6/23- Human Herpes Viruses II Flashcards
What is the genetic material of herpes viruses?
ds-DNA
When are infectious rates of CMV highest?
- Childhood and young adulthood
- Seroprevalence varies among poulations
Modes of CMV transmission?
- Congenital/perinatal
- Direct contact (including sexual)
- Parenteral
Which pts may experience reactivation disease?
Immunocompromised hosts
Pathogenesis of CMV Infections? Immune response?
- Spread by direct contact with infectious materials (saliva, urine, blood, genital secretions), via placenta, and blood products
- Viremia and viruria are common
- Neutralizing Abs and T cell responses develop
- CMI (T and NK cell) responses are particularly important for recovery
Disease syndromes caused by CMV?
- Congenital infection
- Mononucleosis-like illness
- Severe visceral/disseminated disease in immunocompromised pts
When is congenital infection with CMV most severe?
When primary infection occurs during pregnancy
What are some symptoms of severe visceral/disseminated disease in immunocompromised hosts?
- Pneumonia
- Chorioretinitis
- Hepatitis
- Gastroenteritis
- CNS disease
Question 1:
Which of the following agents is least likely to be associated with congenital infectious complications?
A. Rubella
B. Cytomegalovirus
C. Rotavirus
D. Toxoplasmosis
Question 1:
Which of the following agents is least likely to be associated with congenital infectious complications?
A. Rubella
B. Cytomegalovirus
C. Rotavirus
D. Toxoplasmosis
Symptoms of Congenital CMV infection?
- Jaundice
- Petechiae
- Hepatosplenomegaly
- IUGR
- Preterm birth
- MIcrocephaly
- Hydranencephaly
- Death
Clinical sequelae of Congenital CMV?
- Sensorineural hearing loss
- Low IQ
- Chorioretinitis (choroid = middle or vascular coat of the eyeball)
Other
- Microcephaly
- Seizures
- Paresis or paralysis
Symptoms of CMV Mononucleosis?
- Fever (mean 19 days)- common
- Pharyngitis (rare)
- Lymphadenopathy (occasional)
- Lymphocytosis (55-86%)
- Mild hepatitis (high LFTs)- common
Etiologies causing mono-like illness?
- EBV
- CMV
- HIV
- Toxoplasma
CMV retinitis is associated with what? What is it/symptoms?
Associated with advanced immunosuppression (esp AIDS in pre-HAART era)
- Affects neurosensory retina producing necrotizing retinitis
- Often presents with bilateral disease (will go from one eye to the other)
- If untreated, will progress to blindness
- “pizza pie- cheese and ketchup”
What is this?
CMV pneumonia
What is this?
CMV colitis
How is CMV diagnosed?
- Cytopathology (CMV “owl’s eyes” inclusions)
- Antigen/nucleic acid detection
- Culture of tissue, blood, urine, or secretions
- Serologic methods (IgM, rising IgG)
For HIV/AIDS pt, need tissue or positive appearance in eye exam!
What is this?
“Owl’s eyes” inclusions of CMV (cytopathic effect)
What is this?
Cytopathic effect (CPE) of CMV:
- Develops slowly
- Note the linear pattern
Prevention and Control of CMV infections?
- Careful handwashing & hygiene
- Avoid contact with infected materials
- Use blood or tissues from seronegative donors for seronegative infants or transplant recipients
- CMV Ig, or antiviral therapy or prophylaxis (acyclovir, ganciclovir, valganciclovir, foscarnet) should be considered for high risk populations
- Cellular immunotherapy appears promising in transplant patients
Question 2:
Cytomegalovirus has been associated with all but which one of the following syndromes?
A. Congenital infection
B. Mononucleosis-like illness in adults
C. Pneumonia in immunocompromised hosts
D. Symptomatic reactivation disease in immunocompetent adults
Question 2:
Cytomegalovirus has been associated with all but which one of the following syndromes?
A. Congenital infection
B. Mononucleosis-like illness in adults
C. Pneumonia in immunocompromised hosts
D. Symptomatic reactivation disease in immunocompetent adults
Immunocompetent hosts can be CMV + but have no symptoms (typically)
How many people are seropositive for EBV?
90-95% of adults
T/F: Most childhood infections of EBV are asymptomatic
True
What is the major mode of transmission of EBV?
Direct contact with secretions
EBV is associated with which human malignancies?
- African Burkitt’s lymphoma
- Nasopharyngeal carcinoma
- Some B cell lymphomas
Pathogenesis of EBV Infections?
- Acute infection proceeds to persistent and latent infection
- Main control of virus is CTLs and NK cells in immunocompetent individuals
Disease syndromes caused by EBV?
