Herpes Viruses Flashcards
1
Q
classify herpes viruses
A
- Herpes simplex virus, type 1 (HSV1)
- Herpes simplex virus, type 2 (HSV2)
- Varicella-zoster virus (VZV)
- Cytomegalovirus (CMV)
- Epstein-Barr virus (EBV)
- Human herpesvirus 6 (HHV-6)
- Human herpesvirus 7 (HHV-7)
- Human herpesvirus 8 (HHV-8)
2
Q
define the herpvesviridae
A
A family of enveloped viruses with a linear, double-stranded DNA structure. Includes herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesviruses 6, 7, and 8.
3
Q
The capsid of Herpesviridae is helical.
True/False
A
False
It is icosahedral
4
Q
envelopes of Herpesviridae confers resistance to the surrounding environment. True/False
A
False
The envelope is a lipid bilayer covering, which is acquired during virion budding and release from the host cell. Typically less stable in acidic environments and less resistant to dry heat and detergents compared to non-enveloped viruses. Includes some DNA viruses (e.g., herpesvirus, poxvirus, and hepadnavirus) and several RNA viruses (e.g., flavivirus, togavirus, and retrovirus).
5
Q
The envelope is derived from?
A
host cell membrane during virion budding
6
Q
what are the common DNA viruses?
A
A group of viruses that have genetic material composed of deoxyribonucleic acid (DNA). Includes herpesviruses, poxviruses, hepadnaviruses, adenoviruses, papillomaviruses, polyomaviruses, and parvoviruses.
7
Q
herpesviridae replicate in the cytoplasm of the cell. True/False
A
False
DNA viruses replicate in the nucleus of host cells (except Poxviridae).
8
Q
how acyclovir treats herpesviral infections?
A
Guanosine analog (nucleoside analog): initially HSV/VZV-coded thymidine kinase monophosphorylates the guanosine analog to an active intermediate, which is then phosphorylated by cellular kinases
The phosphorylated drug is incorporated into the replicating viral DNA strand and inhibits the viral DNA polymerase → termination of viral DNA synthesis
Selective action in infected cells only → minimal effect on host cells’ DNA replication
The drugs are only activated in cells infected with HSV or VZV. In addition, the DNA polymerase in human cells has very little affinity for the active form of these drugs.
9
Q
what is the latency of Herpesviridae?
A
After primary infection, the HSV remains dormant in the ganglion neurons (e.g., trigeminal, sacral ganglion)
10
Q
what are the sites of latency of:
1) HSV and VZV
2) EBV and CMV
A
- HSV 1 & 2 and VZV persist in nerve cells
* EBV & CMV persist in lymphocytes (CMV in monocytes)
11
Q
what are the triggers of herpesviridae reactivation?
A
triggered by various factors (e.g., immunodeficiency, stress, trauma) → clinical manifestations
12
Q
describe the general clinical features of HSV and VZV?
A
- Infection associated with vesicular lesions of skin/ mucous membranes
- Blister-like lesions, fluid-filled
- Painful
- Ulcerate & become crusted
13
Q
how HSV cause vesicles?
A
Cause disease at the site of inoculation (cell lysis)
14
Q
in what nerve HSV-1 maintains latency?
A
trigeminal ganglion
15
Q
how HSV infections are transmitted?
A
- Transmitted via direct contact with vesicular lesions
- Historically, HSV-1 infected “above the waist” and HSV-2 “below the waist” but epidemiology has changed & either can cause oral or genital disease
- Many acquire HSV in the first few years of life
- 60-90% of adults have had an HSV1 infection
- 15-80% of adults have had an HSV2 infection
- Developing countries have a higher burden of disease
16
Q
what is Herpetic withlow?
A
An infection of the dermal and subcutaneous tissue of the fingers caused by HSV-1 (and less commonly HSV-2). Often secondary to primary oral lesions. Manifests with painful, grouped, nonpurulent vesicles and axillary and/or epitrochlear lymphadenopathy proximal to the infection.
17
Q
what is eczema herpeticum?
