CYTOMEGALOVIRUS INFECTION

dr. Hendra Purnasidha Bagaswoto, M.Sc, Sp.A

SMF Anak RSUP Dr. Soeradji Tirtonegoro Klaten
 Sekitar 1-7% wanita hamil
Penyebab infeksi kongenital menderita infeksi CMV
(yang melibatkan SSP) primer setiap tahunnya
tersering
Human
cytomegalovirus
(CMV)
Komplikasi serius pada
30-40% infeksi CMV pada janin terjadi terutama pada
kehamilan ditransmisikan
ke janin trimester pertama dan awal
trimester kedua

Clin Microbiol Infect 2011:1285 - 93

 CONGENITAL VS PERINATAL

• CMV infection may be acquired in the

newborn via congenital and perinatal
 secondary to exposure to CMV- infected cervical
secretions during vaginal delivery or via ingestion of
CMV-infected breast milk  rarely result in significant
symtomps or sequele in term babies
 Premature babies appear to be at particularly high risk
for CMV-associated disease  septic appearance
 CONGENITAL VS PERINATAL
 Congenital CMV occurs transplacentally and may result in
symptomatic or asymptomatic infection in the neonate
 Difficult to differentiate whether CMV infection was
acquired congenitally or perinatally in infants more than 3
weeks of age  chorioretinitis, intracranial calcification,
microcephaly and hearing loss, are present
 MANIFESTASI KLINIS

Gestational Oligohidramnion, polihidramnion, prematuritas, IUGR

Mukokutaneus Jaundice, ptekiae, purpura, rash, blueberry muffin spot

Liver/ limpa Liver Jaundice, hepatomegali, splenomegali, hiperbilirubinemia

Skeletal Osteochondritis, periostitis, destructive lesions (75-100%),

pseudoparalysis parrot (12%)
Hematologi Trombositopenia
Neurologi Kalsifikasi periventrikular intrakranial, ventrikulomegali, mikrosefal,
kejang, hiper/hipotoni, sensoryneural hearing loss, retardasi mental,
gangguan motorik
Okular  NeurologiKorioretinitis,
dan Hepatosplenomegali
strabismus, atrofiadalah
optik gejala
Gastrointestinal yang paling seringpancreatitis
Enteritis, didapatkan pada CMV kongenital
simtomatik
Lain-lain Pneumonitis, dental defect, poor feeding
Hepatomegali akan menghilang dalam 1 tahun
l Antimicrob Chemot. 2009. 862-7
Ann. N. Y. Acad. Sci. 2010. 144-7
Buku Ajar Neurologi Anak. 2000
 OUTCOME CONGENITAL CMV

• About 10-20% of all children with CCMV infection,

symptomatic or not in the neonatal period will
exhibit neurological damage when followed up

• SNHL, mental retardation, seizures, psychomotor

and speech delays, learning disabilities,
chorioretini- tis, optic nerve atrophy, and defects
in dentition are the most common long-term
consequence
PREVALENSI WANITA HAMIL ????
HOW DO I GET
 Pencegahan infeksi CMV maternal saat
kehamilan

Kontak erat dengan anak < 2 thn dengan CMV, karena ekskresi
CMV pada saliva & urin bisa bertahan berbulan2 sampai
tahunan

Anak dapat menularkan pada anak lain (termasuk di daycare).

30% ibu serokonversi setelah anak berada 1 tahun di daycare

Perlu hygienisitas dan perubahan perilaku

(mis: sarung tangan, hindari co-sleeping)

• Edukasi infeksi CMV congenital dan pencegahannya kepada tenaga

medis (bidan, Sp.OG, Sp.A) dan seluruh ibu hamil (LoE 2b)
Rawlinson WD, et al., 2017
HOW DO I GET
 DIAGNOSIS

VIRUS ISOLATION CMV-DNA BY PCR

(URINE, SALIVA, (URINE, BLOOD, SALIVA
BRONCHOALVEOLAR, AND CSF)
BREAST MILK, CERVICAL
SECRETION CYTOMEGALOVIRUS
INFECTION

HISTOPATHOLOGY DEAFF(Detection
DETECTION of Early Antigen
CMV IgM (OWL’S EYE) Fluorescent Foci)
Virus can be isolated from urine, saliva, cervical
and vaginal secretions, semen, breast milk, tears,
blood products and transplanted organs.

Urine and saliva are the best specimens for culture.

Infants with congenital CMV infection may excrete
CMV in the urine for several years.

J Infect Dis 1975; 132: 472–3.

N Engl J Med 1980; 302: 1073–6.
Diagnosis pada neonatus

Gold
standard

 Diagnosis CMV kongenital juga dapat ditegakkan

dengan mendeteksi IgM spesifik CMV pada neonatus
dengan usia < 3 minggu namun
 Ig M spesifik CMV hanya terdeteksi pada 70%
neonatus terinfeksi CMV

Clin Microbiol Infect. 2011. 1285-93

Ann. N. Y. Acad Sci. 2010. 144-7
 Diagnosis

 Infeksi CMV kongenital dan didapat pada awal kehidupan

tidak dapat dibedakan kecuali virus terdeteksi pada 3
minggu setelah lahir

 IgM pada infeksi aktif dapat bertahan selama 4-12 minggu

→ IgM pasien terdeteksi pada usia 12 minggu, masih
mungkin infeksi didapat pasca lahir namun infeksi
didapat pada neonatus biasanya asimtomatik
 Diagnosis of CMV maternal infection

 A primary infection is confirmed by seroconversion or the

simultaneous detection of immunoglobulin M (IgM) and IgG
antibodies with low functional avidity.

