect Dis. 2013; 13: 99.
  14. Centers for Disease Control and Prevention (CDC). Babesiosis surveillance - 18 States, 2011. MMWR Morb Mortal Wkly Rep. 2012; 61(27): 505–509.
  15. CDC. National Notifiable Diseases Surveillance System. Available at http://www.cdc.gov/osels/ph_surveillance/nndss/nndsshis.htm. Accessed June. ; 27: 2017.
  16. Vannier E, Krause PJ. Human babesiosis. N Engl J Med. 2012; 366(25): 2397–2407.
  17. Gray J, Zintl A, Hildebrandt A, et al. Zoonotic babesiosis: overview of the disease and novel aspects of pathogen identity. Ticks Tick Borne Dis. 2010; 1(1): 3–10.
  18. Haapasalo K, Suomalainen P, Sukura A, et al. Fatal babesiosis in man, Finland, 2004. Emerg Infect Dis. 2010; 16(7): 1116–1118.
  19. Martinot M, Zadeh MM, Hansmann Y, et al. Babesiosis in immunocompetent patients, Europe. Emerg Infect Dis. 2011; 17(1): 114–116.
  20. Zintl A, Mulcahy G, Skerrett HE, et al. Babesia divergens, a bovine blood parasite of veterinary and zoonotic importance. Clin Microbiol Rev. 2003; 16(4): 622–636.
  21. Walter G, Weber GA. study on the transmission (transstadial, transovarial) of Babesia microti, strain „Hannover i, ” in its tick vector, Ixodes ricinus. Tropenmedical Parasitology. ; 1981(32): 228–230.
  22. Gelfand JA, Callahan MV. Babesiosis: An Update on Epidemiology and Treatment. Curr Infect Dis Rep. 2003; 5(1): 53–58.
  23. Hildebrandt A, Hunfeld KP, Baier M, et al. First confirmed autochthonous case of human Babesia microti infection in Europe. Eur J Clin Microbiol Infect Dis. 2007; 26(8): 595–601.
  24. Casati S, Sager H, Gern L, et al. Presence of potentially pathogenic Babesia sp. for human in Ixodes ricinus in Switzerland. Ann Agric Environ Med. 2006; 13(1): 65–70.
  25. Gray JS. Babesia sp.: emerging intracellular parasites in Europe. Pol J Microbiol. 2004; 53 Suppl: 55–60.
  26. Gray J, von Stedingk LV, Gürtelschmid M, et al. Transmission studies of Babesia microti in Ixodes ricinus ticks and gerbils. J Clin Microbiol. 2002; 40(4): 1259–1263.
  27. Katargina O, Geller J, Vasilenko V, et al. Detection and characterization of Babesia species in Ixodes ticks in Estonia. Vector Borne Zoonotic Dis. 2011;11(7):923–8.View ArticlePubMedGoogle Scholar.
  28. Siński E, Bajer A, Welc R, et al. Babesia microti: prevalence in wild rodents and Ixodes ricinus ticks from the Mazury Lakes District of North-Eastern Poland. Int J Med Microbiol. 2006; 296 Suppl 40: 137–143.
  29. Welc-Falęciak R, Bajer A, Paziewska-Harris A, et al. Diversity of Babesia in Ixodes ricinus ticks in Poland. Adv Med Sci. 2012; 57(2): 364–369.
  30. Wójcik-Fatla A, Zając V, Sawczyn A, et al. Prevalence of Babesia microti in Ixodes ricinus ticks from Lublin region (eastern Poland). Ann Agric Environ Med. 2006; 13(2): 319–322.
  31. Skotarczak B, Cichocka A. Isolation and amplification by polymerase chain reaction DNA of Babesia microti and Babesia divergens in ticks in Poland. Ann Agric Environ Med. 2001; 8(2): 187–189.
  32. Asman M, Solarz K, Cuber P, et al. Detection of protozoans Babesia microti and Toxoplasma gondii and their co-existence in ticks (Acari: Ixodida) collected in Tarnogórski district (Upper Silesia, Poland). Ann Agric Environ Med. 2015; 22(1): 80–83.
  33. Humiczewska M, Kuźna-Grygiel W. [A case of imported human babesiosis in Poland]. Wiad Parazytol. 1997; 43(2): 227–229.
