Definisi

T= TOXOPLASMA GONDII
O=OTHERS (HEPATITIS B, SIFILIS,

VARICELLA ZOSTER, HIV, PARVO VIRUS)

R=RUBELLA
C=CITOMEGALOVIRUS
H= HERPES SIMPLEKS VIRUS
HBV virus besar, tidak mampu menembus sawar
darah plasenta, penularan lewat perdarahan saat
kelahiran bayi/amniosintesis

RUBELLA
DEFINISI
Rubella (campak jerman / campak 3 harian)
penyakit demam akut yang ditandai oleh ruam
kulit
Merupakan salah satu dari enam infeksi yang
ditandai dengan ruam kulit( measles, scarlet
fever, rubella, duke`s disease, fifth
disease/erytema infectiosum, and roseola,)
Ringan
Kehamilan : Keguguran, malformasi kongenital

RUBELLA

Rubella mean small red

Spherical,
70 nm in diameter,
nucleocapsid has 42
capsomeres.
Genome: positive-sense,
single-stranded RNA, 1112
kb in size.
Envelope.
Three or four major
structural polypeptides, two
glycosylated.
Replication: cytoplasm.

Morfologi
Famili togaviridae
Genus Rubivirus
Manusia merupakan satu-satunya inang
ditularkan melalui direct droplet contact from

nasopharyngeal secretions, dimulai dengan

traktus respiratorius
Virus bereplikasi di kelenjar limfe upper
respiratory tract menyebar secara
hematogen
Congenital infection terjadi selama maternal
viremia menembus placenta.

Patogenesis
Maternal viremia infection of the

placenta and fetus.

The rubella virus is generally
noncytolytic, allowing cell survival but
resulting in persistently infected cells
with a decreased growth rate and
shortened survival time.
The growth rate of infected cells is
reduced, resulting in fewer numbers of
cells in affected organs at birth.
Rubella virus particles may be retained
in secluded sites

PATOGENESIS
they can undergo recurrent periods of

increased virus production and replication.

Before the development of the maternal
immune response, the virus spreads through
the bloodstream and may affect multiple
maternal tissues, including the placenta.
vascular hypoxia secondary to the rubella
infection of endothelial cells. Damage
endothelial cells small blood vessel
thrombosis.
Intrauterine infection with rubella chronic
persistence of the virus in the newborn.
At birth, detectable in pharyngeal
secretions, multiple organs, cerebrospinal
fluid, urine, and rectal swabs.

MANIFESTASI
KLINIK
Postnatal biasanya
asymptomatic
Anak-anak biasanya gejala prodromal berupa

malaise, fever and anorexia.

Dewasa umumnya lebih parah daripada anak-anak
Klassic rubella low grade fever,
lymphadenopathy daerah posterior cervical
dan occipital , and rash
Rash terjadi setelah 14 days setelah fase invasi virus,
ujud kelainan kulit berupa erythematous,
maculopapular dimulai dari wajah kemudian
menyebar ke badan selama 3 hari
Kadang dijumpai artritis dan pernah dilaporkan
adanya trombositopeni

CONGENITAL RUBELLA SINDROME

(CRS)
Pertama kali dideteksi tahun 1941 pada

kejadian epidemik di Australia

Derajat kerusakan yang ditimbulkan pada
janin tergantung pada trimester berapa ibu
terinfeksi
Pada trimester awal dapat timbul defek
pada 80-85% kehamilan, abortus spontan
terjadi pada 20 % kasus

MALFORMATION IN CONGENITAL
RUBELLA SYNDROME
Brain (small brain size, microcephali,

intracranial calcification)
Eye ( catararact, microphtalmia)
Ear ( hearing defect, organ of corti affected
Heart (patent ductus arteriosus, patent
interventricular septum)
Liver, Spleen (hepatosplenomegali,
trombocytopenic purpura, anemia)
General (low birth weight, increased infant
mortality)
Most of these complications develop in infants
born to mothers who acquire rubella infection
during the first 16 weeks of pregnancy.

