JICNAR○| Journal of the International
Child Neurology Association
A peer reviewed open access e-journal in Child Neurology
Efficacy of Valganciclovir versus Ganciclovir in treatment of
symptomatic cytomegalovirus infection in infants: An open-label
randomized controlled trial
2
Kanij Fatema
1, Md Mizanur Rahman1, Shaheen Akhtar1, Jannatara Shefa
1 Department of Paediatric Neurology, Institute of Pediatric Neurodisorder and Autism (IPNA),
Bangabandhu Sheikh Mujib Medical University,2 Institute of Paediatric Neurodisorder and
Autism (IPNA), Bangabandhu Sheikh Mujib Medical University
Corresponding author: Jannatara Shefa; Email: shefaafnan@yahoo.com; Tel:
+88-0171-5254283.
Received: 18 Feb 2018
Accepted: 21 July 2019
Abstract
Introduction: Congenital cytomegalovirus (CMV) infection is the most common viral infection transmitted via the pla-
centa, causing significant neurodevelopmental impairment in infants and children. Gancyclovir and Valgancyclovir are
two drugs used in the treatment of symptomatic CMV infected case which have limited comparative study. This study
compared the efficacy and tolerability of these two drugs on symptomatic CMV infected infants. Methodology: This was
an open-label randomized controlled trial done to compare oral valganciclovir(VGCV) with injectable ganciclovir (GCV) in
the treatment of symptomatic congenital CMV infected infants. A total of 72 patients were included; 12 patients discontin-
ued the treatment due to noncompliance or side effects. Pre and post-treatment CMV virus levels and adverse effects were
monitored. Psychological, visual, and hearing assessments were performed at baseline and six months post-treatment.
Results: The mean age of the infants in VGCV and GCV group was 7.10±3.58 and 7.50±3.99 months, respectively. Nine-
teen infants presented with developmental delay, 13 with seizure, 4 with a movement disorder. Twenty-one percent of
the infants were preterm, and 38% were low birth weight. Eighteen infants had a neonatal seizure. Twenty-eight infants
of VGCV and 24 infants of the GCV group showed clearance of the virus after six weeks of treatment. No statistical dif-
ference was found in virus clearance. Regarding ophthalmological assessment, infants had chorioretinitis, optic atrophy,
squint, and cortical blindness. On hearing assessment, none of the infants deteriorated after drug administration, while
some showed improved hearing. None of the infants showed deterioration of cognition, while some of the infants showed
improvement in cognitive assessment, but there was no significant difference in two groups. The side effects of GCV were
significantly greater than VGCV (P value <0.05). Conclusion: In symptomatic congenital CMV infection in infants, VGCV
is as efficient as GCV, and the former has fewer side effects.
Keywords: Congenital cytomegalovirus infection; Valganciclovir; Ganciclovir; randomized controlled trial
© 2019 Fatema K et al; licensee JICNA. All rights reserved
Introduction
tational age often correlates with a less favorable outcome
[3][4]. Only about 7 to 10% have a clinically evident dis-
Cytomegalovirus (CMV) is the most common cause of con-
ease at birth [5][6]. Jaundice (62%), petechiae (58%), and
genital infections in humans. The prevalence of CMV
hepatosplenomegaly (50%) are the most frequently noted
is
0.2-2% (average of 0.64%) of pregnancies in the US,
symptoms and constitute the classical triad of congenital
Canada, Australia, and Western Europe. Limited studies
CMV infection (cCMV) infection [7]. Central nervous sys-
from developing countries have shown a prevalence rang-
tem (CNS) involvement is present in approximately two-
ing from 0.6 to 6.1% of pregnancies [1].
thirds of infants with symptomatic cCMV infection [8][9].
