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Herpes Virus Flashcards

1
Q

Herpes Virus Features

A

Large Envelope, ds DNA virus. = Approx 120 - 200 nm in diameter ,
Icosahedral Capsid Symmetry -Surrounded by Lipoprotein Envelope.

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2
Q

What do all herpes viruses have in common?

A

A common virion morphology‡.
A basic mode of replication‡.
The capacity to establish acute , latent and recurrent infections

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3
Q

The space between capsid & envelope is called?

A

Tegument

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4
Q

Tegument - purpose

A

filled by protein and enzymes , that help to initiate replication

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5
Q

Herpes - life cycle

A

1) Recognition of host cell

     ↓

2) Attachment

    ↓

3) Penetration

    ↓

4) Uncoating-split of double stranded DNA.( Linear ds DNA )

↓

Circularisation –becomes circular

    ↓

5) Transcription

   ↓

6) Protein synthesis(α, β, γ)

   ↓

7) Replication - by rolling circle

   ↓

8) Assembly & Envelopment
9) Exocytosis- Lysis & release

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6
Q

Human herpes viruses are grouped into 3 sub-families, based on difference in viral characteristics, which are?

A

Genome structure , tissue tropism , cytopathogenicity , site of latent infection

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7
Q

Human Herpes Simplex type 1 & 2 and Varicella-Zoster virus ( HHV3) are part of which group?

A

α Group‡

  • Short reproductive cycle
  • Latent in sensory neurons
  • Painful skin disease
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8
Q

Human Herpes Simplex type 1 & 2

A

Skin lesions & other diseases‡

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9
Q

Varicella-Zoster virus ( HHV3)

A

Varicella (Chickenpox) & Zoster

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10
Q

Cytomegalovirus (HHV5) (CMV), Human Herpes virus 6 (HHV 6) and Human Herpes virus 7 ( HHV 7 )

A

β Group

  • Long reproductive cycle
  • Latent in WBCs
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11
Q

Cytomegalovirus (HHV5) (CMV)

A

Cytomegalic inclusion disease (CID) , Disseminated diseases in immuno compromised patients‡

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12
Q

Human Herpes virus 6 (HHV 6)

A

Roseola infantum /lymphydenopathy

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13
Q

Human Herpes virus 7 ( HHV 7 )

A

Roseola infantum / febrile seizures

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14
Q

Human Epstein- Barr virus (HHV4) and Human Herpes virus 8

A

γ Group‡

  • Latent in lymphocytes
  • Associated with cancer
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15
Q

Human Epstein- Barr virus (HHV4)

A

Infectious Mononucleosis , Burkitt’s Lymphoma & Nasophyryngeal C‡arcinoma .

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16
Q

Human Herpes virus 8

A

Kaposi’s sarcoma related herpesvirus (HHV8)

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17
Q

Human herpes virus 1 - virus

A

Herpes simplex type 1 ( HSV -1 )

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18
Q

Human herpes virus 1 - Disease caused

A

Oral , Ocular lesion , Encephalitis , Skin lesions

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19
Q

Human herpes virus 1 - Site of latency

A

Neuron-Trigeminal ganglia

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20
Q

Human herpes virus 1 - Transmission

A

Close contact

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21
Q

Human herpes virus 2 - virus

A

Herpes simplex type 2 ( HSV- 2 )

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22
Q

Human herpes virus 2 - Disease caused

A

Genital , Neonatal infection , aseptic meningitis

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23
Q

Human herpes virus 2 - Site of latency

A

Neuron-Sacral ganglia

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24
Q

Human herpes virus 2 - Transmission

A

Close contact , S.T.D.