DIAGNOSIS
Rubella virus tumbuh lambat pada kultur jaringan,

efek CPE rendah jarang dipakai

EIA (Enzyme Immuno Essay) dijumpai Ig M yang
dapat dideteksi 4 hari setelah terjadi rash kulit
Ig G pada penderita biasanya bertahan seumur hidup
Deteksi Akut Rubella jika ditemukan :
Kenaikan 4 x titer antibodi IgG titer antara keadaan

akut dan fase konvalescent pada serum pasien

(Serum sebaiknya diambil antara hari 7-10 setelah rash
dan diulang 2-3 minggu kemudian)
Adanya IgM spesifik rubella
Isolasi virus melalui kultur jaringan positif
Rubella(sekret nasal, blood, throat, urine, or
cerebrospinal fluid (CSF),umumnya virus diisolasi dari
sekret pharyng 1 minggu sebelum rash dan 2 minggu
setelah rash)

Polymerase chain reaction (PCR)

TERAPI
Tidak ada terapi yang spesifik self

limiting disease
Terapinya bersifat suportif
Vaksinasi untuk pencegahan penyakit
Wanita hamil merupakan kontra indikasi
vaksin
Wanita yang sudah divaksinasi dianjurkan
menunggu selama 3 bulan sesudah
vaksinasi untuk hamil

CITOMEGALOVIRUS
Cytomegalovirus (CMV) menginfeksi manusia

semua umur, semua etnik, berbagai tingkat

sosial ekonomi, serta berbagai latar belakang
sosial budaya yang berbeda
Umumnya infeksi bersifat asimtomatik
Infeksi serius pada janin, neonatus, maupun
penderita imunocompremized

Transmisi
Transmisi melalui contact with a person

excreting the virus in saliva, urine, or bodily

fluids.
Congenital CMV infection umumnya dihasilkan
dari transplacental transmission
Virus juga dapat ditularkan melalui
transmitted sexually, via organ transplants,
transplacentally, via breast milk, dan pernah
dilaporkan via blood transfusion (meskipun
jarang).

Cmv
Cytomegaloviruses are ubiquitous herpesviruses

that are common causes of human disease.

The name for the classic cytomegalic inclusion
disease derives from the propensity for massive
enlargement of cytomegalovirus-infected cells.
Icosahedral virus
Lipoprotein envelope, derived from the nuclear
membrane
Genome: linear, ds DNA (240 kbp) is significantly
larger than that of HSV.
Replicate in the nucleus
Single serotype
Replikasi sangat lambat, butuh beberapa hari sampai beberapa

minggu untuk menghasilkan CPE yang tampak pada cell lines

CMV Inclusion Bodies

Intranuclear and oval

owls-eye shape

CLINICAL
MANIFESTATIONS
Congenital infection
IUGR, low birthweight
microcephaly, Hidrocephalus
intracranial calcifications, chorioretinitis,

mental and motor retardation, sensorineural

deficits, hepatosplenomegaly, jaundice,
hemolytic anemia, and thrombocytopenic
purpura. (Fowler and associates, 1992).
Brain (small brain size)

Ventriculomegaly
and calcifications
of congenital
CMV

Perinatal infection
Transmisi terjadi dari maternal secretions,

ingestion of breast milk, atau dari blood

product transfusions
Infeksi tampak setelah usia 3 minggu atau 3
sampai 6 bulan
Seringkali bersifat asymptomatic, kadang juga
menghasilkan gejala yang bervariasi
Sindroma umumnya berkaitan dengan
hepatosplenomegaly, abnormal blood counts
dengan lymphopenia, neutropenia and
thrombocytopenia, abnormal transaminases

Acquired CMV infections

Umumnya asymptomatic pada anak-anak serta

usia dewasa
Gejala yang timbul biasanya berupa fever, fatigue,
pharyngitis, adenopathy, dan hepatitis
Headache, abdominal pain dengan diarrhea,
arthralgias, dan rash pernah dilaporkan
Laboratory abnormalities dapat berupa
thrombocytopenia serta peningkatan
transaminases

DIAGNOSIS
isolation virus dari urine atau saliva 3 minggu

pertama post invasi virus

Culture Virus (+) 1 3 hari setelah incubation
CPE bersifat khas berupa inklusi intra nuklear,
inklusi perinuklear yang membesar(sel-sel
citomegalik/ owl`s eye)
Deteksi DNA pada urine dan serum dengan
menggunakan polymerase chain reaction (PCR)
CMV IgM yang meninggi sering menunjukkan
infeksi akut tetapi harus dikonfirmasi dengan
menggunakan viral culture
Ig G positif yang dapat ditransfer via plasenta
dari ibu kepada janin
Terdapat Ig M antibodi, serta terdapat kultur
positif pada urine dan saliva