A
An acute skin infection that is most commonly caused by HSV-1 and HSV-2 and primarily occurs in patients with pre-existing skin conditions (classically atopic dermatitis). Patients present with fever, malaise, and disseminated, painful, vesicular lesions. Complications include bacterial superinfection and systemic viral dissemination.
18
Q
primary infection with HSV is mainly symptomatic. True/False
A
False.
Majority asymptomatic
19
Q
what are the clinical features of HSV primary infection?
A
• Fever, malaise, myalgia, painful local lymphadenopathy
• Vesicular lesions can be widely distributed
– Palate, pharynx, gingivae, buccal mucosa, tongue
• Can also get milder infections i.e. just lips
20
Q
recurrent oropharyngeal herpes usually involves pharynx. True/False
A
False
Recurrent oral infection:
–Induced by UV light (sun), fever, trauma, stress
–Usually corners of mouth/ lips
21
Q
recurrent oropharyngeal infection is more severe. True/False
A
False
Usually milder than the primary infection
22
Q
what is the herpes galidatorum?
A
Herpes gladiatorum is one of the most infectious of herpes-caused diseases and is transmissible by skin-to-skin contact. it is strongly associated with contact sports—outbreaks in sporting clubs being relatively common. Herpes gladiatorum is characterized by a rash with clusters of sometimes painful fluid-filled blisters, often on the neck, chest, face, stomach, and legs. The infection is often accompanied by lymphadenopathy (enlargement of the lymph nodes), fever, sore throat, and headache
23
Q
herpetic withlow commonly occur due to auto-inoculation after primary oropharyngeal lesion. True/False
A
True
– May occur due to auto-inoculation
– Can be occupational e.g. in healthcare workers
24
Q
what is keratitis
A
inflammation of the cornea. Infectious Staphylococcus, herpes zoster, herpes simplex, and Acanthamoeba. Typically causes severe pain, irritation, redness, watery or purulent secretion, and impaired vision.
25
define herpes keratitis
- -Keratitis: Inflammation of the cornea
- -Mostly unilateral
- -Complications: Recurrent disease (≈30%)/ permanent scarring/corneal damage /blindness
26
herpetic keratitis is mostly bilateral. True/False
False
| unilateral
27
herpetic keratitis can lead to scarring and blindness. True/False
True
28
define Herpetic encephalitis
- -Presents with fever malaise, headache, confusion, behavioral changes, seizures, coma
- -Pathology: hemorrhage, necrosis, edema
- -Typically involves the frontotemporal lobe; often poor outcomes (high mortality)
- -Treatment: IV acyclovir
29
which obes are commonly involved in herpetic encephalitis
temporal lobes
30
what are the clinical features of Herpes Simplex encephalitis
1) Focal neurological deficits (primarily affects the medial temporal lobe)
2) Altered sense of smell and loss of vision
- -Aphasia
- -Memory loss
- -Hemiparesis
- -Ataxia
- -Hyperreflexia
3) Seizures (focal or generalized)
4) Altered mental status (e.g., confusion, disorientation, lowered level of consciousness)
5) Behavioral changes (e.g., hypersexuality, hypomania, agitation)
6) Meningeal signs (e.g., nuchal rigidity, photophobia) may occur.
7) Coma
HSE may resemble bacterial meningitis, but the combination of altered mental status, seizures, and focal neurological deficits are more common for HSE!
31
what are the characteristic features of herpetic encephalitis on imaging
--Magnetic resonance imaging
Most sensitive and specific imaging modality, especially in the early stages
Hyperintense temporal lobe lesions and signal abnormalities (usually in the hippocampus)
--Computed tomography
Often normal during the early stages
A unilateral hypodense zone can be observed in the insular cortex, which may become bitemporal with disease progression.
32
what are the characteristic features of herpetic encephalitis on lumbar puncture
1) PCR (gold standard): direct, early detection of the pathogen
2) Cells
- -Lymphocytic pleocytosis
- -Erythrocytes may be detected in hemorrhagic encephalitis
3) Other parameters
- -Opening pressure: normal or elevated
- -Protein levels: slightly elevated, ↑ cerebrospinal fluid (CSF)/serum albumin ratio
- -Glucose levels: normal
- -Lactate: varies, mainly normal to slightly elevated
33
what are the manifestations of HSV 2 infection?