Primary maternal CMV infection carries a 30-40% risk of
It is the leading nongenetic cause of sensorineural hearing
vertical transmission, with 0.2-2% of secondary infections
loss (SNHL) estimated to be responsible for one-third of all
leading to fetal infection [2]. Infection at an earlier ges-
1
FATEMA K et al. JICNA 2019, 1(1)
cases in children [10]. The other neurological consequences
Methods
are mental retardation, seizures, psychomotor and speech
This study aimed to find out the efficacy and tolerability of
delays, learning disabilities, chorioretinitis and optic nerve
VGCV and GCV in symptomatic CMV infected infants. This
atrophy [11][12][13][14].
was an open-label randomized controlled trial conducted at
cCMV infection is defined as active CMV infection de-
a tertiary care paediatric neurology centre. Relevant per-
tectable within the first three weeks of life. Given the dev-
missions were obtained from the institutional Ethics Com-
astating sequelae of cCMV, it is recommended that treat-
mittee. The following formula was used to determine the
ment should be instituted in infants with cCMV with the
sample size. All infants (0-1 year) who had a neurodevelop-
following criteria: positive CMV DNA PCR plus evidence of
central nervous system involvement, including SNHL and
P 1(1 − P 1) + P 2(1 − P 2)
developmental delay, stigmata of CMV disease even after
N =
× (Zα − Zβ)2
(P 1 − P 2)2
neonatal period in infancy, chorioretinitis and critically ill
preterm infants with life-threatening CMV infection mani-
mental deficit with evidence of CMV infection, as indicated
fested by pneumonitis, hepatitis or encephalitis [10][15].
by a urinary CMV DNA qPCR positivity within one month of
Ganciclovir (GCV) and Valganciclovir (VGCV) are the drugs
attending the center during the study period, were included.
used to treat cCMV. GCV is a synthetic acyclic nucleoside
More than 500 copies of the virus on real-time qPCR in urine
analogue, structurally similar to guanine [15]. GCV pene-
samples was considered a positive result. The study period
trates well into the CNS, a charectaristic that makes it an
was from August 2015 to September 2016. Seventy-two
important treatment agent in the setting of CMV-induced
patients were included, by randomization, with 39 patients
neurodevelopmental injury [16].
in the GCV and 33 in the VGCV group. The primary study
Although GCV appeared to be of value in the short-term
outcome was clearance of the virus from the body, and the
management of CMV infection in infants in some settings,
secondary outcome was an improvement of hearing, vision,
it is less clear whether the use of GCV provided any long-
and psychological function.
term benefit for congenitally or perinatally acquired CMV
A detailed medical history, including presenting com-
infection. Multicenter studies conducted by the National
plaints, birth history, antenatal history, and past history, was
Institute of Allergy and Infectious Diseases Collaborative
taken, followed by a general and systemic examination. In-
Antiviral Study Group (CASG) have shed light on the po-
formed written consent was taken from the guardian or
tential long-term benefits of antiviral therapy. These trials
caregiver. Randomization was done by lottery method. GCV
have focused on the impact of antiviral therapy on symp-
group was entitled as control and VGCV group was entitled
tomatic cCMV infection with CNS involvement [17][18]. A
as case. The terms GCV and VGCV were written on paper
subsequent phase II CASG study of GCV for symptomatic
strips of the same size, shape, and color. They were folded
cCMV showed improvement or stabilization of hearing im-
and mixed up in a container. A blindfold selection was made
pairment in 5(16%) of 30 babies at six months or later, indi-
with the required numbers of slips selected for the desired
cating efficacy [19].On the other hand, studies on Valganci-
sample size. All enrolled infants underwent a baseline vi-
clovir (VGCV), a monovalyl ester prodrug that is rapidly hy-
sual, hearing, and psychological assessment. Following drug
drolyzed to GCV when taken orally, showed that VGCV has
treatment, visual, hearing, and psychological assessment
ten times greater oral bioavailability than oral GCV (53.6%
was performed again at six months and compared to the
vs. 4.8%) [20][? ]. Kimberlin et al. showed in a study that
initial assessment. Assessment of hearing included Brain-
16 mg/kg dose of oral VGCV solution administered twice
stem Auditory-Evoked Responses (BAER)/Auditory Brain-
daily provided GCV concentration compared with that of 6
stem Responses (ABR) or Otoacoustic Emissions (OAEs).
mg/kg/dose of IV GCV [21].