- Infectious mononucleosis (initially described with EBV, although other viruses may produces similar symptoms): pharyngitis, lymphadenopathy, atypical lymphocytes on blood smears
- Oral hairy leukoplakia in HIV-infected persons
- Fatal infection in pts with X-linked lymphoproliferative syndrome
T/F; With EBV, reactivation disease may occur in recognized normal hosts?
False
Clinical manifestations of EBV mononucleosis?
- Fever (76%)
- Pharyngitis (84%)
- Lymphadenopathy (94%)
- Splenomegaly (52%)**
- Lymphocytosis (70%)
- Elevated LFTs (hepatitis) (50-100%)
- Hepatomegaly
**Avoid exercise/strenuous activity to prevent splenic rupture!
What is the DDx for pharyngitis?
- HSV
- Adenovirus
- Mycoplasma
- Bacteria….
What is this?
Development of a rash is particularly common among pts with EBV who are treated with ampicillin
Complications of EBV infections?
Hematalogic:
- Hemolytic anemia
- Neutropenia
- Thrombocytopenia
Respiratory:
- Airway obstruction
- Pneumonia
- Otitis media
Neurologic:
- Encephalitis
- Meningitis
- Myelitis
- Optic neuritis
- CN palsies
- Seizures
- Guillain-Barre syndrome
- Reye syndromes
Cardiac:
- Myocarditis
- Pericarditis
- MI
GI:
- Hepatitis
- Pancreatitis
- Splenic rupture
Renal:
- Nephritis
- Nephrosis
What is this?
Oral hairy leukoplakia seen with EBV
- grey patch on side of tongue
What is this?
“Starry night” histology seen with Burkitt’s lymphoma (can be caused by EBV)
What is this?
Sign of Burkitt’s lymphoma (can be caused by EBV)
What is this? Also seen when?
Atypical lymphocytes seen in EBV mononucleosis
- CTLs- the prmary mediators of recovery and control
Also seen in : CMV, Toxoplasmosis, Hepatitis, Rubella, Roseola, Mumps, Drug reactions
Diagnosis of EBV?
Heterophile Abs
What antibodies are looked at in serodiagnosis of EBV? When is each seen?
IgM-VCA (primary infection)
IgG- VCA (marker of infxn at some time)
IgG-EBNA (appears late; absence or seroconversion indicates primary infection)
Serologic
Profile of EBV infections for:
- Never exposed
- Acute infection
- Recent infection
- Past infection
Management of EBV mononucleosis?
- Antivirals do not have clinical benefit (ACV has antiviral effect)
- Steroids indicated for severe complications
- Should avoid contact sports and heavy lifting during acute illness
Question 3:
An 18 year old college freshman presents with a several week history of illness characterized by sore throat, fatigue, fever and swollen lymph nodes in the neck, axillae and inguinal region. On exam, she is noted to have fever to 102’F, exudative pharyngitis, lymphadenopathy, and hepato-splenomegaly. CBC shows lymphocytosis with atypical lymphocytes. Which of the following is MOST likely to yield the specific diagnosis?
A. Routine throat culture for virus
B. IgM against EBV VCA
C. IgG titer vs. EBNA
D. Positive rapid strep test
Question 3:
An 18 year old college freshman presents with a several week history of illness characterized by sore throat, fatigue, fever and swollen lymph nodes in the neck, axillae and inguinal region. On exam, she is noted to have fever to 102’F, exudative pharyngitis, lymphadenopathy, and hepato-splenomegaly. CBC shows lymphocytosis with atypical lymphocytes. Which of the following is MOST likely to yield the specific diagnosis?
A. Routine throat culture for virus
B. IgM against EBV VCA
C. IgG titer vs. EBNA
D. Positive rapid strep test
- Doesn’t have strep b/c this has been several weeks; subacute
Question 4:
Serum antibody responses against EBV VCA are the most important mediators of recovery from and control of EBV infections.
A. True
B. False
False
- It’s the lymphocytes (cell-mediated immuno-response)
When is HHV 6 mostly acquired?
- Early in childhood (6 mo-2 yrs)
Transmission of HHV 6?
- Direct contact
- Respiratory route
Two variants of HHV 6?
6A and 6B
Disease manifestations of HHV6 (overall)?
- Roseola (6B) aka “Sixth disease”
- Other febrile illness in infancy
- Mono-like illness in adults
- Visceral disease in immunocompromised
- Gliomas?
Clinical manifestations of primary HHV 6 infections?