• Genital herpes (sexually-transmitted)
– Historically HSV-2-associated but now more commonly caused by HSV-1
• Can also cause any of the manifestations of HSV-1 infection
• Characteristic vesicular lesions
– Penis in men
– Labia, vagina & or cervix in women (& urethra may be involved)
– Can also get rectal/ oropharyngeal infection with HSV-2
34
does primary genital herpes cause lymphadenopathy?
Yes
| Painful lymphadenopathy in the groin area
35
define neonatal HSV infection
• Acquired most commonly via the vaginal canal (90%)
–50% chance of neonatal infection if the mother has a primary genital infection at delivery
-However, can be contracted through close contact with someone who has HSV e.g cold sore or herpetic whitlow
• Because of a poor cell-mediated immune response in a neonate, high risk of dissemination and CNS infection
• Consequences include:
-Death
-intellectual disability
-Neurological sequelae
• Most cases occur in babies of mothers who had no signs of HSV infection
36
transmission of HSV to neonate increases with...
Primary HSV infection in seronegative women has the highest transmission rate (followed by non-primary first-episode infection and, then, recurrent or asymptomatic infection).
37
how HSV 1 and 2 are diagnosed?
• Laboratory diagnosis not required for minor infections e.g. cold sores
–Diagnosis based on characteristic clinical features
• Serology
–Only HSV IgG serology assay is commonly available
–Can be type-specific e.g HSV -1 IgG or HSV 2 IgG
–The main role of serology is in determining between acute (new) infection and recurrent infection in the maternal setting.
• Genital herpes: PCR on the vesicular fluid used to confirm and to differentiate HSV-1 from HSV-2
• Herpes simplex encephalitis: PCR on cerebrospinal fluid (CSF)
• Neonatal HSV: Surface swabs for culture, CSF & blood for HSV DNA PCR
38
what are the characteristic findings of Herpes infection with light microscopy?
- -Tzanck smear
- -Multinucleated giant cells (non-specific)
- -Eosinophilic intranuclear Cowdry A inclusion bodies (non-specific)
- -Results available within 1 hour
- -Unable to differentiate between HSV-1 and HSV-2
39
what is the gold standard for definitive diagnosis of HSV?
Culture results available in 48 hours,
| The culture should be taken from a fresh vesicle; cultures of crusted vesicles may yield false-negative results.
40
how HSV 1 or 2 are treated?
1) First-line: oral acyclovir for mild disease
- -In severe cases or immunocompromised patients → IV acyclovir
- -Topical may be helpful if used early
- -In case of acyclovir-resistant HSV-1: foscarnet
2) Valacyclovir
3) Penciclovir
4) Famciclovir
5) Duration: 7–10 days
41
acyclovir have effects also on the latent infection. True/False
False
Only replicating cells. The phosphorylated drug is incorporated into the replicating viral DNA strand and inhibits the viral DNA polymerase → termination of viral DNA synthesis
42
what is foscarnet?
A viral DNA/RNA polymerase and HIV reverse transcriptase inhibitor used to treat acyclovir-resistant HSV infections and as a second-line treatment for CMV retinitis in patients who are immunocompromised.
direct inhibition of viral DNA polymerases by binding to the pyrophosphate binding site of the enzyme
Does not require activation by viral kinase vs acyclovir
43
what's the difference between valacyclovir and famciclovir vs acyclovir
first 2 are prodrugs
44
how HSV 1 and 2 need to be prevented?
• No available vaccine
• Simple hygiene measures
• Education regarding infectious stages
--Oral herpes: avoid oral contact with others and sharing objects that have contact with saliva
--Genital herpes: abstain from sexual activity
• Use of condoms
45
there is a vaccine against HSV 1 or 2. True/False
False
| No vaccine
46
what is the epidemiology of VZV?
