3. CYTOMEGALOVIRUS INFECTIONS
• Ubiquitous virus most populations -infections
in early childhood often asymptomatic
• Clinical disease increasing due to increasing
number of immunocompromised patients
• Belong to the betaherpesvirus subfamily of
herpesviruses double stranded DNA enveloped
• 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
5. 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
Stem cell and solid organ transplant recipients
HIV infected individuals
Cancer patients receiving intensive
6. • Infection in utero: Leading cause of infectious
disease related birth defects
1 in 100 infected; 1 in 1000 present
Mild to severe hearing loss
7. How is CMV transmitted?
• Fetus: Via placenta from the mother
• Human milk
• Blood transfusion, organ transplantation
• Children and adults: Mainly via bodily fluids
(esp. urine, saliva)
8. Who transmits CMV?
• Duration of viral shedding following primary
• 2-3 weeks for adults
• Months to years for young children
• Therefore, CMV is most often transmitted by
• Once infected, the virus remains in the person for life and
my be reactivated from time to time, especially in
• 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
• Postnatal infection mainly occurs through saliva. Sexual
transmission may occur as well as through blood and blood
products and transplanted organ
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.
12. CYTOMEGALOVIRUS INFECTIONS
• transmission from mother via placenta
• clinically normal 80% • causes congenital CMV
• death 1% • Cytomegalic inclusion disease %
• late onset hearing defect / mental
• transmission during birth or breast feeding
• usually asymptomatic
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.
14. SYMPTOMS OF CONGENITAL CMV
• Temporary Symptoms
Jaundice (yellow skin and eyes)
Purple skin splotches
Lung problems Small size at birth
15. SYMPTOMS OF CONGENITAL CMV
• Permanent Symptoms or Disabilities
Lack of coordination
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
• Lung – pneumonitis
• Heart – myocarditis
• Thrombocytopenic purpura, Haemolytic anaemia
• Late sequelae in individuals asymptomatic at birth -
hearing defects and reduced intelligence.
17. CMV RETINITIS
• SMALL FLOATERS, FOGGY OR BLURRED
VISION, LOSS OF CENTRAL OR PERIPHERAL
• ROUTINE EXAM WHEN THE INFECTIOUS
PROCESS IS EARLY AND LOCATED IN THE
• LOSS OF VISION
• RETINAL DETACHMENT
18. LABORATORY 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
• The pp65 CMV antigenemia test is now routinely
used for the rapid diagnosis of CMV infection in
• PCR for CMV-DNA is used in some centers but
there may be problems with interpretation.
19. • 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.
• the presence of CMV IgG antibody indicates past
• The detection of IgM is indicative of primary infection
although it may also be found in immunocompromised
patients with reactivation.
20. • 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
• 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.
• The disease is caused by parasite Toxoplasma
gondii. Toxoplasma gondii are found in three
• (a) Tachyzoites which are the rapidly
multiplying forms found in the blood and body
• (b) Cyst form which contains bradyzoites are
slowly multiplying form found in body tissues.
24. • (c) Sporulated oocyst voided in the faeces of
• The parasite has got affinity for epithelial,
reticuloendothelial and blood cells. The
organism could be grown in monolayer of
lamb testicular cells
26. Mode of transmission:
• Toxoplasma has been reported to be transmitted
by the following ways in man and animals-
(a) Through cat : The cat is the only definitive
host of the parasite. Infected cats shed large
number of oocysts in the faeces . Stray cats
contaminate the soils around the human
habitations and thus play a vital role in the
transmission of toxoplasmosis.
(b) Meat & meat products : Consumption of raw
or under cooked meat or meat products are
important source of toxoplasmosis.
27. • (c) Congenital infection : From infected mother (
dam ) to the fetus
• (d) Other methods:
• Inhalation and ingestion of infected milk may
transmit the infection.
• Infection has been traced to be transmitted
• Experimental transmission can be made by
intramuscular , subcutaneous or intraperitonial
inoculation of infected materials.
28. Life cycle of Toxoplasma sp:
Life cycle in final host:
• Cats become infected by ingestion of rodent
whose tissues contain tachyzoites or
• Infection also occur through the ingestion of
• The cyst wall ( either badyzoites,tachyzoites or
oocyst ) is digested in cat stomsch.
29. • The liberated organisms penetrate the
intestinal wall and initiates schizogonas cycle
followed by gametogonas development.
• The oocysts are produced within 3-10 days
and shade within 1-2 weeks.
• The organisms also invade intestinal organ and
development of tachyzoites, badyzoites,
oocyst as in intermediate host.
30. In intermediate host:
• The I.H(cattle) are infected by ingestion of
• Liberated sporozoites inter into cell wall and
spread via hematogenus route and cause
• Tachyzoites inter into cell and multiply by
31. • Following this process 8-16 tachyzoites
accumulated and infected cell ruptured and
new cells infected.
• In most cases the host survive and antibody
produced which limits the invasiveness.
• Followed by badyzoites formation.
32. • If immunity suppress, cyst may rupture
releasing bradyzoites .
• Bradyzoites become activated and resume the
invasive characteristics of tachyzoites.
• The F.H. is infected by the ingestion of either
bradyzoites, tachyzoites containing tissue of
33. Clinical findings :
• Cattle and buffalo- high rise of temperature
and enlargement of lymph node.
• Sheep - abortion in ewes.
• In goats- high rise of temperature, dyspnea,
diarrhea, muscular tremors, paresis of hind
quarters, erythropenia and anemia.
Pig- Abortion, still births in sows and dyspnea
and wasting in young piglets
• Clinical signs are non- specific and organism is difficult
to demonstrate. Therefore, diagnosis in man and
animals is accompanied by serological tests.
(a) Isolation of T. gondii – Parasites can be
demonstrated from lymph fluid, placenta, cotyledons
(b) Methylene blue dye test: Sabin and Feldman first
This test now a days is carried out by in microtitre
plates and can be judged by employing empty
35. • (c) By complement fixation test(CFT).
• (d) By indirect hemagglutination tests(HI).
• (e) By direct agglutination tests.
• (f) By fluorescent antibody tests(FAT).
• (g) By enzyme linked immuno sorbent assay
• (h) By DNA test
(a)There is no satisfactory treatment. Drugs
like pyremethamine and sulphonamide are
• SDDS (diaminodiphenyl sulfone)@ 100mg /kg
body weight for 14 days is the most effective
treatment. Drugs which have been used in
man and animals are as follows.
(b) Sulphonamide @ 10 mg / kg b.wt. orally