TREATMENT
Self limiting disease
Pada kasus yang berat Ganciclovir (5

mg/kg per dose IV tiap 12 hours untuk 2-3

minggu),
Other regimens :
Foscarnet ditambahkan jika terjadi gangguan

fungsi renal
Cidofosir
Valganciclovir

PREVENTION
Personal protective
Hygienic perseorangan
Menghindari mencium neonatus atau anak dekat

pada mulut
Tidak bergantian alat-alat makan dengan anakanak
Sementara menghindari hubungan intim pada
pasangan yang sedang terinfeksi

Blood products and organ donors

Skrening darah dan organ donor dari CMV

Vaccines

PARVO VIRUS
MORFOLOGI
Virus DNA single stranded
Famili Parvoviridae
Bentuk ikosahedral
Non envelop virus

EPIDEMIOLOGI-MANIFESTASI
KLINIK

Virus ditransmisikan melalui doplet infection

Virus pertama kali bereplikasi di nasofaring
kemudian spreding viremia di bone narrrow
Virus ini menempel erytroid precusor sel di
summsum tulang litik dari sel anemia hebat
Kemudian terjadi flu like sindrom host
antibodi immune complekskemudian terjadi
spreding dari rash yang dimulai di pipi (Slapped
cheek) ekstremitas
Infeksi selama kehamilan virus menembus
plasenta dapat terjadi defec pada janin,
hidrops fetalis, dapat terjadi keguguran

HERPES VIRUS

HERPES SIMPLEK--MORFOLOGI

Famili herpesviridae ( together with varicella

zoster, Epstein-barr virus, Cytomegalovirus)

Virus DNA
Mempunyai selubung
Bentuk ikosahedral dengan 162 capsomer

Herpes Simplex
Virus
dsDNA genome
Icosahedral capsid
Enveloped; nuclear

membrane
HSV-1 and -2

Giant cell induced by

HSV

Neonatal Herpes Simplex

The baby is usually infected perinatally during passage through

the birth canal.

Premature rupturing of the membranes is a well recognized risk

factor.

The risk of perinatal transmission is greatest when there is a florid

primary infection in the mother.

There is an appreciably smaller risk from recurrent lesions in the

mother, probably because of the lower viral load and the presence
of specific antibody.

The baby may also be infected from other sources such as oral

lesions from the mother or a herpetic in a nurse.

EPIDEMIOLOGI
Manusia merupakan satu-satunya inang
Virus sering menjadi laten dan recuren
Neonatal herpes terjadi 1 dari 5000 kelahiran

di USA ( Indonesia unknown)

Sebagian besar infeksi pada neonatal terjadi
pada saat melalui jalan lahir ibu

MANIFESTASI
KLINIS

Dibagi menjadi herpes simpleks tipe 1 dan

Herpes simpleks tipe 2
Herpes simpleks tipe 1
Mengenai labial (fever, pembesaran
kelenjar submandibular, nyeri telan,
gingivostomatiti dengan ulcer ataupun
vesikel
Herpes simpleks tipe 2
Mengenai genital (vesikel/ulcer pada
cervik, vulva ataupun perineum pada
wanita maupun penis pada laki-laki

Bentuk infeksi
Infeksi primer
HSV 1
Virus menembus kulit/mukosa setelah menyebar
via pernafasan atau kontak air liur. Replikasi
awal di tempat infeksi lalu menginvasi ujung
saraf lokal dan dibawa melalui aliran aksonal
retrograd ke ganglion radiks dorsalis
HSV 2
Sama dengan HSV 1 hanya ditularkan via genital

Transplacental infection of the fetus is rare during

pregnancy. Intrauterine HSV infection has

uncommonly been associated with skin lesions,
chorioretinitis, microcephaly, hydranencephaly ,
and microphthalmia.
While primary HSV infections in the first trimester
are associated with higher rates of spontaneous
abortion and stillbirth, infection later in
pregnancy appears more likely to be associated
with preterm labor or growth restriction.
Of greatest concern is the risk of primary
infection acquired at birth which could lead to
herpetic meningitis. The infection rate is 34 to
80% for infants born vaginally during a primary
infection.

