TORCH in Pregnancy

TORCH Infection in PregnancyTORCH Infection in PregnancyTORCH Infection in PregnancyTORCH Infection in Pregnancy

dr. Eddy Tiro, SpOG(K)dr. Eddy Tiro, SpOG(K) Social Obgyn Division Social Obgyn Division

Obstetric and Gynecologic DepartmentObstetric and Gynecologic DepartmentMedical Faculty of Hasanuddin UniversityMedical Faculty of Hasanuddin University

Dr. Wahidin Sudirohusodo HospitalDr. Wahidin Sudirohusodo HospitalMakassarMakassar

What is What is TORCHTORCH INFECTIONINFECTION??What is What is TORCHTORCH INFECTIONINFECTION??

A group of infectious diseases that causes A group of infectious diseases that causes congenital and perinatalcongenital and perinatal infectioninfection

TORCHTORCH is abbreviation of is abbreviation of 44 infectious infectious disease disease ((ToxoplasmosisToxoplasmosis,, RRubella,ubella, CCMV MV dandan HHSV)SV)

TTTTOOOO

RRRRCCCC

HHHH

T.O.R.C.H. COMPLEXT.O.R.C.H. COMPLEX

BVGBSVaricellaListeriaMALARIA

BVGBSVaricellaListeriaMALARIA

HP B19HPVHIVHEPATIT B,C..

HP B19HPVHIVHEPATIT B,C..

CHLAMYDIACHLAMYDIA

HERPESHERPESgenitalisgenitalisHERPESHERPESgenitalisgenitalis

RUBELLARUBELLARUBELLARUBELLA

CYTOMEGALOCYTOMEGALOVIRUSVIRUSCYTOMEGALOCYTOMEGALOVIRUSVIRUS

TOXOPLASMOSISTOXOPLASMOSISTOXOPLASMOSISTOXOPLASMOSIS

SYFILIS

OTHERS

SYFILIS

OTHERS

ToxoplasmosisToxoplasmosisProtozoa Parasit T. gondiiProtozoa Parasit T. gondiiFamily Family : Sarcocystidae: SarcocystidaeTachyzoite Tachyzoite 2-4 & 4-8 2-4 & 4-8 mmOocyst Oocyst 12,1 x 1112,1 x 11mmCyst Cyst 200 200 mm

RubellaRubellaAntigenAntigen : Virus Rubella: Virus RubellaFamily Family : Togaviridae: TogaviridaeSize Size : 60 - 70 nm: 60 - 70 nm

CytomegalovirusCytomegalovirusAntigenAntigen : Virus Cytomegalovirus: Virus CytomegalovirusFamily Family : Herpesviridae: HerpesviridaeSize Size : 180 - 200 nm: 180 - 200 nm

Herpes GenitalisHerpes GenitalisAntigenAntigen : Virus Herpes : Virus Herpes Simpleks-2Simpleks-2Family Family : Herpesviridae: HerpesviridaeSize Size : 180 - 200 nm: 180 - 200 nm

TORCHTORCH

- infected pregnant woman usuallyinfected pregnant woman usually asymptomaticasymptomatic- infection to the fetus gives a various effectinfection to the fetus gives a various effect::

* * no infectionno infection

* mild to heavy infection or death of the fetus* mild to heavy infection or death of the fetus

* the baby born with symptoms: brain, lungs, eyes, or* the baby born with symptoms: brain, lungs, eyes, or

ear damageear damage

TORCH infection have TORCH infection have a few a few resemblanceresemblance::TORCH infection have TORCH infection have a few a few resemblanceresemblance::

Who can be infected by Who can be infected by TORCH ?TORCH ?Who can be infected by Who can be infected by TORCH ?TORCH ?

Every one can be infected by Every one can be infected by TORCHTORCH

What is TORCH examination?What is TORCH examination?What is TORCH examination?What is TORCH examination?

