here was designed to monitor renal transplant recipients prospectively and ...... after transplant). On the other hand, if no evidence of antigenemia develops.
Monitoring and Diagnosis Renal Transplantation BRIAN JOSEPH
M. MURRAY, DANIEL GERBASI, and ROCCO
Departments
of Medicine
Center,
In this
Abstract.
pared.
Buffalo,
study,
tigen (CMV-AG) and monitoring
the
Previous
antibodies
to detect
the
leukocytes
(PBL)
viral may
tional
and
nogbobulin
M CMV
expressed
by
correlated fection.
a more
the
peripheral
and
retinitis),
with
despite
of positive
per
cipients
of
infection) cell
an as
agents
well
as
from
infection
early
symptomatic
to blanket
emptive
therapy” until
infection, have
treated
( 1 ).
there
is
patients
This
could
to prevent seen
the
Antiviral point
full-blown
development
symptoms;
therefore,
permit
particu-
phase,
but
will
progress
also
an
alternative
infection,
namely
could
evidence would infection. of a number
initially
of
MYERS, County
Medical
ap“pre-
be with-
incipient
CMV
be
instituted
in an
last
few
of candidate
Received June 26, 1996. Accepted February 25, 1997. Correspondence to Dr. Brian M. Murray. Nephrology Division. Medical Center, 462 Grider Street, Buffalo, NY 14215. 1448$03.00/0
Journal of the American Society of Nephrology Copyright tO 1997 by the American Society of Nephrology
Erie
this
to the
symptomatic
CMV-AG
it can
as a guide
count
institution
that
permit
The
the
more
rapid
(SV)
reaction
to identify
invasive
assay that
time
to therapy
is and
(J Am Soc
therapy.
diagnosis
(6), the detection of viral genetic
here
was
infection,
of CMV antimaterial by the
designed
prospectively
and
(CMV-AG) of CMV
a subgroup
infection
of CMV
of the conventional
(8).
presented
symptomatic
in
SV
likelihood
response
modification
technique the detection
recipients
ability
the
the processing
of preemptive
vial
chain
study
the
not
findings
1997)
the shell
buffy coat culture genemia (7), and
to
an ap-
patients
the
the
and
it was
a high
Such
upon
determine
virus
be used
had
of
superior
to monitor
8: 1448-1457,
and
infection.
is
helps
of the
be used
to the
Nephrol
test
is related were moni-
could
treatment
Based
threshold
because
of symptoms
symptomatic.
actual
threshold therapy,
unnecessary
are a result
shorter,
onset
fever
of
and,
to monitor
compare
the
renal
utility
of
test and the SV test in as well as their
infection
patients
liable
therefore,
to progress
at high
risk
to
of tissue-
disease.
to
of The
the
symptoms
the same
subsequent
the
Materials This ents
and Methods
was
a prospective
at the
January
Erie
years
urine after
tech-
1gM antibody,
County
County
1992 onwards.
samples transplant
techniques,
I 046-6673/0809-
Erie
the cytomegabovirus antigen the diagnosis and monitoring
anti-T
after transplant not only of de-
who
agents
therapy
at Buffalo,
antiviral
obviate
study,
transplant
(primary
to be
of CMV capable
of CMV
laboratory
at which
test
presymptomatic
prophylaxis
JEAN
transplant,
to become
because
re-
with
for
polymerase
mortality
donor appear
those
infection.
proach
attempt
in the
identifying
GRAY,
instituting
prior
could
including
still
Seronegative
after for
reached
niques
enteritis,
occasional
(1-5).
(reactivation/superinfection)
accurately
held
and
patients
larly at risk. Ideally, management requires a sensitive and reliable tecting
( 10 to 30%)
pneumonitis,
a seropositive
seropositive
PBL
organ transplants (CMV) infection
number (e.g.,
regimens
allograft
the as
50,000
serially
this
degree of symptomatic in> 10 positive cells/5O,000
morbidity
prophylactic
York
clinical
a trigger
destined
for immuthat
developed
proach
of antigenemia
cells
PBL
specificity
than the SV test in
but that the degree
considerable
current
of New
in
could be useful in deciding clinically whether to CMV infection. Alternatively, if antigenemia
often
specific
discovered
sensitive
and a significant invasive disease
University
as
blood
and
tests
As many as 70 to 80% of recipients of solid show laboratory evidence of cytomegalovirus after transplant, develop tissue
VANESSA
tored
was followed-up as well as conven-
urine
likelihood and with a count
center
monoclonal
sensitive
It was
more
number
with the All patients
and
an-
authors’
uses
recipients testing,
antibody.
