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Herpes VirusesHerpes Viruses

Epstein-Barr virusEpstein-Barr virus

CytomegalovirusCytomegalovirus

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CMV & EBV OutlineCMV & EBV Outline

StructureStructureClassificationClassificationMultiplicationMultiplicationClinical manifestationsClinical manifestationsEpidemiologyEpidemiologyDiagnosisDiagnosisControlControl

Baron’s Web Site

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Latent InfectionsLatent Infections

ALLALL herpes viruses can establish latent herpes viruses can establish latent infections. The viral genome may become infections. The viral genome may become incorporated into the host DNA or remain incorporated into the host DNA or remain extrachromosomalextrachromosomal

Latent viruses can be reactivated by stress, Latent viruses can be reactivated by stress, menstruation or uv lightmenstruation or uv light

Reactivation may be asymptomatic or lead Reactivation may be asymptomatic or lead to mild or severe disease.to mild or severe disease.

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Herpes DiagnosisHerpes Diagnosis

Isolation of virus by tissue cultureIsolation of virus by tissue culture herpevirinae cause cytopathic effectsherpevirinae cause cytopathic effectsintranuclear fluorescence of scrapings using intranuclear fluorescence of scrapings using

fluorescent antibodiesfluorescent antibodiesPCR being developedPCR being developed

CMV retiniitis is diagnosed clinicallyCMV retiniitis is diagnosed clinically

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Epstein Barr VirusEpstein Barr Virus

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Epstein-Barr virusEpstein-Barr virus

virus established in lymphoid tissue and virus established in lymphoid tissue and salivary glands - is excreted from salivary salivary glands - is excreted from salivary glands.glands.

Epstein-Barr virus is a transforming DNA virus.Epstein-Barr virus is a transforming DNA virus.

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EBV HistoryEBV History

infectious mononucleosis, first described more infectious mononucleosis, first described more than 100 years ago.than 100 years ago.

in 1958, Michael Burkitt discovered that a in 1958, Michael Burkitt discovered that a malignant tumour, malignant tumour, Burkitt’s lymphomaBurkitt’s lymphoma, was , was infectious.infectious.

in 1959, Michael Epstein and Yvonne Barr in 1959, Michael Epstein and Yvonne Barr cultured a virus from tumours that showed cultured a virus from tumours that showed typical herpes-like morphology.typical herpes-like morphology.

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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.

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.

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EBV DiseasesEBV Diseases

Infectious mononucleosisInfectious mononucleosislymphoproliferative cancer in heart and lymphoproliferative cancer in heart and

bone marrow transplant recipientsbone marrow transplant recipientsBurkitt’s lymphoma (B cell carcinoma) in Burkitt’s lymphoma (B cell carcinoma) in

E. africansE. africansnasopharyngeal carcinoma in Chinesenasopharyngeal carcinoma in Chinese

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Classic MononucleosisClassic Mononucleosis

infectious mononucleosis has an incubation period infectious mononucleosis has an incubation period of 30 to 50 days.of 30 to 50 days.

high fever, malaise, myalgia, cervical high fever, malaise, myalgia, cervical lymphadenopathy, splenomegaly, hepatomegalylymphadenopathy, splenomegaly, hepatomegaly

high fever, pharyngitis, grey-white pharyngeal high fever, pharyngitis, grey-white pharyngeal exudate, skin rashexudate, skin rash

atypical lymphocytosis or leucocytosis: infected B atypical lymphocytosis or leucocytosis: infected B cells, T cells (suppresser and cytotoxic)cells, T cells (suppresser and cytotoxic)

recover due to a strong cell-mediated response recover due to a strong cell-mediated response

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ComplicationsComplications

Carcinoma Carcinoma Burkitt’s lymphoma (B cell carcinoma)Burkitt’s lymphoma (B cell carcinoma) Nasopharyngeal carcinoma.Nasopharyngeal carcinoma.

if there is an immune deficiency especially if there is an immune deficiency especially of T cells - the host is highly susceptible to of T cells - the host is highly susceptible to Epstein-Barr virus.Epstein-Barr virus.