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25
Q

Human herpes virus 3 - virus

A

Varicella Zoster ( VZV )

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26
Q

Human herpes virus 3 - disease caused

A

Chickenpox & herpes zoster

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27
Q

Human herpes virus 3 - site of latency

A

Neuron- Trig.gang

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28
Q

Human herpes virus 3 - transmission

A

Respiratory & Close contact

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29
Q

Alpha- herpesvirinae - primary target cell

A

Mucoepithelial cells – Fast-growing

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30
Q

Human herpes virus 5 - virus

A

Cytomegalovirus ( CMV )

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31
Q

Human herpes virus 5 - primary target cell

A

Leucocytes, Monocytes (M), Lymphocytes(L), Epithelial cells (EC)

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32
Q

Human herpes virus 5 - site of latency

A

Kidneys ; Glands Monocytes (M) Lymphocytes(L)

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33
Q

Human herpes virus 5 - means of spread

A

Close contact, Transfusions, Tissue transplant, Congenital, STD

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34
Q

Human herpes virus 6 - virus

A

Herpes lymphotropic RosealaInfantum

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35
Q

Human herpes virus 6 - primary target cell

A

T cells, M, L, EC

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36
Q

Human herpes virus 6 - site of latency

A

Lymphoid tissue ( T cells )

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37
Q

Human herpes virus 6 - means of spread

A

Respiratory & close contact

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38
Q

Slow-growing , ( Massive enlargment of infected cells ) .

A

Beta - herpesvirinae

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39
Q

Human herpes virus 7 - virus

A

RK virus

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40
Q

Human herpes virus 7 - primary target cell

A

T cells

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41
Q

Human herpes virus 7 - site of latency

A

Lymphoid tissue ( T cells )

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42
Q

Human herpesvirus 4 - virus

A

Epstein-Barr virus ( EBV )

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43
Q

Human herpesvirus 4 - primary target cell

A

B Lymphocytes & EC

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44
Q

Human herpesvirus 4 - site of latency

A

Lymphoid tissue (B cells)

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45
Q

Human herpesvirus 4 - transmission

A

Saliva ( Kissing disease )

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46
Q

Human herpes virus 8 - virus

A

Kaposi’s sarcoma related virus

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47
Q

Human herpes virus 8 - primary target cell

A

Lymphocytes and others

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48
Q

Human herpes virus 8 - transmission

A

Saliva

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49
Q

HHV-5 – diseases caused

A

Congenital CMV infection , Infection in immuno compromised , acquired CMV infection , Mononucleosis like syndrome ( heterophil antibody - negative ) .

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50
Q

HHV-6 – diseases caused

A

Roseola in infant (primary infection) , Lymphydenopathy ,

Infection in allograft recipient - pneumonia , marrow failure

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51
Q

HHV-7 – diseases caused

A

Some cases of Roseola , Febrile seizures in children

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52
Q

HHV-4 Epstein Barr virus - ( EBV ) – diseases caused

A

Infectious mononucleosis ( Kissing Disease) ,Tumor including Burkitt’s lymphoma, Hodgkin’s ds , Nasopharyngeal carcinoma

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53
Q

HHV-8 Kaposi’s sarcoma – diseases caused

A

Associated with Kaposi’s sarcoma

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54
Q

HSV-1 and HSV-2 – features

A
  • Extremely wide spread in human population
  • Establishes latency in nerve cells - reactivation is common
  • There are two distinct types of HSVs Type 1 & Type 2.
  • Structurally & Morphologically indistinguishable
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55
Q

HSV-1 incubation period

A

2-12 days

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56
Q

HSV-2 incubation period

A

3 weeks

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57
Q

Reactivation of HSV 1 and 2 is caused by

A

Stress stimuli such as
UV light , Fever ,
Hormonal changes ,
Surgical trauma to the neuron.

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58
Q

Antibodies prevent reactivation (T/F)

A

False

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59
Q

HSV - pathogenesis

Why is HSV1 more commonly recurrent on mouth whilst HSV2 is more commonly recurrent on genitals?

A

HSV invades and replicates in neurons as well as in epidermal and dermal cells.
Virions travel from the initial site of infection on the skin or mucosa to the (Trigeminal ganglia - HSV-1 and Sacral ganglia- HSV-2) where latency is established.