infection,
the
in circulating
transplant CMV-AG
test was not only
detecting
from
SV for blood
(1gM)
cytomegalovirus
tests in the diagnosis infection were com-
which
be both
of 32 renal with serial
State
(SV) CMV
test,
antigen
Microbiology,
of the
studies
CMV-AG
test. A cohort prospectively
CMV-AG
vial
and
AMSTERDAM, VENUTO
Infection
York.
utility
retrospective
that
culture
New
and the shell of posttransplant
suggested
of Cytomegalovirus
study
involving
Medical
Center,
Starting
all renal
transplant
Buffalo,
New
at the time
of transplant,
CMV and
at least
about
the
CMV
infection.
viremia
viruria
biweekly presence
by both the SV and conventional
by conventional in the renal of symptoms,
Complete
blood
culture transplant and counts,
of urine.
was
and
clinic,
were
any
reason
immunosuppression
to suspect consisted
clinical
were
for
serum
creatinine
CMV
infection. with
were
questioned
examined
and
of induction
culture
Patients
serum transaminase levels were measured at least every Additional viral studies were obtained if the patient became if there
from
blood
were obtained at least every two weeks up to 6 months and tested for CMV-AG level, presence of anti-CMV
seen
plant
recipi-
York,
signs
of and
2 weeks. febrile or Posttrans-
antilymphocyte
Antigenemia
globulin
(Minnesota
MN]
until
8/92,
roids,
and
serum
creatinine
peutic
cycbosporine
ALG
[Upjohn,
azathioprine.
treatment
[University
ATGAM
Cyclosporine
concentration were
was discontinued. except
seropositive
donor
who
a significant
3 mg/dl,
and
anti-CMV
recipients
received
level
once
with
according
infection
was
many) a
CYTOGAM#{174}
of Sny-
as the detection
a new
monoclonal
from
to the protocol
was defined
of 1gM antibody,
thera-
prophylaxis
positive
blood
of
culture
for CMV by conventional techniques, or a new positive urine culture. CMV disease was considered to be present when any of the abovementioned laboratory tests were positive for CMV infection and was associated
with
one
or more
of the
following:
leukopenia
white blood cells (wbc)/mm2), thrombocytopenia lets/mm3), hepatitis (de novo elevation of serum ferase),
pneumonitis
(pulmonary
infiltrates
funduscopic
associated with itis (histological patients
with
changes).
alanine
evidence
infection
of Peripheral
Blood
with
allowed
(charchanges
developed
kocytes media.
(Sigma
polymorphonuclear PBL was divided
the
for SV inoculation
Shell
Vial
0.3
ml
inoculated
PBL
at 700
medium comycin
(100
incubated second
5%
fetal
p.g/ml),
was
Chaska,
The
kit
MN)
contains
polypeptide,
MD).
was
antibody reported
At 24 h after
was
contain approximately were examined. Slides permeabilized.
Two
Culture mL
that
infection,
as described
were
prepared
PBL)
125 WA).
Detection
pp 65 and
a fluores-
(Biotest).
Positive
No significant
(IF) using
difference
of Blood
(urine
or PBL
16 mm MRC-5
X
The
inoculum
culture
nuclear
stain-
the appropriate as number of poswas
and
seen
in mean
Urine
preparations)
culture
was
tubes
remained
tubes
of Anti-CMV
inoculated
(Bartels
Diagnos-
on the monolayer
determined Biowhittaker).
minimizes
positive
false
and
rheumatoid
for
I h
results
resulting
test
Index
by dividing
are interpreted >1.1,
high
Tests
to the manufacturer’s
sample
values
controls.
