Transcript Document

‫بسم هللا الرحمن الرحيم‬
TORCHs Complex
And CRS
PROFESSOR KARIMI
PIRC
Routine prenatal screening
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Difficult interpretation
Different methods for IgM assay (sp.- ppv: 50%-99%)
Mother IgM may last for 3-12 months
Cost effectiveness:
3/75 of IUGR patients : probable TORCHs
So
<<U/S +Ag detection and or IgM avidity test>>
Or in some area
<<Srologic tests for Rubella and Syphilis>>
Fever and Rash in Mother
(suspicious to Rubella)
0
3wk
 + : ……
 - ……. + ……..
 - ……. - …….
 - ……. - .......
6wk
: No interaction
:Infection occured
+ : //
//
- : No interaction
Acquired Toxoplasmosis and CMV
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90% asymptomatic
Most common symptoms :
LAP+ Fever + Fatigue
Occasionally:
Inf. Mono. Like sx
Hepatitis , Encephalitis , Pneumonitis , Myocarditis
Aseptic Meningitis and Mass lesion
Acquired CMV is very similar to EBV
‫‪1‬‬
‫الف) چه موقعی می گوییم نوزادی مبتال به ‪TORCHs‬‬
‫‪ dx‬است؟ و چه عواملی آن را ایجاد می کنند؟‬
Chronic Congenital Infection

Definition: More than one month of
manifestations which present at birth
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Active : ongoing inflammatory process
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Inactive (burned out) :anomaly or damaged
organ remaining as evidence of past infection
CHEAP-TORCHS
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CHEAP: Chickenpox-Hep.B,C,EEnteroviruses -AIDS- Parvovirus B19
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TORCHS: Toxoplasmosis – Others(GBS,
Listeria, Candida, Tuberculosis, LCMV) –
Rubella-Cytomegalovirus – Herpes simplex
virus –STI : gonorrhea, chlamydia,
ureaplasma , papillomavirus
ACUTE CONGENITAL INFECTION:
Fever or Hypotonia ,Resp.D
,Cyanosis, Anorexia, Vomiting ,
HMG:
Sepsis
HSV and Enteroviruses,
‫‪11‬‬
‫ب) در چه مواردی نوزاد را برای سندم تورچ بررسی‬
‫می کنید؟‬
Clinical Diagnosis
It should be considered with any of
the following general findings:
1. IUGR
2. Congenital defects indicating
teratogenesis or damaged organs:
Heart ( PDA , PS,…)
Eye :( glaucoma , chorioretinitis
,strabismus ,…)
Ear : deafness
CNS : (calcification , hydrocephaly,…)
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3- Chronic active infection:
Jaundice –HSMG –Thrombocytopenic
purpura – Rashes – CSF pleocytosis Pneumonitis – Myocaditis – Rhinitis –
Vomiting – Diarrhea-…
Clinical Features
‫‪1‬‬
‫ج ) با بررسی نوزاد برای سندرم تورچ چه اهدافی را‬
‫دنبال می کنید؟‬
1- Effectiveness of vaccination
2- Early detection and interaction
3- Prevention of sequels
4- Determining the cause of patient
problems
‫‪2‬‬
‫الف) در بررسی سندرم تورچ آزمایشات عمومی و‬
‫اختصاصی (غیر از سرولوژی) کدامند؟‬
Nonspecific LAB W/U
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U/S for IC abnormalities such as calcification
Long bone X-Ray , CXR
ECG
CSF analysis
CBC including platelet count
Total IgM , which is neither S o SP .
Tetralogy of Fallot
Patent ductus arteriosus
(PDA)
VENTRICULAR SEPTAL DEFECT (VSD)
Patent ductus arteriosus
X-ray of the lower limbs in a newborn with congenital rubella
syndrome. The ends of the long bones are ragged and streaky in
appearance (the so-called "celery stalk" metaphysical changes),
due to active rubella infection in the bone.
A 3-day-old girl of low
birth weight had
generalized
purpura. Physical
examination revealed a
continuous
murmur at the left upper
sternal border and
hepatosplenomegaly.
Ultrasonography revealed intracranial calcifications
confirming to a periventriclur location
mild hydrocephalus
Calcific. foci in both basal ganglia
cytomegalovirus is the most common followed by toxoplasmosis,
rubella and herpes.
‫‪2‬‬
‫ب) آیا آزمایشات نامبرده شده را برای تمام نوزادان مشکوک‬
‫به تورچ درخواست میفرمائید یا معیارهایی را در نظر‬
‫می گیرید؟‬
‫( در صورتیکه راهنمای خاصی برای درخواست آزمایشات در‬
‫نظر دارید ارائه فرمایید‪).‬‬
‫‪3‬‬
‫الف) تفاوت ها و شباهتهای ‪ Rubella ، CMV‬و ‪Toxopl.‬را‬
‫از نظر بالینی وآزمایشگاهی بطور جداگانه در دو جدول‬
‫منعکس فرمایید‪.‬‬
Cardiac abnormalities
• Cardiomegaly, mostly in CMV
• VSD, ASD, Pulmonic stenosis
and coaractation of the aorta
in Rubella
Microcephaly
• Often associated with other CNS
anomalies
• Isolated microcephaly :
documented in CMV, Rubella ,HSV ,
VZV, T-21 and PKU
hydranencephaly
• Most severe manifestation of the
destructive process
• Cerebral hemispheres replaced by fluid,
brain stem preserved, falx present, absent
or deviated, posterior fossa structures
can be identified
•
reported in Herpes simplex,
Toxoplasmosis and CMV
Hepatosplenomegaly
• Documented in all TORCH
infection
• Often a transient finding
Intra-abdominal Calcifications
• Typical appearance: echogenic foci with
acoustic shadowing
• Peritoneum, intestinal lumen, organ
parenchyma, biliary tree and vascular
structures
• Echogenic bowel in CMV and
Toxoplasmosis
Hydrops, Placenta and Amniotic
fluid
• Hydrops reported in most TORCH but
may be transient
• Placentomegaly is usually associated with
intrauterine infection, but small placentae
have also been reported
• Hydramnios and oligohydramnios have
been reported with similar frequency
Fetal growth restriction
• Estimated weight below the 10th percentile
• common feature with CMV, Rubella, Herpes
simplex and Varicella
• Usually not seen with Toxoplasmosis and
Syphylis
Congenital rubella syndrome
(CRS)
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Incidence less than 1:100,000 live birth
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Infection of fetus during first trimester of pregnancy
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CRS babies continue to shed Rubella virus from
their throats for several months up to a year after
birth and pose a serious risk to pregnant women

