Parvovirus B19 transmission by heat-treated clotting factor concentrates.
BACKGROUND
Human parvovirus B19 (B19) DNA can be frequently detected in plasma-derived coagulation factor concentrates. The production of some clotting factor products includes heat treatment steps for virus inactivation, but the effectiveness of such steps for B19 inactivation is unclear. Moreover, detailed transmission case reports including DNA sequence analysis and quantification of B19 DNA from contaminated heat-treated blood components have not been provided so far. Therefore, the correlation between B19 DNA in blood components and infectivity remains unclear.


METHODS
Asymptomatic B19 infections of two patients with hemophilia A were detected by anti-B19 seroconversion after administration of B19-contaminated heat-treated clotting factors. The suitability of nucleic acid sequence analysis for confirmation of B19 transmission was investigated. Furthermore, the B19 DNA level in blood components was determined and the drug administration was reviewed to calculate the amount of inoculated B19 DNA.


RESULTS
Both B19 transmissions from clotting factor products could be confirmed by identical nucleic acid sequences of virus DNA from patients and blood components while sequences from unrelated controls could be differentiated. One patient received, for 4 days, a total of 180 mL vapor heat-treated prothrombin complex concentrate containing 8.6 x 10(6) genome equivalents per mL of B19 DNA. The other patient received 966 mL of low-contamination (4.0 x 10(3) genome equivalents/mL) dry heat-treated FVIII concentrate over a period of 52 days.


CONCLUSIONS
B19 transmissions can be confirmed by nucleic acid sequencing. However, due to the low variability of the B19 genome, a large part of the B19 genome must be analyzed. The transmissions show that the applied heat treatment procedures were not sufficient to inactivate B19 completely.
Blümel
Johannes
J
Paul-Ehrlich-Institute, Langen, Germany. blujo@pei.de
Schmidt
Ivo
I
Effenberger
Wolfgang
W
Seitz
Holger
H
Willkommen
Hannelore
H
Brackmann
Hans Herrmann
HH
Löwer
Johannes
J
Eis-Hübinger
Anna Maria
AM
D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics; D004340:Drug Contamination; D005169:Factor VIII / Q000627:therapeutic use*; D016679:Genome, Viral; D006467:Hemophilia A / Q000628:therapy; D006358:Hot Temperature; D006801:Humans; D007223:Infant; D008297:Male; D010322:Parvoviridae Infections / Q000097:blood / Q000635:transmission* / Q000821:virology; D016732:Parvovirus B19, Human / Q000235:genetics / Q000302:isolation & purification*; D017422:Sequence Analysis, DNA; D019562:Viral Load; D014766:Viremia; D038301:Virus Inactivation
D004279:DNA, Viral; D005169:Factor VIII