M
from
interference.
low positive standard (LPS) absorbance value is calculated. each
as negative
using an enzyme-linked capture assay The capture 1gM assay methodology
factor
according
served
Immunoglobulin
Levels were (CMV CAP-M,
was
levels
were
package
of CMV-
performed
insert.
in
In brief,
a
is assayed in triplicate and a mean A ratio or index is then prepared for its absorbance
by the mean
as follows:
50, they were treated with 14 days of intravenous gancicbovir 5 mg/kg iv (adjusted for renal function) supplemented by CYTOGAM#{174} 100 mg/kg iv every 4 d for four doses.
Preparation
ing when microscopy.
1449
October 15, 1993, CMV-AG (IF) staining method, using
the lower
goat
Vial Assay
CMV-AG
technique
(CMV
against
demonstrated
0.2
of evidence with dem-
(tubulointerstitial
of CMV
cells
Cell
plate-
the presence of inclusion bodies), and/or gastroenterevidence of inclusion bodies in the mucosa). When
laboratory
directed
Initially,
(IP)
antibodies
cein-conjugated
aminotrans-
in the absence
nephritis
antigenemia.
the Shell
(50/50,000
as frequently,
was
positives
test
could
be
10 during
that
that
94)
±
Seventeen (mean value, of a course of antiviral
asymptomatic note that infection
recurrence in the (Patient
higher
infection
two CMV-AG samples not of 14 and 34, respectively)
devel-
of infection.
before
only
days
CMV-AG
the
onset
level
10
than
of symptoms.
during
test
was re-
of CMV counts
>10
20 of 72 (mean
when
± 50) therapy
ten
it was
count
symptoms
of antigenemia.
only patient who No. 8), symptoms
the
the
CMV-AG
CMV-AG
Indeed on
drawn
of
In contrast,
10 developed
drawn
count nine
No. 9), in whom
all individual
were
in
whose
symptoms.
of symptomatic
bout
(Patient
patient
less than not
CMV-AG > 10
thereafter. no
with
initial
patients
symptomatic. Another 33 (mean value, during antiviral therapy after clinical
resolved. completion
use of different threshold count of > 10 was both
far
However, 274
328 ±173
was
patient
10 shortly
>
so
associated
value,
5, the
symptoms
persistently
infection. were
7 days
to in
mained
first positive culture, culture specimen was
of
and in the final
6, it rose
a sample drawn 10 days before the whereas in the remaining case a positive
in Table
onset
patients,
185 1061
±169
as shown the
1722
167
12
in which
74
1722
±8
transplant,
oped
CMV-AG
(PRE)
1
CMV-AG
highly
Initial
before
1
In cases
Both
reached
3
SEM
day.
counts
(PEAK)
Pre-CMV-AG
Mean
this
CMV-AG
4
8
the
and count
were
85 ± 32) were symptoms had developed after and represented
It was
interesting
to
had recurrent symptomatic appeared to develop at a the initial
associated with were obtained
infection. symptoms in patient
The
last
(values No. 1
Antigenemia
Finally,
tended tions,
Figure
2 shows
that
although
the
peak
Diagnosis been
groups.
and
The
utility
preemptive pares
of
these
antiviral
various therapy
the number
tests was
of patients
to
assessed.
would
instituting
Table
have
been
6 com-
parameters, would have
identified
urine
cultures
that
particular
test.
could
not
be used
because
detected after
until-on the
onset
antibody
was
tients
detected
SV test
before
onset
ten; CMV-AG, of these therapy sequently
before after
would
developed threshold the PBL
initial
values
as a trigger
of intervention
would
have
with
therapy
of symptoms detection
resulted
(SV,
who
six;
CMV-AG, allows
instituted
never
of
sub-
I 1). The one
to select therapy.
10 positive
cells
of all ten
an average
46 days
of unexplained
four
for preemptive
in treatment
a
use of either
test to
(range,
paBoth
of preemptive
of patients (SV,
1gM
per
symp-
of 8 days
before
to 16 days
1000.0
-
100.0
-
can
the
sibility
of preemptive
onset
in
presymptomatic
administered after
can
timed
to coincide way,
widespread study of renal
transplant
test
and
SV
tiveness ondary
was the
detect
the
goal
Unlike
to assess technique
0
c,) 10.0
if either
infection
. .
.
..
