Journal of Clinical Immunology

, Volume 38, Issue 5, pp 628–634 | Cite as

Low Rates of Poliovirus Antibodies in Primary Immunodeficiency Patients on Regular Intravenous Immunoglobulin Treatment

  • Beatriz T. Costa-Carvalho
  • Kathleen E. Sullivan
  • Patrícia M. Fontes
  • Fernanda Aimé-Nobre
  • Isabela G. S. Gonzales
  • Elaine S. Lima
  • Celso Granato
  • Maria Isabel de Moraes-PintoEmail author
Original Article



Poliovirus has been nearly eliminated as part of a world-wide effort to immunize and contain circulating wild-type polio. Nevertheless, poliovirus has been detected in water supplies and represents a threat to patients with humoral immunodeficiencies where infection can be fatal. To define the risk, we analyzed antibodies to poliovirus 1, 2, and 3 in serum samples collected over a year from patients with primary immunodeficiency diseases (PID) on regular intravenous immunoglobulin (IVIG) replacement.


Twenty-one patients on regular IVIG replacement therapy were evaluated: Twelve patients with common variable immune deficiency (CVID), six with X-linked agammaglobulinemia (XLA), and three with hyper IgM syndrome (HIGM). Over 1 year, four blood samples were collected from each of these patients immediately before immunoglobulin infusion. One sample of IVIG administered to each patient in the month before blood collection was also evaluated. Poliovirus antibodies were quantified by seroneutralization assay.


All IVIG samples had detectable antibodies to the three poliovirus serotypes. Despite that, only 52.4, 61.9, and 19.0% of patients showed protective antibody titers for poliovirus 1, 2, and 3, respectively. Only two patients (9.5%) had protective antibodies for the three poliovirus serotypes on all samples. Most patients were therefore susceptible to all three poliovirus serotypes.


This study demonstrates the need for ongoing vigilance regarding exposure of patients with PID to poliovirus in the community.


Primary immunodeficiency diseases poliovirus antibodies intravenous immunoglobulin Global Polio Eradication Initiative antibody deficiency common variable immunodeficiency X-linked agammaglobulinemia Hyper IgM syndrome 


Financial Support

This study was funded by the FAPESP (2011/06136-6), a Brazilian Funding Agency.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


