Herpes Virus Infections

Front 1

Does Herpes Simplex Viruses cause localized or disseminated diseases?

Back 1

Disseminated diseases

Front 2

What is HSV1 associated with?

Back 2

Fever blisters

Front 3

What is HSV2 associated with?

Back 3

Genital herpes

Front 4

What is true of all herpesviruses with regards to their hosts?

Back 4

The disease manifestations of the herpes infection depends on the host

Front 5

Who are the hosts of herpes simplex virus infections?

Back 5

Healthy children and adults
-HSV usually causes a primary infection in childhood
-HSV reactivation infections occur during adulthood

Immunocompromised hosts
-these individuals are more likely to have reactivation infections
-these individuals are more likely to have more severe disease their bodies cannot control

Front 6

What is needed to transmit herpes simplex virus?

Back 6

DIRECT contact with the person shedding the virus from the mucous membranes. These individuals DO NOT need to have a visible lesion (they are more contagious if they do though). HSV is EASY to transmit.

Front 7

What is the incubation period of HSV?

Back 7

1 week

Front 8

What is the primary host defense against herpes simplex viruses?

Back 8

Cell-mediated immunity, however cell-mediated immunity cannot prevent primary infection or recurrence.

Front 9

What is the primary tissue response to infection with alpha herpesviruses (HSV and VZV)?

Back 9

Skin manifestations and vesicles

Front 10

Does reactivation and recurrence of HSV infection occur in everyone with the infection?

Back 10

NO, it varies depending on the host

Front 11

What are the clinical manifestations of herpes simplex viruses?

Back 11

Recurrence is KEY

Oral lesions:
-With primary disease you are likely to have ulcerations and blisters all around the outside and inside of the mouth; you could end up in the hospital; this is a MUCH worse disease due to a complete lack of immunity against it
-With secondary disease/ recurrence you usually see fever blisters that tingle

Genital lesions:
-With primary infection it can cause a febrile illness with ulcers and vesicles, lymphadenopathy, systemic illness, and it is painful.
-With secondary infection it can just cause vesicles, they usually come out in the same place as the first infection, they tingle.

All of these skin vesicles and blisters are clear and painful but eventually they burst and go away.

Front 12

What do Herpes simplex virus infections look like in immunocompromised hosts?

Back 12

They are extensive, painful, last a LONG time, and persistent. The patient's body cannot handle the disease. An example is perirectal herpes in MSM.

Front 13

What are some other serious HSV infections?

Back 13

Karytoconjunctivitis- the herpes virus infects the cornea and conjunctiva; you have ragged, dendritic ulcers in the eye, pertetic karyotitis, etc... This is caused by people with fever blisters rubbing their eyes.

Herpes Encephalitis- the fever blister virus goes from the PNS to the CNS instead of out to the skin

Front 14

What does herpes simplex viral infections in a newborn look like

Back 14

It is usually fatal. It is a disseminated infection where the baby is covered in convalescing lesions. The baby has NO immune protection against this virus. They often have encephalitis. The virus is usually transmitted at the time of birth.

Front 15

How do you diagnose herpes simplex virus infections?

Back 15

The clinical picture is the most important. A Tzanck smear from a lesion can be done to show multi-nucleated giant cells with viral inclusions. The viruses cause epithelial cells to coalesce (all alpha herpes viruses do this; POX viruses DO NOT).

Other tests that can be done but usually aren't are Direct fluorescent antigen assays (DFA) or PCR on substance from the lesion or culture of the virus.

Front 16

What is the treatment for herpes simplex viral infections?

Back 16

Nucleoside analogues- acyclovir (cheap), famciclovir (expensive) or valacyclovir (expensive).

Nothing is usually require for fever blisters but for all other manifestations you treat.

Front 17

What does treatment do for herpes simplex viral infections?

Back 17

It is life-saving for immunosuppressed hosts, neonatal disseminated herpes infection and encepthalitis. It also acts to shorten the disease course and decrease shedding and transmission of genital herpes.

Front 18

How can you prevent herpes simplex viral infections?

Back 18

Antiviral prophylaxis is usually given to prevent reactivation infections and prevent new lesions from popping up, esp. with genital herpes. Prophylaxis is acyclovir for 1+ year.