0 1.0
-
S. 0.1
-
Asymptomatic Figure
2. Distribution
of peak
Syndrome Only CMV-AG
counts
Hepatitis in patients
with
CMV
Retinitis infection.
shorten
the
while
encourage
to compare
thus
monitor-
CMV their
antigen effec-
A sec-
could
guide
limiting resistance.
infection.
technique
and
is In
will
CMV
to
and
replication.
of serial
I
-
>
viral
the
I
0
infection
the utility
of symptomatic
.
I
of
both
is
be restricted
with and
pos-
of or shortly
can
treatment could
the
infection
at the time
hospitalization
that
so
even
opened CMV
of early
recipients
to determine
viremia
which
evidence
such
or
are
prophylaxis,
therapy
early
presymptomatic
has
chain plasma
tests
of
(1 1). This
beginning
designed
was
presence
of posttranspbant
that
in diagnosis
polymerase these
the period
culture
the
peripheral
cases,
of antivirals
ing
technology
In many
and prevent
This
similar
16 h after
in circulating
(8).
exhibiting
use
(7) uses
of such
as
in the
preemptive
it is hoped
with
monoclonal
DNA
phase.
of infection
and
rapidly
the presence
Finally,
therapy
with
the
CMV
to all patients
patients
duration
test
of
permit
uses
as early
directly
of symptoms
transplantation,
those this
to detect
preparations
to detect
patient
before the
(6)
antigen
prompt
a number
which
more
antigens
they
years,
technique
of the patient.
that
few
to be made SV
traditionally
permitting
introduced,
antigens
be used of the
to detect
fever).
viral
leukocytes
reaction sensitive
be detected
cases
to institution
CMV-AG
not
symptomatic
However,
of the
threshold
patients onset
led
of
1453
has
tests
last
been
culture
CMV
early
leukocytes
respectively,
test could
in many
number
were
of symptoms.
respectively.
have
blood
presence
of ten
onset
CMV-AG
symptoms
nature
different
tomatic
six of ten),
criteria
seven
symptoms
results
The
after
or a positive
in a considerable
quantitative
50,000
in only
and
15 days,
symptoms.
of 2 days
of clinical
positive and
of clinical
at an average
positive
Raising
average-l4
Positive
blood
viral
in cell
The
to detect
as been
The
to early
products
inoculation.
identified
for empiric therapy by a number of potential well as the time after transplant at which they by
viral
have
infection
sensitivity.
infection
of suitable
In the
tests
of CMV
greater antibodies
as guides
also
who
diagnosis.
diagnostic
diagnosis
as
of CMV
by the lack
accurate
newer
Tests
treatment
hampered
and
Diagnostic Therapy
Vial Assay
Discussion
CMV-AG
to be higher in patients with CMV disease manifestait did not appear to clearly differentiate between these
Comparison of Utility of Various Guides to Instituting Preemptive
the Shell
Versus
be used
preemptive
1454
Journal
Table
of the American
6. Utility
of various
Factor
Society
tests
of Nephrology
in guiding
the
institution
of preemptive
therapy
for
CMV
Positive Blood Culture (Shell Vial)
infection
Positive Blood Culture (Conventional)
Positive Urine Culture
Positive 1gM
CMV-AG >0
CMV-AG >10
CMV-AG >50
21
11
8
16
11
18
11
10
10
8
10
9
10
9
42
46
43
42
58
72
47
Numberof patients identified
Number symptomatic
Days
after
transplant Days
(-)
before
or after
-8
-8
-3
-6
+15
+14
+7
(+)
symptoms
institution of antiviral therapy such as pneumonitis and retinitis
CMV
antigenemia
before serious ensued.
was detected
CMV
complications
in a high percentage
(76%)
of renal transplant recipients in this study. As shown in Figure 1 CMV-AG was usually first detected 4 to 8 wk after transplant, which is in agreement with the known natural history of ,
posttransplant
CMV ( 1 ). The
investigators
positive difference
and previous reports of other of positive SV tests (50%) and
conventional cultures could be explained
more
sensitive
virus
at a lower
than
less specific, Without
sible
to resolve
this
the
burden
counts
being
issue
likely
that
a positive
greater
it was
CMV-AG
tests
of a kidney tests done low counts
that
patients
tests
for
the
these
low
extremely
patients
and
and
may
have
nous peroxidase switched to the detection,
which
been
of
risk
rule
and
Such false positives when the peroxidase the
result
carries
of
was
an even
doing this, our experience was similar Ferguson (12). Finally, this data suggests
(70%) the
of
posttransplant
all with very occurred in laboratory with
were identified technique was in by
endoge-
specificity.
