Mono causing Herpes Virus

Question 1

Most important factor in ability to infect

Answer 1

Cell attachment. Number one requirement

Question 2

Herpes viruses

Answer 2

All can cause latent infections. 8 main human pathogens. DNA viruses.

Question 3

HSV-1

Answer 3

cold sores

Question 4

HSV-2

Answer 4

genital Herpes lesions

Question 5

HSV-3

Answer 5

chickenpox and shingles

Question 6

HSV-4

Answer 6

aka EBV. Most common cause of Infectious Mononucleosis (IM). Associated with Burkitt’s lymphoma and nasopharyngeal cancer

Question 7

HSV-5

Answer 7

aka CMV. congenital disease + disease in immunocompromised

Question 8

First indications for mono

Answer 8

atypical lymphocytes up! liver enzymes up, throat culture negative (not strep). Symptoms: hoarseness, difficulty swallowing, sore throat, fever, fatigue, myalgia, enlarged tonsils, lymph nodes (cervical), splenomegaly

Question 9

Atypical lymphocyte description

Answer 9

larger, nucleus looks lacey and spread out. Latent infection in B cells. viral genome does not normally integrate into the cellular DNA but forms circular episomes which reside in the nucleus.

Question 10

DDX - other possibilities

Answer 10

Infectious mononucleosis due to CMV or EBV (more common than CMV), streptococcal pharyngitis, retropharyngeal abscess, gonococcal pharyngitis, and toxoplasmosis

Question 11

IM - characteristics

Answer 11

Primary EBV infection: usually subclinical in childhood. Adolescents and adults: 50% symptomatic infection. IM is usually a self-limited disease. Atypical lymphocytes (activated CD8+ T cells). Cytokines cause disease symptoms. Complications occur rarely but may be serious (e.g. splenic rupture, meningoencephalitis). In few, chronic IM can occur (patient dies of lymphoproliferative disease or lymphoma)

Question 12

Incubation and transmission of IM

Answer 12

30-50 days. Transmitted primarily by saliva. Can be spread by asymptomatic individuals.

Question 13

Children show symptoms of mono less. Why?

Answer 13

The symptoms are mostly due to the immune system response. Since they have less developed system, they don’t show it as well.

Question 14

Testing for IM

Answer 14

Heterophile AB (reaction to RBCs from other animal - weird but it works. Show up around 2wks). Negative in 10-15%, so need more specific ones to EBV (IgG and IgM)

Question 15

Pathogenesis - carrier

Answer 15

Lifelong carrier state: low grade infection kept in check by the immune defenses. EBV is able to immortalize B-lymphocytes in vitro and in vivo. Few EBV-immortalized B-cells can be demonstrated in the circulation -which are continually cleared by immune surveillance mechanisms.

Question 16

Epidemiology

Answer 16

In developed countries, 2 peaks of infection are seen: the first ages 1 - 6 yr and the second 14 – 20 yr. Eventually 80-90% of adults are infected. In developing countries, infection occurs at a much earlier age so that by the age of two, 90% of children are seropositive.

Question 17

Diseases associated with HSV-4

Answer 17

top 4 most common. 1. Infectious Mononucleosis 2. Burkitt’s lymphoma 3. Nasopharyngeal carcinoma 4. Lymphoproliferative disease and lymphoma in the immunosuppressed. 5. X-linked lymphoproliferative syndrome 6. Chronic infectious mononucleosis 7. Oral leukoplakia in AIDS patients 8. Chronic interstitial pneumonitis in AIDS patients.

Question 18

Burkitt’s lymphoma

Answer 18

B cell malignancy. Common in children in Africa and Papua New Guinea. Found in areas with malaria (causes immunosuppression). Responds well to chemo.

Question 19

Complications of EBV

Answer 19

Ampicillin rash (like Joc! Test first!). Airway obstruction. Splenic rupture (life threatening but rarer)

Question 20

Risks of immunosuppressed individuals

Answer 20

Lymphomas. encephalitis, myocarditis, hepatitis, malignant B cell tumors. EBV and AIDS: oral hairy leukoplakia

Question 21

Tx for IM/EBV

Answer 21

Antivirals ineffective. No vaccine! Just deal with it and wait it out.

Question 22

CMV DDX

Answer 22

CMV most common in immunosuppressed transplant patients. Must differentiate from CMV, HSV, and fungi such as Histoplasma capsulatum, Cryptococcus neoformans, Mucor and Aspergillus. (All of these organisms can cause pneumonia and gastritis)

Question 23

CMV characteristics

Answer 23

CMV = one of most successful human pathogens. Transmitted vertically or horizontally usually with little effect on normal host. Developed countries: 40% of adolescents infected and ultimately 70% of the population developing countries, over 90% of people are ultimately infected. Transmission may occur in utero, perinatally or postnatally. Once infected, you have a friend for life

Question 24

CMV congenital infection

Answer 24

Transmission to fetus may occur following primary or recurrent CMV infection. 40% chance of transmission to the fetus following a primary infection. Possible during all stages of pregnancy. Damage to fetus results from destruction of host cells. Can cause problems much later in life of child

Question 25

CMV infection (not in fetus)

Answer 25

Usually asymptomatic except for a few cases of IM (clinically indistinguishable from EBV). Can cause Infectious Mono: Fever, pharyngitis, lymphadenopathy, splenomegaly (although less common than in EBV). Also self limiting. No run to heterophiles AB, test for specific AB

Question 26

CMV symptoms in immunosuppressed

Answer 26

Spiking fevers most common symptom. Recipients of bone marrow: Pneumonitis most common. Recipients of solid organ transplants: Hepatitis, Thrombocytopenia, Pneumonitism, Vasculopathy after cardiac transplantation or graft rejection

Question 27

CMV and AIDS

Answer 27

25% of patients develop disease due to CMV. Disseminated disease common. 90% of infections are retinitis. Esophagitis, Colitis, Encephalitis, Polyradiculopathy: flaccid paralysis result

Question 28

CMV pathogenesis

Answer 28

Replicates in many types of tissues and cells. Primary infection is followed by latent infection in granulocyte precursors and macrophages. Formation of giant cells (cytomegaly). Postnatal infection mainly occurs through saliva. Sexual transmission may occur as well as through blood and blood products and transplanted organ.

Question 29

CMV Diagnostic tests

Answer 29

Cell culture; Histological exam of “suspect” tissues; DFA (fluorescent dye-labeled AB); PCR and other molecular methods; Virus in urine; Serology: finding of CMV IgM (ELISA or EIA)

Question 30

CMV treatment

Answer 30

Gancyclovir (acyclovir variant). Same mode of action as acyclovir. Foscarnet can be used in cases of resistance. No vaccine.