Prophylaxis is ALWAYS given to immunocompromised hosts with herpes.

Front 19

What 2 diseases are caused by the same alpha herpes virus and which one occurs with primary infection vs. secondary infection?

Back 19

Varicella (chicken pox) which occurs following primary infection and Zoster (shingles) which occurs following secondary/reactivation infection

Front 20

Who are the hosts that get chicken pox?

Back 20

Mostly healthy children get chicken pox. Adults can get it as well if they did not have it as a child. If this occurs in older individuals (20+) they will get a worse form of the disease. Healthy, pregnant women who get chicken pox get a TERRIBLE form of this disease and are likely to die.

Immunosuppressed patients can also get chicken pox. They have an increased risk of visceral involvement and disseminated disease.

Front 21

Who are the hosts for Zoster (reactivation of the virus)?

Back 21

To get Zoster you HAD TO HAVE HAD chicken pox as a child.

Mostly older individuals are at risk for Zoster. This is likely due to decrease cell-mediated immunity and decreased VSV antigens. Out of all the people that are 85 years old, 50% of them have had Zoster.

Zoster also occurs in immunocompromised hosts. It results in a MUCH worse disease and can cause outbreaks and reactivation. These patients have no cellular immunity. They get a severe reaction that is more likely to disseminate. These patients include people with AIDS, who have had a transplant, are on steroids or have had a hematologic malignancy.

Front 22

How contagious is Varicella and how is it spread?

Back 22

Varicella is VERY VERY contagious (it can cause outbreaks). It is spread from the respiratory tract and this can start occurring even before the skin lesions appear. The virus initially infects the respiratory tree, goes viremic and shows up as pox. People generally show no symptoms until the pox show up. You are much more contagious prior to the pox showing up when you are asymptomatic. Varicella can also be spread from the skin lesions.

Front 23

What is the incubation time of Varicella?

Back 23

11-21 days; you are spreading the virus a few days before you show the pox

Front 24

What is the relationship between Varicella and Zoster?

Back 24

They are the EXACT same virus but just result in different clinical presentations.

Front 25

What happens if you are exposed to someone with chickenpox?

Back 25

You get chickenpox, NEVER zoster

Front 26

What happens if you are exposed to someone with Zoster?

Back 26

You will get chickenpox if this is your first exposure to the virus. YOU DO NOT GET ZOSTER.

Front 27

What are some key characteristics about Zoster infection and transmission?

Back 27

Zoster is reactivation of a virus you are already infected with (VSV from when you had chickenpox). Zoster can NEVER be transmitter from person to person. It is a sporadic disease due to reactivation of this virus and you NEVER see outbreaks since there is no transmission. The lesions from Zoster are contagious but they can ONLY cause chickenpox in people who have never been exposed to VZV before. Respiratory secretions are not contagious.

Front 28

What is the primary host defense against VZV?

Back 28

Cell-mediated immunity

Front 29

What are the clinical manifestations of chickenpox?

Back 29

Chickenpox is a systemic disease ALWAYS. It goes through the respiratory tract, is asymptomatic, goes viremic, gets the skin and causes rash. Other symptoms include fever and malaise/crankiness. Th rash shows up in crops that continually erupt thus your body is covered by lesions in different stages. These lesions are clear vesicles/blisters; they become pustules; the blisters become cloudy; they crust over and heal. This is a VERY itchy rash but is not painful and usually doesn't cause scarring.

Chickenpox can cause respiratory complications such as pneumonia in older patients.

Chickenpox is generally fatal for pregnant women (the fetus is okay though).

Front 30

What is one key difference between the rash caused by chickenpox and the rash caused by smallpox?

Back 30

The chickenpox rash comes in bursts whereas the small pox rash comes all at once (you don't have lesions of different ages).

Front 31

What are the clinical manifestations of Zoster?