Examination to know or to diagnoseExamination to know or to diagnoseTORCHTORCH infection infection

TOXOPLASMOSISTOXOPLASMOSISTOXOPLASMOSISTOXOPLASMOSIS

• Toxoplasma gondii cause congenital infection in 1/10.000 until 80/10.000 pregnancy

• Congenital toxoplasmosis infection correlate with primary infection of the mother during pregnancy

• Transmission of mother to fetus more common in pregnant women who was infected at the end of gestation

• Infection in early gestation make more heavy defect

• Overall, 30-40% of infected pregnant women result congenital infection of neonates

Cat’s feces (containCat’s feces (contain oocystoocyst))

Infected meat (containInfected meat (contain cyst cyst))

Infected pregnant womanInfected pregnant woman

Infected Donor’s Organ/ BloodInfected Donor’s Organ/ Blood

Source of Toxoplasmosis Source of Toxoplasmosis infectioninfectionSource of Toxoplasmosis Source of Toxoplasmosis infectioninfection

TrophoozoitTrophoozoit

cystcyst

OocystOocyst

3 shape of Toxoplasmosis gondii:3 shape of Toxoplasmosis gondii: 3 shape of Toxoplasmosis gondii:3 shape of Toxoplasmosis gondii:

Food : vegetable and fruit that polluted by Food : vegetable and fruit that polluted by cat’s feces (source of cat’s feces (source of oocystoocyst))Fresh and uncooked meat (contain cyst)Fresh and uncooked meat (contain cyst)Mucous contaminated (mouth & eye)Mucous contaminated (mouth & eye)vertically fromvertically from mother mother to child to childBlood Blood transfusiontransfusionOrgan Organ transplantationtransplantation

How is the transmission of How is the transmission of Toxoplasmosis ?Toxoplasmosis ?How is the transmission of How is the transmission of Toxoplasmosis ?Toxoplasmosis ?

Is Toxoplasmosis infection Is Toxoplasmosis infection harmful ?harmful ?Is Toxoplasmosis infection Is Toxoplasmosis infection harmful ?harmful ?

If infected adult or If infected adult or children have good immunity, children have good immunity, Usually is not Usually is not harmfulharmful

IgG (+) IgM (+)

Jakarta 50,1 4,9

West Java 68,3 8,6

East Java 43,2 4,9

Central java 57,9 6,1

Bali 39,8 1,0

West Nusa Tg 53,8 3,8

Sumut + Aceh 48,5 4,4

Riau 55,9 1,1

North Sulawesi 46,3 2,1

South Sulawesi 44,6 2,3

S. Kalimantan 48,6 -

Total 53,0 5,4

% (+)Area

The Positivity of Toxoplasma IgG and IgM in Women

Source : Prodia, Jan-August, 2001

Toxoplasma gondiiToxoplasma gondii

Mother Infant

Primary infection 40% Congenital infection eye, brainAsymptomatic

90% Asymptomatic at birth

With antibodies Protected

Mental retardation 20%Visual affection 45%

at 18 years

??

44%

71%

Congenital toxoplasmosisUltrasonographic Findings

• Calcification– Intrahepatic– Intracranial

• Splenomegaly

• Hydrocephalus – Classical triad: hydrocephalus, intracranial

calcification and chorioretinitis

Toxoplasmosis

Liver calcification Cerebral calcification

Hydrocephalus

Recommendation of maternal treatment

Infected mother:Treat placental infection

Minimum 3 weeks with Spiramycin 9 MIU/day or Azithromycin 0.5 g 3 days /week

Treat fetal infectionuntil birth

Spiramycin (alternating with P/S/ F) Fansidar 2 tablets once per week untill birth

Not necessary to follow maternal serology

Criteria for congenital infected infant

IgG at birth reflects the mother

Follow-up needed.

IgG positive at 1 year of age: infected infant

IgM positive in 55%

dependent on gestational age at infection

and maternal treatment

Parasites / antigen identified in amniotic fluid,

placenta. cordblood

No treatment

Mothers infected before pregnancy

need no treatment

Future Recommendation for Indonesia

Frequency of Toxoplasma infection varies from area to area. In most places so high that serological testing is justified

Any testing has to be combined with correct treatment and follow-up of the children to 1 year of age.