≥90% of adults in temperate climates are VZV IgG positive, indicating a previous primary infection
• Most people are infected in early childhood
Highly contagious before & during symptoms
• Rates of infection >90% among susceptible household contacts
Reactivation of the latent virus is known as herpes zoster or shingles
• Occurs in ~30% over a lifetime
• Risk increases with age as cell-mediated immunity wanes
47
reactivation of latent VZV cause...
shingles (herpes zoster)
48
what are shingles?
A dermatomal rash with painful blistering caused by the reactivation of the varicella-zoster virus (VZV). Pain can precede the rash. Initial infection with VZV usually occurs early in life, presenting as chickenpox (varicella), and the virus subsequently remains dormant in dorsal root ganglia. Immunosuppressed individuals are at particular risk of VZV reactivation.
49
why the risk of getting shingles increases with age?
• Risk increases with age as cell-mediated immunity wanes
| Immunosuppressed individuals are at particular risk of VZV reactivation.
50
what are the clinical features of chickenpox?
1)Incubation period: 2 weeks (10–21 days)
Prodromes
2)1–2 days prior to the onset of exanthem
--Presents with constitutional symptoms (e.g., fever, malaise)
--More common with primary infection in adults (less typical in children, in which rash is often the first sign of infection)
3))Exanthem phase: duration: ∼ 6 days
4)Presentation
--Widespread rash starting on the trunk, spreading to the face, scalp, and extremities
--Simultaneous occurrence of various stages of rash: erythematous macules → papules → vesicles filled with a clear fluid on an erythematous base → eruption of vesicles → crusted papules → hypopigmentation of healed lesions
--Severe pruritus
--Fever, headache, and muscle or joint pain
51
where VZV virus remains for latency?
dorsal root ganglia
52
what are prodromal symptoms of chickenpox?
constitutional symptoms (e.g., fever, malaise)
53
what is the pathophysiology of chickenpox?
During the incubation period, the virus attaches to respiratory mucosa, then spreads to regional lymph nodes and via the bloodstream to the liver and spleen (primary viremia).
After the 2-3 week incubation period, there is a secondary viremia; at this stage, the patient is generally unwell and febrile and 1-2 days later the skin lesions develop.
The virus causes skin lesions by lysing epithelial cells (vesicles, then crusts).
54
how VZV causes vesicles
The virus causes skin lesions by lysing epithelial cells (vesicles, then crusts).
55
chickenpox rash spread centripetally or centrifugally?
Centrifugally.
Centripetal spread = extremities to trunk
Centrifugal spread = trunk to extremities
56
children are at increased risk of severe chickenpox infection. True/False
False
Most childhood varicella is not severe
Complications much more likely in adults
57
what are the most common complications of chickenpox
1) Skin
- -Bacterial superinfection (including impetigo, phlegmon, necrotizing fasciitis), which often leads to scarring and is managed with antibiotics
- -Reactivation of latent VZV results in shingles (herpes zoster)
- -Scarring
2) Central nervous system
- -Acute cerebellar ataxia (∼ 0.1% of cases) → good prognosis, mainly self-limiting after several weeks
- -Encephalitis (very rare) → cramps, coma, poor prognosis
3) Lungs
- -Pneumonia (viral or bacterial)
4) Fetus (chickenpox during pregnancy)
- -Congenital varicella syndrome
58
cerebellitis seen with chickenpox is life-threatening. True/False
False
| good prognosis, mainly self-limiting after several weeks
59
what is congenital varicella syndrome?
neonatal varicella-zoster infection as a result of intrauterine transmission during the first and second trimester. Results in low birth weight, cicatricial scarring along dermatomes, limb atrophy, ocular defects (e.g., chorioretinitis, cataracts, microphthalmos), and/or neurological abnormalities (e.g., cortical atrophy, seizures, neurogenic bladder). A rare condition in the US because of maternal immunity due to vaccination, or prior exposure to the virus.
60
what are the characterisitc clinical features of shingles?
