Beruflich Dokumente
Kultur Dokumente
4th ESCMID School, Clin Microbiol Infect Dis, Szeged, Hungary, 2005
Human herpesviruses
Herpesviridae
Betaherpesvirinae
human cytomegalovirus (HCMV)
or human herpesvirus 5 (HHV5)
large number of genetic
variants
HCMV epidemiology, 1
Humans are the only reservoir for human CMV
Sources of infection: oropharyngeal secretions, urine,
cervical and vaginal secretions, semen, breast milk,
tears, feces and blood
Transmission occurs by
hand to mouth contact with infected body fluids
sexual contact
blood transfusion
organ or bone marrow transplants
from infected pregnant women to the fetus or newborn
breastfeeding
HCMV epidemiology, 2
Up to 60% of children become infected before the age
of 14 years
The prevalence in adults varies widely (40-100%) and
is dependent on the geography and the socioeconomic
status of the population
Intermittant shedding of CMV from many sites is
common in seropositive hosts
Virus excretion may last for years in congenital,
perinatal and early postnatally infected hosts
Seroepidemiology of HCMV
Clinical findings
Normal host
Primary infection in the normal host usually results in
mononucleosis (about 8% of infectious mononucleosis cases)
Rare complications include pneumonia, hepatitis and
CNS disease
In children <7 years of age, CMV infection may result in
severe liver or respiratory disease
Infection induces both a humoral (IgM, IgG and IgA) and
a cell mediated immune (CMI) response
Recurrent infection is rare in the normal host, but common in
the immunocompromised
Clinical findings
Immunocompromised host
Both the morbidity and the mortality are increased for
primary and recurrent infections in the immunocompromised
Viral excretion is more intense and prolonged with
immunosuppression, and chronic viremia may occur
The antibody response is similar in primary infection and
reactivation, but the CMI is depressed
CMV infection predisposes to fatal bacterial, fungal and
parasitic infections
Maternal situation
Intrapartum
Breast milk
0.2-2.2%
Seropositive
5%
50%
Seropositive mother
25%
Virolactia
65-70%
(mean 1%)
85-90% asymptomatic
at birth
10% of survivors
are normal
~ 3 out of 1000 newborns suffer
from a congenital CMV infection
symptomatic at birth:
2 800 (7%)
fatal
survivors with
disease:
sequelae::
sequelae
340
2 200
(10%)
(90%)
asymptomatic at birth:
37 200 (93%)
survivors with
sequelae::
sequelae
5 600
(15%)
healthy
survivors:
31 200
(85%)
Fatal outcome and /or sequelae of all live births: 8140 (0.2%)
*Rothe et al., 2000
Country
Year
Population
infected
Infection
(%)
Women
Doyle et al.
Texas-USA 1996
HIV
AIDS
6.5
21
Congenital
CMV infection
1.2%
(22/1828)
Endogenous infection
Pregnant women
Fetus
Viremia
Infection of
oropharynx
Virus in
amniotic fluid
Infection of fetal
endothelial cells
Fetal viruria
Fetal viremia
Viral replication in
target organs (kidney)
Laboratory findings
atypical lymphocytosis
elevated hepatic transaminases
negative heterophilic antibody response
M-G-
M-G+
M+G+
M+G-
Primary CMV
infection
Prenatal diagnosis at
weeks 21-23 of gestation
Follow-up
test later
60
50
40
30
20
10
0
0
10
15
20
25
30
35
Vp150
Vp82
Vp65
Vp28
rp150
3) Is easy to standardize
rp52
rp130
r
4) Is easy to interpret
rp38
Purified
native
viral
proteins
Recombinant
proteins
CKS
Landini, 2000
Why?
When?
At 21-23 weeks of
gestation
Positive result
qPCR
Level of fetal risk
Low
<105 GE/ml
High
105 GE/ml
Conclusion
Congenital CMV infections prenatally can
be diagnosed
Question
Can the prenatal diagnosis identify fetuses at
high risk of CMV-related symptoms?
CMV-GE/ml
N= newborns
F= fetuses
N F
N N
FN
N N
F
106
105
N
104
F
F
103
F
N (n 56)
Uninfected
NN N
NN
Infected
asymptomatic
Infected
symptomatic
Pregnancy outcomes
Landini, 1999
Asymptomatic
CMV-infected newborns
Neonatal follow-up
virus isolation
from urine
-
Neonatal follow-up
AIDS
Esophagitis
Gastritis
Enterocolitis
Fever/hepatitis
Pancreatitis
Pneumonitis
Retinitis
Encephalopathy
Polyradiculopathy
+
+
+
++
+
+
+
+
++
++
+
+
-
+
+
+
++
+
-
Cecal ulceration
CMV colitis
Mucosal inflammation with mucosal hemorrhage, edematous
fields and polypoid lesions. Biopsis demonstrated viral inclusions
with CMV
http://www.endoatlas.com/co_co_08.html
CMV retinitis
Normal retina
Characteristic inclusion
in liver
Inclusions in lung
Therapeutic approaches
Antiviral prophylaxis
Pre-emptive treatment
Treatment of an established disease
Antiviral prophylaxis
An antiviral drug is administered before any active
CMV infection is detected, in order to prevent its
occurrence
This prophylaxis is recommended for renal transplant
recipients
when the donor or recipient is seropositive
if the recipient is subjected to an immunosuppressive regimen
Pre-emptive therapy
Antiviral treatment is initiated when CMV positivity*
is detected in the blood or bronchoalveolar lavage
fluid by using sensitive method in
bone marrow
liver or
lung recipients
or