Remember: IgM neg infants may be infected

Sample 1

- recent primary infection ?- old infection with residual IgM ?

Infection acquired > 4 Infection most likely

Additional Guidelines :First sample should be collected early in pregnancy and preferably tested with both IgG & IgM* if IgG-/IgM- : non immune patient, education and serologic follow up (every trimester; in high risk areas every 6-8 weeks)** If IgM + without IgG, it may be the beginning of infection, retest 2-3 weeks later, if the result unchanged : unspecific IgM

Babill Stray-Pedersen

- Prenatal Diagnosis - Maternal Treatment - Follow up the Mother and Newborn

IgG - / IgM - IgG - / IgM + **

confirmatory tests needed3 weeks later (IgG, IgM)

Recent

infectionPrimary

Follow up

Serological Monitoring of Toxoplasmosis in Pregnant Women

continue with IgG Avidity

IgG + / IgM -

immunepatient

IgG + / IgM + IgG - / IgM -

IgG Avidity

Patient Education and Serologic Follow up

Non Immune patient *

continued untill the end of pregnancyAsk the laboratory to

High Avidity

infectioninfection

High IgG

ProbableRecent

Low IgG

Old

IgG + / IgM +

pregnancy

Non immunepatient *

Low Avidity

acquired <4mos ago

until the end of

If the tests is taken in

months ago

2nd half of pregnancy,look on the titer of IgG

Dangerous!Dangerous! for for….…. Dangerous!Dangerous! for for….….

FetusFetus,, if pregnant woman is being if pregnant woman is being primarilyprimarily infectedinfected (the 1(the 1stst infection for the life time) or infection for the life time) or

The person with The person with bad immune systembad immune system (AIDS, cancer, person who undergo organ (AIDS, cancer, person who undergo organ transplantation)transplantation)

What happen to the baby What happen to the baby if mother infected when she was if mother infected when she was Pregnant?Pregnant?

Can be:Can be:

spontaneous abortionspontaneous abortion still birthstill birth Hydrocephalus, eye disorder,Hydrocephalus, eye disorder,

ear (listening disorder), ear (listening disorder),

brain calcification, convulsionbrain calcification, convulsion

If the mother infected, If the mother infected, will the fetus be infected too?will the fetus be infected too?

Not alwaysNot always.. As pregnancy As pregnancy getting oldergetting older whenwhen the mother primarily infected, the mother primarily infected,The more possibility the fetus get infectedThe more possibility the fetus get infected

What is the effect for the fetus ?What is the effect for the fetus ?What is the effect for the fetus ?What is the effect for the fetus ?

More young gestational ageMore young gestational age when the when the mother primarily infected,mother primarily infected,more bad effect will appearmore bad effect will appear..

What is the symptom of thisWhat is the symptom of this infection ?infection ?What is the symptom of thisWhat is the symptom of this infection ?infection ?

Commonly Commonly asymptomaticasymptomatic, the symptom, the symptomis usually unspecificis usually unspecific (flu like) (flu like) So the doctor or the patients usuallySo the doctor or the patients usuallydidn’t recognize it.didn’t recognize it.

Clinical diagnosis hard Clinical diagnosis hard to be diagnosedto be diagnosed

Commonly Commonly asymptomaticasymptomatic, the symptom, the symptomis usually unspecificis usually unspecific (flu like) (flu like) So the doctor or the patients usuallySo the doctor or the patients usuallydidn’t recognize it.didn’t recognize it.

Clinical diagnosis hard Clinical diagnosis hard to be diagnosedto be diagnosed

Is there any other way to diagnoseIs there any other way to diagnoseThis infection ?This infection ?Is there any other way to diagnoseIs there any other way to diagnoseThis infection ?This infection ?

