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Cytomegalovirus

Dr.T.V.Rao MD
Cytomegalovirus
Cytomegalovirus (from the
Greek cyto-, "cell", and -
megalo-, "large") is a viral
genus of the viral family
known as Herpesviridae or
herpes viruses. The species
that infects humans is
commonly known as human
CMV (HCMV) or human
herpesvirus-5 (HHV-5), and
is the most studied of all
cytomegaloviruses
Properties of the CMV
Belong to the betaherpesvirus subfamily of
herpesviruses
double stranded DNA enveloped virus
Nucleocapsid 105nm in diameter, 162 capsomers
The structure of the genome of CMV is similar to
other herpesviruses, consisting of long and short
segments which may be orientated in either direction,
giving a total of 4 isomers.
A large no. of proteins are encoded for, the precise
number is unknown.
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tegument
200 nm
envelope
glycoproteins
capsid
DNA core
Human Cytomegalovirus
Virion Structure
Why are herpes viruses (and especially CMV) so
fascinating from an evolutionary standpoint?
1.They are ancient

2.Latency = highly evolved

3.While many viruses deal with evolution passively
(i.e. mutate), herpesviruses actively target
mechanisms

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Human Cytomegalovirus
A complex -herpes virus
Large genome (230kb)
Slow replicating
Restricted host range

Infects 60-90% of the population worldwide, typically
asymptomatic infection

Infection in immunocompromised individuals life
threatening
Stem cell and solid organ transplant recipients
HIV infected individuals

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Spread of CMV
CMV spreads from person
to person through body
fluids, such as blood,
saliva, urine, semen and
breast milk. CMV spread
through breast milk usually
doesn't make the baby
sick. However, if pregnant
and develop an active
infection, can pass the
virus to baby.
Consequences of CMV Infections
Cancer patients receiving intensive chemotherapy
regimens can get infected
Infection in utero: Leading cause of infectious disease
related birth defects
1 in 100 infected; 1 in 1000 present
symptoms/pathology
Mild to severe hearing loss
Cognitive deficits
Physical abnormalities

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Pathogenesis
Once infected, the virus
remains in the person for life
and my be reactivated from
time to time, especially in
immunocompromised
individuals.
The virus may be transmitted
in utero, perinatally,or
postnatally.
Perinatal transmission occurs.
.
Clinical Manifestations
Congenital infection - may result in cytomegalic
inclusion disease
Perinatal infection - usually asymptomatic
Postnatal infection - usually asymptomatic. However,
in a minority of cases, the syndrome of infectious
mononucleosis may develop which consists of fever,
lymphadenopathy, and splenomegaly. The
heterophile antibody test is negative although
atypical lymphocytes may be found in the blood.
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Clinical Manifestations
Immunocompromised
patients such as transplant
recipients and AIDS patients
are prone to severe CMV
disease such as
pneumonitis, retinitis, colitis,
and encephalopathy.
Reactivation or reinfection
with CMV is usually
asymptomatic except in
immunocompromised
patients.

Complications
CMV mononucleosis.
This syndrome
resembles infectious
mononucleosis, but
the Epstein-Barr
virus (EBV) causes
classic
mononucleosis
Complications
Intestinal
complications. CMV
infection of intestines
can result in
diarrhoea, fever and
abdominal pain;
inflammation of colon;
and blood in stool.
Complications
Nervous system complications.
A variety of neurological
complications have been
reported as a result of CMV
infection in the nervous system.
These may include
inflammation of your brain
(encephalitis).
Lung complications. CMV can
cause inflammation of lung
tissue (pneumonitis)
Congenital Infection
Defined as the isolation of
CMV from the saliva or urine
within 3 weeks of birth.
Commonest congenital viral
infection, affects 0.3 - 1% of all
live births. The second most
common cause of mental
handicap after Down's
syndrome and is responsible for
more cases of congenital
damage than rubella.
Transmission to Foetus
Transmission to the
foetus may occur
following primary or
recurrent CMV infection.
40% chance of
transmission to the foetus
following a primary
infection.
May be transmitted to the
foetus during all stages of
pregnancy.

Cytomegalic Inclusion
Disease
CNS abnormalities - microcephaly, mental retardation,
spasticity, epilepsy, periventricular calcification.
Eye - choroidoretinitis and optic atrophy
Ear - sensorineural deafness
Liver - hepatosplenomegaly and jaundice which is due to
hepatitis.
Lung - pneumonitis
Heart - myocarditis
Thrombocytopenic purpura, Haemolytic anaemia
Late sequelae in individuals asymptomatic at birth - hearing
defects and reduced intelligence.
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CMV retinitis
Laboratory Diagnosis
Virus Isolation
conventional cell culture is regarded as gold standard but
requires up to 4 weeks for result.
More useful are rapid culture methods such as the
DEAFF test which can provide a result in 24-48 hours.
Serology
the presence of CMV IgG antibody indicates past infection.
The detection of IgM is indicative of primary infection
although it may also be found in immunocompromised
patients with reactivation.
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Treatment
Congenital infections - it is not
usually possible to detect congenital
infection unless the mother has
symptoms of primary infection. If so,
then the mother should be told of the
chances of her baby having
cytomegalic inclusion disease and
perhaps offered the choice of an
abortion.
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Treatment
Perinatal and postnatal
infection - it is usually not
necessary to treat such
patients.
Immunocompromised
patients - it is necessary
to make a diagnosis of
CMV infection early and
give prompt antiviral
therapy. Anti-CMV agents
in current use are
ganciclovir, forscarnet,
and cidofovir.

Prevention
CMV infection can be contagious if the infected
person comes in close or intimate contact with
another person. One should avoid kissing and sexual
contact with an infected person.
The virus may also spread among young children
in day care settings.
When planning blood transfusions or organ
transplants, the CMV status of the donor can be
checked to avoid passing CMV to a recipient who has
not had CMV.
Prevention
No licensed vaccine is available. There is a
candidate live attenuated vaccine known
as the Towne strain but there are
concerns about administering a live
vaccine which could become latent and
reactivates.
Prevention of CMV disease in transplant
recipients is a very complicated subject
and varies from center to center. It may
include the following measures.
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Prevention
Screening and matching the CMV status of the donor
and recipient
Use of CMV negative blood for transfusions
Administration of CMV immunoglobulin to
seronegative recipients prior to transplant
Give antiviral agents such as acyclovir and ganciclovir
prophylactically.

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Programme Created by
Dr.T.V.Rao MD for Medical and
Paramedical Students in
Universal Health Care
Email.
doctortvrao@gmail.com
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