Supported by an unrestricted investigator-initiated grant from Baxter Healthcare and National Institutes of Health, National Institute of Child Health and Human Development Project Grant R01 HD41224.
Virologic and clinical features of primary infection with human parvovirus 4 in subjects with hemophilia: frequent transmission by virally inactivated clotting factor concentrates
Article first published online: 2 NOV 2011
© 2011 American Association of Blood Banks
Volume 52, Issue 7, pages 1482–1489, July 2012
How to Cite
Sharp, C. P., Lail, A., Donfield, S., Gomperts, E. D. and Simmonds, P. (2012), Virologic and clinical features of primary infection with human parvovirus 4 in subjects with hemophilia: frequent transmission by virally inactivated clotting factor concentrates. Transfusion, 52: 1482–1489. doi: 10.1111/j.1537-2995.2011.03420.x
- Issue published online: 10 JUL 2012
- Article first published online: 2 NOV 2011
- Received for publication August 11, 2011; revision received September 5, 2011, and accepted September 13, 2011.
BACKGROUND: Human parvovirus 4 (PARV4) is a newly discovered parvovirus prevalent in injecting drug users and other groups with histories of parenteral exposure including persons with hemophilia exposed to non–virally inactivated clotting factor concentrates. To investigate its potential ongoing transmission to persons with hemophilia treated with plasma-derived, virally inactivated clotting factors, we screened a large cohort of persons with hemophilia for antibody seroconversion to PARV4 over a 5-year observation period.
STUDY DESIGN AND METHODS: Samples from 195 persons with hemophilia enrolled in the Hemophilia Growth and Development Study cohort were screened for PARV4 antibodies at the start and end of a 5-year period of treatment with exclusively virally inactivated clotting factor concentrates. Samples collected at intermediate time points from subjects seroconverting over the study period were screened to narrow down the seroconversion time and investigate immunoglobulin (Ig)M responses, duration of acute viremia, and clinical presentations.
RESULTS: PARV4 seroprevalence at the outset of the study was 44%. Over the observation period, nine subjects (seven human immunodeficiency virus positive) seroconverted for anti-PARV4 (incidence, 1.7%/year). Infected subjects showed relatively prolonged durations of viremia (mean, 7 months) and weak, transient IgM responses during acute infections. Clotting factors inactivated by solvent/detergent or by wet or dry heat were infectious. The most common clinical presentations were rashes and exacerbation of hepatitis.
CONCLUSION: This study identifies PARV4 as a transfusion-transmissible agent that is resistant to viral inactivation. Of concern, infections may still regularly occur in those exposed to plasma-derived blood products. Urgent evaluation of the incidence of PARV4 in treated individuals and disease associations of PARV4 infections is required.