YesYes, the diagnosis of this infection, the diagnosis of this infectionDepends on Depends on laboratory examinationlaboratory examination

What are the laboratory exam.?What are the laboratory exam.?What are the laboratory exam.?What are the laboratory exam.?

Protozoa parasite IdentificationProtozoa parasite Identification(tissue culture, inoculation on mice,(tissue culture, inoculation on mice,DNA-PCR detection).DNA-PCR detection).These exam. are complicated, and These exam. are complicated, and need a lot of time and expensiveneed a lot of time and expensive

ToxoplasmosisToxoplasmosis antibody exam:antibody exam: IgM, IgG, IgA and IgG AvidityIgM, IgG, IgA and IgG Avidity

What are IgM, IgG, IgA andWhat are IgM, IgG, IgA andIgG Avidity ?IgG Avidity ?What are IgM, IgG, IgA andWhat are IgM, IgG, IgA andIgG Avidity ?IgG Avidity ?

IgM, IgG and IgAIgM, IgG and IgA are are ImmunoglobulinImmunoglobulin that will rise that will rise If these is an infectionIf these is an infection

IgG AvidityIgG Avidity is binding strength is binding strength of of IgG IgG antibody andantibody and antigenantigen

Purpose ofPurpose of IgG Avidity exam. IgG Avidity exam.

To To predict the time of infectionpredict the time of infection In assumption of primer infection In assumption of primer infection ((IgG (+) and IgMIgG (+) and IgM (+) (+)) on the same serum) on the same serum,,

If there is hesitationIf there is hesitation : :IgM (-), andIgM (-), and IgG IgG stabile stabile or or IgM (-) and IgG rise significantlyIgM (-) and IgG rise significantly

High levelHigh level : prediction of infection: prediction of infection > 4 months> 4 months before exam. before exam.Low levelLow level : prediction of infection: prediction of infection < < 4 months4 months before exam.before exam.

USA 15-40 %

14 % 31%

Japan 7%9%

50%

40-60%

35%

Toxoplasma-antibodies in pregnant women

60 %

73 %60 %

45-70%

45%

Indonesia 53 %

12%45-55%

12%

Incidence of primary infection in pregnancy: 0.1 - 1 per 100

How we interpret ?How we interpret ?

IgG (+) and IgM (-)IgG (+) and IgM (-)

• Have been infected before (long time Have been infected before (long time infection) and now isinfection) and now is ImmuneImmune. . The mother didn’t need to be examined againThe mother didn’t need to be examined again except except high level of IgG (+)high level of IgG (+)• There is possibility that doctor will ask for There is possibility that doctor will ask for IgG Avidity exam. IgG Avidity exam. Or Or if there is other consideration doctor will askif there is other consideration doctor will ask for this exam. 1 more time (3 weeks later) for this exam. 1 more time (3 weeks later) toto eliminateeliminate the presence of primary the presence of primary infection infection

• PossibilityPossibility of new primary infection of new primary infection or long time infection but IgM or long time infection but IgM

is still is still detecteddetected (slowly disappear) = persistent. (slowly disappear) = persistent. • Need IgG AvidityNeed IgG Avidity examination examination directlydirectly on the same on the same serum serum to predict the timeto predict the time of infection,of infection, before before oror after pregnancy after pregnancy. .


IgG (+) and IgM (+)IgG (+) and IgM (+)

Infection that occur Infection that occur before pregnancybefore pregnancyDidn’t need attention, only primaryDidn’t need attention, only primaryInfection when the mother pregnantInfection when the mother pregnantIs Is harmful,harmful, especiallyespecially on 1 on 1stst TM TM

we need to know we need to know When the examination done When the examination done

In pregnancyIn pregnancy

we need to know we need to know When the examination done When the examination done

In pregnancyIn pregnancy


IgG (-) and IgM (-)IgG (-) and IgM (-)

Never been infectedNever been infected. If the woman are. If the woman arePregnant, we need to exam. on the nextPregnant, we need to exam. on the nexttrimester, until the 3trimester, until the 3rdrd trimester, trimester, If the result remain negativeIf the result remain negative


IgG (-) and IgM (+)IgG (-) and IgM (+)

• This case is This case is rarerare. May be. May be • A A beginningbeginning of infection. Must be of infection. Must be examined again 3 weeks laterexamined again 3 weeks later is the IgG become positive/not?. is the IgG become positive/not?.

