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The
intravenous immune globulin preparation Gammagard was
solely responsible for a hepatitis C virus outbreak
which occurred between 1993 and 1994, according to a
report from the U.S. Centers for Disease Control and
Prevention (CDC).
"Gammagard
(Baxter Healthcare Corporation, Deerfield, IL) was the
only intravenous immune globulin (IGIV) product
implicated in the transmission of Hepatitis C Virus,"
researcher Joseph S. Bresee and colleagues wrote
("Hepatitis C Virus Infection Associated with Administration of
IGIV," Journal of the American Medical
Association, November 20, 1996;276(19): 1563-1567).
Beginning
in October 1991, plasma used to make IGIV was screened
using single-antigen (fast-generation) tests for
antibody to hepatitis C virus (anti-Hepatitis C Virus), and anti-Hepatitis C Virus-positive
units of plasma were discarded. More sensitive
multiantigen (second-generation) tests were licensed
in March 1992, and by November of 1992, IGIV was
produced using plasma donations screened with these
testing procedures. Intravenous immune globulin
manufactured exclusively from second-generation
screened plasma was fast distributed in early 1993.
"Several
outbreaks of non-A, non-B hepatitis associated with
IGIV administration have been reported," Bresee
et al. wrote. "All but one of these outbreaks
were associated with preparations of IGIV that were
manufactured in Europe; one was associated with a
prelicensure U.S. product. Retrospective analysis of
these outbreaks confirmed these non-A, non-B hepatitis
cases as Hepatitis C Virus infections. Immune globulin products (IGIV
and intramuscular immune globulin) licensed in the
United States have not been previously associated with
transmission of bloodborne agents including Hepatitis C Virus."
In
February of 1994, Baxter Healthcare Corporation issued
a voluntary recall of its two IGIV preparations,
Gammagard and Polygam, in response to reports of acute
hepatitis C among persons who received Gammagard. As
of January 1996, 134 cases of Hepatitis C Virus infection among
Gammagard recipients had been reported to the CDC. As
a result of these cases reports, CDC researchers
initiated an investigation to determine the risk and
risk factors for Hepatitis C Virus infection among persons who had
received IGIV products in the United States.
In
this report, Bresee et al. presented the results of a
cohort study involving patients with immune
deficiencies who received Gammagard and other
manufacturers' IGIV products at a large immunology
center.
Of
341 people who received IGIV between March 1, 1993 and
February 22, 1994 at the Allergy/Clinical Immunology
Program at Children's Hospital in Boston,
Massachusetts, 278 (82 percent) were enrolled in the
study.
Bresee
et al. found that 23 of 210 participants who received
IGIV Gammagard (11 percent) became infected; none of
the 52 who received other IGIV products exclusively
became infected. In a multivariate analysis, Hepatitis C Virus
infection was associated only with Gammagard produced
from plasma screened by second-generation (multiantigen)
anti-Hepatitis C Virus tests (P = .03). Hepatitis C virus RNA was
detected in Gammagard, and the risk of transmission to
recipients increased with increasing quantity of Hepatitis C Virus
RNA infused, from 0 percent for those who received no
Hepatitis C Virus RNA-positive lots to 29 percent for the quartile
of patients receiving the greatest amount (P <
.001). At least nine different lots of Gammagard were
required to account for all cases.
The
researchers suggested that the data from this study
are generalizable to other populations since the risk
of infection was not limited to specific lots, but
rather was associated with the type of plasma
screening used in production.
'This
outbreak serves as a reminder of the possible risks
associated with the administration of blood products,
even though multiple steps are taken to decrease the
potential for transmission of viruses by these
products," Bresee et al. wrote. "As the Food
and Drag Administration has requested, all
U.S.-licensed IGIV products now have viral
inactivation steps included in the manufacturing
process ... to further reduce the likelihood of viral
transmission. Additionally, all immunoglobulin
products (including those which have not been
associated with hepatitis C) that lack a viral
inactivation step(s) are now screened by PCR tests for
Hepatitis C Virus RNA, and only product that is Hepatitis C Virus RNA negative is
released for distribution. In this study, no persons
who received only Hepatitis C Virus RNA-negative material became
infected. Although the presence of Hepatitis C Virus RNA in immune
globulin products may not necessarily correlate with
infectivity, these safeguards should help prevent
future transmission of Hepatitis C Virus by these products."
The
corresponding author for this study is Eric E. Mast,
Hepatitis Branch, U.S. Centers for Disease Control and
Prevention, Mailstop G-37, 1600 Clifton Road, Atlanta,
GA 30333.
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By
Salynn Boyles, Senior Editor
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