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Sean Doyle National University of Ireland, Maynooth, Ireland.

Parvovirus B19 I nfection in S eronegative and S eropositive I ndividuals – I mplications for B lood P roduct S afety. Sean Doyle National University of Ireland, Maynooth, Ireland. Bern, Switzerland. 15 June 2006. PARVOVIRUS B19.

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Sean Doyle National University of Ireland, Maynooth, Ireland.

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  1. Parvovirus B19 Infection in Seronegative and Seropositive Individuals – Implications for Blood Product Safety. Sean Doyle National University of Ireland, Maynooth, Ireland. Bern, Switzerland. 15 June 2006.

  2. PARVOVIRUS B19 Capsid Proteins: B19 VP1 and VP2 (70% identical). Capsid VP2 is the main protein used for antibody detection. VP2-N v VP2-D.

  3. Incidences of Parvovirus B19 Transmission Individual Apparent Infectious Ref. Dose (B19 DNA) • Female, 36 yr SD Plasma (107-108 GE/ml) Koenigbauer et al. 2000: Transfusion. • Male, 16 mo. B19 IgG- plasma protein Blumel et al. • complex 2002: Transfusion. • 8.6 x 106 GE/ml (180 ml)) • 1.5 x 109 GE • Male, 5yr B19 IgG- plasma protein Blumel et al. • complex 2002: Transfusion. • 4 x 103 GE/ml (996 ml)) • 3.9 x 106 GE • Male, 47 yr B19 IgG- Wu et al. • Factor VIII Concentrate 2005: Transfusion. • (1.3 x 103 IU/ml) • 2 x 104 IU

  4. Incidences of Parvovirus B19 Transmission • Pooled SD plasma administration • 100 volunteers • > 107 GE/ml=> B19 seroconversion • <104 GE/ml => No seroconversion • Davenport et al. 2000: Blood. • Brown et al. 2002: Transfusion. • Retrospective study of similar plasma pools (n = 30). • B19 IgG levels : 65+ 18 IU/ml. • B19 IgG may be capable of preventing recipient B19 infection when transfused with plasma contaminated with low levels of parvovirus B19 (< 104GE/ml). • Daly et al. 2002: J. Clin Microbiol.

  5. B19 IgG……….Protective Effect? B19 IgG+ Blood Products. B19 DNA Levels: 6 x 102 –2.2 x 106 GE/ml. Individual Recipients (n = 14)…… -> No Symptoms or B19 Seroconversion. Plentz et al. 2005: Transfusion.

  6. Some outstanding questions……… 1. Does B19 IgG presence minimise the risk of infection with B19 contaminated materials? 2. How do B19 seropositive individuals respond to re-exposure the virus? 3. What is the protective level of B19 IgG which may prevent re-infection? 4. B19 IgG reactivity against linear epitopes of VP2- A marker of recent infection? (Soderlund et al. 1995).

  7. Specimen and Plasma Pool Details Group No.Plasma pool ID (B19 DNA (IU))   Recipient Code (Daly et al. 2002: J. Clin Microbiol.) Group I (SP) 01002 PS3 (3.2 x 1010) 01052 N.A. 01098 PS3 (3.2 x 1010) Group II (SN) 01023 PS2A (103.5 GE/ml) ~ 7 x 104 IU 01053 PS2A (103.5 GE/ml) 01055 N.A. Group III (SN-SC) 01005 PS1 (4.4 x 1010) 01048 PS1 (4.4 x 1010) 01057 PS1 (4.4 x 1010) 01069 PS3 (3.2 x 1010) B19 IgG levels 72 IU/ml B19 IgG 65+ 18 IU/ml B19 IgG 59 IU/ml B19 IgG Doyle and Corcoran, 2006: J Infect. Dis.

  8. Seroconversion Profiles –1/2 1. B19 IgM Detection 2. B19 IgG Detection VP2-N I II III I II III 3. B19 IgG Detection VP1-N I II III Doyle and Corcoran, 2006: J. Infect. Dis.

  9. Seroconversion Profiles –2/2 4. B19 IgG Detection (VP1-D) 5. B19 IgG Detection (VP2-D) I II III I II III Doyle and Corcoran, 2006: J. Infect. Dis.

  10. Conclusions & Implications… 1. B19 IgG seropositive individuals do not exhibit symptoms of re-infection- even at high IU B19 DNA . 2. B19 IgG [VP2-N] levels of 19 IU/ml prevent sero- positive recipient re-infection & B19 IgG levels rise in response to repeat exposure (except B19 IgG [VP2-D]). 3. B19 IgG (65+ 18 IU/ml) appear to prevent B19 transmission to seronegative recipients at levels of < 7 x 104 IU B19 DNA in SD plasma. 4. High levels of B19 IgG cannot prevent recipient infection in the presence of 3.2 –4.4 x 1010 IU B19 DNA. 5.B19 IgG [VP2-D]- marker of recent exposure.

  11. Memory B cell B cell memory B cell Established against VP2-N VP1-N VP1-D Plasma cell B19 infection Activated Th cell APC CD4 B19 associated cytokines IL-1b IL-6 Joint inflammation in RA IFN-g Suppressed during pregnancy IL-2 Present at maternal-fetal interface TNF-a IL-8 B19-specific Ig IgG IgM Appears 15 days post-infection VP1-N lifelong VP1-D declines slowly VP2-N lifelong VP2-D disappears within 6 months NS1 associated with acute & persistent infection Appears 10 days post-infection VP1-N VP1-D VP2-N VP2-D NS1-N Chronic B19 infection-inability to produce neutralizing antibodies

  12. QUALITY OF LIFE AND MANAGEMENT OF LIVING RESOURCES Contributors and colleagues: Amanda Corcoran Paul Daly EU 5th Framework ‘Parvovirus’ Consortium QLK2-CT-00877. sean.doyle@nuim.ie

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