The hearing was ascertained as normal, mild, moderate, or
severe impairment. An infant was tagged as improved or de-
Intravenous administration of GCV necessitates pro-
teriorated based on improvement in hearing status and the
longed hospital stay. The major side effect of GCV is hema-
psychological assessment using the mental scale of BSID-
tologic, including leucopenia, neutropenia, and thrombocy-
II( Baily Scale of Infant Development II) at baseline and six
topenia. Other rare side effects are bone marrow suppres-
months following first administration of the drug [23].
sion, raised liver enzymes, hypokalemia, and renal impair-
VGCV was administered orally at 16 mg/kg/dose 12
ment [22]. There are no definite guidelines on whether IV
hourly for 42 days and GCV, intravenously 6 mg/kg/dose
GCV or oral VGCV should be used for symptomatic cCMV
12 hourly for 42 days.
24 Infants who had chorioretinitis
infected infants. There are minimal studies regarding this,
were treated for six months, but they were not included in
particularly in resource-limited settings where the problem
the study protocol and are not discussed in this paper. In
is more prevalent. Whether the orally bioavailable VGCV
all the infants, urinary CMV qPCR was done at 6 weeks of
is as effective as GCV in improving sensory hearing loss in
drug treatment. Baseline and weekly complete blood count
symptomatic newborns still needs to be ascertained.
(CBC), Serum glutamic pyruvic transaminase (SGPT) and
serum creatinine levels were done to determine any side ef-
fects. Other investigations were also performed based on
2
FATEMA K et al. JICNA 2019, 1(1)
the clinical indication. Computed tomography (CT) or mag-
Table 1 Baseline characteristics of studied infants (N=60)
netic resonance imaging (MRI) was done to determine the
Baseline characteristics
Control (GCV)
Case (VGCV)
P value
extent of disease and exclude any other comorbid condition.
(n=30)
(n=30)
In suspected cases, a metabolic panel was done to exclude a
n(%)
n (%)
metabolic disorder.
Age ( months)
Nine patients from the GCV group and three patients from
<5
11(36.7%)
10(33.3%)
5-10
12(40.0%)
14(46.7%)
0.684†
the VGCV group discontinued treatment owing to noncom-
> 10
7(23.3%)
6(20.0%)
pliance or adverse effects and dropped out of the study.
Mean±SD
7.50±3.99
7.10±3.58
Seven patients from GCV group dropped out due to ad-
Sex
verse effects, including phlebitis (2) neutropenia (3) and
Male
12(40.0%)
13(43.3%)
0.793†
hypersensitivity (2) reaction. In the VGCV group, one pa-
Female
18(60.0%)
17(56.7%)
Gestational age
tient discontinued due to pancytopenia. Also, one patient
Term
23(76.7%)
24(80.0%)
from the GCV group and two patients from the VGCV arm
Preterm
7(23.3%)
6(20.0%)
0.754†
discontinued due to personal issues. Infants with concomi-
Birth weight
tant suspected neurometabolic or neurodegenerative disor-
Normal
17(56.7%)
16(53.3%)
der and preexisting renal disease or pancytopenia were ex-
LBW
10(33.3%)
13(43.3%)
0.491†
IUGR
3(10.0%)
1(3.3%)
cluded from the study.
Milestones of development
Data were entered using SPSS (version 16.0) [24] and
Age appropriate
3(10.0%)
8(26.7%)
double-checked before analysis. Descriptive statistics such
Motor delay
22(73.3%)
11(36.7%)
as frequency tabulation, mean, median, standard deviation,
Speech delay
1(3.3%)
1(3.3%)
0.037*
Chi-square test, and t-tests were performed to find out the
GDD
4(13.3%)
10(33.3%)
Presenting complaints
test of significance. Statistical significance was fixed at a P
Developmental delay
7(23.3%)
12(40.0%)
value of <0.05.
Seizure
6(20.0%)
7(23.3%)
Abnormal movement
1(3.3%)
3(10.0%)
0.168†
Multiple clinical features
16(53.3%)
8(26.7 %)
Total
30(100.0%)
30(100.0%)
Results
Perinatal asphyxia
Yes
11(36.7%)
15(50.0%)
Study population: Overall seventy-two patients under one
No
19(63.3%)
15(50.0%)
0.297†
year of age were included in this study. Sixty of them com-
Postnatal problems
pleted six months of follow up and thus underwent outcome
No
18(60.0%)
12(40.0%)
evaluation. Infants in the VGCV arm had significantly in-
Neonatal seizure
9(30.0%)
9(30.0%)
creased delay in motor development compared to the GCV
Infection
2(6.7%)
5(16.7%)
Cardiac problem
3(10.0%)
2(6.7%)
0.360†
group (P= 0.037). Demographic characteristics are shown
Neonatal jaundice
0(0.0%)
2(6.7%)
in Table 1.