  1. 1.
    Polio Global Eradication Initiative, 2018.
  2. 2.
    Nkowane BM, Wassilak SG, Orenstein WA, Bart KJ, Schonberger LB, Hinman AR, et al. Vaccine-associated paralytic poliomyelitis. United States: 1973 through 1984. JAMA. 1987;257:1335–40.CrossRefPubMedGoogle Scholar
  3. 3.
    Shaghaghi M, Parvaneh N, Ostad-Rahimi P, Fathi SM, Shahmahmoodi S, Abolhassani H, et al. Combined immunodeficiency presenting with vaccine-associated paralytic poliomyelitis: a case report and narrative review of literature. Immunol Investig. 2014;43:292–8.CrossRefGoogle Scholar
  4. 4.
    Shahmahmoodi S, Mamishi S, Aghamohammadi A, Aghazadeh N, Tabatabaie H, Gooya MM, et al. Vaccine-associated paralytic poliomyelitis in immunodeficient children, Iran, 1995–2008. Emerg Infect Dis. 2010;16:1133–6.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Shahmahmoodi S, Parvaneh N, Burns C, Asghar H, Mamishi S, Tabatabaie H, et al. Isolation of a type 3 vaccine-derived poliovirus (VDPV) from an Iranian child with X-linked agammaglobulinemia. Virus Res. 2008;137:168–72.CrossRefPubMedGoogle Scholar
  6. 6.
    Hidalgo S, Garcia Erro M, Cisterna D, Freire MC. Paralytic poliomyelitis caused by a vaccine-derived polio virus in an antibody-deficient Argentinean child. Pediatr Infect Dis J. 2003;22:570–2.PubMedGoogle Scholar
  7. 7.
    Guo J, Bolivar-Wagers S, Srinivas N, Holubar M, Maldonado Y. Immunodeficiency-related vaccine-derived poliovirus (iVDPV) cases: a systematic review and implications for polio eradication. Vaccine. 2015;33:1235–42.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wyatt HV. Poliomyelitis in hypogammaglobulinemics. J Infect Dis. 1973;128:802–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Grassly NC. The final stages of the global eradication of poliomyelitis. Philos Trans R Soc Lond Ser B Biol Sci. 2013;368:20120140.CrossRefGoogle Scholar
  10. 10.
    Fried AJ, Bonilla FA. Pathogenesis, diagnosis, and management of primary antibody deficiencies and infections. Clin Microbiol Rev. 2009;22:396–414.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bearden D, Collett M, Quan PL, Costa-Carvalho BT, Sullivan KE. Enteroviruses in X-linked Agammaglobulinemia: update on epidemiology and therapy. J Allergy Clin Immunol Pract. 2016;4:1059–65.CrossRefPubMedGoogle Scholar
  12. 12.
    Kew OM, Sutter RW, Nottay BK, McDonough MJ, Prevots DR, Quick L, et al. Prolonged replication of a type 1 vaccine-derived poliovirus in an immunodeficient patient. J Clin Microbiol. 1998;36:2893–9.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Khetsuriani N, Prevots DR, Quick L, Elder ME, Pallansch M, Kew O, et al. Persistence of vaccine-derived polioviruses among immunodeficient persons with vaccine-associated paralytic poliomyelitis. J Infect Dis. 2003;188:1845–52.CrossRefPubMedGoogle Scholar
  14. 14.
    Martin J. Vaccine-derived poliovirus from long term excretors and the end game of polio eradication. Biologicals. 2006;34:117–22.CrossRefPubMedGoogle Scholar
  15. 15.
    Dunn G, Klapsa D, Wilton T, Stone L, Minor PD, Martin J. Twenty-eight years of poliovirus replication in an immunodeficient individual: impact on the global polio eradication initiative. PLoS Pathog. 2015;11:e1005114.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    de Silva R, Gunasena S, Ratnayake D, Wickremesinghe GD, Kumarasiri CD, Pushpakumara BA, et al. Prevalence of prolonged and chronic poliovirus excretion among persons with primary immune deficiency disorders in Sri Lanka. Vaccine. 2012;30:7561–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Gelfand EW. Differences between IGIV products: impact on clinical outcome. Int Immunopharmacol. 2006;6:592–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Kaveri SV, Maddur MS, Hegde P, Lacroix-Desmazes S, Bayry J. Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy. Clin Exp Immunol. 2011;164(Suppl 2):2–5.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Nobre FA, Gonzalez IG, Simao RM, de Moraes Pinto MI, Costa-Carvalho BT. Antibody levels to tetanus, diphtheria, measles and varicella in patients with primary immunodeficiency undergoing intravenous immunoglobulin therapy: a prospective study. BMC Immunol. 2014;15:26.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Simao-Gurge RM, Costa-Carvalho BT, Nobre FA, Gonzalez IG, de Moraes-Pinto MI. Prospective evaluation of Streptococcus pneumoniae serum antibodies in patients with primary immunodeficiency on regular intravenous immunoglobulin treatment. Allergol Immunopathol (Madr). 2017;45:55–62.CrossRefGoogle Scholar
  21. 21.
    Sutter RW, Pallansch MA, Sawyer LA, Cochi SL, Hadler SC. Defining surrogate serologic tests with respect to predicting protective vaccine efficacy: poliovirus vaccination. Ann N Y Acad Sci. 1995;754:289–99.CrossRefPubMedGoogle Scholar
  22. 22.
    Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: a meta-analysis of clinical studies. Clin Immunol. 2010;137:21–30.CrossRefPubMedGoogle Scholar
  23. 23.
    Quartier P, Debre M, De Blic J, de Sauverzac R, Sayegh N, Jabado N, et al. Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. J Pediatr. 1999;134:589–96.CrossRefPubMedGoogle Scholar
  24. 24.
    Fischer GW, Hunter KW, Hemming VG, Wilson SR. Functional antibacterial activity of a human intravenous immunoglobulin preparation: in vitro and in vivo studies. Vox Sang. 1983;44:296–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Fischer GW, Weisman LE, Hemming VG. Directed immune globulin for the prevention or treatment of neonatal group B streptococcal infections: a review. Clin Immunol Immunopathol. 1992;62:S92–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Planitzer CB, Modrof J, Kreil TR. West Nile virus neutralization by US plasma-derived immunoglobulin products. J Infect Dis. 2007;196:435–40.CrossRefPubMedGoogle Scholar
