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Transcript
Herpes Viruses
Epstein-Barr virus
Cytomegalovirus
1
5/4/2017
CMV & EBV Outline
Structure
Classification
Multiplication
Clinical manifestations
Epidemiology
Diagnosis
Control
2
Baron’s Web Site
5/4/2017
Latent Infections
 ALL herpes viruses can establish latent
infections. The viral genome may become
incorporated into the host DNA or remain
extrachromosomal
Latent viruses can be reactivated by stress,
menstruation or uv light
Reactivation may be asymptomatic or lead
to mild or severe disease.
3
5/4/2017
Herpes Diagnosis
Isolation of virus by tissue culture
 herpevirinae cause cytopathic effects
intranuclear fluorescence of scrapings using
fluorescent antibodies
PCR being developed
CMV retiniitis is diagnosed clinically
4
5/4/2017
Epstein Barr Virus
5
5/4/2017
Epstein-Barr virus
virus established in lymphoid tissue and salivary
glands - is excreted from salivary glands.
Epstein-Barr virus is a transforming DNA virus.
6
5/4/2017
EBV History
infectious mononucleosis, first described more
than 100 years ago.
in 1958, Michael Burkitt discovered that a
malignant tumour, Burkitt’s lymphoma, was
infectious.
in 1959, Michael Epstein and Yvonne Barr
cultured a virus from tumours that showed
typical herpes-like morphology.
7
5/4/2017
EBV and Burkitt’s lymphoma
were shown to be the same virus
when a lab technician acquired
mononucleosis while working
with the Burkitt’s lymphoma
virus.
8
5/4/2017
EBV Diseases
Infectious mononucleosis
lymphoproliferative cancer in heart and
bone marrow transplant recipients
Burkitt’s lymphoma (B cell carcinoma) in
E. africans
nasopharyngeal carcinoma in Chinese
9
5/4/2017
Classic Mononucleosis
infectious mononucleosis has an incubation period
of 30 to 50 days.
high fever, malaise, myalgia, cervical
lymphadenopathy, splenomegaly, hepatomegaly
 high fever, pharyngitis, grey-white pharyngeal
exudate, skin rash
atypical lymphocytosis or leucocytosis: infected B
cells, T cells (suppresser and cytotoxic)
recover due to a strong cell-mediated response
10
5/4/2017
Complications
Carcinoma
 Burkitt’s
lymphoma (B cell carcinoma)
 Nasopharyngeal carcinoma.
if there is an immune deficiency especially
of T cells - the host is highly susceptible to
Epstein-Barr virus.
11
5/4/2017
Infectious Mononucleosis
Diagnosis
clinical symptoms
differential blood count - lymphocytosis,
neutropenia, large atypical cells.
heterophile antibodies
antibodies to EBV nuclear antigen
antibodies to EBV capsid antigen
12
5/4/2017
Infectious Mononucleosis
Transmission
direct oral contact
exposure to saliva
fomites
arthropod vectors
13
5/4/2017
Exposure
early in Africa and Asia, later in
industrialized countries
70% of college age persons have never had
exposure - very susceptible to the virus.
95% of middle aged adults are seropositive.
14
5/4/2017
Portal of Entry
oropharynx
attaches to the epithelium
moves to the Parotid gland
viremia
latent in throat and blood
 subclinical
15
asymptomatic
5/4/2017
Epstein-Barr Virus - Symptoms
sore throat, high fever, cervical
lymphadenopathy, grey-white pharyngeal
exudate, skin rash, enlarged liver and spleen.
Leucocytosis: infected B cells, T cells
(suppresser and cytotoxic)
recover due to a strong cell-mediated response
(T cell).
16
5/4/2017
Cancer
 Transformation of the cell by virus
 Helper virus if the transforming virus is
defective
 Co-carcinogen, chemical, cigarette smoke
17
5/4/2017
Transformed cells:
 lose
contact inhibition
 continue to divide
 form random aggregations
 can become invasive
Not warts: Papovavirus
18
5/4/2017
Primary Hepatocellular
Carcinoma
Icteric symptoms:
 jaundice,
dark urine, pale stools
Highest incidence:
 Central Africa
 Southeast
China
 Pacific Islands, Borneo, Sarawak, Taiwan
 250,000 to1,000,000 deaths worldwide
per year
U.S.A. 5000 deaths / year
19
5/4/2017
Human T-cell Leukemia Virus
HTLV1 & HTLV2
retroviruses with no oncogenes
Adult T-cell leukemia and lymphoma
- Southern Japan, Carribean Islands, West
Africa
20
5/4/2017
Epstein Barr
Southern China, Asia
suspect co-carcinogen:
- nitrosamines in salted fish
oncogenes not reported.
21
5/4/2017
Burkitts Lymphoma
 East Africa, Papua New Guinea
 at risk: 6 -14 year old males
 tumor of immature B-cells
22
5/4/2017
Human Papillomavirus
cervical, penile, vulval, and rectal cancer
viral genome integrated into host genome
Co-carcinogens
- cigarette smoke
- HSV herpes
23
5/4/2017
Cytomegalovirus
24
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Cytomegalovirus
Urine isolate
25
5/4/2017
Intranuclear inclusions
The cell swells
and a large
inclusion body
forms in the
nucleus.
26
5/4/2017
Cytomegalovirus
Nuclear & cytoplasmic inclusions
27
5/4/2017
Transmission: CMV
not highly infectious, virus found in saliva,
urine and blood.
infants and children acquire CMV from
other children.
congenital. In utero, at birth during perinatal
period.
28
5/4/2017
Congenital: CMV
29
the following possibilities relate to the
congenital type.
severe deformities and death.
survive with serious defects - physical and
mental.
survive with out deformities.
newborns: - Enlarged liver and spleen,
jaundice, capillary bleeding, microcephaly,
ocular inflammation.
5/4/2017
Disseminated
cytomegalovirus
fever, severe diarrhea, hepatitis, arthritis,
pneumonia, high mortality.
activation of inapparent infection.
also due to:
immunosuppressive
therapy.
cancer.
AIDS.
30
5/4/2017
Virus in blood or organ:
post transfusion.
post organ transplant.
31
5/4/2017
Cytomegalovirus mononucleosis:
teenage, young adult similar to other mono.
32
5/4/2017
Transmission:
saliva, respiratory mucus, milk, urine,
semen, cervical secretions, feces and
lymphocytes.
33
5/4/2017
Differential Diagnosis:
the differential diagnosis in neonates must
include toxoplasmosis, rubella, herpes
simplex, bacterial sepsis.
in adults it must be differentiated from
Epstein-Barra and hepatitis A & B.
34
5/4/2017
Laboratory diagnosis: CMV
virus can be grown from all organs.
many serological tests.
35
5/4/2017
Treatment: CMV
gancyclovir, foscarnet, hyperimmune CMV
immunoglobulin, have some effect.
interferon does not prevent infection or
promote recovery.
36
5/4/2017
Prevention:CMV
no animal can be found that can be infected
with CMV.
Two deterents:
vaccine stimulated antibodies may not be
protective. Patients already seropositve can
be reinfected.
a vaccine could be oncogenic.
37
5/4/2017
Epidemiology of CMV
 40-100% positive for the antibodies.
newborns 7.5% positive in the USA & UK.
woman of child bearing age were 20-100% positive
in many countries that were studied (pregnant virus in the urine).
IV drug users were 100% positive for the
antibodies.
homosexual males were 30% positive for the
antibodies - high percentage shed virus.
38
5/4/2017