Others
0(0.0%)
1(3.3%)
Clinical parameter: Infants presented with developmen-
tal delay, seizures, abnormal involuntary movements, visual
†not significant;∗significant; LBW Low Birth Weight; IUGR Intrauterine
Growth Retardation
and hearing impairment (see Table 2).
Perinatal status: The two study groups were not statisti-
cally different in terms of gestational age, birth weight, peri-
natal asphyxia, and neonatal presentation. However, the in-
in the VGCV compared to the GCV group.
cidence of neonatal seizures was the same in both groups
Adverse effect of drugs: GCV treated infants had phlebitis
(30%)
(see Table 3). Clinical outcome: After six months
(16.7%), which was absent in the VGCV group as they had
of treatment, no significant improvement was noted in vi-
oral administration of the drug. In the GCV group, the most
sual status, although the number of infants with normal eye
common side effect was infection (23.3%). However, there
finding increased after treatment. Chorioretinitis resolved
was a significant difference in the number of infants with-
in five infants from the GVC group and in one infant from
out any adverse effects between the two groups (VGCV 60%
the VGCV group. Most infants in both groups had a mild
vs. GCV 23.3%) (p <0.5). Thus VGCV had more tolerabil-
form of hearing impairment. However, the number of in-
ity than GCV (Table 6). Overall, no significant difference
fants returning to normal hearing was equal in both groups.
was found in the control and case groups regarding virus
No statistical difference was found in the cognitive status of
clearance from urine, improvement of hearing, visual, and
the GCV recipients at six months follow up while the VGCV
psychological status.
group showed a statistically significant improvement psy-
chological status (p = 0.016) (Table 4) on the mental scale
of BSID-II.
Discussion
Clearance of virus: At six weeks of therapy, urinary CMV
qPCR did not show any statistically different viral clearance
CMV is the most common cause of congenital infections in
between the two groups, although the clearance was higher
humans and has a profound impact on infants’ health. In-
3
FATEMA K et al. JICNA 2019, 1(1)
Table 2 Distribution of studied infants by visual, auditory and psy-
Table 4 Distribution of infants by effect of intervention (N=60)
chological status before and after 6 month of intervention (N=60)
Parameters
Control
Case
P value
Parameters
Control (GCV)
Case(VGCV)
(n=30)
(n=30)
(n=30)
(n=30)
n(%)
n(%)
N(%)
N(%)
Clearance of virus
24(80.0%)
28(93.3%)
0.128
Visual status
Before
After
Before
After
Auditory status normalization
6(20.0%)
4(13.3%)
0.488
Normal
16(53.3%)
17(56.7%)
15(50.0%)
19(63.3%)
Visual status normalization
1(3.3%)
4(13.3%)
0.161
Chorioretinitis
5(16.7%)
4(13.3%)
7(23.3%)
2(6.7%)
Optic atrophy
5(16.7%)
5(16.7%)
6(20.0%)
6(20.0%)
Chorioretinitis resolved
1(3.3%)
5(16.7%)
0.085
Squint
1(3.3%)
1(3.3%)
0(0.0%)
0(0.0%)
Cognitive status improved
5(16.7%)
7(23.3%)
0.518
Cataract
0(0.0)
0(0.0%)
0(0.0%)
1(3.3%)
Free from side effects
7(23.3%)
18(60.0%)
0.003*
Cortical blindness
1(3.3%)
1(3.3%)
2(6.7%)
2(6.7%)
∗significant
Others
2(6.6%)
2(6.4%)
0(0.0%)
0(0.0%)
P value
0.999†
0.373†
Auditory status
Normal
12(40.0%)
18(60.0%)
17(56.7%)
21(70.0%)
clues in the antenatal history to suspect cCMV [28]. Post-
Mild HI
7(23.3%)
5(16.7%)
11(36.7%)
6(20.0%)
natally, infants in this study had neonatal seizures (30%),
Moderate HI
7(23.3%)
6(20.0%)
2(6.7%)
3(10.0%)
Severe HI
4(13.3%)
1(3.3%)
0(0.0%)
0(0.0%)
infection (11.6%), cardiac problem (8.33%), neonatal jaun-
P value
0.884†
0.351†
dice (3.3%), developmental delay (31.6%), visual (45%)
Psychological status
and hearing( 51%) impairment. The results were in keeping
Normal
4(13.3%)
7(23.3%)
1(3.3%)
8(26.7%)
Mild Impairment
15(50.0%)
17(56.7%)
17(56.7%)
17(56.7%)
with similar studies done by Suresh B. Boppana, Ornoy and
Severe impairment
11(36.7%)
6(20.0%)
12(40.0%)
5(16.7%)
Diav-Citrin [29][30].
