Tmd175 Slide Congenital Cmv Infection

7/26/2019 Tmd175 Slide Congenital Cmv Infection

http://slidepdf.com/reader/full/tmd175-slide-congenital-cmv-infection 1/37

Congenital CMVinfection

Infectious and Tropical Pediatric Division

Department of Child Health

Medical Faculty, University of Sumatera Utara

Congenital CMV infectionCongenital CMV infection

• Approximately 0.15–2% of live births• Leading cause of sensorineural deafness

• Major cause of mental retardation, cerebral

• Approximately 10% death in symptomatic

newborns

• Lifelong habilitation for impaired survivors

• Fetus: Via placenta from the mother • Human milk

• Blood transfusion or an

How is CMV transmitted?

transplantation

• Children and adults: Mainly via bodily

fluids (esp. urine, saliva)(esp. urine, saliva)(esp. urine, saliva)(esp. urine, saliva)

Transmission of CMV through the placenta

barrier and infection of the fetus

Transmission of CMV through the placenta

barrier and infection of the fetus

Infected mother viraemia infection of placenta trophoblasts

Infection of fetal

Infection ofthe oropharynx

endothelial cells

Viralreplication intarget organs

(kidney)

Fetal viruria

rus namniotic fluid

Fetal viraemia

MATERNAL CMV INFECTIONDURING PREGNANCY

• Primary maternal infection leads tofetal infection in 30-50% of cases--10-15% of these have overt clinical

• Secondary maternal infection lesslikely to lead to fetal infection (1-2% )

but can do so and may lead to severedisease (Boppana et al, NEJM 2001, 344:

Rates of primary CMV infection

during pregnancy

Rates of primary CMV infection

during pregnancy

Study (Location)Study (Location)Study (Location)Study (Location) Rate as % of Rate as % of Rate as % of Rate as % of Rate as % of Rate as % of Rate as % of Rate as % of % cong CMV,% cong CMV,% cong CMV,% cong CMV,

PregnanciesPregnanciesPregnanciesPregnancies SeronegativesSeronegativesSeronegativesSeronegatives primary mat inf primary mat inf primary mat inf primary mat inf

Stern 1.1 4.1 45

(London)

rant cot an . .

Stagno (USA, 0.57 1.4 47

mid-income)

Ahlfors (Sweden) 0.32 1.4 43

Griffiths (London) 0.30 0.86 20

Symptomatic CongenitalCMV Infection

• Jaundice (67%)• Petechiae (76%)

• Microcephaly (53%)

• Chorioretinitis (20%)

• Seizure (7%)

• Fatal outcome (10%)

Boppana et al. (1999) Pediatrics 104:55

Sequelae of CongenitalCMV Infections

• Neurological sequelae are the mostcommon, and most severe:• >90% of newborns with symptomatic

con enital CMV infection have visual

audiologic and/or other neurologicalsequelae

• - 5-17% of newborns withasymptomatic congenital CMVinfection develop neurologicalsequelae (esp. hearing loss)

Sequelae of CongenitalCMV Infections

• Cranial CT is a good predictor ofsequelae in neonates with congenitalCMV infection

• Most common abnormalit is

intracerebral calcification (typicallyperiventricular)

• Boppana et al (Pediatrics 99:409,1997) reported that 90% of neonates

with abnormal CT scan developed atleast 1 sequelae

• Only 1/17 neonates with normal CThad IQ < 70

SEQUELAE OF SYMPTOMATICCONGENITAL CMV INFECTION

• Seizures

• Chorioretinitis

• Periventricular calcifications

• Sensorineural hearing loss

• motor deficits

CHORIORETINITIS

Congenital CMV

CHARACTERISTICS ASSOCIATED WITH

INCREASED RISK OF SEQUELAE

• Primary maternal infection

• Symptomatic congenital CMV

• Presence of neonatal neurological

abnormalities

• Abnormal head CT scan

• Chorioretinitis in the newborn

CLINICAL IMPACT OF

CONGENITAL CMV INFECTION

Frequency of sequelae

Symptomatic (7%) Asymptomatic (93%)

Infant death 10% 0

Hearing loss 60% 7 –15%Mental retardation 45% 2 –10%

Cerebral palsy 35% <1%

Chorioretinitis 15% 1 –2%

Diagnosis of CongenitalCMV Infections

• Isolation of CMV from urine or otherbody fluid (CSF, blood, saliva) in thefirst 21 days of life is considered