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Infectious MononucleosisDiagnosis

Infectious MononucleosisDiagnosis

clinical symptomsclinical symptomsdifferential blood count - lymphocytosis, differential blood count - lymphocytosis,

neutropenia, large atypical cells.neutropenia, large atypical cells.heterophile antibodiesheterophile antibodiesantibodies to EBV nuclear antigenantibodies to EBV nuclear antigenantibodies to EBV capsid antigenantibodies to EBV capsid antigen

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Infectious MononucleosisTransmission

Infectious MononucleosisTransmission

direct oral contactdirect oral contact

exposure to salivaexposure to salivafomitesfomitesarthropod vectorsarthropod vectors

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ExposureExposure

early in Africa and Asia, later in early in Africa and Asia, later in industrialized countriesindustrialized countries

70% of college age persons have never had 70% of college age persons have never had exposure - very susceptible to the virus.exposure - very susceptible to the virus.

95% of middle aged adults are seropositive.95% of middle aged adults are seropositive.

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Portal of EntryPortal of Entry

oropharynx oropharynx attaches to the epitheliumattaches to the epitheliummoves to the Parotid glandmoves to the Parotid glandviremiaviremialatent in throat and bloodlatent in throat and blood

subclinical asymptomaticsubclinical asymptomatic

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Epstein-Barr Virus - SymptomsEpstein-Barr Virus - Symptoms

sore throat, high fever, cervical sore throat, high fever, cervical lymphadenopathy, grey-white pharyngeal lymphadenopathy, grey-white pharyngeal exudate, skin rash, enlarged liver and spleen.exudate, skin rash, enlarged liver and spleen.

Leucocytosis: infected B cells, T cells Leucocytosis: infected B cells, T cells (suppresser and cytotoxic)(suppresser and cytotoxic)

recover due to a strong cell-mediated response recover due to a strong cell-mediated response (T cell).(T cell).

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CancerCancer

Transformation of the cell by virusTransformation of the cell by virus Helper virus if the transforming virus is Helper virus if the transforming virus is

defectivedefective Co-carcinogen, chemical, cigarette smokeCo-carcinogen, chemical, cigarette smoke

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Transformed cells:Transformed cells:

lose contact inhibitionlose contact inhibition continue to dividecontinue to divide form random aggregationsform random aggregations can become invasivecan become invasive

Not warts: PapovavirusNot warts: Papovavirus

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Primary Hepatocellular Carcinoma

Primary Hepatocellular Carcinoma

Icteric symptoms:Icteric symptoms: jaundice, dark urine, pale stoolsjaundice, dark urine, pale stools

Highest incidence:Highest incidence: Central AfricaCentral Africa Southeast ChinaSoutheast China Pacific Islands, Borneo, Sarawak, TaiwanPacific Islands, Borneo, Sarawak, Taiwan

250,000 to1,000,000 deaths worldwide per 250,000 to1,000,000 deaths worldwide per yearyear

U.S.A. 5000 deaths / yearU.S.A. 5000 deaths / year

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Human T-cell Leukemia VirusHuman T-cell Leukemia Virus

HTLV1 & HTLV2HTLV1 & HTLV2retroviruses with no oncogenesretroviruses with no oncogenes

Adult T-cell leukemia and lymphomaAdult T-cell leukemia and lymphoma- Southern Japan, Carribean Islands, West - Southern Japan, Carribean Islands, West AfricaAfrica

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Epstein BarrEpstein Barr

Southern China, AsiaSouthern China, Asiasuspect co-carcinogen:suspect co-carcinogen:

- nitrosamines in salted fish- nitrosamines in salted fishoncogenes not reported.oncogenes not reported.

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Burkitts LymphomaBurkitts Lymphoma

East Africa, Papua New GuineaEast Africa, Papua New Guinea at risk: 6 -14 year old malesat risk: 6 -14 year old males tumor of immature B-cellstumor of immature B-cells

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Human PapillomavirusHuman Papillomavirus

cervical, penile, vulval, and rectal cancercervical, penile, vulval, and rectal cancerviral genome integrated into host genomeviral genome integrated into host genome

Co-carcinogensCo-carcinogens- cigarette smoke- cigarette smoke- HSV herpes- HSV herpes

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CytomegalovirusCytomegalovirus

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CytomegalovirusCytomegalovirus

Urine isolateUrine isolate

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Intranuclear inclusionsIntranuclear inclusions

The cell swells The cell swells and a large and a large inclusion body inclusion body forms in the forms in the nucleus.nucleus.