1) Fever, headaches, fatigue
2) Dermatomal distribution typically of 1–3 dermatomes on one side of the body, most commonly between T3 and L3 → torso, hips, waist, groin, and ventral region of the upper legs)
3) Severe pain (usually precede the pain)
- -Usually described as “burning”, “throbbing”, or “stabbing”
- -Allodynia may occur
4) Rash
- -Erythematous maculopapular rash that quickly evolves into vesicular lesions
- -Vesicles are initially clear → pustulation and rupture typically occur after 3 or 4 days
- -Crusting and involution typically occurs between day 7 and 10
- -Lesions may become necrotic (herpes zoster gangrenosum), generalized (herpes zoster generalizations) or may not present at all (zoster sine herpete).
5) Paresthesia
6) Itching
7) Motor deficits (rare)
8) Disseminated disease (rash involves more than the primary 1–3 dermatomes) may occur in immunocompromised individuals
61
what is post-herpetic neuralgia?
A complication of shingles characterized by attacks of acute, intense pain in areas previously affected by the rash. Presents in 10–15% of cases and has a strong association with advanced age. Symptoms may subside with time or persist. Treatments include tricyclic antidepressants (e.g., amitriptyline) and gabapentin.
62
what is the Herpes Zoster ophtalmicus?
1) reactivation of VZV in the ophthalmic division of the trigeminal nerve
2) Clinical features
- -Fever and skin symptoms as in shingles
- -Herpes zoster keratitis
- -Involvement of the ophthalmic nerve: reduced corneal sensitivity with severe pain in the innervated regions (forehead, bridge and tip of the nose)
- -Involvement of the nasociliary nerve:
a) Severe intraocular infection is possible (uveitis, iritis, conjunctivitis, keratitis, and optic neuritis)
b) Zoster lesion on the tip of the nose = positive Hutchinson's sign
63
what are the risks of VZV in pregnancy?
* High risk of complications of chicken pox in pregnant woman (pneumonia)
* Small risk of congenital varicella syndrome in the baby (rare) if an expectant mother gets chicken pox in the first 20 weeks of pregnancy
* High risk of severe disseminated varicella in the neonate if a mother gets chicken pox around the time of delivery
64
what is Ramsy-Hunt syndrome?
eactivation of VZV in the geniculate ganglion, affecting the facial (VII) and vestibulocochlear (VIII) cranial nerves. Also known as Ramsay Hunt syndrome, it typically presents with fever, pain and an erythematous maculopapular rash in the auditory canal and pinna, as well as facial paralysis, vertigo, and sensorineural hearing loss.
65
how VZV is laboratory diagnosed?
* Uncomplicated primary infection in childhood: clinical diagnosis, laboratory testing not usually required
* Other situations (e.g. infection in hospitalised patients): detection of VZV DNA by PCR on fluid from skin lesions
* Detection of VZV IgG in blood is used if evidence of previous primary infection or vaccination is required
66
what is the best confirmatory test of VZV infection?
PCR
Material: vesicle fluid
Amniotic fluid, chorionic villi, or fetal blood may be used in suspected fetal infection.
67
what are the management options of primary VZV infection?
1)Generally no treatment for uncomplicated chicken pox in immunocompetent children
2)Consider the treatment of chicken pox in adolescents and adults
•Oral aciclovir or valaciclovir x 5 days
3)Treatment advised in:
--Neonates
--Immunocompromised patients
--Complicated varicella zoster
•IV aciclovir may be needed
4)Treatment advised if any of the following:
--Age >50
--Moderate to severe rash or pain
--Involvement of the face/ eye
--Acute complication of infection
--Immunocompromised state
5)Mild to moderate:
--Oral aciclovir or valaciclovir x 7 days
6)Severe (e.g. ocular or neurologic)
--IV aciclovir 10mg/kg TDS x 7-14 days
68
what are the indications of VZV treatment
- -Immunosuppressed individuals
- -Primary infection in adults and in unvaccinated adolescents ≥ 13 years
- -Individuals on long-term salicylate therapy (e.g., aspirin)
69
when acyclovir should be started in case of chickenpox?
Antiviral therapy should be initiated as early as possible (before
48 hours of rash onset) since the effectiveness of antiviral treatment decreases as the disease progresses!
70
do shingles transmissible?
Yes
| Althughless than chickenpox
71
how VZV is prevented?
