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Revaccination of adult patients following allogeneic haematopoietic stem cell transplantation: CELL recommendations


Authors: T. Kabut 1;  I. Kocmanová 2;  P. Žák 3;  M. Kouba 4;  L. Drgoňa 5;  M. Navrátil 6;  P. Múdrý 7;  P. Sedláček 8;  J. Haber 9;  N. Mallátová 10;  D. Dóczyová 11;  J. Novák 12;  E. Faber 13;  B. Weinbergerová 1;  J. Štěrba 7;  J. Mayer 1;  Z. Ráčil 4
Authors‘ workplace: Interní hematologická a onkologická klinika, FN Brno a LF MU, Brno 1;  Oddělení klinické mikrobiologie, FN Brno a LF MU, Brno 2;  IV. interní hematologická klinika, FN Hradec Králové, Hradec Králové 3;  Ústav hematologie a krevní transfuze, Praha 4;  Klinika onkohematológie, LF UK a Národný onkologický ústav, Bratislava 5;  Klinika hematoonkologie, FN Ostrava a LF OSU, Ostrava 6;  Klinika dětské onkologie, FN Brno, Brno 7;  Klinika dětské hematologie a onkologie, FN v Motole, Praha 8;  Klinika hematologie, Všeobecná fakultní nemocnice, Praha 9;  Pracoviště parazitologie a mykologie, Nemocnice České Budějovice a. s., České Budějovice 10;  Transplantačná jednotka kostnej drene – Klinika detskej hematológie a onkológie, Detská fakultná nemocnica s poliklinikou, Bratislava 11;  Interní hematologická klinika, FN Královské Vinohrady, Praha, Za Českou leukemickou skupinu – pro život (CELL) 12
Published in: Transfuze Hematol. dnes,25, 2019, No. 3, p. 269-280.
Category:

Overview

Allogenic haematopoietic stem cell transplantation is associated with a significant alteration of the immune functions and patients after haematopoietic stem cell transplant are at high risk of infectious complications that are associated with significant mortality. Increased susceptibility to infections is caused by many factors such as an immature immune system during the first months after transplantation or functional hyposplenism. Gradual decrease of specific antibodies in most patients with loss of specific immunity acquired in childhood following a vaccination series has also been described. Revaccination after haematopoietic stem cell transplantation is a widely accepted practice for preventing these risks. Patients are indicated for revaccination with inactivated vaccines against Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type B, pertussis, tetanus, diphtheria, poliomyelitis, influenza and hepatitis B and with live vaccines against measles, rubella, mumps in some cases. Vaccination with inactivated vaccines is initiated according to current recommendations as early as 3 months after transplantation for some types of vaccines. For most vaccines, vaccination consists of 2 to 3 doses 1–2 months apart. Vaccination with live antiviral vaccines is only indicated in selected patients and starts not sooner than 24 months after transplantation. This article presents specific recommendations for vaccination and an overall summary of this topic based on current international recommendations for revaccination of haematopoietic transplant patients.

Keywords:

opportunistic infections – vaccination – haematology – haematopoietic stem cell transplantation – allogeneic haematopoietic transplantation – revaccination


Sources

1. Ullmann AJ, Schmidt-Hieber M, Bertz H, et al. Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016. Ann Hematol 2016;95(9):1435–1455.

2. van den Brink MR, Velardi E, Perales MA, et al. Immune reconstitu-tion following stem cell transplantation. Hematology Am Soc Hematol Educ Program 2015;2015:215–219.

3. Sahin U, Toprak SK, Atilla PA, et al. An overview of infectious complications after allogeneic hematopoietic stem cell transplantation. J Infect Chemother 2016;22(8):505–514.

4. Schuster MG, Cleveland AA, Dubberke ER, et al. Infections in hematopoietic cell transplant recipients: results from the organ transplant infection project, a multicenter, prospective, cohort study. Open Forum Infect Dis 2017;4(2):ofx050.

