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Virology 07 Herpesviruses clinical correlates*


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The major difference between HSV-1 and HSV-2 is:
Preferential sites of recurrence
Two things that HSV-1 is the cause of:
~95% of orofacial herpes
10-30% of primary genital herpes
What does HSV-2 cause?
Recurrent genital herpes
When do the vast majority of HSV-1 infections occur?
During early childhood & are asymptomatic
The most common clinical manifestation of HSV-1 is:
In Recurrent herpes labialis, where does the virus lay dormant?
trigeminal ganglion
What is the most common cause of corneal blindness in the U.S.?
Keratoconjunctivitis - HSV (normally HSV-1)
A child or young adult presents with headache, fever, behavioral changes, speech difficulties, hallucinations, and focal seizures. An HSV-related disease to consider is:
HSV encephalitis
How is neonatal herpes acquired?
Contact of neonate with infected genital secretions during passage through the birth canal
What is the “gold standard” for diagnosis of an HSV infection?
viral culture
What are two complications of chickenpox in children?
1. Bacterial superinfection of lesions
2. Cerebellar ataxia
What are some complications of chickenpox in adults?
1. Encephalitis
2. Varicella pneumonia (pregnant women and adults)
What results from reactivation of latent VZV?
Dermatomal zoster
What is the classic triad of signs of EBV infection?
What are four things caused by CMV in an immunocompromised host?
What causes Exanthem subitum in infants and a mononucleosis-like syndrome in adults?
Human Herpes Virus 6
What does Human Herpes Virus 8 cause?
Kaposi’s sarcoma
Multicentric Castleman’s Disease
Body Cavity B lymphoma
What is used to treat acute episodes of HSV?
What are the basic ideas in Herpes virology
Mild disease enhances transmission
Latency and reactivation
Importance of cell-mediated immunity
Morbidity: congenital/neonatal disease, immunocompromised, cancers
Where is a HSV-1 recurrent infection likely to manifest
Most likely oral
Where is a HSV-2 recurrent infection most likely to be
Most likely genital
What are the factors implicated in HSV reactivation
Trigeminal ganglion decompression
Third molar surgery
Sunlight (UV)
Epithelial Trauma
What are the characteristics of asymptomatic shedding of HSV
Occurs with both HSV-1 and HSV-2
The only form of recurrence in >50% of patients
Detected by culture on 0.5-2% of days
May be associated with very mild lesions that are not recognized as HSV
Typically lasts <1.5 days
Reduced but not eliminated by acyclovir
What are some potential interventions to reduce neonatal Herpes morbidity
Prevention of exposure (Abstinence, C-section)
Potential therapeutic interventions
Established: Rapid treatment of neonates with suggestive clinical picture
Controversial: Improved early diagnosis of infected neonates (24-48 hr cultures-- controversial); 3rd trimester acyclovir in mothers with identified risk; Antiviral prophylaxis of exposed neonates (positive culture at delivery indicates exposure)
What are some HSV infections in immunosuppressed patients
Herpes labialis
How can HSV infection be diagnosed
Viral culture (gold standard)
Tzanck smear
Culture with monoclonal antibody staining
Serology (glycoprotein G can be used to distinguish HSV-1 and HSV-2)
DNA probes
Polymerase chain reaction
How are Chickenpox and Zoster transmitted
Transmission by aerosol (rarer for zoster) and direct contact
How does Varicella with cerebellar ataxia present
Ataxia usually simultaneous with rash (can precede the rash)
Ataxia accompanied by HA, vomiting, lethargy
25% have fever, nuchal rigidity, nystagmus
Seizures are rare
What are some diagnostic findings in Varicella with Cerebellar ataxia
Clinical diagnosis sufficient in typical cases
CSF usually normal. Pleocytosis (<100 WBC) in 25%
EEG - diffuse slow wave activity (20%)
MRI - rarely see focal cerebellar or brain stem lesions
How does Varicella encephalitis present
Symptoms usually appear about one week after rash (though may be earlier or later). Acute or gradual onset.
Fever, HA, vomiting, altered mental status
Focal neurologic findings -- hyper/hypo-reflexia, hemiparesis, sensory changes
Seizures 29-52% of cases
What are risk factors for more severe Varicella disease
Late pregnancy
Steroid use- Includes inhaled steroids
Other immunocompromise
Non-vaccinated, varicella naive
What is the definition of Disseminated zoster
>20 vesicles outside primary dermatome and/or visceral or CNS involvement
Incidence and severity increase with degree of immunocompromise, especially CMI
Epstein Barr Virus is implicated in what cancers
Burkitts lymphoma (Africa)
Nasopharyngeal carcinoma (Asia)
Oral hairy leukoplakias
Lymphoproliferative syndrome (especially in the immunocompromised)
How does CMV mononucleosis syndrome present
Fever, malaise, mild adenopathy and hepatosplenomegaly, little sore throat
Mild hepatitis
Lymphocytosis, 20% atypicals
Heterophile antibodies positive in about half
IgM seroconversion
What are some characteristics of CMV post-transfussion syndrome
Risk: 3-4% per unit of whole blood
Follows 5-20% of exposures
Incubation average 3 weeks (range 1-6 wks)
Symptomatic in 30%
Fever, malaise, hepatitis splenomegaly
Relative lymphocytosis, with atypicals
How does CMV in the immunocompromised host present
neutropenia, leading to fungal infections
What is the Antigenemia (pp65) test
CMV antigen production in neutrophils predicts positive blood culture in bone marrow transplant patients
What are some characteristics of Congenital CMV
-50% of pregnant women are susceptible
-2% of these develop primary infection
-Virus shed in saliva, milk, urine, from cervix
-1% infected in utero, mostly primary
-90% initially subclinical, developmental problems later (e.g., mental retardation, deafness)
-10% cytoplasmic inclusion disease: petichiae, hepatosplenomegaly, jaundice, microcephaly, chorioretinintis
What are some diseases caused by HHV-6 or 7
Infectious mononucleosis-like syndrome
Infections in immunocompromised
-Fever in BMT patients
What are some characteristics of HHV-8
Cause of:
-Kaposi’s sarcoma
-Multicentric Castleman’s Disease
-Body Cavity B lymphoma
Primary infection unknown
Probably sexually transmitted
What is valacyclovir
An oral acyclovir prodrug which gives higher blood drug levels
What is acyclovir used for
HSV treament for:
-Acute episodes
-Recurrences (benefit is very modest)
-Suppression of recurrences in patients with frequent recurrences
How is chickenpox treated
Do not treat children
Use acyclovir for adults or the immunocompromised
When is Zoster treated
Antivirals are recommended for age greater than 50, severe pain, immunocompromised, or eye involvement
Pain should always be managed aggressively
What are some characteristics of live-attenuated varicella vaccine
Developed in Japan in the 1970s
Indicated to prevent/reduce complications of varicella
70-90% effective in preventing varicella
>99% effective in preventing “severe” varicella
High dose formulation can prevent zoster
1 dose for children, 2 doses above age 12
Vaccination required in many states
How are CMV infections managed
-Tissue, blood screening
-Immunoglobulin prophylaxis: CMV-Ig reduces incidence of severe infections post-transplant
-Prophylactic antivirals
Vaccine: none licensed
Ganciclovir- including ocular implants. Can cause bone marrow toxicity

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