1. Varicella vaccine (for prevention of chickenpox in children >12 months)
2. Zoster vaccine (for prevention of shingles in older people)
– 66% efficacy but falls with increasing age
72
VZV vaccine is live or killed?
live, so contraindicated in pregnants, and neonates
73
at what age VZV vaccines are administered?
1)Chickenpox: live vaccine that is recommended for:
--Children: 1st dose at 12–15 months, 2nd dose at 4–6 years (see “Immunization schedule”)
--Persons aged ≥ 13 years with insufficient immunity (with or without previous vaccination)
2)Shingles: live vaccine
≥ 50 years: zoster immunization is generally recommended
74
what are the indications of VZV immunoglobulin?
1)Pregnant women with no evidence of immunity
2)Immunosuppressed individuals with no evidence of immunity
3)Newborn infants, if the mother was infected 5 days before or up to 2 days after birth
4)Premature babies
> 28 weeks if the mother has no evidence of immunity
< 28 weeks regardless of the mother's immunity status
5)Infants < 1 year of age
--Implementation: within 10 days following exposure (ideally within 4 days after exposure)
75
describe primary CMV infection
* Typically, mild or asymptomatic especially in young children
* May uncommonly cause an infectious mononucleosis-like syndrome
* Infection acquired from most bodily secretions (saliva, urine, breast milk), blood, tissue/organs (transplant)
76
primary CMV infection is typically symptomatic or asymptomatic?
asymptomatic
77
what type of diseases can be caused by primary CMV infection?
mononucleosis-like illness
78
CMV establishes latency in...
monocytes, macrophages (cells of myeloid lineage)
79
reactivation of CMV is commonly seen...
immunocompromized patients
80
what is the epidemiology of CMV
* Acquired by 40-60% by mid adult life in developed countries
* Seroprevalence varies between countries
* Higher rate of seropositivity and earlier acquisition in developing countries
* Higher rate of seropositivity in those with multiple intimate exposures
81
what are the features of congenital CMV infection?
• Primary infection in pregnancy may lead to congenital CMV in the baby
--Estimated that 1% of all newborns are infected at birth
--10-15% of these are symptomatic at birth
• Small size
• Microcephaly, intra-cerebral calcifications, chorioretinitis, encephalitis
• Jaundice, hepatomegaly, rash, thrombocytopenia
• Unilateral or bilateral deafness
--A further 10-15% who appear normal at birth present with sequelae
• Sensorineural hearing loss
• Developmental delay
82
CMV uses what receptors to infect cells?
integrins
83
what are the signs of congenital CMV infection?
* Small size
* Microcephaly, intra-cerebral calcifications, chorioretinitis, encephalitis
* Jaundice, hepatomegaly, rash, thrombocytopenia
* Unilateral or bilateral deafness
84
what is the characteristic feature of CMV on histopathology?
ow;-eye appearance
85
inclusions of CMV are in the cell nucleus or cytoplasm?
Nucleus (in hepres inclusion are both in nucleus and cytoplasm)
86
what are the remote effects of congenital CMV infection?
* Sensorineural hearing loss
| * Developmental delay
87
what is the location of intracerebral calcifications seen with congenital CMV
periventricular (vs toxoplasmosis, calcifications seen in basal ganglia)
88
what are the features of CMV infection in immunocompromised patients?
CMV reactivation is an important cause of complicated infection in immunocompromised hosts
• HIV-positive patients with a low CD4 count
CMV retinitis
• Transplant patients
CMV colitis (commonest manifestation), pneumonitis etc.
89
at what CD4 count, CMV infection usually manifests?
Among HIV-positive patients, manifestations of CMV disease usually occur when the CD4 count is ≤ 50!
90
how CMV is transmitted?
- -Blood transfusions
- -Sexual transmission
- -Droplet transmission
- -Transplant-transmitted infection (e.g., bone marrow, lungs, kidneys)
91
how CMV is diagnosed?
1) PCR for CMV DNA is the method of choice in immunosuppressed patients
- Blood PCR performed to detect reactivation in immunosuppressed patients e.g. post-transplant
- Quantitative PCR (i.e. amount of virus in the blood) is used to monitor response to treatment
- Urine/ saliva PCR performed in suspected congenital CMV infection
2) Serology (IgM, IgG and avidity testing)
- may be –ve if immunosupressed
3)Histology e.g. for colitis
92
what is the test of choice to detect CMV infection in immunocompromised patients?