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CytomegalovirusCytomegalovirus

Nuclear & cytoplasmic inclusionsNuclear & cytoplasmic inclusions

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Transmission: CMV Transmission: CMV

not highly infectious, virus found in saliva, not highly infectious, virus found in saliva, urine and blood. urine and blood.

infants and children acquire CMV from infants and children acquire CMV from other children.other children.

congenital. In utero, at birth during congenital. In utero, at birth during perinatal period.perinatal period.

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Congenital: CMVCongenital: CMV

the following possibilities relate to the congenital the following possibilities relate to the congenital type.type.

severe deformities and death.severe deformities and death.survive with serious defects - physical and mental.survive with serious defects - physical and mental.survive with out deformities.survive with out deformities.newborns: - Enlarged liver and spleen, jaundice, newborns: - Enlarged liver and spleen, jaundice,

capillary bleeding, microcephaly, ocular capillary bleeding, microcephaly, ocular inflammation.inflammation.

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Disseminated cytomegalovirusDisseminated

cytomegalovirus

fever, severe diarrhea, hepatitis, arthritis, fever, severe diarrhea, hepatitis, arthritis, pneumonia, high mortality.pneumonia, high mortality.

activation of inapparent infection.activation of inapparent infection.also due to:also due to:

immunosuppressive therapy.immunosuppressive therapy. cancer.cancer. AIDSAIDS..

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Virus in blood or organ:Virus in blood or organ:

post transfusion.post transfusion.post organ transplant.post organ transplant.

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Cytomegalovirus mononucleosis:Cytomegalovirus mononucleosis:

teenage, young adult similar to other mono.teenage, young adult similar to other mono.

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Transmission:Transmission:

saliva, respiratory mucus, milk, urine, saliva, respiratory mucus, milk, urine, semen, cervical secretions, feces and semen, cervical secretions, feces and lymphocytes.lymphocytes.

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Differential Diagnosis:Differential Diagnosis:

the differential diagnosis in neonates must the differential diagnosis in neonates must include toxoplasmosis, rubella, herpes include toxoplasmosis, rubella, herpes simplex, bacterial sepsis.simplex, bacterial sepsis.

in adults it must be differentiated from in adults it must be differentiated from Epstein-Barra and hepatitis A & B.Epstein-Barra and hepatitis A & B.

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Laboratory diagnosis: CMVLaboratory diagnosis: CMV

virus can be grown from all organs.virus can be grown from all organs.many serological tests.many serological tests.

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Treatment: CMVTreatment: CMV

gancyclovir, foscarnet, hyperimmune CMV gancyclovir, foscarnet, hyperimmune CMV immunoglobulin, have some effect.immunoglobulin, have some effect.

interferon does not prevent infection or interferon does not prevent infection or promote recovery.promote recovery.

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Prevention:CMVPrevention:CMV

no animal can be found that can be infected no animal can be found that can be infected with CMV.with CMV.

Two deterents:Two deterents:vaccine stimulated antibodies may not be vaccine stimulated antibodies may not be

protective. Patients already seropositve can protective. Patients already seropositve can be reinfected.be reinfected.

a vaccine could be oncogenic.a vaccine could be oncogenic.

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Epidemiology of CMVEpidemiology of CMV

40-100% positive for the antibodies.40-100% positive for the antibodies.newborns 7.5% positive in the USA & UK.newborns 7.5% positive in the USA & UK.woman of child bearing age were 20-100% positive woman of child bearing age were 20-100% positive

in many countries that were studied (pregnant - in many countries that were studied (pregnant - virus in the urine).virus in the urine).

IV drug users were 100% positive for the IV drug users were 100% positive for the antibodies.antibodies.

homosexual males were 30% positive for the homosexual males were 30% positive for the antibodies - high percentage shed virus.antibodies - high percentage shed virus.