• Serologic tests are unreliable; IgMtests currently available have bothfalse positive and false negative

results• PCR may be useful in selected cases

Detection: screening for maternal

CMV infection

Detection: screening for maternal

CMV infection

• CMV IgG antibody – sensitive and specific

screen for past infection

specificity

• Antibody avidity testing can increase accuracy

of detection of primary infection

• No test for immune mothers who will transmit

Advanced CMV diagnosisAdvanced CMV diagnosis

IgM confirmation by Western blot

Isolation of the virus from urine,

saliva and blood

A confirmatory test for CMV-IgMA confirmatory test for CMV-IgM

New immunoblotNew immunoblotNew immunoblotNew immunoblot

1) Contains both structural

and nonstructural proteins

Purified

native

roteinsVp65

µµµµ

be confirmed withrecpUL32

3) Agrees with consensus of

different ELISAs4) Is easy to standardize

5) Is easy to interpret

Recombinant

proteins

x ( % )

Congenital CMV infectionsCongenital CMV infectionsLow IgG avidity is linked to primaryLow IgG avidity is linked to primaryLow IgG avidity is linked to primaryLow IgG avidity is linked to primary

infectioninfectioninfectioninfection

Weeks after beginning of symptoms

A v i d i t y i n

5 10 15 20 25 30 35

Evaluation of mothers at risk of

transmitting CMV to the fetus

Evaluation of mothers at risk of

transmitting CMV to the fetus

Positive Negative

Test for IgG antibodyat first prenatal visit

Negative,

no further testing

Positive =

primary infection

Test for IgM Antibody

IgG Positive =

Seroconversion

Negative,

no further tests

Retest later

Refer for prenatal diagnosis

Intervention: using results of maternal

screening to prevent congenital CMVdisease

Intervention: using results of maternal

screening to prevent congenital CMVdisease

Possible interventionPossible interventionPossible interventionPossible intervention• Counsel regarding

prevention (seroneg

ProblemsProblemsProblemsProblems• No proven means to

prevent maternal

• Use prenatal diagnosis,

abort infected fetus

• Use antivirals to prevent

or treat fetal infection

n ec on

• ~75% infected fetuses

will be normal

• No available antiviraltreatment for prenatal

Antiviral Therapy

Infection?

• 100 Neonates enrolled to receive 6 weeks of IVganciclovir (6 mg/kg/dose q 12 hours)

Phase lll randomized trial of ganciclovir for

symptomatic congenital CMV infectionsinvolving the CNS

untreated)

• Hearing Improvement was more likely in the GCVtreated group at 6 and 12 mos (OR 4.31, 4.03)

• 29/46 (63%) GCV recipients experiencedneutropenia, compared with 9/43 (21%) untreatedcontrol patients

Kimberlin et al, J. Pediatrics,143:17,2003

USE OF GANCICLOVIR IN SYMPTOMATICCONGENITAL CMV INFECTION

• 12 newborns treated for 2 weeks with 5mg/kg/day or 7.5 mg/kg/day + 3 months of 10

mg/day 3x/week

• Abnormal liver and haematologic function

appeared to clear faster with higher dose

• Although outcome appeared better with

higher dose, CNS sequelae appeared in bothgroups

from Nigro et al, J Pediatr 1994; 124: 318

A PHASE II STUDY OF GANCICLOVIR IN 47

NEWBORNS WITH SYMPTOMATIC CONGENITAL

CMV INFECTION

• Patients with CNS disease treated with8mg/kg/d or 12mg/kg/d iv for 6 weeks

• 19 % of participants had neutropenia

• 12 mg/kg reduced viral shedding; sheddingreturned when drug was discontinued

• 3 patients had improved hearing at 6

months; 25 had abnormal hearing

from Whitley et al, J Infect Dis, 1997; 175: 1080

Antiviral Therapy for

Congenital CMV Infection?