HSV1 prefers to establish latency in Trigeminal ganglia whilst HSV2 prefers Sacral ganglia (which innervates the genitals)

Innervate - supply an organ with nerves

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60
Q

Acute Gingivostomatitis, Herpes Oro-labialis infection ,

A

Oropharyngeal infections

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61
Q

Acute Gingivostomatitis occurs in early childhood (T/F)

A

True

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62
Q

Acute Gingivostomatitis - symptoms

A

Fever , painful vesicular lesions on gums , lips & oral mucosa ,
these vesicles may rupture leaving a red based ulcer

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63
Q

Herpes Oro-labialis infection - symptoms

A

Milder recurrent form

Crops of vesicles at the mucocutaneous junction of lips or nose:

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64
Q

Corneal ulcers & lesions of conjunctival epithelium

A

Herpetic Keratoconjunctivitis

65
Q

Dendritic ulcer or vesicles on the eye lids

A

Recurrent Herpetic Keratoconjunctivitis

– Can lead to blindness

66
Q

Diseases caused by HSV-1

A 
1- Oropharyngeal  infections :
2- Herpetic  Keratoconjunctivitis
3- Encephalitis :
4- Herpetic Whitlow : fingers
5- Eczema Herpeticum:
6. Meningitis
67
Q

Encephalitis is more common (T/F)

68
Q

Encephalitis involves where? How high is mortality?

A

Involves temporal lobe with high mortality.

69
Q

PCR assay for viral DNA in CSF for which viral infection?

A

Encephalitis

70
Q

Herpetic Whitlow also called

A

Fingers herpes infection

71
Q

Who mostly contracts Herpetic Whitlow?

A

Healthcare workers, Dentists

72
Q

Genital Herpes - transmission

A

Sexual contact

73
Q

Genital herpes - symptoms

A

Vesiculo ulcerative lesions ( painful multiple ) of cervix , vulva , vagina , & perineum of females & On Glans or shaft of penis in males .

74
Q

Neonatal herpes - transmission

A

Acquired in utero , during , or after birth

75
Q

Severe in the newborn so , pregnant females with recurrent herpes should deliver by C .S . - which viral infection?

A

Neonatal herpes

76
Q

Specimen - Herpes virus

A

Vesicular fluid (from vesicles) - Corneal scrapping , Skin swab .

77
Q

Lab ID methods

A

Light Microscopy
Tzanck smear
Giesma stained smear

78
Q

Tzanck smear - describe method + results

A
    • Smear prepared from scrapping from the base of vesicles are stained with 1 % aq. soln. of Toluidine Blue O.
    • Multinucleated giant cells with faceted nuclei & homogenously stained ‘ground glass’ chromatin

– Tzanck cells seen

79
Q

Giesma stained smear -

A

Intranuclear Cowdry type A inclusion bodies

80
Q

Direct immunofluorescence

A

Cell scrapings from lesions – stained with monoclonal antibodies with a fluorescence dye.
Viral inclusion bodies appear in microscope as a bright green Intra nuclear particles

81
Q

Most appropriate test to confirm the diagnosis of HSV

A

Polymerase Chain Reaction ( PCR ) Assay

82
Q

For detection of viral DNA ( genome ) in CSF ,vesicular fluid , skin scraping

A

Polymerase Chain Reaction ( PCR ) Assay

83
Q

Tissue culture - Herpes Virus

A

Grown in human embryonic fibroblasts , Hep-2 cells or HeLa cells .

84
Q

Result - culture

A

( CPEs ) - Swollen rounded cells ( enlarged & appear ballooned ) appear within 1-3 days . Fusion of infected cells results in syncytium formation .

85
Q

What is serology mainly used for with respect to Herpes Virus?

A

Epidemiological studies

86
Q

Serological methods - Herpes Virus

A

Ab (IgM) detection by ELISA , RIA and Western blot Test .or Complement FixationTest (CFT) .