5. Ogonek J, Kralj Juric M, Ghimire S, et al. Immune reconstitution after allogeneic hematopoietic stem cell transplantation. Front Immunol 2016;7:507.

6. Seggewiss R, Einsele H, et al. Immune reconstitution after allogeneic transplantation and expanding options for immunomodulation: an update. Blood 2010;115(19):3861–3868.

7. Chaudhry MS, Velardi E, Malard F, et al. Immune reconstitution after allogeneic hematopoietic stem cell transplantation: time to T up the thymus. J Immunol 2017;198(1):40–46.

8. Carpenter PA, Englund JA, et al. How I vaccinate blood and marrow transplant recipients. Blood 2016;127(23):2824–2832.

9. Hammerquist RJ, Messerschmidt KA, Pottebaum AA, et al. Vaccinations in asplenic adults. Am J Health Syst Pharm 2016;73(9):220–228.

10. Chong PP, Avery RK. A comprehensive review of immunization practices in solid organ transplant and hematopoietic stem cell transplant recipients. Clin Ther 2017;39(8):1581–1598.

11. Staehelin C, Hirzel C, Hauser C, et al. Vaccinations for immunocompromised hosts – focussing on patients after a hematological stem cell or organ transplantation, with HIV or with functional or anatomical asplenia. Ther Umsch 2016;73(5):281–289.

12. Lexová P, Manďáková Z, Kynčl J, et al. Spalničky – význam onemocnění a aktuální situace v Evropě. Oddělení epidemiologie infekčních nemocí SZÚ 2018. [cit. 2.11.2018]. Dostupné na www: http://www.szu.cz/tema/prevence/vyskyt-spalnicek-v-cr.

13. Fabiánová K, Zavadilová J, Šebestová H, et al. Syndrom dávivého kašle. Pertuse a parapertuse v České republice v roce 2017 – epidemiologická situace a přehled očkování proti pertusi. Zprávy SZÚ 2018;27(3–4):75–83.

14. Ljungman P, Cordonnier C, Einsele H, et al. Vaccination of hematopoietic cell transplant recipients.Bone Marrow Transplant 2009;44(8):521–526.

15. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):309–318.

16. Cordonnier C, Einarsdottir S, Cesaro S, et al. Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis 2019;19(6):e200–e212.

17. L‘Huillier AG, Kumar D. Immunizations in solid organ and hematopoeitic stem cell transplant patients: A comprehensive review. Hum Vaccin Immunother 2015;11(12):2852–2863.

18. Kroger T, Sumaya CV, Pickering LA, et al. General recommendations on immunization – recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60(2):1–64.

19. Yri OE, Torfoss D, Hungnes O, et al. Rituximab blocks protective serologic response to influenza A (H1N1) 2009 vaccination in lymphoma patients during or within 6 months after treatment. Blood 2011;118(26):6769–6771.

20. Shah GL, Shune L, Purtill D, et al. Robust vaccine responses in adult and pediatric cord blood transplantation recipients treated for hematologic malignancies. Biol Blood Marrow Transplant 2015;21(12):2160–2166.

21. Pao M, Papadopoulos EB, Chou J, et al. Response to pneumococcal (PNCRM7) and haemophilus influenzae conjugate vaccines (HIB) in pediatric and adult recipients of an allogeneic hematopoietic cell transplantation (alloHCT). Biol Blood Marrow Transplant 2008;14(9):1022–1030.

22. de Lavallade H, Garland P, Sekine T, et al. Repeated vaccination is required to optimize seroprotection against H1N1 in the immunocompromised host. Haematologica 2011;96(2):307–314.

23. Bonanni P, Grazzini M, Niccolai G, et al. Recommended vaccinations for asplenic and hyposplenic adult patients. Hum Vaccin Immunother 2017;13(2):359–368.

24. Bhalla P, Forrest GN, Gershon M. Disseminated, persistent, and fatal infection due to the vaccine strain of varicella-zoster virus in an adult following stem cell transplantation. Clin Infect Dis 2015;60(7):1068–1074.

