education

1. CYTOMEGALOVIRUS
• Largest virus in Herpes viridae family
• Causes massive enlargement of infected host
cells
• CMV belongs to beta-subfamily.
• its dsDNA is the largest among herpesviruses,
which consists of 240 kbp nucleotides.
• Cytomegaloviruses are strictly species-specific.
• Human CMV does not infect animals

3. Cell-type specificity
In vivo, CMV infects kidney and salivary
glands;where it undergoes latency.
• In vitro, CMV replicates only in human fibroblast
cellline and produces a characteristic cytopathic
effect (CPE) as Owl's eye appearance
• Cell- to-cell spread: CMV is almost always closely
associated with the cells and spread primarily cell-
to cell,

5. Clinical Manifestations
• congenital and perinaial infections, CMV
mononucleosis in adults and severe infection in
immunocompromized and transplant recipients.
Congenital CMV Infection
• CMV is probably the most common intrauterine
infection associated with congenital defects.
• About 1 % of infants born are infected wilh CMV.

6. Congenital defects include
• petechiae, hepatosplenomegaly, and jaundice
(60-80% of cases).
• less common defects include-microcephaly,
cerebral
• calcifications, intrauterine growdi retardation,
and prematurity (30-50% of cases).
• Occasional defects are inguinal hernias and
• chorioretinitis.
• Risk is maximum
• Mortality rate is very high (20%).

7. PerinatalCMV Infection
• Transmission to the newborn occurs either during:
• Delivery-through infected birth canal or
• Postnatal-through infected breast milk/secretions
from mother.
• Most of the infected infants remain asymptomatic,
but
• shed virus in urine from 8-12 weeks of age, up to
several years.
• few premature babies develop interstitial
pneumonitis.

8. lmmunocompetent Adults
• In healthy adults, CMV produces an infection
following blood transfusion called mononucle osis-
like syndrome.
In the lmmunocompromlzed Host
• CMV produces markedly severe infection in
immunosuppressed individuals
• ln AIDS patients with CD4 T cell count <50/μL
CMV may cause chorioretinitis,
gastroenteritis,dementia and other disseminated
CMV infection.

9. • Organ transplant recipients: CMV is probably
the most common viral infection occurs in
transplant recipients.
• lnfection occurs usually between 1 and4 months
following transplantation
• Bilateral interstilial pneumonia : 15-20% of bone
marrow transplant recipients.
• Febrile leukopenia: solid organ transplant
recipients.
• Obliterative bronchiolitis in lung transplants
• Graft atherosclerosis in heart transplants.

10. Epidemiology
Various modes of transmission include:
• Oral and respiratory spread is the predominant
mode.
• Transplacental route (transmission from mother to fetus).
• Blood tra,isfusion: Risk of transmission is about 0.1-
10% per blood until transfused.
• Organ transplantation.
• Sexual contact (in young adults).
Transmission: Close person-to-person contact is required for
transmission

11. • Reservoir: Humans are the only known host
for CMV.
• Source: Virus may be shed in urine, saliva,
semen, breast milk, and cervical secretions,
and is carried in circulating while blood cells.
• Risk factors such as low socioeconomic status
and poor personal hygiene

12. Laboratory Diagnosis
• Detection of Inclusion Bodies
• In urine, CMV produces characteristic
perinuclear cytoplasmic inclusions in addition
to the usual intranuclear inclusions seen in
other herpesviruses (Owl's eye appearance)

13. Virus lsolotion
CMV can be isolated from throat washings and urine.
• Human fibroblasts are the most ideal cell lines, specific
forCMV.
Cytopathic effect: After 2-3 weeks of incubation
• Typical CMV inclusions
• Multinucleated giant cells are seen.
• Enlargement of infected host cells.

14. • Multinucleated giant cells

15. Shell vial technique can be followed for early growth detection
(1-2 days).
• It involves centrifugation of cell culture (mixed with the specimen) to
enhance the cell contact and viral replication followed by detection of
early CMV antigen in the infected cells by direct fluorescence
technique.
• It is very useful in CMV mononucleosis where viral load is low and
CPE takes several weeks to appear.

16. • Antibody Detection
• ELISA and rapid tests are available for detecting serum antibodies.
• IgM antibodies are indicative of active infection, but appear only
after 4 weeks of primary infection.
• IgG antibodies persist for life and suggest either past infection or
recurrent infection.
• Fourfold rise of IgG indicates recurrent infection.
• Antigen Detection
• CMV-specific pp65 antigen can be detected in peripheral blood
leukocytes by using specific monoclonal antibody.
• It is highly specific and reliable method.

17. MoleculorMethods
• Molecular methods such as PCR can be used to detect specific
CMV DNA in blood or body fluids such as CSF
• PCR assays are rapid, highly sensitive, specific and have
replaced the gold standard culture technique in most
laboratories.
• Real lime PCR can quantitate the viral load

18. TREATMENT
• CMV does not respond to acyclovir
• Ganciclovir: It is the drug of choice for cytomegalic
inclusion disease
• It is given by intravenous route.
• Valganciclovir: It is a pro-drug of ganciclovir that
can be given orally .
• Foscamet: It inhibits CMV DNA polymerase, without
undergoing phosphorylation.
• Cidofovir: It is also given alternative to ganciclovir,
but is nephrotoxic.
• CMV immunoglobulin: It is given along with
ganciclovir for bone marrow transplant recepients

19. Prophylaxis
• Both ganciclovir and valganciclovir have been
used successfully for prophylaxis and pre-
emptive therapy in transplant recipients
• CMV immunoglobulin has shown to be
effective in preventing congenital infection
when given to mother during pregnancy.