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, 11–12 kb in size.
• Envelope.
• Three or four major structural
polypeptides, two glycosylated.
• Replication: cytoplasm.
• Assembly: budding through host
cell membranes. All viruses
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
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
CMV Inclusion Bodies

Intranuclear and oval

“owl’s-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 anak-anak
 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 complekskemudian 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 bio-
availability 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 afull-term, 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?