25. Alexander KE, Tong PL, Macartney K, et al. Live zoster vaccination in an immunocompromised patient leading to death secondary to disseminated varicella zoster virus infection. Vaccine 2018;36(27):3890–3893.

26. Horwitz SM, Negrin RS, Blume KG, et al. Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplanta-tion for aggressive non-Hodgkin lymphoma. Blood 2004;103(3):777–783.

27. Issa NC, Marty FM, Gagne LS, et al. Seroprotective titers against 2009 H1N1 influenza A virus after vaccination in allogeneic hematopoietic stem cell transplantation recipients. Biol Blood Marrow Transplant 2011;17(3):434–438.

28. Mahler MB, Taur Y, Jean R, et al. Safety and immunogenicity of the tetravalent protein-conjugated meningococcal vaccine (MCV4) in recipients of related and unrelated allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2012;18(1):145–149.

29. Parkkali T, Olander RM, Ruutu T, et al. A randomized comparison between early and late vaccination with tetanus toxoid vaccine after allogeneic BMT. Bone Marrow Transplant 1997;19(9):933–938.

30. Engelhard D, Zakay-Rones Z, Shapira MY, et al. The humoral immune response of hematopoietic stem cell transplantation recipients to AS03-adjuvanted A/California/7/2009 (H1N1)v-like virus vaccine during the 2009 pandemic. Vaccine 2011;29(9):1777–1782.

31. Mohty B, Bel M, Vukicevic M, et al. Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients. Haematologica 2011;96(6):896–904.

32. Kumar D, Chen MH, Welsh B, et al. A randomized, double-blind trial of pneumococcal vaccination in adult allogeneic stem cell transplant donors and recipients. Clin Infect Dis 2007;45(12):1576–1582.

33. Inaba H, Hartford CM, Pei D, et al. Longitudinal analysis of antibody response to immunization in paediatric survivors after allogeneic haematopoietic stem cell transplantation. Br J Haematol 2012;156(1):109–117.

34. Cordonnier C, Labopin M, Chesnel V, et al. Randomized study of early versus late immunization with pneumococcal conjugate vaccine after allogeneic stem cell transplantation. Clin Infect Dis 2009;48(10):1392–1401.

35. Parkkali T, Käyhty H, Ruutu T, et al. A comparison of early and late vaccination with Haemophilus influenzae type b conjugate and pneumococcal polysaccharide vaccines after allogeneic BMT. Bone Marrow Transplant 1996;18(5):961–967.

36. Siber G, Werner B, Halsey N, et al. Interference of immune globulin with measles and rubella immunization. J Pediatr 1993;122:204–211.

37. Kumar D, Humar A, Plevneshi A, et al. Invasive pneumococcal disease in adult hematopoietic stem cell transplant recipients: a decade of prospective population-based surveillance. Bone Marrow Transplant 2008;41(8):743–747.

38. Engelhard D, Cordonnier C, Shaw PJ, et al. Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey. Br J Haematol 2002;117:444–450.

39. Youssef S, Rodriguez G, Rolston KV, et al. Streptococcus pneumoniae infections in 47 hematopoietic stem cell transplantation recipients: clinical characteristics of infections and vaccine-breakthrough infections, 1989–2005. Medicine (Baltimore) 2007;86(2):69–77.

40. Schutze GE, Mason EO, Wald ER, et al. Pneumococcal infections in children after transplantation. Clin Infect Dis 2001;33(1):16–21.

41. Olarte L, Lin PL, Barson WJ, et al. Invasive pneumococcal infections in children following transplantation in the pneumococcal conjugate vaccine era. Transpl Infect Dis 2017;19(1):e12630.

42. Kulkarni S, Powles R, Treleaven J, et al. Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants. Blood 2000;95(12):3683–3686.

43. Sheridan JF, Tutschka PJ, Sedmak DD, et al. Immunoglobulin G subclass deficiency and pneumococcal infection after allogeneic bone marrow transplantation. Blood 1990;75(7):1583–1586.