  34. Moniuszko A, Dunaj J, Swięcicka I, et al. Co-infections with Borrelia species, Anaplasma phagocytophilum and Babesia spp. in patients with tick-borne encephalitis. Eur J Clin Microbiol Infect Dis. 2014; 33(10): 1835–1841.
  35. Welc-Falęciak R, Pawełczyk A, Radkowski M, et al. First report of two asymptomatic cases of human infection with Babesia microti (Franca, 1910) in Poland. Ann Agric Environ Med. 2015; 22(1): 51–54.
  36. Żukiewicz-Sobczak W, Zwoliński J, Chmielewska-Badora J, et al. Prevalence of antibodies against selected zoonotic agents in forestry workers from eastern and southern Poland. Ann Agric Environ Med. 2014; 21(4): 767–770.
  37. Eberhard ML, Walker EM, Steurer FJ. Survival and infectivity of Babesia in blood maintained at 25 C and 2-4 C. J Parasitol. 1995; 81(5): 790–792.
  38. Cursino-Santos JR, Alhassan A, Singh M, et al. Babesia: impact of cold storage on the survival and the viability of parasites in blood bags. Transfusion. 2014; 54(3): 585–591.
  39. Wormser GP, Prasad A, Neuhaus E, et al. Emergence of resistance to azithromycin-atovaquone in immunocompromised patients with Babesia microti infection. Clin Infect Dis. 2010; 50(3): 381–386.
  40. Gubernot DM, Nakhasi HL, Mied PA, et al. Transfusion-transmitted babesiosis in the United States: summary of a workshop. Transfusion. 2009; 49(12): 2759–2771.
  41. Leiby DA. Babesiosis and blood transfusion: flying under the radar. Vox Sang. 2006; 90(3): 157–165.
  42. Johnson ST, Cable RG, Tonnetti L, et al. Seroprevalence of Babesia microti in blood donors from Babesia-endemic areas of the northeastern United States: 2000 through 2007. Transfusion. 2009; 49(12): 2574–2582.
  43. Brennan MB, Herwaldt BL, Kazmierczak JJ, et al. Transmission of Babesia microti Parasites by Solid Organ Transplantation. Emerg Infect Dis. 2016; 22(11).
  44. Goodell AJ, Bloch EM, Krause PJ, et al. Costs, consequences, and cost-effectiveness of strategies for Babesia microti donor screening of the US blood supply. Transfusion. 2014; 54(9): 2245–2257.
  45. Gorenflot A, Moubri K, Precigout E, et al. Human babesiosis. Ann Trop Med Parasitol. 1998; 92(4): 489–501.
  46. Leiby DA, Chung APS, Cable RG, et al. Relationship between tick bites and the seroprevalence of Babesia microti and Anaplasma phagocytophila (previously Ehrlichia sp.) in blood donors. Transfusion. 2002; 42(12): 1585–1591.
  47. Linden JV, Wong SJ, Chu FK, et al. Transfusion-associated transmission of babesiosis in New York State. Transfusion. 2000; 40(3): 285–289.
  48. Popovsky MA, Lindberg LE, Syrek AL, et al. Prevalence of Babesia antibody in a selected blood donor population. Transfusion. 1988; 28(1): 59–61.
  49. Tonnetti L, Thorp AM, Deisting B, et al. Babesia microti seroprevalence in Minnesota blood donors. Transfusion. 2013; 53(8): 1698–1705.
  50. Hunfeld KP, Allwinn R, Peters S, et al. Serologic evidence for tick-borne pathogens other than Borrelia burgdorferi (TOBB) in Lyme borreliosis patients from midwestern Germany. Wien Klin Wochenschr. 1998; 110(24): 901–908.
  51. Hunfeld KP, Lambert A, Kampen H, et al. Seroprevalence of Babesia infections in humans exposed to ticks in midwestern Germany. J Clin Microbiol. 2002; 40(7): 2431–2436.
  52. Foppa IM, Krause PJ, Spielman A, et al. Entomologic and serologic evidence of zoonotic transmission of Babesia microti, eastern Switzerland. Emerg Infect Dis. 2002; 8(7): 722–726.
  53. Hunfeld KP, Brade V. Zoonotic Babesia: possibly emerging pathogens to be considered for tick-infested humans in Central Europe. Int J Med Microbiol. 2004; 293 Suppl 37: 93–103.
