Virology of the hepatitis A epidemic in Italy.
We studied the virologic aspects of a hepatitis A epidemic that occurred among hemophilia patients in Italy between 1989 and 1992. Twelve lots of factor VIII concentrate manufactured by the solvent-detergent chromatographic technique and suspected of contamination by the hepatitis A virus (HAV) were analyzed by a two-step, nested polymerase chain reaction (PCR) procedure. PCR was applied to 1-ml samples of factor VIII concentrate and 100-microliters serial serum samples available from 2 patients. Particular care was taken to rule out the possibility of false-positive results during analysis. Results demonstrated PCR amplification of the 3'-region of the VP3 gene in 5 of the 12 implicated lots of factor VIII and in the serial serum samples of both patients. PCR amplification also revealed that the gene sequences detected in patients' sera were identical to the sequences detected in the product they had received. In all, 3 VP3 sequences (found to be 96-99% identical) were amplified. Further characterization of the HAV found in the factor VIII concentrate and the patients' sera was attempted by PCR amplification of the VP1/2A region. Successful amplification of this region was achieved in the serum of only 1 patient and in the concentrate he received. This fourth amplified sequence was identical in both serum and factor VIII concentrate. Attempts to transmit hepatitis A from the contaminated lots to 3 chimpanzees resulted in no signs of infection after 10 months of observation. Based on the Italian experience, persons with severe hemophilia who receive large-pool concentrate are at potential risk for HAV infection and should be vaccinated against HAV or use an alternative to solvent-detergent-prepared concentrate.(ABSTRACT TRUNCATED AT 250 WORDS)
National Institutes of Health, National Institute of Allergy and Infectious Diseases, Hepatitis Viruses Section, Bethesda, Md 20892.
R H
RH
Purcell
P M
PM
Mannucci
S
S
Gdovin
A
A
Gringeri
M
M
Colombo
A
A
Mele
N
N
Schinaia
N
N
Ciavarella
S U
SU
Emerson
D000328:Adult; D000818:Animals; D001483:Base Sequence; D002648:Child; D003902:Detergents; D004196:Disease Outbreaks; D004340:Drug Contamination; D005169:Factor VIII / Q000009:adverse effects* / Q000302:isolation & purification; D006467:Hemophilia A / Q000150:complications* / Q000628:therapy; D006506:Hepatitis A / Q000150:complications / Q000453:epidemiology* / Q000635:transmission / Q000821:virology; D006507:Hepatovirus / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D012997:Solvents
D003902:Detergents; D012997:Solvents; D005169:Factor VIII