44. Jackson LA, Gurtman A, van Cleeff M, et al. Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine compared to a 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naive adults. Vaccine 2013;31(35):3577–3584.

45. Clutterbuck EA, Lazarus R, Yu LM, et al. Pneumococcal conjugate and plain polysaccharide vaccines have divergent effects on antigen-specific B cells. J Infect Dis 2012;205(9):1408–1416.

46. Jackson LA, Gurtman A, van Cleeff M, et al. Influence of initial vaccination with 13–valent pneumococcal conjugate vaccine or 23– valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older. Vaccine 2013;31(35):3594–3602.

47. Gandhi MK, Egner W, Sizer L, et al. Antibody responses to vaccinations given within the first two years after transplant are similar between autologous peripheral blood stem cell and bone marrow transplant recipients. Bone Marrow Transplant 2001;28(8):775–781.

48. Meisel R, Kuypers L, Dirksen U, et al. Pneumococcal conjugate vaccine provides early protective antibody responses in children after related and unrelated allogeneic hematopoietic stem cell transplantation. Blood 2007;109(6):2322–2326.

49. Cordonnier C, Ljungman P, Juergens C, et al. Immunogenicity, safety, and tolerability of 13 - valent pneumococcal conjugate vaccine followed by 23 – valent pneumococcal polysaccharide vaccine in recipients of allogeneic hematopoietic stem cell transplant aged ≥2 years: an open-label study. Clin Infect Dis 2015;61(3);313–323.

50. Cordonnier C, Labopin M, Chesnel V, et al. Immune response to the 23 – valent polysaccharide pneumococcal vaccine after the 7 – valent conjugate vaccine in allogeneic stem cell transplant recipients: results from the EBMT IDWP01 trial. Vaccine 2010;28(15):2730–2734.

51. Sigurdardottir ST, Center KJ, Davidsdottir K. Decreased immune response to pneumococcal conjugate vaccine after 23 – valent pneumococcal polysaccharide vaccine in children. Vaccine 2014;32(3):417–424.

52. O‘Brien KL, Hochman M, Goldblatt D, et al. Combined schedules of pneumococcal conjugate and polysaccharide vaccines: is hyporesponsiveness an issue? Lancet Infect Dis 2007;7:597–606.

53. McNair J, Smith, A, Bettinger J, et al. Invasive Haemophilus influenzae type b infections in children with cancer in the era of infant HIB immunization programs (1991–2014): a report from the Canadian Immunization Monitoring Program Active. Pediatr Infect Dis J 2018;37(7):726–728.

54. Roy V, Ochs L, Weisdorf D, et al. Late infections following allogeneic bone marrow transplantation: suggested strategies for prophylaxis. Leuk Lymphoma 1997;26(1–2):1–15.

55. Ochs L, Shu XO, Miller J, et al. Late infections after allogeneic bone marrow transplantations: comparison of incidence in related and unrelated donor transplant recipients. Blood 1995;86(10):3979–3986.

56. Parkkali T, Käyhty H, Anttila M, et al. IgG subclasses and avidity of antibodies to polysaccharide antigens in allogeneic BMT recipients after vaccination with pneumococcal polysaccharide and Haemophilus influenzae type b conjugate vaccines. Bone Marrow Transplant 1999;24(6):671–678.

57. Molrine DC, Guinan EC, Antin JH, et al. Donor immunization with Haemophilus influenzae type b (HIB)-conjugate vaccine in allogeneic bone marrow transplantation. Blood 1996;87(7):3012–3018.

58. Parkkali T, Käyhty H, Hovi T, et al. A randomized study on donor immunization with tetanus-diphtheria, Haemophilus influenzae type b and inactivated poliovirus vaccines to improve the recipient responses to the same vaccines after allogeneic bone marrow transplantation. Bone Marrow Transplant 2007;39(3):179–188.