  54. Łętowska M. (red.). Medyczne zasady pobierania krwi, oddzielania jej składników i wydawania, obowiązujące w jednostkach organizacyjnych publicznej służby krwi. Instytut Hematologii i Transfuzjologii, Warszawa 2010.
  55. Lobo CA, Cursino-Santos JR, Alhassan A, et al. Babesia: an emerging infectious threat in transfusion medicine. PLoS Pathog. 2013; 9(7): e1003387.
  56. Borggraefe I, Yuan J, Telford SR, et al. Babesia microti primarily invades mature erythrocytes in mice. Infect Immun. 2006; 74(6): 3204–3212.
  57. Hemmer RM, Ferrick DA, Conrad PA. Role of T cells and cytokines in fatal and resolving experimental babesiosis: protection in TNFRp55-/- mice infected with the human Babesia WA1 parasite. J Parasitol. 2000; 86(4): 736–742.
  58. Okła H, Jasik KP, Słodki J, et al. Hepatic tissue changes in rats due to chronic invasion of Babesia microti. Folia Biol (Krakow). 2014; 62(4): 353–359.
  59. Fang DC, McCullough J. Transfusion-Transmitted Babesia microti. Transfus Med Rev. 2016; 30(3): 132–138.
  60. Vannier E, Gewurz BE, Krause PJ. Human babesiosis. Infect Dis Clin North Am. 2008; 22(3): 469–88, viii.
  61. Usatii N, Khachatrian A, Stratidis J. Spontaneous splenic rupture due to Babesia microti infection: Case report and review of the literature. IDCases. 2014; 1(4): 63–65.
  62. Kuwayama DP, Briones RJ. Spontaneous splenic rupture caused by Babesia microti infection. Clin Infect Dis. 2008; 46(9): e92–e95.
  63. Guru PK, O Horo JC, Lehrke HD, et al. Exchange transfusion for babesiosis when, how, and how long? Indian J Crit Care Med. 2016; 20(11): 674–676.
  64. Krause PJ, McKay K, Gadbaw J, et al. Tick-Borne Infection Study Group. Increasing health burden of human babesiosis in endemic sites. Am J Trop Med Hyg. 2003; 68(4): 431–436.
  65. Krause PJ, Gewurz BE, Hill D, et al. Persistent and relapsing babesiosis in immunocompromised patients. Clin Infect Dis. 2008; 46(3): 370–376.
  66. Vyas JM, Telford SR, Robbins GK. Treatment of refractory Babesia microti infection with atovaquone-proguanil in an HIV-infected patient: case report. Clin Infect Dis. 2007; 45(12): 1588–1590.
  67. Robinson MW, Hutchinson AT, Dalton JP, et al. Peroxiredoxin: a central player in immune modulation. Parasite Immunol. 2010; 32(5): 305–313.
  68. Müller S, Liebau E, Walter RD, et al. Thiol-based redox metabolism of protozoan parasites. Trends Parasitol. 2003; 19(7): 320–328.
  69. Park H, Hong SH, Kim K, et al. Characterizations of individual mouse red blood cells parasitized by Babesia microti using 3-D holographic microscopy. Sci Rep. 2015; 5: 10827.
  70. Rudzinska MA. Ultrastructure of intraerythrocytic Babesia microti with emphasis on the feeding mechanism. J Protozool. 1976; 23(2): 224–233.
  71. Kapishnikov S, Weiner A, Shimoni E, et al. Oriented nucleation of hemozoin at the digestive vacuole membrane in Plasmodium falciparum. Proc Natl Acad Sci U S A. 2012; 109(28): 11188–11193.
  72. Massimine KM, McIntosh MT, Doan LT, et al. Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum. Antimicrob Agents Chemother. 2006; 50(9): 3132–3141.
  73. Cui L, Su Xz. Discovery, mechanisms of action and combination therapy of artemisinin. Expert Rev Anti Infect Ther. 2009; 7(8): 999–1013.
  74. Olafson KN, Ketchum MA, Rimer JD, et al. Mechanisms of hematin crystallization and inhibition by the antimalarial drug chloroquine. Proc Natl Acad Sci U S A. 2015; 112(16): 4946–4951.