P value
0.229†
0.016*
CMV infection may cause impaired fetal growth. The
†not significant;∗significant; HI Hearing impairment
risk of intrauterine transmission after primary CMV infec-
tion during pregnancy approaches 40%, with an increased
Table 3 Adverse effects following drug treatment (tolerability)
risk of adverse fetal effects if infection occurs during the
(N=60)
first half of pregnancy [31]. This has also been evidenced
in this study. In the current study, the incidence of low birth
Adverse effects
Control
Case
weight (LBW) and intrauterine growth retardation (IUGR)
(n=30)
(n=30)
were 38.3% and 6.6%, respectively, although it was not sta-
tistically significant. The results were in keeping with a sim-
No side effects∗
7(23.3%)
18(60.0%)
ilar study done by Yoshinaga-Itano et al. [32].
Pancytopenia
0(0.0%)
1(3.3%)
The clearance of virus from urine at six weeks of treat-
Neutropenia
3(10.0%)
3(10.0%)
ment was an important outcome parameter for this study.
Anemia
4(13.3%)
3(10.0%)
In the current study, 93.4% of VGCV treated infants showed
Infection
7(23.3%)
3(10.0%)
clearance of virus from urine at six weeks, while only two
Phlebitis
5(16.7%)
0(0.0%)
infants (6.6%) showed nonclearance of the virus. On the
Hypersensitivity reaction
4(13.3%)
2(6.7%)
contrary, in GCV treated infants, six infants (20%)showed
Total
30(100.0%)
30(100.0%)
nonclearance of the virus. However, there was no statistical
*P=0.039
difference between these two groups. Only limited clinical
trials so far have compared the two drugs studied. In a re-
lated study done by Lombardi et al., 8 out of 12 newborns
fants with CMV infection at birth have higher rates of hear-
suffering from symptomatic cCMV who were treated with
ing impairment and neurodevelopmental sequelae [25].
oral VGCV, 15 mg/kg every 12 hours for six weeks showed
Even though there is a growing number of studies on CMV
virus clearance while nonclearance of the virus was seen in
infection, there is no highly effective and safe antiviral ther-
33.3% [33]. In another study where CMV infected infants
apy currently available for the treatment of cCMV infection.
were treated with the two regimens viral shedding disap-
Clinical trials are in progress [26][27].
peared in 3/6 infants treated with GCV 5 mg/kg twice daily
This study aimed to further contribute to studies under-
for two weeks, While in the GCV group who received 7.5
taken in resource-limited settings. This open-label, random-
mg/kg twice daily for two weeks, followed by 10 mg/kg
ized controlled study compared the efficacy and tolerabil-
three times a week for three months, all six infants showed
ity of VGCV and GCV in cCMV infected infants. Infants in
cessation of viruria[34]. Thus the duration of the drug
both groups were comparable based on their baseline char-
seemed to be a significant factor for clearance of the virus.
acteristics except for motor developmental delay, which was
The majority of infants in both groups had mild cogni-
significantly higher in the VGCV treated infants (P=0.037).
