1

CYTOMEGALOVIRUS
ILMU PENYAKIT DALAM

DR.T.V.RAO MD
 2
CYTOMEGALOVIRUS
INFECTIONS
• Ubiquitous virus most
populations -infections in
early childhood often
asymptomatic
• Latency
• Clinical disease
increasing due to
increasing number of
immunocompromised
patients

DR.T.V.RAO MD
 PROPERTI 3

ES
• 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.

DR.T.V.RAO MD
 4
VIRUS
STRUCTURE
ENVELOPED,
SLIGHTLY
PLEOMORPHIC
SPHERICAL
120 – 200 NM IN
DIAMETER

CAPSID
ENVELOPE
TEGUMENT
GENOME
DOUBLE
STRANDED DNA
PER VIRION
DR.T.V.RAO MD
 5

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), herpes viruses “actively” target mechanisms

DR.T.V.RAO MD
 VIROLO 6

GY
• Virion:
• Spherical, enveloped, 150-200 nm in diameter
• Genome: Double-stranded DNA, linear, 240 kbp, reiterated sequences
• Proteins: only a few have been characterized
• Replication: Nucleus, bud from nuclear membrane
• Virus classification: Group I: ds DNA; Family: Herpesviridae; Genus:
Cytomegalovirus; Species: Human herpesvirus 5 (HHV-5)

DR.T.V.RAO MD
 7

Human Cytomegalovirus
A complex -herpesvirus
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
Cancer patients receiving intensive chemotherapy regimens

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

DR.T.V.RAO MD
 8

Human Cytomegalovirus
Virion Structure

envelope
glycoproteins
tegument
capsid
200 nm DNA core

DR.T.V.RAO MD
 9

HOW IS CMV SPREAD?

• Person to person contact (kissing, sexual contact,

getting saliva or urine on hands and then touching
eyes, or the inside of nose or mouth)
• Through the breast milk of an infected woman
• Infected pregnant women can pass the virus to
their unborn babies
• Blood transfusions and organ transplantations

DR.T.V.RAO MD
 PATHOGENE 10

SIS
• 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.
• Perinatal infection is acquired mainly through infected genital secretions,
or breast milk. Overall, 2 - 10% of infants are infected by the age of 6
months worldwide. Perinatal infection is thought to be 10 times more
common than congenital infection.
• Postnatal infection mainly occurs through saliva. Sexual transmission may
occur as well as through blood and blood products and transplanted organ.

DR.T.V.RAO MD
 11
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 heterophil
antibody test is negative although atypical lymphocytes may be found
in the blood.
• 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.

DR.T.V.RAO MD
 CYTOMEGALOVIRUS 12

INFECTIONS
• Fetus
• transmission from mother via placenta
• clinically normal 80%
• causes congenital CMV
• death 1%
• Cytomegalic inclusion disease %
• late onset hearing defect / mental retardardation 15%
• Infant
• transmission during birth or breast feeding
• usually asymptomatic

DR.T.V.RAO MD
 13

PREGNANT WOMEN AND CMV

• Contact with the saliva

or urine of young
children is a major cause
of CMV infection among
pregnant women.
• Risk of CMV infection is
likely to be reduced by
careful attention to good
personal hygiene, such
as hand washing.

DR.T.V.RAO MD
 CONGENITAL 14

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 the fetus may occur following primary or
recurrent CMV infection. 40% chance of transmission to the fetus
following a primary infection.
• May be transmitted to the fetes during all stages of pregnancy.
• No evidence of teratogenicity, damage to the fetus results from
destruction of target cells once they are formed.

DR.T.V.RAO MD
 15

SYMPTOMS OF CONGENITAL CMV

Temporary Symptoms
Liver problems
Spleen problems
Jaundice (yellow skin and eyes)
Purple skin splotches
Lung problems
Small size at birth
Seizures
Permanent Symptoms or Disabilities
Hearing loss
Vision loss
Mental disability
Small head
Lack of coordination
Seizures
Death

DR.T.V.RAO MD
 16
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.