- High fever (>39’C)
- Irritability, malaise
- Inflamed tympanic membrane
- Nasal congestion
- Other: diarrhea, cough, abnormal breath sounds, vomiting, rash, seizures (a viral illness in a kid that lasts a little too long)
In Roseola, the rash isn’t actually all that common (10-20%ish)
Timeline of Roseola (HHV 6)?
- Febrile illness for 3-5 days
- Followed by development of a diffuse rash as the fever abates
How can HHV 6 present in immunocomproimsed pts?
- Asymptomatic reactivations
- Primary infection with fever and rash
- Graft dysfunction/rejection, pneumonitis, encephalitis
Diagnosis of HHV6?
- Clinical manifestations of typical illness
- Significant increase in Ab titers
- Nucleic acid and antigen detection
- Culture of HHV 6 from peripheral blood
Treatment of HHV 6?
Anecdotes support effectiveness of ganciclovir and foscarnet for treatment of severe disease
What are some characteristics of HHV 7?
- Most closely related to HHV6
- Common childhood infection
How do the time and rate of infection vary between HHV6 and 7?
Infections of HHV7 are later and at a slower rate than HHV6
When does viremia occur with HHV7?
- Primary infection
- Reactivated infection
What are some clinical manifestations of HHV7?
(In viremic pts):
- Fever
- Seizures
- URI
- Gastroenteritis
Question 5:
A 9-month old infant is brought to you by her father, who complains that she has had high fever and irritability for the past several days. This morning he noted that her fever was gone, but he is worried that she now has a skin rash. Her exam is normal except for a generalized maculopapular rash. What is the most likely etiology of this illness?
A. Herpes simplex type 1
B. Varicella-zoster virus
C. Cytomegalovirus
D. Human herpes type 6
Question 5:
A 9-month old infant is brought to you by her father, who complains that she has had high fever and irritability for the past several days. This morning he noted that her fever was gone, but he is worried that she now has a skin rash. Her exam is normal except for a generalized maculopapular rash. What is the most likely etiology of this illness?
A. Herpes simplex type 1
B. Varicella-zoster virus
C. Cytomegalovirus
D. Human herpes type 6
What is the agent of HHV8? Similarity to what other virus?
Gamma-herpes virus
- Genetic organization similar to EBV
Mechanism of HHV 8 infection?
- Encodes antigens expressed in lytic infection and during latency (used for serosurveys of infection)
- Not readily isolated in culture
- Common variants in host human genes may influence control of HHV8 infections
Epidemiology of HHV8?
Seroprevalence rates vary:
- Low among healthy heterosexuals in US
- Somewhat higher in Mediterranean and East Africa
- Highest rates among HIV-infected patients (especially those with KS), and among persons in some parts of Africa and South America
Transmission of HHV8?
- Patterns of infection suggest sexual transmission in some populations
- Oral or other transmission possible in populations where disease is endemic
Pathogenesis of HHV8?
- Infects endothelial and spindle cells in vascular tumor tissue of Kaposi’s sarcoma
- Genome encodes proteins associated with proliferation, mitogenic activity, and anti-apoptotic activity
What are some clinical manifestations of HHV8?
Mononucleosis-like illness in HIV-infected pt Human tumors:
- Kaposi’s sarcoma (almost always, these tumors are associated with HHV8)
- Primary effusion and body cavitary lymphomas Multicentric Castleman’s disease (angiofollicular lymph node hyperplasia)
What are some variant of Kaposi’s sarcoma?
Risk group?
Survival?
What are the risk group and survival time of people with Kaposi’s sarcoma: classic variant?
- Elderly men
- E Europe and Mediterranean
- Years to decades
What are the risk group and survival time of people with Kaposi’s sarcoma: Endemic variant?
- African children and adults
- Months to years
What are the risk group and survival time of people with Kaposi’s sarcoma: immunosuppression variant?
- Organ transplant recipients
- Months to years
What are the risk group and survival time of people with Kaposi’s sarcoma: Epidemic or AIDS-associated variant?
- Especially homo or bi-sexual men
- Weeks to months (worst outcome)
What is this?
Purplish lesion seen in Kaposi’s sarcoma (HHV8)
- Seen commonly on extremities, but can be elsewhere
- Often on skin/mucosa
Treatment of HHV8?
- Chemotherapy
- Radiation
- Antiviral therapy
- Other
What is herpes simiae? Infects who?
Herpes B
- Common pathogen of old world monkeys
- Highly pathogenic fo rhumans
How is herpes simiae (herpes B) acquired?
- Animal bites
- Intimate contact with lesions
Symptoms of herpes simiae (herpes B)?
CNS involvement is a common lethal complication
Treatment for Herpes simiae (herpes B)?
Effective antiviral therapy
- Must be instituted early in course of disease