Cesarean section is recommended for all women

in labor with active genital lesions or prodromal

symptoms such as vulvar pain.
For patients with preterm premature rupture
of membranes remote from term complicated by
recurrent maternal HSV infection, the risks of
prematurity should be weighed against the
risk of neonatal HSV disease in considering
expectant management. Prophylactic treatment
with antiviral agents (eg, acyclovir) may be
considered if expectant management is chosen.

DIAGNOSIS
Perubahan histopatologi yang terjadi meliputi

giant cell dengan inklusion bodies

mikroskop
Serologi

VARICELLA ZOOSTER
Varicella Zoster is a member of the herpes virus

family.
Varicella also known as Chickenpox, is the acute
primary disease.
Incubation Period 15 days and is communicable
2 days before and 5 days after the onset of rash.
After an initial episode of infection with Varicella
Zoster leading to Chickenpox , the virus may
persist in a latent state in the posterior root
ganglia of the spinal cord for year. Reactivation
results in Herpes Zoster.

DIAGNOSIS & TERAPI

Viral DNA by PCR
Serologik detection by Ig M or Ig G antibodies
Self limiting diseases
The pregnancy should be monitored closely

by USG, so that Hydrops Fetalis can be treated

by Fetal Transfusion

VARICELLA ZOOSTER
Varicella Zoster is a member of the herpes virus

family.
Varicella also known as Chickenpox, is the acute
primary disease.
Incubation Period 15 days and is communicable
2 days before and 5 days after the onset of rash.
After an initial episode of infection with Varicella
Zoster leading to Chickenpox , the virus may
persist in a latent state in the posterior root
ganglia of the spinal cord for year. Reactivation
results in Herpes Zoster.

 It is highly contagious, self-limiting disease of

childhood
that is transmitted by respiratory droplets or
close contact.
CLINICAL FEATURES include vesicular eruptions
often on mucosal surfaces first followed by a
rapid dissemination in a centripetal pattern. New
lesions appear every 2-4 days and each crop
is associated with fever. The rash
progresses from macules to vesicles and then to
pustule in 24 hours

Maternal

varicella infection in the first 20 weeks of

pregnancy can cause VARICELLA EMBRYOPATHY also
called Congenital Varicella Syndrome in
approximately
1-2% of cases characterised by hallmark cicatricial
lesions in dermatomal pattern, limb hypoplasia,
contractures and can also involve the eye and central
nervous system. The prognosis is poor if an infant be
infected.
Diagnosis is by Prenatal Ultrasound and MRI may
show Oligohydramnios, IUGR, hydrops, limb
deformities and microcephaly.

THERAPY
ACYCLOVIR (800mg 5 times daily at 4 hourly

intervals for 7 days)

ACYCLOVIR 5mg/kg 8 hourly IV until patient is
improving
Class-C antiviral agent used in the treatment of
Varicella Zoster.
Many studies have showed the safety of Acyclovir
use in pregnancy. In 1993, Center for Disease
Control published data showing no risk of
fetal abnormalities in patients exposed in the first
trimester receiving Acyclovir.
VALACYCLOVIR and FAMCYCLOVIR have a better bioavailability and a less frequent dosing than Acyclovir
with similar efficacy.

Case 1
You are called to examine a 1-day-old male because the nurse
concerned that he is jaundiced. He was born by spontaneous
vaginal delivery to a 19-year-old gravida1, para1 after afullterm, uncomplicated pregnancy. The mother had no illnes
during the pregnancy, she did not use tobacco, alcohol, or
drugs, and the only medication that she took was pre natal
vitamins. She denied any significant medical history of genetic
syndrome or illness among children. The infant mildly jaundiced
but has a notable abnormally small head circumference
(microcephaly). His cardiovascular examination is normal. His
liver and spleen are enlarged on palpation of the abdomen.
Neurologc exam is notable for the lack of startle response to a
loud noise. CT scan of his head reveals intracerebral
calcification. The pediatrician explain to the child`s mother that
the virus involved is the most commonly transmitted
tranplacental viral infection

Question
What the most likely cause of this infant`s condition ?
How did he likely acquire this?
What is the test of choice to confirm the diagnosis?