10 -20% of babies with CRS die within 1 year
CRI Classification
1-Classical form
Eye defect ( microphthalmia , cataract :20 50%, Retinopathy: salt and pepper )
CHD :50% (PDA : 20-50% -Ps and As )
Microcephaly – Deafness (unilat. or bilat.)
2- Extended CRS
Transient longitudinal bone radiolucencies
Dental enamel defect – Blueberry muffin baby –
Retinitis
CRI Classification
3- Late onset CRS : minimal S&S at birth , but
sever multisystem dx develops after 3-6
months – panencephalitis – PCP – Interstitial
pneumonia – convulsion – rashes
4- Isolated defects: language retardation
strabismus – deafness – neo. Hepatitis
REVISED CLASSIFICATION
(confirmed – probable – possible – absent CRS )
CNS involvement in Rubella:
Abnl Tone ,irritability ,Bulged
fontanel , convulsion :25% ,
high protein in CSF without
pleocytosis , NDD :25%
Infant with CRS
Cataracts
caused by CRS
other causes:
HSV, VZV, Galactosemia, Lowe sx
Congenital Rubella: Retinopathy
(Salt-and-pepper retinopathy)
Congenital Rubella Syndrome
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•
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•
severe bilateral deafness
severe bilateral visual defects
cataract
corneal opacity
Roger Mulholland: was born with rubella
His mother Jane contracted the disease
when she was pregnant
•When Roger was born, he was a small baby, covered in blood
blisters.
•Within a day it was confirmed that he was blind and had severe
brain damage.
•He was later found to have four separate heart defects and to be
completely deaf.
fetus with non-immune hydrops and anasarca
stillborn
molar placenta
small, low set malformed ears,
micro retrognathia
syndactyly of third and fourth digits
simian crease
Clinical manifestations of congenital rubella and time of maternal
infection.
- - - -, deafness; - - – - - –, central nervous system deficit;
— — —., heart disease; – – – –., cataract/glaucoma; ——, neonatal
purpura
Frequency of virus excretion
with age of infants with CRS
Cytomegalovirus
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DNA virus
The most common congenital infection affecting 1% of all
live births
Prolonged virus shedding
5-10%of infected neonates demonstrate clinical
manifestations that potentially could be identified by
prenatal sonography
Ventriculomegaly, Intracranial calcifications and
oligohydramnios are the most frequently reported findings
Neonatal NDD : 20-30%
90% of survivors get late complications
5-15% with no demonstrable disease at birth get some
abnormality (deafness)
CMV Congenital Infection (Late)
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Ventriculomegaly
Cerebral atrophy and Mental retardation
Psychomotor delay and Seizures
Learning difficulties and language delay
Chorioretinitis / Optic atrophy
Intracranial calcifications
Long bone radiolucencies and dental
abnormalities
Pneumonitis
CMV
 CMV
has several patterns :
1- Marked HSMG with Jaundice – Renal
Tubular cells  cmv inclusion
2- Thrombocytopenic purpura with jaundice
3- Neurologic abnormality and
microcephaly
CMV
4- Persistent Interstitial Pneumonia :It is
often associated with HSMG and atypical
lymphocytosis ( also it was acquired
before or during birth or in NB period)
5- Asymptomatic infection ( 95%) :15% of
asymptomatic CMV – shedding ( it may
continue for years : in first month it is in
favor of cong. CMV infection ) babies
develop Sensorineural hearing loss
Toxoplasmosis
Classic criteria :chorioretinitis – IC calcification –
hydrocephalus is uncommom
1- Asymptomatic (70-90%):common with later
development of subtle abnl. Eg.: chorioretinitis [95% -85% :bilateral (visual defect and reduced IQ – deafness )]
 screening test:0.02%
2- Generalized form : HSMG – LAP – jaundice – Fever –
Rash – sometimes Neurologic abnl.
3- Neurologic manifestations ( predominant )
4- Isolated defects :MR- Deafness – Microphthalmiachorioretinitis ,Strabismus , Nystagmus ,NDD,
Hydrocephalous
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‫ب( دو تست سرولوژی کمک کننده برای هر کدام از سه‬