Back 31

Zoster results in a dermatomal rash. The virus comes out from the ganglion where it was latent for years and follows that nerves distribution. It erupts along that ganglion. The vesicles last for weeks but they go away eventually and do not result in scarring usually. The rash is vesicular, extensive can coalesce, become pustular and eventually crust over. Another common symptom in pain which can start even before the rash shows up. This stabbing/lanceating pain can last for years. Other symptoms include edema, alodenia (anything on the body is painful), and burning. If the virus is in the trigeminal nerve it can involve the cornea and be a much worse disease.

Front 32

What is the major complication associated with Zoster?

Back 32

Post-herpetic neuralgia (pain that lasts for years).

Front 33

What happens in Zoster and Chickenpox infections in immune compromised hosts?

Back 33

They are likely to get much worse forms of the disease. Zoster and Chickenpox can both disseminate. Zoster can start out following the dermatome but due to a complete lack of immune response, spread all over the body.

Front 34

How do you diagnose VZV?

Back 34

The clinical picture is the MOST important. A tzanck smear can be used from the lesion to show multi-nucleated cells with viral inclusions. Direct fluorescent antigen assays (DFA) or PCR can be used from scraps of the lesion. Culture is not super common but can be done.

Front 35

How do you treat VZV infection?

Back 35

You treat VZV infections the same way you treat HSV infections. You use nucleoside analogs such as acyclovir, famciclovir or valacyclovir. People with Zoster need a higher dose of these drugs though because the virus is not as susceptible to the drugs in those infections. Treatment is not usually required for typical chickenpox in kids. Treatment is ESSENTIAL in immunosuppressed hosts or pregnant women with chickenpox, diseeminated Zoster or Herpes encephalitis. You treat EVERYONE with shingles/Zoster. You want to treat adults with chickenpox as well since they are more likely to have visceral involved due to the disease and can be hospitalized from it.

Front 36

Does treatment of Zoster prevent Post-herpetic neuralgia?

Back 36

NO

Front 37

What does treatment do for Zoster and Chickenpox?

Back 37

Treatment shortens the disease course and decreases the transmission and shedding of the virus. The sooner you treat the patient, the less likely they are to spread the disease.

Front 38

Are herpes lesions superficial or deep?

Back 38

Herpes lesions are superficial. They look and feel awful but as soon as you give acyclovir they clear up in a few days and do not leave a scar.

Front 39

How do you prevent VZV infection?

Back 39

VACCINE

There is a live attenuated vaccine available against varicella. It is REQUIRED for children and for ALL healthcare workers who have not had chickenpox. People can check whether or not they have had chickenpox by getting an IgG titer to check for chickenpox antibodies. This vaccine might cause the person to have a few pox.

There is a live attenuated vaccine for Zoster. This is given to patients that are 50 years or older. This vaccine contains the same exact virus but in 14-fold higher concentration. It is used to prevent Zoster and post-herpetic neuralgia.

The chickenpox vaccine is USELESS for a person older than 60 years old.

There is also Varicella immune globulin that can be given in situations of life-threatening varicella. This shot contains high titer passive antibody against VZV. It is given to pregnant women with varicella. It provides immediate immunity. Acyclovir is given alongside this.

Front 40

Can you get Shingles more than once in a lifetime?

Back 40

Yes, if you live long enough you can get it more than once. Immunocompromised hosts also get Shingles more than once.

Front 41

What is one KEY characteristics of shingles and where it spreads on the body?

Back 41

Shingles rash will never (except for aberrant nerves) cross the midline of the body.

Front 42

What type of herpes virus is the Epstein-Barr virus?

Back 42

It is a gamma herpes virus that is latent in lymphocytes.

Front 43

Who are the hosts infected by the Epstein-Barr virus?

Back 43

Healthy children and adults
- it is common in young kids in developing countrries. They are either asymptomatic or have a small fever and recover quickly
-healthy people do not usually reactivate with this viral infection

Immunocompromised hosts
-they can get a primary infection that is disastrous or can reactive prior EBV infection

Front 44

Is EBV infection common in the developing world?

Back 44

Not really, most people have antibodies against it.

Front 45

How is EBV infection transmitted?

Back 45

Direct contact with people shedding the virus from their mucous membranes (oral secretions).

It can also transmitted through organ transplantation

Front 46

What are the clinical manifestations of EBV infection?