87
Q

TORCH

A

( Toxoplasmosis ; Other –(Varicella) ; Rubella ; Cytomegalovirus & Herpes simplex ) in pregnant women

88
Q

Acyclovir - MoA and administration

A

Inhibits viral DNA polymerase enzyme.

Topical , Oral or IV.

89
Q

Acyclovir affects latency.

A

Does not affect latency.

90
Q

Drug of choice for acyclovir resistance cases

91
Q

Prevention - genital herpes

A

Avoid contact with individual with lesion .

Safe sexual practice. Use of condom

92
Q

Varicella

A

Chickenpox

93
Q

Zoster

94
Q

Prevalence rate - varicella

A

‡Highly communicable , with an attack rate of 90% in close contacts

95
Q

Shingles occurs regularly (T/F)

A

False, it occurs sporadically

96
Q

Shingles reservoir

A

Humans only

97
Q

Where does reactivation of varicella zoster virus begin in adults?

A

reactivation of latent VZV present in trigeminal ganglia in adult life

98
Q

Varicella - transmission

A

Airborne droplets & direct contact from varicella patients

Vesicular fluid of Zoster patients - in susceptible child

99
Q

Pathogenesis - VZV

A

VZV infects the mucosa of the upper respiratory tract

Multiplies in the regional Lymph Nodes .

Primary viremia and spread to liver and spleen.

Secondary viremia follows with viral spread to the skin.

Typical rash occurs ( Centripetal distribution - highest on Trunk ) .

VZV remains latent in neurons of trigeminal ganglia for life.

100
Q

Incubation period - Varicella

A

10-14 days

101
Q

Symptoms - Varicella

A

Mild fever & rash

102
Q

Rash - Varicella

A

First appear on Face & Trunk , spread rapidly to extremities

103
Q

Rash formation process

A

Flat macules become papules, then vesicles followed by crust formation.

The crust is often shed off and heals without scarring.

104
Q

Does cropping occur in varicella?

A

Characteristic feature of varicella rash , fresh vesicles appear in crops/groups , so all the stages can be seen simultaneously.

105
Q

Reactivation for latent vzv

A

When the vesicles reactivate, intensive pains occur

106
Q

VZV affecting eyes and face

A

Keratitis , Conjunctivitis & Iritis.

107
Q

Bell’s Palsy

A
    • causes a temporary weakness or paralysis of the muscles in the face.
    • can occur when the nerve that controls your facial muscles becomes inflamed, swollen, or compressed.
108
Q

Zoster of the seventh nerve ganglion can cause?

A

Bell’s Palsy

109
Q

The clinical presentations of varicella or zoster are so characteristic that laboratory confirmation is rarely required (T/F)

110
Q

Specimen for Varicella / Zoster

A

Smears from vesicular lesions , respiratory secretions .

111
Q

Direct Virus Demonstration

A

Light Microscopy: Tzanck smear

Cytology: Cowdry’s A type intra nuclear inclusion bodies (Giemsa Stain)

Direct Immunofluorescence: Viral inclusion bodies in microscope - bright green + intranuclear

PCR: detection of viral DNA

112
Q

Serology tests

A

Specific VZV Abs using ELISA ; CFT or Neutralisation test

113
Q

Neutralization test

A

Used to quantify the titer of neutralizing antibody for a virus.
Serum antibody sample to be tested is diluted and mixed with a viral suspension.
This is incubated to allow the antibody to react with the virus.

114
Q

DOC for vzv

A

Acyclovir , Famciclovir or Valacyclovir

115
Q

Acyclovir does not affect Latency of vzv (T/F)

116
Q

Prevention methods

A
  1. Active immunization-Live attenuated varicella vaccine Single dose .Children aged : 1- 10 years .
  2. Passive immunization-

Varicella Zoster Immunoglobulins ( VZIG )

Given to:

    • Immuno compromised children exposed to infection.
    • Mothers infected near term ( before delivery ) and their infants ( immediately after delivery).
117
Q

Infection Control Measures

A

Patients infected with VZV should be kept in isolation ( Airborne & Contact Precautions )

118
Q

Largest virus in Herpesviridae family is?