tive impairment in this study (53.33%). It is known that
Antenatal history is an important clue to diagnose cCMV
infants with CMV infection are at risk of developmental de-
infection. In this study, a very small number of infants had
lay, particularly in cognitive functioning [32][35]. The cur-
antenatal history findings of maternal fever, rash, or history
rent study suggests that both GCV and VGCV treatment of
of previous miscarriages. This is in keeping with a simi-
cCMV infected infants resulted in the improvement of cog-
lar study done by Ehab Abd, where only 6% had similar
nitive status. VGCV treated infants showed significantly im-
4
FATEMA K et al. JICNA 2019, 1(1)
proved cognitive status at six months follow up (P<0.5) as
rioration in hearing at six months follow up compared with
assessed by the BSID-II mental scale, while GCV treated in-
no treatment group (P=0.06) [43]. Lombardi et al., who
fants showed no significant improvement in cognitive sta-
treated symptomatic cCMV infants with oral VGCV, found
tus. This observation was in keeping with other related
that while there was no deterioration in hearing in any of
studies. However, a study by Amir et al. who treated 23
the subjects, two infants demonstrated improved hearing
infants with symptomatic cCMV infection with IV GCV fol-
status at 6 to 8 months follow-up [33]. In another random-
lowed by oral VGCV until the age of 12 months showed psy-
ized controlled trial, where GCV was given within the first
chomotor retardation at age one year in 18% which was
month at 12 mg/kg/d intravenously for six weeks, twenty-
considerably lower than the 55% reported in the past [36].
one (84%) of 25 ganciclovir recipients demonstrated im-
In another study conducted in 100 neonates who were en-
proved or maintained normal hearing at months compared
rolled in a controlled trial, six weeks of intravenous GCV
to controls (p=0.06). On follow up at 1 year or beyond
at 12 mg/kg/day was given compared to no antiviral treat-
only five (21%) of 24 subjects treated with ganciclovir had
ment. The results showed that fewer treated subjects had
worsening of hearing compared to 13(68%) of 19 control
neurodevelopmental delays compared to those who did not
patients (P<0.01) [44]. The same researchers in a more
receive antiviral therapy [37]. However, no comparative
recent study reported that infants receiving six months of
randomized trial has been published comparing the efficacy
VGCV therapy, compared with those receiving six weeks of
of VGCV and GCV on the improvement of cognitive status.
VGCV treatment, have improved hearing outcomes [45].
These studies however support the importance of treating
The major toxicity in patients receiving GCV and VGCV is
CMV infected infants with antiviral drugs, which may result
hematologic abnormalities, particularly neutropenia [22].
in improvement of cognitive status.
In the current study, adverse effects observed were neu-
CMV infection can cause a spectrum of ocular manifes-
tropenia, anemia, infection, pancytopenia, hypersensitivity
tations. A substantial portion of infants in this study had
reaction, and phlebitis. In terms of adverse effects there was
abnormal eye findings, including chorioretinitis (20%), op-
a significant difference between the two groups with 60% of
tic atrophy (18.33%), cortical blindness, and squint. These
VGCV recipients free from any adverse effects compared to
findings are in keeping with a related study where choriore-
23.3% of the GCV recipients (P<0.05). Also,infants who
tinitis, squint, and optic atrophy were the most common ab-
were treated with GCV had phlebitis (16.7%) as they had IV
normalities [28][38]. Like most other studies, chorioretini-
medication. No statistically significant difference was found
tis was the commonest eye finding in CMV infected children.
in neutropenia (10.0%) in both groups. This is similar to
Treatment resulted in the improvement of visual function,
findings from a related study where neutropenia was seen in
although not statistically significant. Following VGCV treat-
63% of infants with GCV therapy and 38% in VGCV treated
ment, five infants had resolution of chorioretinitis while in
infants. (P> 0.5).
the GCV group, only one infant had a resolution of chori-
Neutropenia related sepsis, however, was rarely a prob-
oretinitis. In another study from Bangladesh, Mahbub et al.
lem and dangerous neutropenia has rarely been described,
also observed that while the visual function improved in a
and is easily resolved by diminishing drug doses or inter-
larger proportion of infants treated with ganciclovir, the re-
rupting therapy for 3 -7 days [46]. Other rare side effects
sults were not statistically significant [39]. In contrast to
are bone marrow suppression, elevated liver enzymes, hy-
these observations, Shoji et al. showed statistically signifi-
pokalemia, and renal impairment which were not observed
cant improvement or resolution of chorioretinitis in 50% of
in the current study [19]. Seven infants in the GCV group
infants who were treated with IV GCV [40].