In
to that of Landry that the incidence
and of
of
antibody,
suggestfor
again
proved
more
their
sensitive
(nine
patients)
of these
clinical
highly
specific
utility.
for
in obtain-
Although
the blood
sensitivity However,
tests
Conven-
the long delay
than
enhanced cases.
patients SV blood
CMV.
to be
diag-
CMV-AG
the specificity symptomatic
were
although
culture
the
by SV
consisted in the as in our previous
nature of the CMV-AG test proved symptomatic from asymptomatic ill-
ness
with
in that
only
patients
CMV-AG
counts
of
> 10 were
symptomatic. studies
have
as early
compared
detectors
the
CMV-AG
40. They detected antigenemia cultures were positive in almost of these
sis. However,
most
CMV-AG
and
test
antigenemia have
week
also
not only found
earlier.
that
Erice
tests
other
was
to be more CMV-AG et al.
in only 70%, and required
studies
SV cultures
(14)
test
of posttransplant
tion. Wunderli et a!. (13) prospectively transplant recipients and found evidence
a combination
why we CMV-AG
ten
study (9), the quantitative helpful in differentiating
Previous
probably
all
sensitive
cultures
1gM
laboratory
Positive
urine
but unfortunately
most of this of asymptomatic
SV technique
expo-
1gM
infection.
diagnosis
reduces
was
and culture,
reducing
cultures
ing the results
with
blood
CMV
culture
of a new
in the majority of asymptomatic at low levels, whereas positive
CMV,
CMV-AG technique, detection
recovery positive
together
blood
posttrans-
and sufficiently
of
warrant
urine
symptoms,
is not
conventional
the
with
detectable
assay
to
in detecting
2 1 patients
urine
developed
latter
symptomatic
load.
of the
and
low
or development
developed
counts were detected (nine of 1 1), albeit
tional
positive,
tests
greater
seven that
infection CMV-AG,
in confirming
recipients
one reason technique for
by
CMV-AG
86 CMV-AG
interference
of
positive
ten
in the group
too
compared
(84%)
Only
and
inadvertent
these
evidence
nosis
culture
(58%).
antibody
only
blood
not uncommon,
viral
positive
out
of CMV,
symptoms
activity. This immunofluorescence we feel
any other
SV
is
sensitive
(89%)
also
the
tests that were not were bow counts seen
Of the
(95%),
infection
patients)
were
a higher
CMV
(six
or during the illness. Finally,
cannot
at low
lack
cultures
plant
were
that
the
five were positive, These five positives
we
were
counts
higher
donor.
or asymptomatic, transplants
CMV-AG
believe
rare in seronegative
did not exhibit
Although
represent false positives. only during the period use
symptoms of clinical
a seronegative
who
CMV.
the
of
it is impos-
of the
requires
CMV-AG cultures
in this group, only ( 1/50,000 PBLs).
three sure,
were
from
we
sensitivity
culture
the onset of clinical after the resolution
in the absence
but
symptomatic
prophylactic monitoring. The CMV-AG test proved
ing
if it was
standard,
the
The was
circulating
alternatively,
detected
First,
Second, many of the positive accompanied by positive blood before phase
or,
reference
reasons:.
more
in detecting
definitively,
to the
following
suggesting
tests
of viral
low
is due the
count,
two
an independent
discrepancy for
(33%) was much lower. either if the CMV-AG test
the other
bevel
with
virus.
test
infection incidence
infection,
seronegative-seronegative
104
infection
25%, whereas they suggested optimal
the detection SV cultures
be detected, the
CMV-AG
on
in
diagno-
found than
renal
SV that
compared
sensitive can
screened
of CMV
for
the
infec-
that have
have
found
with
CMV
the of but
average, test
1 to be
Antigenemia
more organ
sensitive transplants.
itive
bone
than the Boeckh
marrow
SV
assay
in
transplant
CMV-AG
test carried
transplant
CMV
1 70 recipients
et a!. (15),
recipients,
and
was
length
the first positive of time between
detectable
versus
7 days)
CMV-AG reasons
may
CMV-AG screening have
at an earlier and to permit
ever,
in light
testing
at
period
(4
of our
least
evidence
accounted
to
8 wk
of
antigenemia
We the
also
found
study,
On
develops and
the
by
we
within remained
tomatic.