A

Cytomegalovirus - Size = 150 – 200 nm

119
Q

Effect of Cytomegalovirus in host cells

A
  • Causes massive enlargement of infected host cells
120
Q

How does Cytomegalovirus present in healthy adults?

A

Asymptomatic infection

121
Q

High risk group for Cytomegalovirus

A
  • Organ transplant patient .

- HIV patients

122
Q

Congenital CMV infection does not pose serious effect on foetus or new borne (T/F)

A

False; Congenital CMV infection may be fatal to foetus or new borne.

123
Q

CMV transmission

A

in utero , perinatally or post natally

124
Q

Infectious virions appear in urine & saliva from time to time (T/F)

125
Q

CMV - mode of transmission

A

1- Close contact with most body fluids ( Saliva , urine , vaginal secretions & semen ).

2- Transplacental & Perinatal Transmission (Secondary to exposure to Infected birth canal ) & Breast feeding .

3- Sexually through semen & cervical secretions .

4- Blood transfusion .

5- Organ transplantation

126
Q

Pathogenesis of CMV

A

First infects upper respiratory tract And lymphocytes .

During their circulation lymphocytes spread the virus to other lymphocytes & monocytes in spleen & lymph nodes.

Finally spread to a variety of epithelial cells of salivary glands , kidney tubules , testes & cervix.

127
Q

What viral response maintains virus in latent state?

A

The virus elicits both humoral & cell mediated response that maintains virus in latent state.

128
Q

Latent virus can reactivate with immunosuppression (T/F)

129
Q

Congenital CMV

A

Perinatal (before and after birth)

Postnatal (after birth)

130
Q

Immunocompromised CMV

A
  • Transplant patients
    • Cancer patients- chemotherapy
    • HIV patients
131
Q

CMV can cause mononucleosis type symptoms (T/F)

132
Q

CMV mononucleosis type symptoms are the leading cause of morbidity and mortality

133
Q

Heterophil Antibody Test- positive for CMV mononucleosis symptoms

A

( Heterophil Antibody Test- Negative )

134
Q

Cytomegalic Inclusion Disease (CID)

A

Series of signs and symptoms caused by cytomegalovirus infection, toxoplasmosis or other rare infections such as herpes or rubella viruses.
It can produce massive calcification of the central nervous system, and often the kidneys.

Intrauterine infection :– Congenital CMV Infection -> Death

Hepatospenomegaly

Jaundice

Thrombocytopenic purpura (abnormal decrease in platelets)

Hemolytic anaemia (RBCs destroyed faster than they are made)

Microcephaly

Cerebral calcifiaction

High mortality

Mental retardation

135
Q

Direct Virus Demonstration - CID

A

Light microscopy - Giemsa stain – owl’s eye cells; large, multinucleated
Direct immunofluorescence and ELISA – finding antigens
PCR (most rapid + sensitive) & Nucleic Acid Hybridization – Finding CMV DNA

136
Q

Serology - CID

A

Panel of tests for TORCH

137
Q

Culture - CID

A

Sample used is throat washing & urine . CMV grows in human fibroblast cell culture

After 3-5 weeks CPE{ Cyto- Pathic- Effect} with small foci of swollen transluscent cells with large intranuclear inclusions.

138
Q

Ganciclovir - CID

A

Inhibits viral DNA polymerase enzyme
Intravenous route
DOC

139
Q

Other drugs for CID

A

Valganciclovir (orally – immunocompromised) and Foscarnet (resistant)

140
Q

Gangiclovir does not affect CID latency (T/F)

141
Q

Prevention + control – CID

A

Good hygienic personal practice , careful hand washing after contact with diapers or oral secretions .