‫عامل ‪ Rubella ،CMV‬و ‪ Toxoplasmosis‬را نام‬
‫ببریدوآنها را تفسیر کنید؟‬
‫‪.‬‬
Immune responses in congenitally acquired infection
In general there are 3 approaches for
Serologic diagnosis:
1- Evaluation of neonatal and maternal serum
for IgG
2- IgM evaluation in cord blood for screening
>20mg/dl:1/3- ½ contamination with
maternal blood so, IgA is more helpful
3- IgM is negative in 50% of proved cong. Inf.,
Although 2/3 of high IgM : no sp. Factor
could be found ,so IgM can not bring up an
specific Infect. dx.
1- CRS
1. Isolation (nose, throat ,blood, urine, and CSF)
2. IgM : helpfull but has FP (RF or ANA or maternal
blood contamination :with cord blood )
3. IgG Comparison (3mo : 4-8 times- 6-8mo
:undetectable)
4. Rubella IgG - ELIZA
5. Rubella immunoblot test
6. Avidity test
*HIT: 2-3 days after Rash is detectable , peak at
3-4 wks - cross placenta ,but is neg. after 4-6 mo*
Diagnosis of CRS
1. Anti-rubella IgM Ab in neonatal serum
2.Culturing rubella virus from the infant
( nasopharynx , urine or tissue)
‫پاسخ ایمنی در سندرم سرخجه مادرزادی‬
‫• ‪ IgG‬اختصاصی موجود در سرم در زمان تولد متعلق به مادر‬
‫است ولی ‪IgM‬اختصاصی متعلق به خود نوزاد است پس برای‬
‫تشخیص می توان از شناسایی ‪ IgM‬در خون نوزاد استفاده نمود‬
‫• معمو ًال در ‪ %100‬نوزادان مبتال به ‪ CRS‬از بدو تولد تا ‪ 5‬ماهگی‬
‫‪ IgM‬شناسایی می گردد‬
‫• این میزان در سن ‪ 6-12‬ماهگی به ‪ %60‬و در ‪ 12-18‬ماهگی‬
‫به ‪ %40‬کاهش می یابد و بعد از ‪ 18‬ماهگی بندرت یافت می شود‬
‫تست های آزمایشگاهی‬
‫• تهیه یک میلی لیتر خون از هر نوزاد مشکوک به ‪ CRS‬در‬
‫اسرع وقت بعد از تولد‬
‫• در راستای اهداف مراقبت‪ ،‬یک نمونه خون برای تأیید یا رد ‪CRS‬‬
‫کافی بنظر می رسد‬
‫• اگر اولین نمونه برای ‪ IgM‬سرخجه منفی بود و شک زیاد‬
‫کلینیکی یا اپیدمیولوژیک وجود دارد یک نمونه ثانویه باید‬
‫درخواست شود‬
2-Toxoplasmosis
1. Isolation: tachyzoite in placenta
2. PCR in fluids
3. Serology :
Specific IgG : - Sabin Feldmandye
-IFA
- DF
- ELIZA( double sandwich
IgM:s:75% -sp: 100%)
-IgM immunosorbant agg. Assay
(ISAGA): the most sessitive
5.Agg Ac/HS
6 .Elifa / ( immunofilteration assay)
TOXOPLASMOSIS:
1- Neg. IgM and IgG :No dx
2- S (-ve)  S (+ve ) or 4 fold rising : Infection
3- IFA >1/500 (IgG) or +ve Dye test for IgM
(+ve) :Infection
4- Negative IgM with ELIZA or ISAGA : against
dx
5- IgG in Newborn has produced since 3rd
months of life : sp.Ab/ total Ab : static or
decline or rise
* Remember that <24 wks of GA : IgM will be
negative even with ISAGA*
3-CMV
1- Isolation with viral culture ( Amniotic fluid
-Urine or Saliva) or DNA hybridization
2- Viral detection : PCR- DNA in Urine or
Saliva or IN. Inclusion body (25-50%):up to
3 weeks
(IN body :HSV and HZV )
3- IgM
4-Accessory findings : LFT leucopenia and
thrombocytopenia ,
5- IgG steady level for 6 months is diagnostic
‫‪4‬‬
‫برای هر کدام از موارد مثبت چه درمانی را شروع‬
‫می کنید و چگونه بیمار را پیگیری می نمایید؟‬
Treatment
1-CMV:
5-Fluorodeoxyuridine / Cytosine arabinoside
/ IFN –inducers / Acyclovir
Foscarnet : Retinitis – Cidofovir :Adult CMV
Retinitis
Gancyclovir : 6 weeks (high TA- DHBlow PMN) +/ - ccsx
Treatment (continue)
2-Toxoplasmosis
Sulfadiazine + Perimethamine + Folinic acid : 12
months with CBC F/U
Ccsx :CSF protein >1g/dl and or Chorioretinitis
3-Rubella
Isolation till culture neg.
Hemorrage :no response to ccsx but IVIG is
beneficial
Glaucoma and CHF need emergency Rx ,but
Cataract not .
‫‪5‬‬
‫• غیر از سه عامل فوق معیارهای مهم تشخیص بالینی و‬
‫آزمایشگاهی را در مورد عوامل زیر طی جدولی ارائه‬
‫فرمایید‪.‬‬
‫معیار تشخیصی‬
‫عامل‬
‫‪HIV‬‬
‫‪HSV‬‬
‫‪VZV‬‬
‫‪…….‬‬
‫بالینی‬
‫آزمایشگاهی‬
Human Immunodeficiency Virus (HIV)
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Infection rates variable
Risk of vertical transmission 20-40%, mostly
peripartum
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Screening and treatment can almost completely
reduce vertical transmission
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C/S reduces risk of transmission x 4-fold
Viral counts <1000 - negligible risk to fetus

