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) ha s been thought to occur after infusion of human intravenous immunoglob ulin (IVIG), as anti-HCV and/or HCV RNA was commonly found in that pro duct. Recently, however, HCV RNA was detected in the serum of recipien ts of IVIG. Establishment of a causal relationship between IVIG therap y and HCV infection in recipients was attempted. Study Design and Meth ods: 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 th e IVIG shared by some recipients. Ali the viral RNA detected were char acterized with a line probe assay, restriction fragment length polymor phism analysis of the 5'-noncoding and core regions, and sequencing of the nonstructural 5 region. Results: On the basis of both clinical an d laboratory data, a relationship could be established between the IVI G therapy and the acquisition of the HCV infection by the recipients. Several HCV strains were detected among the recipients, with most of t he recipients coming from the same hospital presenting with closely re lated strains. Moreover, an HCV strain almost identical to the main st rain detected among the recipients was found in one batch of the IVIG that probably was shared by most of them. Follow-up studies and evalua tion of low-avidity anti-HCV IgG suggested that both acute primary inf ections and reinfections were produced. In one case, direct evidence o f reinfection by a different HCV strain was obtained. Conclusion: The results did not exclude the possibility that a second HCV strain assoc iated with a further, unidentified batch of the IVIG could have contri buted to this outbreak.