Safe sexual practice including usage of condom reduces transmission .

Isolation of infected new borne .

Screening of transplant donors & recipient for CMV antibodies .

142
Q

Etiological agent

A

Materials known or reasonably expected to contain a pathogen

143
Q

Etiological agent of infectious mononucleosis

A

Epstein Barr Virus

144
Q

Which cells does EBV infect?

A

Infects lymphoid cells - B lymphocytes

145
Q

EBV transmission

A

Saliva ( kissing disease ).

Rarely by blood or marrow transfusion . By

Sharing contaminated - Glasses , Cups & Tooth brushes.

146
Q

Infectious mononucleosis - symptoms

A

High fever , sore throat , headache , myalgia , nausea & abdominal pain

Also associated with: pharyngitis , generalized lymphadenopathy , hepatosplenomegaly and fatigue

147
Q

EBV Associated tumors/malignancies

A

Burkitt’s lymphoma – Africa - childhood (swelling of jaw - affects B lymphocytes).

Lymphoma – (Post –transplant lymphomas) in immunodeficient patients.

Nasopharyngeal carcinoma - Asia-Chinese.

Hodgkin’s lymphoma (non-painful enlarged lymph nodes in the neck, under the arm, or in the groin - affects WBCs)

148
Q

Burkitt’s lymphoma

A

Cancer starts in immune cells called B-cells - fast growing human tumor

149
Q

Post-transplant lymphoma

A

Can be a result of both solid organ transplant (kidney, lung, heart, liver, lung) and allogeneic bone marrow or stem cell transplants

150
Q

Nasopharyngeal carcinoma

A

Rare tumor of the head and neck which originates in the nasopharynx

151
Q

Hodgkin’s lymphoma

A

Cancer originates from a specific type of white blood cells called lymphocytes

152
Q

Infectious mononucleosis - pathogenesis

A

Replicates in nasopharyngeal epithelium .

Spreads to salivary glands & oropharyngeal lymphoid tissue .

Further replication results in viraemia with subsequent infection of reticuloendothelial system , liver , spleen and B lymphocytes.

Host immune response include Cytotoxic T Lymphocytes (CTLs) - Characteristic Atypical Lymphocytes found in peripheral blood (whole blood).

153
Q

How do this virus cause tumors?

A

DNA becomes integrated with the host chromosome giving the infected cell the ability to proliferate indefinitely resulting in malignancy / tumor .

154
Q

Pathogenesis - EBV

A

Downey cells (abnormal lymphocytes) seen

155
Q

Samples - EBV

A

Saliva , peripheral blood (P.S.) & lymphoid tissue

156
Q

Tests EBV

A

Direct immunofluorescence

PCR and Nucleic Acid Hybridization :- For detection of viral DNA , most sensitive .

157
Q

Direct immunofluorescence

A

Cell scrappings from lesions are stained with monoclonal antibodies conjugated with a fluorescence dye . Viral inclusion bodies appear in Microscope as a Bright Green Intranuclear particles

158
Q

Monospot test ( horse RBCs ) / monospot test

A

Heterophil antibodies have the ability to agglutinate red blood cells of different animal species. The Paul-Bunnell test uses sheep erythrocytes( RBCs)

159
Q

Serology - EBV

A

A) Detection of Non-specific Heterophil Antibodies:

Patients with Acute Infectious Mononucleosis develop transient non-specific Abs that agglutinate sheep RBCs / horse RBCs.

These are detected by Paul Bunnel or Monospot tests + ve.

B) Detection of specific antibodies by ELISA , Indirect Immunofluorescence:

 Presence  of  IgM  antibody  to  Viral Capsid antigen  (VCA) – Suggest Acute Primary Infection .                                      High  IgG  antibodies  to  VCA  - Seen in Burkitt’s lymphoma , Nasopharyngeal carcinoma  &  Past infection .

Virology (7 decks)

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