Laboratory diagnosis and molecular epidemiology of an outbreak of hepatitis C virus infection among recipients of human intravenous immunoglobulin in Spain

Background: Passive transfer of antibody to hepatitis C virus (HCV) has been thought to occur after infusion of human intravenous immunoglobulin (IVIG), as anti-HCV and/or HCV RNA was commonly found in that product. Recently, however, HCV RNA was detected in the serum of recipients of IVIG. Establishment of a causal relationship between IVIG therapy and HCV infection in recipients was attempted. Study Design and Methods: Anti-HCV and HCV RNA sequences were investigated In serum samples from 39 persons who received a human IVIG product in seven different hospitals in Spain. HCV RNA was also investigated in two batches of the IVIG shared by some recipients. Ali the viral RNA detected were characterized with a line probe assay, restriction fragment length polymorphism analysis of the 5'-noncoding and core regions, and sequencing of the nonstructural 5 region. Results: On the basis of both clinical and laboratory data, a relationship could be established between the IVIG therapy and the acquisition of the HCV infection by the recipients. Several HCV strains were detected among the recipients, with most of the recipients coming from the same hospital presenting with closely related strains. Moreover, an HCV strain almost identical to the main strain detected among the recipients was found in one batch of the IVIG that probably was shared by most of them. Follow-up studies and evaluation of low-avidity anti-HCV IgG suggested that both acute primary infections and reinfections were produced. In one case, direct evidence of reinfection by a different HCV strain was obtained. Conclusion: The results did not exclude the possibility that a second HCV strain associated with a further, unidentified batch of the IVIG could have contributed to this outbreak.