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:
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~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:
- Gingivomatitis
- 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?
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1. Bacterial superinfection of lesions
2. Cerebellar ataxia - What are some complications of chickenpox in adults?
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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?
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fever
pharyngitis
lymphadenopathy - What are four things caused by CMV in an immunocompromised host?
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Retinitis
Pneumonitis
Colitis
Neuropathies - What causes Exanthem subitum in infants and a mononucleosis-like syndrome in adults?
- Human Herpes Virus 6
- What does Human Herpes Virus 8 cause?
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Kaposi’s sarcoma
Multicentric Castleman’s Disease
Body Cavity B lymphoma - What is used to treat acute episodes of HSV?
- Acyclovir
- What are the basic ideas in Herpes virology
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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
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Fever
Trigeminal ganglion decompression
Third molar surgery
Sunlight (UV)
Epithelial Trauma
Stress
Immunosuppression - What are the characteristics of asymptomatic shedding of HSV
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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
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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
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Herpes labialis
Gingivostomatitis
Esophagitis
Pneumonitis
Hepatitis
Cutaneous
Disseminated - How can HSV infection be diagnosed
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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
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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
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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
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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
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Late pregnancy
Neonates
Steroid use- Includes inhaled steroids
Other immunocompromise
Non-vaccinated, varicella naive - What is the definition of Disseminated zoster
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>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
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Burkitts lymphoma (Africa)
Nasopharyngeal carcinoma (Asia)
Oral hairy leukoplakias
Lymphoproliferative syndrome (especially in the immunocompromised) - How does CMV mononucleosis syndrome present
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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
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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
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retinitis
encephalitis
pneumonitis
viremia
hepatitis
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
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Mother:
-50% of pregnant women are susceptible
-2% of these develop primary infection
-Virus shed in saliva, milk, urine, from cervix
Baby
-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
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Roseola
Infectious mononucleosis-like syndrome
Infections in immunocompromised
-Fever in BMT patients
-Encephalitis
-Pneumonitis - What are some characteristics of HHV-8
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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
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HSV treament for:
-Acute episodes
-Recurrences (benefit is very modest)
-Suppression of recurrences in patients with frequent recurrences - How is chickenpox treated
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Do not treat children
Use acyclovir for adults or the immunocompromised - When is Zoster treated
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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
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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
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Prevention
-Tissue, blood screening
-Immunoglobulin prophylaxis: CMV-Ig reduces incidence of severe infections post-transplant
-Prophylactic antivirals
Vaccine: none licensed
Treatment:
Ganciclovir- including ocular implants. Can cause bone marrow toxicity
Foscarnet-nephrotoxicity
Cidofovir-nephrotoxicity