and one infant in the VGCV group discontinued treatment
The prevalence of sensorineural hearing loss caused by
owing to adverse effects, particularly fever due to neutrope-
cCMV infection (symptomatic and asymptomatic) at birth is
nia, phlebitis, and hypersensitivity. These infants were not
5.2%, and late-onset hearing loss at six years is 15.4% [12].
included in the statistical analysis. Thus comparing the ef-
Previously several studies have shown that drug treatment
fect of intervention between the two drugs, VGCV recipients
either prevents deterioration of hearing status or improves
showed significantly improved psychological status, and a
it
[39][41][42]. In the current study, no statistically sig-
high proportion of patients did not show any adverse effects.
nificant difference was found at six months follow up in
The current study suggests that all infants with neurodevel-
audiology assessments. Most infants in both groups had
opment deficits should be screened for CMV infection. CMV
only mild hearing impairment. However, following treat-
PCR positive infants should be treated with either GCV or
ment with VGCV at six months, the number of infants with
VGCV, preferably VGCV, as the latter showed improved cog-
normal hearing increased to 21(70.0%) from 17(56.7%). In
nitive outcome and lesser side effects.
one infant, the hearing loss deteriorated from mild to mod-
erate. On the other hand, in the GCV group, only six infants
had normal hearing following intervention.
Conclusion
No similar comparative study has been done with GCV
and VGCV with regard to hearing status. A related study
From the present study, it can be concluded that both VGCV
done by Lauren Nassetta et al. who treated infants with IV
and GCV have nearly similar efficacy in treating symp-
GCV found that there was either improvement or no dete-
tomatic CMV infected infants. Both drugs showed similar
5
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Abbreviations
ABR Auditory Brainstem Responses
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Leung AKC, Sauve RS, Davies HD. Congenital cy-
BAER Brainstem auditory evoked responses
tomegalovirus infection. Journal of the National
cCMV Congenital cytomegalovirus infection
Medical Association. 2003 mar;95(3):213-8. Avail-
CMV Cytomegalovirus
GCV Ganciclovir
GDD Global developmental delay
HI Hearing impairment
IV intravenous
[4]
Naing ZW, Scott GM, Shand A, Hamilton ST, van
OAE Otoacoustic emissions
Zuylen WJ, Basha J, et al. Congenital cytomegalovirus
PCR Polymerase chain reaction
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qPCR Quantitative polymerase chain reaction
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SNHL Sensorineural hearing loss
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VGCV Valganciclovir
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Pass RF. Cytomegalovirus Infection.
Pediatrics
Acknowledgments
in Review.
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Available
Ethical approval was obtained from Bangabandhu Sheikh
Mujib Medical University.
[6]
Crowley B. Ganciclovir treatment of symptomatic con-
Competing interests
genital cytomegalovirus infection. The Journal of an-
timicrobial chemotherapy. 2002 sep;50(3):435-6; au-
The authors have declared that they have no competing in-
terests.
[7]
Griffiths PD. The 2001 Garrod lecture. The treat-
Authors’ contributions
ment of cytomegalovirus infection. The Journal
All the authors contributed to data collection and also crit-
of antimicrobial chemotherapy. 2002 feb;49(2):243-
ically reviewed the manuscript. The final version of the
manuscript was approved by all the authors.
This is an Open Access article distributed under the terms of
[8]
Yamamoto AY, Mussi-Pinhata MM, Cristina P, Pinto
the Creative Commons Attribution License which permits un-
G, Moraes Figueiredo LT, Jorge SM. Congenital cy-
restricted use, distribution, and reproduction in any medium,
tomegalovirus infection in preterm and full-term new-
provided the original work is properly credited. The Cre-
born infants from a population with a high seropreva-
ative Commons Public Domain Dedication waiver applies to
lence rate. The Pediatric infectious disease journal.
the data made available in this article,unless otherwise stated.
Cite this article as:
Fatema K, Rahman MM, Akhtar S, Shefa J. Efficacy of Val-
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McDonald JM, Raghuveer TS, D’Alessandro MP. Can
ganciclovir Versus Ganciclovir in Treatment of Symptomatic
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Cytomegalovirus Infection in Infants: An Open-Label ran-
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