DR.T.V.RAO MD
 CMV RETINITIS 17

SMALL FLOATERS
FOGGY OR BLURRED VISION
LOSS OF CENTRAL OR PERIPHERAL
VISION

ROUTINE EXAM WHEN THE

INFECTIOUS PROCESS IS EARLY AND
LOCATED IN THE PERIPHERAL RETINA

LOSS OF VISION

RETINAL DETACHMENT

DR.T.V.RAO MD
 18

CMV
retinitis

DR.T.V.RAO MD
DR.T.V.RAO MD CMV retinitis 19
 CYTOMEGALOVIRUS
20
INFECTIONS
• Diagnosis DIFFICULT
• presence of virus or antibody to CMV does not indicate
that current disease is due to CMV
• Different strategies used in different clinical situations

isolation of virus from urine

Congenital
within CMV
30 days of birt h

* antigen detection in
buffy coat - indicates
immunocompromised
viraemia

patient

* CMV specific Ig G positive indicates past infection

DR.T.V.RAO MD
 LABORATORY 21

DIAGNOSIS
• Direct detection
• biopsy specimens may be examined histologically for
CMV inclusion antibodies or for the presence of
CMV antigens. However, the sensitivity may be low.
• The pp65 CMV antigenemia test is now routinely
used for the rapid diagnosis of CMV infection in
immunocompromised patients.
• PCR for CMV-DNA is used in some centers but there
may be problems with interpretation.

DR.T.V.RAO MD
 22
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.
DR.T.V.RAO MD
 23
LABORATORY
DIAGNOSIS
• Serologic testing
• Paired antibody titers (4-fold increase in convalescent phase
compared to acute phase)
• ELISA to determine if acute infection, prior infection, or
passively acquired maternal antibody in an infant is present.
• CMV IgM titers for congenital infection
• Other tests include CF test, fluorescence assays (CMV pp65
antigenemia test, IFA, ACIF), indirect haemagglutination & PCR
• CMV should be suspected if a patient has symptoms of infectious
mononucleosis but has negative test results for mononucleosis and Epstein-
Barr virus, or if they show signs of hepatitis, but has negative test results for
hepatitis A, B, and C.

DR.T.V.RAO MD
 24
PCR BASED SCREENING
METHODS

• PCR is more sensitive than shell vial or antigenemia

assays
• Some patients may be pre-emptively treated
unnecessarily using PCR strategies
• Quantitative PCR may be more sensitive than qualitative
PCR
• No criteria for standard treatment threshold exist for
quantitative CMV PCR

DR.T.V.RAO MD
 TREATME 25

NT
• 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.
• 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.

DR.T.V.RAO MD
 PREVENTI 26

ON
• 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.
• 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.

DR.T.V.RAO MD
 REDUCE CHANCES OF CONTRACTING 27

CMV
• Wash hands often with soap and water for 15-20 seconds,
especially after wiping runny noses, changing diapers,
picking up toys, etc. If soap and water are not available,
use alcohol-based hand gel.
• Use soap and water or a disinfectant to clean hard surfaces
that have been contaminated by secretions
• Don’t share food, drinks, or eating utensils with young children
• Don’t kiss young children on the lips—give them a big
hug and a kiss on top of the head.
• If you work in a day care center, limit close contact with
children younger than 2½ years of age, especially if
you've never been infected with CMV or don't know if
you've been infected.

DR.T.V.RAO MD
 CDC STATS: 28

WWW.CDC.GOV/CMV
• Every hour, congenital CMV causes one child to
become disabled
• Each year, about 30,000 children are born with
congenital CMV infection
• About 8,000 children each year suffer permanent
disabilities caused by CMV
• About 1 in 150 children is born with congenital CMV
infection
• About 1 in 750 children is born with or develops
permanent disabilities due to CMV

DR.T.V.RAO MD
 EPIDEMIOLO 29

GY

• CMV is one of the most successful human

pathogens, it can be transmitted vertically
or horizontally usually with little effect on
the host.
• Transmission may occur in utero,
perinatally or postnatally. Once infected,
the person carries the virus for life which
DR.T.V.RAO MD
may be activated from time to time, during
which infectious virions appear in the urine
 30

PREVENTION

SIMPLE HAND WASHING WITH SOAP AND

WATER IS EFFECTIVE IN REMOVING THE VIRUS
FROM THE HANDS.
DR.T.V.RAO MD
 RAISE CMV AWARENESS?

DR.T.V.RAO MD 31
 32

VISIT FOR MORE ARTICLES OF INTEREST ON

INFECTIOUS DISEASES

DR.T.V.RAO MD
 33

•Programme Created By Dr.T.V.Rao MD

for Medical and Paramedical Students in
the Developing World
• Email
• doctortvrao@hotmail.com

DR.T.V.RAO MD