Sean Doyle National University of Ireland, Maynooth, Ireland. Parvovirus B19 Infection in Seronegative and Seropositive Individuals – Implications for Blood Product Safety. Bern, Switzerland. 15 June 2006.
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.
Individual Apparent Infectious Ref. Dose (B19 DNA) Female, 36 yr SD Plasma ( GE/ml)Koenigbauer et al. 2000: Transfusion. Male, 16 mo. B19 IgG- plasma protein Blumel et al. complex 2002: Transfusion. 8.6 x 10 6 GE/ml (180 ml)) 1.5 x 10 9 GE Male, 5yrB19 IgG- plasma protein Blumel et al. complex 2002: Transfusion. 4 x 10 3 GE/ml (996 ml)) 3.9 x 10 6 GE Male, 47 yrB19 IgG- Wu et al. Factor VIII Concentrate 2005: Transfusion. (1.3 x 10 3 IU/ml) 2 x 10 4 IU Incidences of Parvovirus B19 Transmission
Retrospective study of similar plasma pools (n = 30). B19 IgG levels : IU/ml. B19 IgG may be capable of preventing recipient B19 infection when transfused with plasma contaminated with low levels of parvovirus B19 (< 10 4 GE/ml). Daly et al. 2002: J. Clin Microbiol. Pooled SD plasma administration 100 volunteers > 10 7 GE/ml=> B19 seroconversion No seroconversion Davenport et al. 2000: Blood. Brown et al. 2002: Transfusion. Incidences of Parvovirus B19 Transmission
B19 IgG……….Protective Effect? B19 IgG+ Blood Products. B19 DNA Levels: 6 x 10 2 –2.2 x 10 6 GE/ml. Individual Recipients (n = 14)…… -> No Symptoms or B19 Seroconversion. Plentz et al. 2005: Transfusion.
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? 4. B19 IgG reactivity against linear epitopes of VP2- A marker of recent infection? (Soderlund et al. 1995). 3. What is the protective level of B19 IgG which may prevent re-infection?
Group No. Plasma pool ID (B19 DNA (IU)) Recipient Code(Daly et al. 2002: J. Clin Microbiol.) Group I (SP) 01002PS3 (3.2 x ) 01052N.A PS3 (3.2 x ) Group II (SN) 01023PS2A ( GE/ml) ~ 7 x 10 4 IU 01053PS2A ( GE/ml) 01055N.A. Group III (SN-SC) 01005PS1 (4.4 x ) 01048PS1 (4.4 x ) 01057PS1 (4.4 x ) 01069PS3 (3.2 x ) Doyle and Corcoran, 2006: J Infect. Dis. Specimen and Plasma Pool Details B19 IgG levels 72 IU/ml B19 IgG 59 IU/ml B19 IgG IU/ml B19 IgG
1. B19 IgM Detection2. B19 IgG Detection VP2-N 3. B19 IgG Detection VP1-N Seroconversion Profiles –1/2 Doyle and Corcoran, 2006: J. Infect. Dis. I I II III I
4. B19 IgG Detection (VP1-D) 5. B19 IgG Detection (VP2-D) Seroconversion Profiles –2/2 Doyle and Corcoran, 2006: J. Infect. Dis. IIII III
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 ( IU/ml) appear to prevent B19 transmission to seronegative recipients at levels of < 7 x 10 4 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 IU B19 DNA. 5. B19 IgG [VP2-D]- marker of recent exposure.
Plasma cell APC Activated Th cell CD4 B19-specific Ig Appears 10 days post-infection VP1-N VP1-D VP2-N VP2-D NS1-N 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 IgG Chronic B19 infection-inability to produce neutralizing antibodies B19 infection Memory B cell IL-1 IL-6Joint inflammation in RA IFN- Suppressed during pregnancy IL-2 Present at maternal-fetal interface TNF- IL-8 B19 associated cytokines B cell memory Established against VP2-N VP1-N VP1-D
Contributors and colleagues: Amanda Corcoran Paul Daly EU 5 th Framework ‘Parvovirus’ Consortium QLK2-CT QUALITY OF LIFE AND MANAGEMENT OF LIVING RESOURCES