 IgG antibodies persist for life. For the 1st weeks after primary
infection, the functional avidity of IgG class antibodies is very low
and rises to a peak in 4–5 mo.

 Testing for CMV is not routinely recommended for all women during
pregnancy or for newborn babies.

 CMV testing is currently recommended for pregnant women who

develop an acute viral illness or when ultrasound reveals a foetal
abnormality.

 Work in high risk settings (e.g. in child care centres) or have very
young children at home.

Nelson 18th , Textbook of Pediatrics

 LABORATORIUM
 Gold standard  isolation virus CMV pada urin / saliva
dalam minggu 1st – 3 rd
dalam kehidupan (Ross et al., 2011)
 PCR  sensitifitas 93% dan spesifisitas 100 % (Ross et al,
2011)
 SEROLOGI (ELISA) IgM sensitifitas 72,95 % dan
spesifisitas 62,06 % (Bathia, 2004)
 ANTIGENEMIA pp65:
- sensitifitas > 90% dan spesifisitas >90%. (Bij et al, 1988)
- sensitifitas 89,18% dan spesifisitas 100%. (Bathia, 2004)
 Tata laksana infeksi CMV

Foscarne
Gancyclovir t
(prodrug:
Valgancyclovir) Cidofovir

3
Terbukti efektif untuk
antiviral
Terbukti efektif untuk
CMV kongenital
CMV kongenital
sistemik
Ann. N. Y. Acad Sci. 2010. 144-7
 Hasil penelitian

Gancyclovir Plasebo

Perbaikan gangguan 21 dari 25 (84%) 10 dari 17 (59%)

pendengaran atau
tetap normal
(baseline-6 bulan)
Perburukan gangguan 5 dari 24 (21%) 13 dari 19 (68%)
pendengaran
(baseline-1 tahun)
Netropenia 29 dari 46 (63%) 9 dari 43 (21%)

Kesimpulan:
Terapi gancyclovir yang dimulai pada saat neonatus pada CMV
kongenital simtomatik dengan gangguan SSP terbukti mencegah
gangguan pendengaran yang signifikan sampai dengan 1 tahun
pasca terapi
Company Logo
 Pencegahan transmisi vertikal infeksi
CMV

• Pemberian Hiperimunoglobulin tidak

direkomendasikan secara rutin pada ibu
hamil dengan infeksi CMV primer untuk
pencegahan infeksi CMV kongenital,
karena bukti belum adekuat (LoE 2C)

• Pemberian rutin terapi antiviral tidak

direkomendasikan untuk mencegah infeksi CMV
kongenital, pada saat kehamilan (LoE3)

Rawlinson WD, et al., 2017

 Tatalaksana infeksi CMV fetal selama masa
kehamilan
• Pemberian Hiperimunoglobulin tidak
direkomendasikan secara rutin pada ibu hamil dengan
infeksi CMV primer untuk pengobatan infeksi CMV
fetal, karena bukti belum adekuat (LoE 2B)

• Pemberian rutin terapi antiviral

Ganciclovir, valganciclovir,
foscarnet, cidofovir
 kategori C
Aciclovir, valaciclovir,
famciclovir
 kategori B
tidak direkomendasikan untuk
mencegah/mengobati infeksi CMV
kongenital, pada saat kehamilan.
• Karena bukti keamanan dan
efektivitas belum adekuat (LoE 2C)
Rawlinson WD, et al., 2017
• Maternal CMV shedding in breast milk (BM) of seropositive
mothers can be detected in colostrum and ends about 3
months after birth
• Yasuda et al. showed that 21 of the 24 seropositive mothers
(87.5%) had detectable CMV DNA in their BM & most of the
BM samples became positive for CMV DNA 2 weeks after
delivery.
• Several other studies, rates of CMV virolactia among
seropositive women have been reported to be between 6.2%
and 80%
• In our study, 85 of the 200 BM samples (42.5%) and 80
of the total 178 BM samples (44.9%) from mothers of
CMV-IgG seropositive infants were CMV PCR positive
• Breastfeeding is not contra-indicated for infants born to
mothers who are who are seropositive carriers of
cytomegalovirus (CMV) (if the infant is term)

• Decisions about breastfeeding of very low birth weight

infants (birth weight 1500 g) by mothers known to be CMV-
seropositive should be made with consideration of the
potential benefits of human milk versus the risk of CMV
transmission

• Freezing and pasteurization can significantly de- crease the

CMV viral load in milk
• Heating at 62.5°C for 30 minutes or 72°C for 5
seconds (in thin film) destroyed viral infectivity
and late viral RNA  Unfortunately, destroyed
some of the biochemical and immunological
qualities of the milk

• Freezing at 20°C for 4–10 days did not effectively

destroy infectivity
TERIMA KASIH