PCR
93
what is the avidity testing?
IgG avidity assays measure the binding strength between IgG antibodies and virus that can help distinguish a primary CMV infection from a past infection. Following primary CMV infection, IgG antibodies have low binding strength (low avidity) then over 2-4 months mature to high binding strength (high avidity).
94
what is the treatment approach of CMV infection?
1) No treatment for mild infections/ infectious mononucleosis like syndrome in immunocompetent hosts
2) IV ganciclovir or oral valganciclovir (prodrug) used for
- -End organ disease e.g. colitis, pneumonitis
- -Viraemia in immunocompromised
* note aciclovir not active against CMV
95
does CMV mononucleosis need to be treated by antiviral drugs?
no
96
why acyclovir is not active against CMV?
CMV thymidine kinase does not activate acyclovir.
97
how does ganciclovir work?
1)Guanosine analog (nucleoside analog): initially phosphorylated to 5' monophosphate by the CMV-coded UL97 kinase (serine/threonine kinase) → further phosphorylated to the triphosphate by cellular kinases
The phosphorylated drug is incorporated into the replicating viral DNA strand and inhibits the viral DNA polymerase → termination of viral DNA synthesis
Lower selectivity than acyclovir and penciclovir → can affect host cell's DNA replication
98
how do CMV infections need to be prevented?
1)No vaccine available at present but clinical trials are in progress
2)Neonatal
• No CMV screening in pregnancy
• Neonates screened clinically at birth as indicated
• CMV-negative blood is used for infants in NICUs
3)Transplant recipients
• Transplant donor & recipient screening, matching where possible
• CMV-negative blood for transfusions
• CMV immunoglobulin to seronegative recipients before transplant
• Prophylactic administration of antiviral agents such as ganciclovir
99
CMV can be prevented by vaccination. True/False
False
| there is no vaccine
100
do all pregnant women need to be screened for CMV?
NO
No CMV screening in pregnancy
Neonates screened clinically at birth as indicated
101
what is the EBV?
A double-stranded, enveloped DNA virus that causes mononucleosis. Most adults are carriers of the virus. Infection is associated with Hodgkin lymphoma, Burkitt lymphoma, primary central nervous system lymphoma, gastric cancer, and nasopharyngeal carcinoma.
102
primary infection with EBV is often symptomatic. True/False
False
• Primary infection usually occurs during childhood (often asymptomatic)
• Primary infection in adolescents/ young adults can present as infectious mononucleosis (= glandular fever)
103
how primary EBV infection in adolescents commonly manifests?
Primary infection in adolescents/ young adults can present as infectious mononucleosis (= glandular fever)
104
how EBV is transmitted?
* Saliva, close oral contact
| * “Kissing disease”
105
what are the clinical features of IM?
• Exudative pharyngitis
• Lymphadenopathy
• Splenomegaly (15-65%)
• Hepatitis/ hepatomegaly
• Rash, typically after ampicillin treatment for presumed “strep throat”
(DDx. CMV, HIV, toxoplasmosis)
Fatigue is themost important manifestaiotn
106
differentiate lymphadenopathy of IM and Streptococcal tonsillitis?
posterior cervical lymph node chain and geralized vs anterior cervical and submandibular
107
how IM is diagnosed?
• Heterophile antibody (“Monospot”/ “Paul-Bunnell” test)
- Detected at the end of first week; 10% false negative
• Antibodies to the virus itself
- Antibody to viral capsid antigen (VCA) - early
- Antibody to nuclear antigens (EBNA)- later
108
what are the characteristic findings on blood smear of patients with IM
atypical lymphocytes which are activated T cells (not B)
109
EBV establishes latency at what cells?