As
between
I 2 and
level
immediately CMV-AG the
infection
of
risk
as shown
syndrome small,
and
This
may
have
in patients 2 the
with
mortality infection,
result
policy
antiviral
and
signs
within
a few
days
emia
Table
of
>
of CMV
alone
will
use
but not
of
disease short.
prophylactic
symptoms
to-
Indeed,
symptomatic (Table 7).
often
be
and the viral
therapy.
in the presence
status
to
transplants,
early
patient with was excellent
some
The achieved
with
(fever,
no CMV chills,
resolved
rapidly
antigen-
exhibited
on patient
and
a dramatic
graft
of
further
graft
be less
draw larger
many
related viremia
and
Infection
Development
7, the
survival
of CMV
incidence
of a concurrent
over
patients
control
conclusions. of patients
for
our
therapy. the question
count
ex-
have
been
with
preemp-
it impossible
controlled to assess
of which
of >50/50,000
the criterion for institution eight of the ten patients antiviral therapy. However, most
were
CMV
test is the therapy
we had used
to institute
therapy,
of an additional
symptomatic,
albeit
the criterion this
15 patients,
tomatic. If the objective and to include as many
None
(n
=
11)
0
Asymptomatic (n
actually
used
mildly.
of a positive
357 10)
as
would
have
most
of whom
If, on the
CMV-AG
resulted
in treatment
were
never
is for treatment to be truly subsequently symptomatic
survival
Graft
Survival ( 1 yr)
Patient Survival
( 1 yr)
54%
63%
91%
±
1
36%
91 %
91%
±
180
10%
100%
symp-
preemptive patients as
11)
Symptomatic (n
4
is
degrees therapy.
of preemptive therapy; this led to with symptomatic CMV receiving treatment was not truly preemptive
already
hand,
was
to
studies in the cost-
preemptive
PBLs
of This
rather than waiting disease developed. was small, and the
makes
when
was
group
previous
may
of intervening
group
and in
infection.
(9) and
Prospective, will be required
surveillance
in the
CMV
improvement CMV
in part, to our policy
A CMV-AG
Rejection
infec-
of rejection
highest
symptomatic
infected
suitable
Peak CMV-AG
fati-
to ongoing viremia. should be treated, and
I-Yr Survival CMV
often
easy
being contemplated. We evaluated the utility of several of antigenemia in identifying patients for preemptive
test
when
“asymptomillness,
malaise
patient
efficacy of preemptive Finally, there remains
in that
symp-
than
such
a febrile
nonspecific
in Table
and
a considerable
definitive groups
most
with
symptomatic
while
study.
experienced
with
at least
other
of persistent
patients
recurrences,
reported to increase posttransplant morbidity ( 16). This, however, was not our experience
who
perience
two
not experiencing
As shown
and
due,
may initially.
may have been “asymptomatic”
require
this study. patients
therapy although
tion has been even mortality
absence
counts
manifestations the
the classic
to develop
could
of patients
(transaminasemia) even
10, and although
7. Impact
when,
had
counts of 35 and 74 and 67 and 186, that a similar degree of antigenemia
of a feeling
that such
l455
of > 10 after a course of antideveloped recurrent symptoms
patient
develops
patients,
Vial Assay
tive therapy early in the course of infection until manifestations of tissue-invasive However, the number of patients involved
corresponds
with disease
of
patients asymp-
peak
positive-to-negative
therapy,
sweats)
after
antigenemia
represents
were there-
manifestations,
count
of vigorous
was seen in any and graft outcome
With
disease
of disease
the
all patients
symptoms. The
the number
duration
been
our
onset
patients
However, the
with
for
10 either shortly
that usually
CMV-AG
CYTOGAM#{174} in high-risk gether
the
to a peak
between
alone.
was
is
specific
CMV-AG
symptomatology.
