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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.
Dr.T.V.Rao MD 3
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
Dr.T.V.Rao MD 5
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
Dr.T.V.Rao MD 6
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
Dr.T.V.Rao MD 8
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.
Dr.T.V.Rao MD 10
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.
Dr.T.V.Rao MD 17
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.
Dr.T.V.Rao MD 19
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.
Dr.T.V.Rao MD 20
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.
Dr.T.V.Rao MD 23
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.
Dr.T.V.Rao MD 24
Programme Created by
Dr.T.V.Rao MD for Medical and
Paramedical Students in
Universal Health Care
Email.
doctortvrao@gmail.com
Dr.T.V.Rao MD 25

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cytomegalovirus-140608065721-phpapp01.pdf

  • 2. 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
  • 3. 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. Dr.T.V.Rao MD 3
  • 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), herpesviruses “actively” target mechanisms Dr.T.V.Rao MD 5
  • 6. 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 Dr.T.V.Rao MD 6
  • 7. 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.
  • 8. 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 Dr.T.V.Rao MD 8
  • 9. 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. .
  • 10. 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. Dr.T.V.Rao MD 10
  • 11. 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.
  • 12. Complications CMV mononucleosis. This syndrome resembles infectious mononucleosis, but the Epstein-Barr virus (EBV) causes classic mononucleosis
  • 13. Complications Intestinal complications. CMV infection of intestines can result in diarrhoea, fever and abdominal pain; inflammation of colon; and blood in stool.
  • 14. 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)
  • 15. 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.
  • 16. 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.
  • 17. 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 17
  • 19. 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 19
  • 20. 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. Dr.T.V.Rao MD 20
  • 21. 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.
  • 22. 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.
  • 23. 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. Dr.T.V.Rao MD 23
  • 24. 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. Dr.T.V.Rao MD 24
  • 25. Programme Created by Dr.T.V.Rao MD for Medical and Paramedical Students in Universal Health Care Email. doctortvrao@gmail.com Dr.T.V.Rao MD 25