  75. Ehrhardt K, Davioud-Charvet E, Ke H, et al. The antimalarial activities of methylene blue and the 1,4-naphthoquinone 3-[4-(trifluoromethyl)benzyl]-menadione are not due to inhibition of the mitochondrial electron transport chain. Antimicrob Agents Chemother. 2013; 57(5): 2114–2120.
  76. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006; 43(9): 1089–1134.
  77. Wittner M, Rowin KS, Tanowitz HB, et al. Successful chemotherapy of transfusion babesiosis. Ann Intern Med. 1982; 96(5): 601–604.
  78. Krause PJ, Lepore T, Sikand VK, et al. Atovaquone and azithromycin for the treatment of babesiosis. N Engl J Med. 2000; 343(20): 1454–1458.
  79. Pradel G, Schlitzer M. Antibiotics in malaria therapy and their effect on the parasite apicoplast. Curr Mol Med. 2010; 10(3): 335–349.
  80. Andrews NW, Webster P. Phagolysosomal escape by intracellular pathogens. Parasitol Today. 1991; 7(12): 335–340.
  81. Wittner M, Lederman J, Tanowitz HB, et al. Atovaquone in the treatment of Babesia microti infections in hamsters. Am J Trop Med Hyg. 1996; 55(2): 219–222.
  82. Hughes LM, Lanteri CA, O'Neil MT, et al. Design of anti-parasitic and anti-fungal hydroxy-naphthoquinones that are less susceptible to drug resistance. Mol Biochem Parasitol. 2011; 177(1): 12–19.
  83. de Souza NB, de Andrade IM, Carneiro PF, et al. Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies. Mem Inst Oswaldo Cruz. 2014; 109(5): 546–552.
  84. Schlenke P. Pathogen inactivation technologies for cellular blood components: an update. Transfus Med Hemother. 2014; 41(4): 309–325.
  85. Grellier P, Benach J, Labaied M, et al. Photochemical inactivation with amotosalen and long-wavelength ultraviolet light of Plasmodium and Babesia in platelet and plasma components. Transfusion. 2008; 48(8): 1676–1684.
  86. Tonnetti L, Proctor MC, Reddy HL, et al. Evaluation of the Mirasol pathogen [corrected] reduction technology system against Babesia microti in apheresis platelets and plasma. Transfusion. 2010; 50(5): 1019–1027.
  87. Rosenberg YJ, Evans CB. Resistance of mice suppressed for IgM production to Babesia microti infection. Nature. 1979; 281(5729): 302–304.
  88. Parrodi F, Jacobson RH, Wright IG, et al. The effect of immune serum and complement on the in vitro phagocytosis of Babesia rodhaini. Parasite Immunol. 1991; 13(5): 457–471.
  89. Chapman WE, Ward PA. Babesia rodhaini: requirement of complement for penetration of human erythrocytes. Science. 1977; 196(4285): 67–70.
  90. Jeong YI, Hong SH, Cho SH, et al. Induction of IL-10-producing CD1dhighCD5+ regulatory B cells following Babesia microti-infection. PLoS One. 2012; 7(10): e46553.
  91. Raffalli J, Wormser GP. Persistence of babesiosis for >2 years in a patient on rituximab for rheumatoid arthritis. Diagn Microbiol Infect Dis. 2016; 85(2): 231–232.
  92. Igarashi I, Waki S, Ito M, et al. Role of CD4+ T cells in the control of primary infection with Babesia microti in mice. J Protozool Res. 1994; 4: 164–171.
  93. Hardy R. Chapter 7: B Lymphocyte Development and Biology. W: Paul W.E. (red.) Fundamental Immunology. Lippincott Williams & Wilkins, Philadelphia. ; 2008: 237–269.
  94. Vallerskog T, Gunnarsson I, Widhe M, et al. Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin Immunol. 2007; 122(1): 62–74.
  95. Bouaziz JD, Yanaba K, Tedder TF. Regulatory B cells as inhibitors of immune responses and inflammation. Immunol Rev. 2008; 224: 201–214.
  96. Silva JC, Cornillot E, McCracken C, et al. Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions. Sci Rep. 2016; 6: 35284.
  97. Castle SC. Clinical relevance of age-related immune dysfunction. Clin Infect Dis. 2000; 31(2): 578–585.

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