59. Cheng MP, Pandit A, Antin JH, et al. Safety and immunogenicity of conjugate quadrivalent meningococcal vaccination after hematopoietic cell transplantation. Blood Adv 2018;2(11):1272–1276.

60. Patel SR, Ortín M, Cohen BJ, et al. Revaccination of children after completion of standard chemotherapy for acute leukemia. Clin Infect Dis 2007;44(5):635–642.

61. Křížová P, Musílek M, Okonji Z, et al. Invazivní meningokokové onemocnění v České republice v roce 2017. Zprávy CEM SZÚ 2018; 27(1). [cit. 6.11.2018]. Dostupné na www: http://www.szu.cz/tema/prevence/invazivni-meningokokove-onemocneni-v-ceske-republice-v-roce-7.

62. Česká vakcinologická společnost ČLS. Doporučení České vakcinologické společnosti ČLS JEP pro očkování proti invazivním meningokokovým onemocněním. 2018. [cit. 6.11.2018]. Dostupné na www: http://www.vakcinace.eu/doporuceni-a-stanoviska.

63. Olkinuora H, Käyhty H, Davidkin I, et al. Immunity after (re)vaccination of paediatric patients following haematopoietic stem cell transplantation. Acta Paediatr 2012;101:373–377.

64. Ljungman P, Wiklund-Hammarsten M, Duraj V, et al. Response to tetanus toxoid immunization after allogeneic bone marrow transplantation. J Infect Dis 1990;162(2):496–500.

65. Papadopoulos EB, Young JW, Kernan NA, et al. Use of the tetanus toxoid, reduced dose diphtheria and pertussis vaccine (Tdap) in allogeneic transplant (alloHCT) recipients. Blood 2008;112:2214.

66. Small TN, Zelenetz AD, Noy A, et al. Pertussis immunity and response to tetanus-reduced diphtheria-reduced pertussis vaccine (Tdap) after autologous peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 2009;15(12):1538–1542.

67. Ljungman P, Duraj V, Magnius L. Response to immunization against polio after allogeneic marrow transplantation. Bone Marrow Transplant 1991;7(2):89–93.

68. Pauksen K, Hammarström V, Ljungman P, et al. Immunity to poliovirus and immunization with inactivated poliovirus vaccine after autologous bone marrow transplantation. Clin Infect Dis 1994;18(4):547–552.

69. Ljungman P, de la Camara R, Perez-Bercoff L, et al. Outcome of pandemic H1N1 infections in hematopoietic stem cell transplant recipients. Haematologica 2011;96(8):1231–1235.

70. Nichols WG, Guthrie KA, Corey L, et al. Influenza infections after hematopoietic stem cell transplantation: risk factors, mortality, and the effect of antiviral therapy. Clin Infect Dis 2004;39(9):1300–1306.

71. Ljungman P, Ward KN, Crooks BN, et al. Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 2001;28 (5):479–484.

72. Engelhard D, Mohty B, de la Camara R, et al. European guidelines for prevention and management of influenza in hematopoietic stem cell transplantation and leukemia patients: summary of ECIL-4 (2011), on behalf of ECIL, a joint venture of EBMT, EORTC, ICHS, and ELN. Transpl Infect Dis 2013;15(3):219–232.

73. Natori Y, Shiotsuka M, Slomovic J, et al. A double-blind, randomized trial of high-dose vs standard-dose influenza vaccine in adult solid-organ transplant recipients. Clin Infect Dis 2018;66(11):1698–1704.

74. Engelhard D, Nagler A, Hardan I, et al. Antibody response to a two-dose regimen of influenza vaccine in allogeneic T cell-depleted and autologous BMT recipients. Bone Marrow Transplant 1993;11(1):1–5.

75. Karras NA, Weeres M, Sessions W, et al. A randomized trial of one versus two doses of influenza vaccine after allogeneic transplantation. Biol Blood Marrow Transplant 2013;19(1): 109–116.