used to differentiate
testing
tended
mean
after
then rises
maximum
in Figure
subsequent
other hand 10 remained
5, symptoms
and
to be higher
favor if no
in that
On the below
respective
,
count
time
tended
in Table 2 1 1 the
before
recurring
gability Whether
hand,
10 was
>
8). That
complained
other
antigen
No.
antigenemia only one
toms developing between respectively. This suggests
lowest
one week. persistently
shown
now
(Patient
the Shell
count, more often it took a week or two for to fall to < 10. As many as five of the patients
exhibited recurrent viral therapy, but
atic”
detect
highest
12 weeks,
surveillance
of symptomatic
usually counts
to
the
who developed a CMV-AG of greater than symptomatic at the time or developed symptoms after, whose
of 8
we did not SV result
failure
during
that a CMV-AG
development
our
in this
transplant).
CMV infection is unlikely no longer cost-effective.
above, positive
although the longer that we utilized (14
for
particularly
after
the
chose 2 weeks for logistical (6-month) follow-up. How-
experience
weekly,
fall in CMV-AG antigen counts
post-
an average
result, samples
time. We long-term
that
in diagnosing
days prior to shell vial culture. As outlined detect any difference in the time to the first
versus
of solid
of 59 seroposfound
of 95%
a sensitivity
infection
in a study
Versus
100%
1456
Journal
possible,
then
might
be
have 4
our
in
the
counts
positive
to low
blood
delayed
culture
therapy
results
were,
qualified
at 34
and
as symptoms
48,
as
One
and
opinion,
for
guiding
preemptive
problem
with
this study
time
SV
a guide
then
Use
of
and
earlier
than
niques
remain
tive.
can the
Their
detect
patients, six of blood and urine late
to be
1gM antibodies patients, making
poorly
very
high
sensitivity
more likely than the who are not destined studies
The and
be
test
as performed
required
nor
Drug
Standardization
thus
of symptoms
findings
are
and
is the
similar
we
labor costs, can months of weekly
of
cost.
test
be done profiling
for approximately $40. would cost approximately
we
followed-up
that
of CMV
as expressed
by
per 50/000
PBLs
renal
biweekly
peripheral
findings
evidence
the
blood
samples.
CMV-AG
infection quantification
correlated
test
and
whether
of antigenemia antiviral
therapy.
fever
could
TB,
We was
Balfour
for for
6.
7.
because
it was
often
result
in the
the
pre-
This
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the CMV-AG
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of more
CE, Shapiro GPJ. Levin
available
with
the
2.
issue.
be transferred
immunofluorescent
question
but
this
currently
and
,
intensive,
vious
can
1.
therefore,
is not
with
results
groups ( 1 1 17), and we were between the values assayed
munoperoxidase
counts
our
are,
it directly
a concern
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tech-
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kits
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the
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helps
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they
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compared
remains
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might blanket
we
are
is longer
seen
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even
PCR
are
resolve
in our
whether
However,
there
that
to definitively
have
laboratories.
other dence
means
Administration-approved
and it is not clear
most
antigen test to identify to become symptomatic,
will
commercially
and
symptoms
count
of asymptomtest
were
infection
(1 1). However,
standardized
actual
CMV-AG
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test
the
treatment
the
symptomatic
it too
is the fact that we did not do a
antigenemia
that
for
have
therapy.
evidence
as
treatment
specificity
have
concurrent evaluation of detection of viral DNA in peripheral blood leukocytes by polymerase chain reaction (PCR). Furthermore, there is evidence that PCR techniques are even more
sensitive
that
a high
unnecessary
believe
because
likelihood
would
too
assay
cessing
and would
obtained
SV
had
avoiding We
their
but
criterion
patients
the
and
thus
patients.
Both
and
resolved.
additional eight Conventional
in our
two
therapy.
respectively,
the
in our eight
atic
the
of symptoms
infection,
would
symptoms
useful for guiding preemptive therapy. not seen in up to 30% of symptomatic insensitive
threshold
for
levels
onset
threshold
by approximately
treated,
clinical
(SV)
by 4 days
of this
mild
in treatment of an were never symptomatic.
culture
Use
a suitable
of therapy
have
peaked
spontaneously
that
actually
would
developed
CMV-AG
resulted whom
> 10.
institution patients
patients
of Nephrology
suggest
count
eight
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additional
a
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