• Ganciclovir has been shown to be effectivetherapy for certain CMV infections in

immunocompromised hosts (e.g., retinitis

or enterocolitis in HIV-infected atients

• Neonatal experience with ganciclovir islimited, the toxicity of the drug is

considerable (e.g., platelets, neutrophils),

and oral bioavailability unreliable

Ganciclovir Therapy for

Congenital CMV? 2006

• A six week course of IV ganciclovir mayreduce the rate of long-term hearing loss inneonates with symptomatic CMV infection

• However, this regimen is associated withsignificant toxicity, long-term followupdata are lacking, and the optimal durationof therapy (if any) is unknown

• Potential benefits of antiviral therapy for

asymptomatically infected neonates maybe greater

Antiviral Therapy for

Congenital CMV? 2006

• Current role for IV ganciclovir uncertain:therapy “may be considered for patientswith symptomatic congenital CMV diseaseinvolving the CNS” (Kimberlin et al, 2003)

• 2006 Red Book says that it “is notrecommended routinely because ofinsufficient efficacy data”

• ?? Treatment of neonates with worsening

retinitis or hepatitis, severe pneumonia, orpersistent severe thrombocytopenia ??Duration of therapy ??

Prevention of CMV

Infections?

• A vaccine to prevent CMV infections

is desperately needed

• Trials of candidate vaccines areunderway

• CMV Vaccine development a “Level

One” priority !!

How is congenital CMV

prevented?

• Many different ways to

prevent CMV

• Our approach:

• Hygiene, especiallyHygiene, especiallyHygiene, especiallyHygiene, especiallyhandwashing handwashing handwashing handwashing

• Education about CMVEducation about CMVEducation about CMVEducation about CMV

and how to prevent itand how to prevent itand how to prevent itand how to prevent it

through hygiene through hygiene through hygiene through hygiene

How do we communicate

this message?

The End

Tmd175 Slide Congenital Cmv Infection

Documents

Transcript of Tmd175 Slide Congenital Cmv Infection

The Healthcare Cost of Symptomatic Congenital CMV Disease ...

CMV Newsletter

Risk of Intrauterine Growth Restriction Among Infants With ... · Risk of Intrauterine Growth Restriction Among Infants With and Without Congenital Cytomegalovirus (CMV) Infection

Tmd175 Slide Malaria

CMV Studies

Tmd175 Slide Laboratory Diagnostic Hiv and Aids

Long-Term Hearing Outcomes of Symptomatic Congenital CMV ... · Six Months versus 6 weeks Valganciclovir (VGC) for infants with Symptomatic CMV • Confirmation CMV from urine or

Tmd175 Slide Pharmacology of Antifungi - Anthelminthics - Antiprotozoal

What Child Care Providers, Teachers and Pregnant Women ... · Child Care and CMV Approximately 0.1% of babies, or 4,000 babies, are born disabled by congenital CMV every year in the

EI After NICU Discharge: “Where Should We Begin? · 2020. 12. 17. · –Congenital infections: CMV, Herpes, Rubella, Syphilis, toxoplasmosis 2007 Position Statement: Principles

CMV 101 Congenital Cytomegalovirus Infection The Elephant ...

Burden of Congenital Cytomegalovirus (CMV) Infection and ......2018/09/13 · Goderis et al. Hearing Loss and Congenital CMV Infection: A Systematic Review. Pediatrics 2014 Dollard

CMV Diagnosis and Management in children - Home … findings NEONATE Congenital, intrapartum and postnatal routes of infection Postnatal Cervical secretions during vaginal delivery

CMV genomics in congenital infections: relevance to ...

GLOBAL RESPONSE TO CONGENITAL CYTOMEGALOVIRUS (CMV) AWARENESS THROUGH A PEDIATRIC HOSPITAL BLOG WEBSITE Gail J. Harrison, M.D., Cara C. Lyons, Michael.

Congenital CMV 101: From Prevention to Treatment...2018/01/26 · Congenital toxoplasmosis (toxo) Congenital rubella syndrome Congenital cytomegalovirus (CMV) 15 29 13 16 42 80 83

Symptomatic congenital CMV infection after recurrent ... · Symptomatic congenital CMV infection after recurrent ... or tumor. When mild signs and ... genital CMV infection in populations

RNASET2-deficient leukoencephalopathy mimicking ......LETTER TO THE EDITOR Open Access RNASET2-deficient leukoencephalopathy mimicking congenital CMV infection and Aicardi-Goutieres

WHAT IS CMV?...WHAT IS CMV? CMV IS A COMMON VIRUS WHICH CAN INFECT PEOPLE OF ALL AGES. CMV is the most common cause of non-hereditary congenital hearing loss. A pregnant mother who

Cytomegalovirus (CMV) and pregnancy eng 0310.pdf · 2.3. Retrospective diagnosis of congenital CMV infection in children 17 2.4. Prevention of congenital CMV infection 17 2.5. Treatment