Clinical manifestations
1. generally asymptomatic for first few months of life;
mean age of onset of symptoms is 1 year
2. Common manifestations include failure to thrive,
HSMG , oral candidiasis , recurrent diarrhea,
recurrent bacterial infections, and PCP between
3-6 months of age
3. Anemia, neutropenia, and thrombocytopenia are
common
HSV
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Intrapartum infection
disseminated disease - chorioretinitis, meningitis,
encephalitis, NDD , seizures and death
Hydranencephaly is the only sonographic sign
reported antenatally
Microcephaly, intracranial calcifications are
potentially detectable
Primary infection >>>secondary infection
HSV II - 75%; HSV I - 25% cases
HSV Classification
1- Disseminated :
sepsis like signs - acute
hepatic failure -coagulation abnl. - fever
without other symptoms (in the first 6
weeks of life should be considered )
2- CNS dx. : in any infant with meningitis
but a negative gram stain HSV – PCR
should be sent and acyclovir started
empirically
HSV
3-SKIN ,EYE ,and MUCOUS MEMBRANE
(SEM ) in combination or isolated and
usually progresses to CNS or disseminated
dx. , so infants with apparent SEM must
undergo a LP – Recurrent dx. Can be
suppressed with oral acyclovir therapy
HSV Diagnosis
 Culture
 DF Abx
stain (s. and rapid: 2 hr)
PCR from CSF and Serum
HSV:
Vidarabin or Acyclovir : 60 mg /dl:3 doses x
21 days in CNS and disseminated but 14
days in SEM dx : then follow by PCR
Parvovirus