Back 46

Pharyngitis- painful and with lots of swelling
Lymphadenopathy in the neck
MALAISE
Splenomegaly
Mild hepatitis
No skin lesions and NO vesicles
Might have a maculopapular rash that comes and goes

Front 47

What are the complications of EBV infection?

Back 47

Compromised airways
Splenic rupture
Hepatitis
Pancytopenia- bone marrow suppression

Front 48

What are the clinical effects of EBV infections in immunocompromised hosts?

Back 48

Primary infection results in REALLY BAD mono; it can involve some organs and even result in some organ death

Lymphoma
Post-transplant lymphoproliferative disorder

Front 49

How do you diagnose EBV infection?

Back 49

Clinical picture is KEY!
Blood smear looking for atypical lymphocytes; these are activated T cells responding to B cells infected with EBV
Monospot test- you do an IgG antibody against sheep RBCs (cross-reactive antibody test); VERY HELPFUL
EBV antigen titers against various antigens (expensive)
EBV PCR of serum; ALWAYS done in immunocompromised hosts
Culture- NOT DONE

Front 50

What is the treatment for EBV infection?

Back 50

THERE IS NONE
A healthy host will end up doing fine
An immunocompromised host could end up being seriously hurt or die

Sometimes pregnazone is give to decrease airway swelling

Front 51

How can you prevent EBV infection?

Back 51

People are screened for EBV to know who is at risk

Front 52

What type of herpes virus is Cytomegalovirus?

Back 52

It is a beta herpes virus that infects monocytes.

Front 53

Who are the hosts for EBV infection?

Back 53

Fetuses can get it through the placenta if mom has a primary CMV infection; this is disastrous for the fetus

Healthy children and adults- they commonly get it and don't even realize they had it; only have a small fever and don't feel well for a few days

Immunocompromised hosts such as AIDS patients and transplant patients= MAJOR PROBLEM

Front 54

How is CMV transmitted?

Back 54

Direct contact is needed with the person who is shedding the virus from their mucous membranes. This occurs through the oral secretions, semen, or vaginal secretions.

Blood can also transfer it- screen blood donations

Organ donation, esp the kidneys, can relay this- screen them

Front 55

What are the clinical manifestations of congenital CMV infection?

Back 55

Microcephaly (small head), mental retardation (cranial calcifications), petechiae (not a rash due to CMV but a rash due to a low platelet count), jaundice, hepatosplenomegaly. All organs can be involved.

This is common when the mom has CMV during the baby's 1st trimester

Front 56

What are the clinical manifestations of mono-like syndrome caused by CMV in healthy people?

Back 56

Mono
Larger spleen
Fever
Malaise
Splenohepatomegaly
Looks like EBV mono so you must differentiate between the two

Front 57

What are the clinical manifestations of CMV infection in immunocompromised hosts?

Back 57

Primary infection is either acquired by the patient or obtained through an organ transplant. If a patient gets a primary CMV infection through organ transplant it is BAD!!! You prophylax EVERYONE in this situation.

These patients can also get secondary/reactivation infections

In AIDS patients you can get retinitis (people can go blind), or issues in the gut, kidney, lungs, etc...

Front 58

How do you diagnose CMV infections?

Back 58

PCR of the blood

Serology- looks for an IgM to IgG switch

Tissue histopathology distinctive "owl's eye" cells with viral intranuclear inclusions; you can make a diagnose if you see this

Culture- NOT USED

Front 59

What is the treatment for CMV infection?

Back 59

Ganciclovir and valganciclovir

Foscarnet or Cidofovir can be used but they are toxic

Front 60

How do you prevent CMV infection?

Back 60

Antiviral prophylaxis is used routinely in transplant patients (they can be on valganciclovir for months).

Currently there is NO vaccine

Front 61

What is Human Herpesvirus-6?

Back 61

Antibodies against this virus are found in almost everyone.

It causes roseola in infants resulting in a HIGH fever for a few days, then the fever stops and a rash appears.

It is a very common infection and is self-limiting; healthy people do fine.

It can cause disseminated infection and death in immunosuppressed patients.

Front 62

What is Human Herpesvirus 8?

Back 62

It causes Kaposi's sarcoma in AIDS patients and transplant recipients.