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31

CMV EPi

Infects humans of all ages

Seroprevalence increases with age, 50% by 30, 60-80% by 60

Prevalence peaks 2 - 5 (day care or school) and young adults (sexual)

Crowded living is risk factor

Routes of infection
- oral 30-70% infection rates in daycare
- sexual transmission
- blood transfusions (now blood depleted of WBC)
- organ transplantation - CMV-negative recipients at greatest risk for disease

32

Epidemiology of congenital CMV

C in torch

Leading infectious cause of birth defects

Primary: maternal infection poses much greater risk to fetus than reactivation

Infection in early pregnancy (first 12 - 16 weeks) poses highest risk to developing fetus

Infx in mother almost always asymptomatic, no warning the fetus is at risk

CMV infection detected in 1% of newborns and is most common identified infectious cause of birth defects

Risk of CMV transmission to fetus and rate of symptomatic fetal infection are much Ghiberti with primary maternal infection

In primary infection 90% of babies become infected and of those, many have congenital abnormalities

33

Clinical manifestations: congenital CMV

Slide 37

Petechial rash - blueberry muffin baby

CMV retinitis

Brain malformations
- periventricular calcification
- enlarged ventricles
- microcephalic
Leads to seizures cognitive deficits

Jaundice with hepatosplenomegaly

Hearing loss - can occur at birth if symptomatic CMV, can occur over first several years if infx asymptomatic

Even if no symptoms at birth can develop sensorineural hearing loss, visual impairment, psychomotor and or intellectual disabilities later in life

34

CMV in immunocompromised patients pic slide 38

HIV: reactivation with CD4 < 50 less common with HAART

Tranpslants

Any other immunosuppressed

Can get bad viral pneumonia, retinitis
Esophagitis with round solitary ulcer

35

CMV mononucleosis

Slide 39

Mononucleosis like syndrome

79% EBV, 21% CMV

Frequent manifestation of priamry CMV infx in young adult

Syndrome: fever 2 - 4 weeks, fatigue, mild h epatitis, lymphocytosis and small % of atypical lymphocytes in blood
- exudative pharyngitis frequently absent
- lymphadenopathy less common

Heterophile antibody negative
- IgM class antibody that agglutinate RBC from certain species like sheep

36

Epstein Barr Virus

Infects and transforms B lymphocytes
- binds to cd21 on B cells, some become latently infected
- also infects epithelial cells in oral cavity

37

EBV diseases

Mono

Cancer: burkitts lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma (B cells affected)

Lymphoproliferative disorders (psottransplant lymphoproliferative disease, oral hairy leukoplakia)

Seroprevalence 50% by age 5, 90 by age 20

Spread by oral secretions - the kissing disease

Often asymptomatic can be shed for years

38

EBV clinical symptoms: IM

Slide 42

Classic triad
- lymphadenopathy
- splenomegaly - avoid contact sports
- exudative pharyngitis

Fever malaise and rash can appear if mistakenly treated with ampicillin

War b/w infected B cells and the T cell response
- pharyngitis due to respond to infected epithelial cells
- fatigue due to energy needed to power robust T cell response so you are tired al the time

39

EBV lab finding and diagnosis

Slide 43

Symptoms

Peripheral blood smear: see atypical lymphocytes (Activated T cells, called Downey cells)

CBC; activated T cells, can comprise up to 80% of total WBC

Serology: heterophile AB positive (monospot test) - Ab that cause sheep red cells to clumb

EBV: heterophile + mono
CMV: heterophile - mono

40

EBV associated malignancies and lymphoproliferative disorders

slide 44

Burkett lymphoma
- jaw tumor of African children, EBV--> chromosomal translocation leading to activation of cmyc oncogene

Other lymphomas- Hodgkin, T cell head and neck, CNS (in HIV infected)

Nasopharyngeal carcinoma - cancer of epithelial cells common in males of Chinese origin

Post-transplant lymphoproliferative disorder (PTLD) - occurs in setting of immunosuppression associated with transplantation, can range from B cell expansion to lymphomas

Oral hairy leukoplakia**: excessive wart like growth of papillae on tongue, in advanced HIVi and othe rimmunosuppressed
- one of most common virally induced oral diseases in HIV patients
- cant be scrapped off like oral thrush

41

HHV - 6 - Roseola

Most common cause of roseola infantry
- rose red rash of children (sudden rash - exanthum subitum), virtually all children infected by 4 yo
- HHV causes ~10% roseola

Undifferentiated febrile illness without rash
- HHV6 accounts for 5 - 25% of ED visits for fever in infants

HIGH FEVER febrile seizures common with roseola
- responsible or 1/3 febrile seizures in children up to 2 years old

Lymphotropic virus (infects CD4+ T cells in particular); causes transient immunosuppresion and can exacerbate disease with other viruses

42

HHV6 exanthum subitum


Slide 47

Abrupt onset of high fever (104) that persists 2 to 5 d

Child is normally fussy and irritable

Rash develops coincidental with abatement of fever
- rash first appears on neck, behind ears and on back
- it blossoms
- spread to trunk and abdomen
- some rash on face and arms and legs
- maculopapular in appearance, not itchy or uncomfortable
- no treatment no vaccine

43

HHV 8 (KSHV)

Slide 49

Cell tropism for CD19+ B cells, macrophages, endothelial cells

Painless purplish macules, nodules or plaques

Tumors mostly on skin, but can involve any organ

Pathology shows spindle shaped tumors with red cells

44

LAb diagnosis of Herpes Viruses

No point of care ot true rapid tests

For HSV1/2 and VZV molecular is recommended

Serology still primary method for otherwise healthy populations for EBV

For CMV and HSV1/2 serology is limited to pregnant women with fetal abnormalities requiring TORCH investigation or for donor/recipient screening prior to transplant

Old fashioned: culture
Tzanck test (look for multinucleated cells in skin vessels)