  27. 27.
    Orange JS, Du W, Falsey AR. Therapeutic immunoglobulin selected for high antibody titer to RSV also contains high antibody titers to other respiratory viruses. Front Immunol. 2015;6(431)Google Scholar
  28. 28.
    Rockman S, Lowther S, Camuglia S, Vandenberg K, Taylor S, Fabri L, et al. Intravenous immunoglobulin protects against severe pandemic influenza infection. EBioMedicine. 2017;19:119–27.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Davidkin I, Jokinen S, Broman M, Leinikki P, Peltola H. Persistence of measles, mumps, and rubella antibodies in an MMR-vaccinated cohort: a 20-year follow-up. J Infect Dis. 2008;197:950–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Heininger U, Cherry JD, Stehr K. Serologic response and antibody-titer decay in adults with pertussis. Clin Infect Dis. 2004;38:591–4.CrossRefPubMedGoogle Scholar
  31. 31.
    Pavlov DN. Poliovirus vaccine strains in sewage and river water in South Africa. Can J Microbiol. 2006;52:717–23.CrossRefPubMedGoogle Scholar
  32. 32.
    Paul JR, Trask JD, Gard S. II. Poliomyelitic virus in urban sewage. J Exp Med. 1940;71:765–77.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Centers for Disease C, and Prevention. Outbreaks following wild poliovirus importations—Europe, Africa, and Asia, January 2009–September 2010. MMWR Morb Mortal Wkly Rep. 2010;59:1393–9.Google Scholar
  34. 34.
    Sullivan KE, Bassiri H, Bousfiha AA, Costa-Carvalho BT, Freeman AF, Hagin D, et al. Emerging infections and pertinent infections related to travel for patients with primary immunodeficiencies. J Clin Immunol. 2017;37:650–92.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Doganay M, Demiraslan H. Refugees of the Syrian civil war: impact on reemerging infections, health services, and biosecurity in Turkey. Health Secur. 2016;14:220–5.CrossRefPubMedGoogle Scholar
  36. 36.
    Centers for Disease C, and Prevention. Update on vaccine-derived polioviruses—worldwide, July 2009–March 2011. MMWR Morb Mortal Wkly Rep. 2011;60:846–50.Google Scholar
  37. 37.
    Fiore L, Plebani A, Buttinelli G, Fiore S, Donati V, Marturano J, et al. Search for poliovirus long-term excretors among patients affected by agammaglobulinemia. Clin Immunol. 2004;111:98–102.CrossRefPubMedGoogle Scholar
  38. 38.
    Galal NM, Bassiouny L, Nasr E, Abdelmeguid N. Isolation of poliovirus shedding following vaccination in children with antibody deficiency disorders. J Infect Dev Ctries. 2012;6:881–5.CrossRefPubMedGoogle Scholar
  39. 39.
    Halsey NA, Pinto J, Espinosa-Rosales F, Faure-Fontenla MA, da Silva E, Khan AJ, et al. Search for poliovirus carriers among people with primary immune deficiency diseases in the United States, Mexico, Brazil, and the United Kingdom. Bull World Health Organ. 2004;82:3–8.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Duintjer Tebbens RJ, Pallansch MA, Kalkowska DA, Wassilak SG, Cochi SL, Thompson KM. Characterizing poliovirus transmission and evolution: insights from modeling experiences with wild and vaccine-related polioviruses. Risk Anal. 2013;33:703–49.CrossRefPubMedGoogle Scholar
  41. 41.
    Aghamohammadi A, Abolhassani H, Kutukculer N, Wassilak SG, Pallansch MA, Kluglein S, et al. Patients with primary immunodeficiencies are a reservoir of poliovirus and a risk to polio eradication. Front Immunol. 2017;8(685)Google Scholar
  42. 42.
    Domingues CM, de Fatima Pereira S, Cunha Marreiros AC, Menezes N, Flannery B. Introduction of sequential inactivated polio vaccine-oral polio vaccine schedule for routine infant immunization in Brazil’s National Immunization Program. J Infect Dis. 2014;210(Suppl 1):S143–51.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Galama JM, Gielen M, Weemaes CM. Enterovirus antibody titers after IVIG replacement in agammaglobulinemic children. Clin Microbiol Infect. 2000;6:630–2.CrossRefPubMedGoogle Scholar
  44. 44.
    Nobre FA, Gonzalez IG, de Moraes-Pinto MI, Costa-Carvalho BT. Protective levels of varicella-zoster antibody did not effectively prevent chickenpox in an X-linked agammaglobulinemia patient. Rev Inst Med Trop Sao Paulo. 2015;57:455–7.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Ng E, Sanmartin C, Elien-Massenat D, Manuel DG. Vaccine-preventable disease-related hospitalization among immigrants and refugees to Canada: study of linked population-based databases. Vaccine. 2016;34:4437–42.CrossRefPubMedGoogle Scholar
  46. 46.
    Kopel E, Kaliner E, Grotto I. Lessons from a public health emergency—importation of wild poliovirus to Israel. N Engl J Med. 2014;371:981–3.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Beatriz T. Costa-Carvalho
    • 1
  • Kathleen E. Sullivan
    • 2
  • Patrícia M. Fontes
    • 1
    • 3
  • Fernanda Aimé-Nobre
    • 1
  • Isabela G. S. Gonzales
    • 1
  • Elaine S. Lima
    • 4
  • Celso Granato
    • 4
  • Maria Isabel de Moraes-Pinto
    • 3
    • 5
    Email author
  1. 1.Division of Allergy Clinical Immunology and Rheumatology, Department of PediatricsUniversidade Federal de São PauloSão PauloBrazil
  2. 2.Division of Allergy Immunology, The Children’s Hospital of PhiladelphiaUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  3. 3.Division of Pediatric Infectious Diseases, Department of PediatricsUniversidade Federal de São PauloSão PauloBrazil
  4. 4.Division of Infectious Diseases, Department of MedicineUniversidade Federal de São PauloSão PauloBrazil
  5. 5.Research Laboratory, Division of Pediatric Infectious DiseasesFederal University of Sao PauloSão PauloBrazil

Personalised recommendations