* EBV persists in B-cells
* Stimulates B-cells in tissue culture to proliferate indefinitely
* T-cells are essential in limiting the proliferation of EBV-infected B-cells
* Impairment of T-cell immunity (e.g. post-organ transplant, in HIV infection) can result in EBV-associated malignancies
110
give examples of EBV associated malignancies
• B- cell lymphomas
- Burkitt’s lymphoma, Hodgkin’s lymphoma
• Nasopharyngeal carcinoma
• T-cell lymphomas
• Post-transplant lymphoproliferative disease (PTLD)
111
what is Burkitt'slymphoma
```
An aggressive (high-grade) B-cell lymphoma that is most common in children. Associated with translocation t(8;14) in 75% of cases, and commonly with EBV infection. In adults, it occurs in association with HIV infection.
In Africa commonly involves the jaw, In develped countries-abdomen
```
112
what is oral hairy leukoplakia?
An aggressive (high-grade) B-cell lymphoma that is most common in children. Associated with translocation t(8;14) in 75% of cases, and commonly with EBV infection. In adults, it occurs in association with HIV infection.
113
what antivirals are used to treat EBV infection?
There are no antivirals to treat EBV
• No antiviral treatment available (acyclovir of little value)
• Supportive care for infectious mononucleosis
• Advise against contact sports
• Rituximab (monoclonal antibody against CD20) used as part of regimen in treatment of EBV-associated B cell tumours
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why patients with IM should avoid contact sports for at least 1 month
to avoid splenic rupture
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is there a vaccine against EBV
NOT CURRENTLY
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What monoclonal antibody is used for EBV associated B cell malignancies?
Rituximab
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HHV-6 cause...
roseola infantum (also HHV-7)
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what are the features of HHV-6
• Most children infected by age 2: almost universal seropositivity
• Shed in saliva after infection
• Can reactivate in immunosuppression
e.g. stem cell transplant/ solid organ transplant
• Integrated HHV-6: ~1% of population inherited as part of the germline
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HHV-7 cause roseola infantum. True/False
True
| Althgouh less commonly than HHV-6
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what is roseola infantum?
A viral exanthematous infection caused by the human herpesvirus 6 (HHV-6; in rare cases, HHV-7) that mainly affects infants and toddlers. Characterized by high fever, which ends abruptly after 3-5 days, followed by the sudden appearance of a maculopapular truncal rash that sometimes spreads to the face and extremities, fading within two days.
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what is the most common cause of febrile seizures in children <2
HHV-6 infection
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what are the risks of HHV-6 in immunocompromised people
- Can reactivate in immunosuppression and cause bone marrow suppression and encephalitis
e. g. stem cell transplant/ solid organ transplant
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Hw HHV-6 is diagnosed?
usually clinicaly
| PCR
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how HHV-6 infection is treated?
mainly supportive
| • In serious cases e.g. encephalitis in immunocompromised ganciclovir may be used
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is there a vaccine against HHV 6 or 7?
no
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what is the HHV-8?
A double-stranded DNA herpesvirus primarily associated with primary effusion lymphoma and Kaposi sarcoma in patients who are HIV-positive. Transmitted orally or sexually and horizontal
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how HHV-8 is transmitted?
• Mainly sexually transmitted, also horizontal transmission in children
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what is the epidemiology of HHV-8
* Uncommon in developed countries (<5% seropositivity)
| * Higher rates of seropositivity in developing countries and MSM
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what are the manifestations of HHV-8 activation in HIV patients?
Kaposi Sarcoma and
• HHV-8 also linked to AIDS-related body cavity lymphoma (a type of non-Hodgkin’s lymphoma occurring in body cavities e.g. pleural space/ peritoneal cavity)
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how Kaposi sarcoma is treated?
* Antiretroviral therapy for AIDS-related Kaposi sarcoma
| * Chemotherapy may be needed in extensive disease
131
Can Granny catch the shingles from Johnny’s chickenpox?
Answer: No; shingles is caused by reactivation of latent virus- has to be already dormant in the nerve root.
Granny can only get shingles from reactivation of her own latent virus.
This is wrong
Although shingles is due to reactivation, exposure to persons with chickenpox is one of the main factors to contribute to reactivation
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what is the site of latency of HHV 6 and 7?
CD4 T cells
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what is the site of latency of HHV-8
tissues