76. Fukatsu Y, Nagata Y, Adachi M, et al. Serum IgM levels independently predict immune response to influenza vaccine in long-term survivors vaccinated at >1 year after undergoing allogeneic hematopoietic stem cell transplantation. Int J Hematol 2017;105(5):638–645.

77. Machado CM, Cardoso MR, da Rocha IF, et al. The benefit of influenza vaccination after bone marrow transplantation. Bone Marrow Transplant 2005;36(10):897–900.

78. Avetisyan G, Aschan J, Hassan M, et al. Evaluation of immune responses to seasonal influenza vaccination in healthy volunteers and in patients after stem cell transplantation. Transplantation 2008;86(2):257–263.

79. Roll D, Ammer J, Holler B, et al. Vaccination against pandemic H1N1 (2009) in patients after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Infection 2012;40(2):153–161.

80. Gueller S, Allwinn R, Mousset S, et al. Enhanced immune response after a second dose of an AS03 adjuvanted H1N1 influenza A vaccine in patients after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2011;17(10):1546–1550.

81. Knöll A, Boehm S, Hahn J, et al. Long-term surveillance of haematopoietic stem cell recipients with resolved hepatitis B: high risk of viral reactivation even in a recipient with a vaccinated donor. J Viral Hepat 2007;14(7):478–483.

82. Knöll A, Boehm S, Hahn J, et al. Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant 2004;33(9):925–929.

83. Pompili M, Basso M, Hohaus S, et al. Prospective study of hepatitis B virus reactivation in patients with hematological malignancies. Ann Hepatol 2015;14(2):168–174.

84. Onozawa M, Hashino S, Darmanin S, et al. HB vaccination in the prevention of viral reactivation in allogeneic hematopoietic stem cell transplantation recipients with previous HBV infection. Biol Blood Marrow Transplant 2008;14(11):1226–1230.

85. Jaffe D, Papadopoulos EB, Young JW, et al. Immunogenicity of recombinant hepatitis B vaccine (rHBV) in recipients of unrelated or related allogeneic hematopoietic cell (HC) transplants. Blood 2006;108(7):2470–2475.

86. Costa E, Buxton J, Brown J, Templeton KE, Breuer J, Johannessen I. Fatal disseminated varicella zoster infection following zoster vaccination in an immunocompromised patient. BMJ Case Rep 2016; bcr2015212688; DOI: 10.1136/bcr-2015-212688.

87. Leung TF, Chik KW, Li CK, et al. Incidence, risk factors and outcome of varicella-zoster virus infection in children after haematopoietic stem cell transplantation. Bone Marrow Transplant 2000;25(2):167–172.

88. Suzuki J, Ashizawa M, Okuda S, et al. Varicella zoster virus meningoencephalitis after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 2012;14(4):7–12.

89. Blennow O, Fjaertoft G, Winiarski J, et al. Varicella-zoster reactivation after allogeneic stem cell transplantation without routine prophylaxis – the incidence remains high. Biol Blood Marrow Transplant 2014;20(10):1646–1649.

90. Onozawa M, Hashino S, Haseyama Y, et al. Incidence and risk of post-herpetic neuralgia after varicella zoster virus infection in hematopoietic cell transplantation recipients: Hokkaido Hematology Study Group. Biol Blood Marrow Transplant 2009;15(6):724–729.

91. Ljungman P, Lewensohn-Fuchs I, Hammarström V, et al. Long-term immunity to measles, mumps, and rubella after allogeneic bone marrow transplantation. Blood 1994;84(2): 657–663.

92. Ljungman P, Aschan J, Barkholt L, et al. Measles immunity after allogeneic stem cell transplantation; influence of donor type, graft type, intensity of conditioning, and graft-versus host disease. Bone Marrow Transplant 2004;34(7):589–593.

93. Kawamura K, Yamazaki R, Akahoshi Y, et al. Evaluation of the immune status against measles, mumps, and rubella in adult allogeneic hematopoietic stem cell transplantation recipients. Hematology 2015;20(2):77–82.

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