Cytomegalovirus

Herpes

==Cytomegalovirus:==

* Belongs to the _______ virus family
* Exposure increases with age

Saliva Urine Cervical secretions

==Transmission of CMV occurs when coming into contact with the virus through:==

* _______
* Blood
* _______
* Breast milk
* _______ _______
* Semen

36

91

In the US \~ ___% of children 6-11 years old are CMV+

By 80 years old seropositivity increases to ___%

no

mild

Most healthy children and adults infected with CMV will have ___ symptoms or might develop only a ______ mononucleosis-like illness

reactivate

mother

==Once infected with CMV:==

* Virus can _________, but healthy immune system prevents this in most cases
* A _________ carrier can transmit virus to fetus which causes developmental issues in infant.
* Acute symptoms at birth
* Permanent disabilities
* Both

\

In-utero

prenatal

==Diagnosis of Congenital CMV:==

either _________ through amniocenteses OR in the _________ period for from direct assessment of the infant in the postnatal period.

21

Testing for congenital CMV must be completed in ____ days from birth otherwise it is IMPOSSIBLE to distinguish congenital from acquired.

amniocenteses

* A test offered during pregnancy to check if a baby has a genetic or chromosomal condition.
* It involves removing and testing a small sample of cells from amnioticfluid (the fluid that surrounds the baby in the womb)

CMV

21

___ is the most common intrauterine infection in the US with \~ __% of pregnant women being symptomatic (like mononucleosis)

universal

US

_________ = 0.64-.70% of live births

_________ = 0.2 to 2.2% (congenital) with estimated 0.5 to 1.0 newborns infected in the prenatal period

Symptoms

* Generalized petechiae
* Hyperbilirubinemia
* Hepatosplenomegaly
* Purpuric rash (3-10mm)
* Microcephaly
* Seizures
* Focal or general neurologic deficits
* Retinitis
* Intracranial calcifications

**F**ocal/general neurologic deficits

**H**yperbilirubinemia

**G**eneralized petechiae

**S**eizures

**H**epatosplenomegaly

**R**etinitis

**I**ntracranial calficiations

**M**icrocephaly

**P**urpuric rash

CMV Symptoms:

Fat Hairless Gumbo SHRIMP

(FHGSHRIMP)

90 to 95

Most aka ___ to ____% of infants w/ congenital CMV will **NOT** have any clinically significants apparent symptoms at birth.

No

Are newborns screened from CMV in the US?

blood spot

It is possible to ID children with CMV by obtaining a newborn _________ _________ for analysis

urine or saliva

Typically diagnosed through detection within _________ or _________ within the first 3 weeks of life (21 days)

mother exposure during pregnancy

What would lead to testing at birth?

referred NBHS

Utah, Illinois, Connecticut, Iowa, New York, and Virginia participates in a screening for cCMV following a _________ _________

Sequela

Any abnormal condition that follows and is the result of a disease, treatment, or injury, such as paralysis after poliomyelitis, deafness after treatment with an ototoxic drug, or scar formation after a laceration

Sequela

Both symptomatic and asymptomatic infants may later develop _________.

* More severe and frequent in the symptomatic infants.

CMV Sequela

* SNHL
* Retinitis
* Mental Retardation
* Microcephaly
* Seizure
* Cerebral palsy

10 to 15

SNHL is most common sequela of cCMV

__% to __%

30 to 50

HL occurs in __% to __% of children with **symptoms** at birth

8 to 12

HL occurs in in __% to __% of children who are **asymptomatic** at birth

Mild to profound

Unilateral or bilateral

fluctuating progressive

* No predictable audiometric configuration
* _________ to _________
* Laterality: Unilateral or bilateral
* Some involve 4-8k Hz only - others all frequencies are involved
* HL may be _________ and/or _________
* Develop within the first years for some

50

\~ __% of the cases of CMV related HL are late-onset/and/or progressive.

__(Not always detected at birth…. ~7% of cCMV cases were detected)__

21

25

Recent estimates:

* __% of Hl at birth is cCMV related
* Late onset HL = __% of HL in children by age 4 likely CMV related.

(Suggest that CMV is the leading non genetic cause of HL in Peds for the US)

Pathogenesis

==Animal and human studies on temporal bone suggest:==

* CMV may be present in the **epithelium** and **neural cells of the inner ear.** 
* Cause U__amage by virus-mediated damage to neural cells and/or cause inflammatory responses resulting in damage__ to the auditory apparatus therefore causing HL
* Doesn’t explain late onset or progressive loss!!!

audiologic evaluations

changes

JCIH treatment:

* Babies ID’s early need impediment and more frequent _________ _________ to allow close monitoring
* _________ in hearing should be considered in treating the HL
* May program HAs more often.
* Communication methods/needs to accommodate a changing HL

regular

vision

CDC recommendations:

* _________ hearing checks
* routine _________ screening
* Developmental milestone checks

Multi-disciplinary team

* Infectious disease specialists
* Otolaryngology
* Neurology
* Primary care/Pediatrician
* Audiology
* Opthamology

\

(Dahle et al., 2000)

Longitudinal study (24 years)

860 children with CMV were studied                   (651 asymptomatic, 209 symptomatic)

Test battery:

* ABR (chloral hydrate)
* Air and bone conduction if AC>25 dBnHL
* Tympanometry
* VRA (from 9 months to 3 years old)

Longitudinal study outcomes:

* Bilateral moderate to severe SNHL                       (equally severe in asymptomatic patients)
* Delay onset of hearing loss                                    (wide age range: 6 months to 16.4 years)
* Gradually progressive                                            (sometimes sudden decreases reaversed w/ steroids)
* Threshold fluctuations without progression of their loss (may experience improvement)
* Low frequencies (250 and 500 Hz) less stable than higher frequencies

flat

high

Audiometric pattern:

* _________ hearing loss was the predominant threshold configuration
* Initially by a sloping _________-frequency loss may gradually progress to include the lower frequencies
* Upward sloping (symptomatic)
* Downward sloping (asymptomatic)

Symptomatic audio

upward sloping

Asymptomatic audio

downward sloping

laboratory

CNS

growth and development

==Medical management/evaluation:==

* A general medical examination
* _________ procedures to document the diagnosis of CMV
* An examination to determine damage to the _________ (EEG)
* Assessment of the child’s _________ and _________.

antiviral treatment

==Medical management==

Prolonged _________ _________ for cCMV with SNHL showed improvement (58-79%) in hearing status and no deterioration in unaffected ears at baseline.

==Pharmacological Treatment:==

==Ganciclovir==

(inhibitor of viral DNA synthesis) **antiviral drug may have a beneficial effect in newborns affected** by severe congenital CMV infection such as preventing hearing deterioration

* Maintained normal hearing or stops the progression of hearing loss in 76% of infants when baseline compared to tests 6 months later
* Significant side effects including __**bone marrow suppression**__, therefore if severe-profound hearing loss is present at birth, the doctors will likely not administer Ganciclovir due to physical risk and limited benefit in terms of hearing restoration.

6 to 12

Hearing eval:

* Audiogram
* ABR
* OAR
* Tympanometry

If suspected a child should be routinely monitored:

* Child should be assessed every __ to __ months

Speech and language therapy

* Must be tailored to needs

Appropriate counseling for the parents!

vaccine

No approved _________ for prevention of CMV

Hand washing

_________ _________ is the #1 preventer

(esp when pregnant or trying to get pregnant)

day care

mothers

toddlers

_________ _________ providers and _________ of _________ are at the highest risk of contraction

Young children

This population tend to secrete the virus in their saliva and urine for many months following the first infection.

\[typically asymptomatic\]