Human parvovirus B19 ( DNA virus )
- erythema infectiosum in childhood
- chronic arthropathy
- chronic bone marrow failure (immunodeficient)
- aplastic crisis (Sickle disease)

Incubation 4-14 days
Respiratory droplet spread
High fever, “Slapped cheek syndrome’ : non specific
rash.
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Parvovirus and fetus
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Hydrops (anaemia, myocarditis)
Adults : 60% sero-positive
1/3 fetuses affected in acute infection
Fetal loss rare with appropriate treatment
Assess serology – IgG , IgM, paired
serology
Serial ultrasound, intrauterine transfusion
Varicella and pregnancy

Mild immunocompromise of pregnancy
increases risk

10% develop pulmonary complications main cause of mortality
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Fetal effects
Preterm delivery
Varicella syndrome
Neonatal varicella
Varicella Syndrome
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Cutaneous scarring
Limb hypoplasia
Missing/ hypoplastic digits
Limb paralysis/muscle atrophy
Psychomotor retardation and Convulsions
Microcephaly and Cerebral atrophy
Chorioretinitis/ choriod scarring/optic disc
hypoplasia , Cataracts
Horner’s Syndrome
Early childhood Zoster
SYPHILIS

several patterns:
1- Asymptomatic infection : the most
common type
2- Symptomatic dx :usually manifested by
a rash : vesicular or bullous or may be
EM (demarcated on diaper , palms and
soles)
3- Chronic Rhinitis ( “the snuffles”) :often
blood – tinged with fissures of the lips
SYPHILIS
4- HSMG
5- Monocytosis :sometimes ALC >1500/ml
+/- Hemolytic anemia
6- Lytic bone lesion with periosteal reaction
or metaphyseal destruction
7- Nephrotic syndrome
8- Neurosyphilis (CSF – VDRL - … )
THANKS A LOT