• If not, meansIf not, means non specific IgMnon specific IgM, , means that the mother means that the mother is notis not infected infected

Primary infection diagnosisPrimary infection diagnosis

ConversionConversion of of IgG from negativeIgG from negativeto positive or significant to positive or significant rising rising IgGIgG titertiter((>> 2 x) on serial examination 2 x) on serial examination after 3 weeksafter 3 weeks

IgM positiveIgM positive and/or and/or IgA positiveIgA positive

Low level of IgG Avidity Low level of IgG Avidity

CongenitalCongenital infection diagnosis infection diagnosis

IgM positiveIgM positive and/or and/or IgA positiveIgA positive

Persisting Persisting positive IgG onpositive IgG onThe first year after born The first year after born (serial examination)(serial examination)

Interpretation of serologic examination Interpretation of serologic examination of Congenital Toxoplasmosisof Congenital Toxoplasmosis

IgG IgM

+ - * Maybe IgG from mother not a congenital

infection

* Maybe an ongoing infection, IgM is still <<

or has been dissapear

* IgM and IgG exam. 1 months again

+ + * Maybe congenital infection

* Maybe a non spesifik IgM

* IgM examination 1 week later and/

or IgA examination

- - * Not infected

Interpretation

''Cord Blood'''Cord Blood'

Interpretation of congenital Toxoplasmosis Serologik test

'Cord Blood'

IgG IgM

+ - * Maybe IgG from mother not a congenital

infection

* Maybe an ongoing infection, IgM still <<

Interpretation

Interpretation of congenital Interpretation of congenital Toxoplasmosis Toxoplasmosis SerologicSerologic

IgM from mother Serum vs. NeonatesIgM from mother Serum vs. Neonates

Who needs Who needs Toxoplasmosis exam.?Toxoplasmosis exam.?

The woman that will pregnant (ideal)The woman that will pregnant (ideal)Pregnant womanPregnant woman(if (if the previous exam negativethe previous exam negative or or unknownunknown, , minimally checked every TM minimally checked every TM The new born baby whose mother infectedThe new born baby whose mother infectedWhen she was pregnantWhen she was pregnantSuspected patientsSuspected patients

Is Toxoplasmosis infectionIs Toxoplasmosis infectionCan be cured ?Can be cured ?

• Therapy is Therapy is not 100% curenot 100% cure but canbut can prevent more damageprevent more damage.. SSo we need an o we need an immediate therapy immediate therapy after diagnosed. after diagnosed.

• If the baby infected, give therapy If the baby infected, give therapy

until 1 year old. until 1 year old.

TOKSOPLASMOSIS Therapy

• Sulfonamida • Pyrimethamine

Administration: Adult dose of pyrimethamine: 50-75 mg/oral 1x/day, Combine with sulfonamida 1 - 4 gr for 1-3 weeks => and reduce half of doses of each drugs for 4-5 weeks.Side effect: damage of blood cell if given in high doses.Lack of folic acid stimulate agranulositosis. Urtikaria can appear in therapy

• Spiramycin (Rovamycine)

– The most active makrolide antibiotic to Toxoplasmosis

as Bakterioside

– Concentration in placenta is very high (6.2 mg/L), so can

prevent maternal infection infiltrate to the fetus.

– Safe for fetus

– Well tolerated for pregnant woman

– Spiramycin dose for congenital Toxoplasmosis infection:

3 x1gr/day, for 3 weeks and repeated after an interval of 2

weeks until labor.

• Spiramycin doses for congenital toxoplasmosis prophylaxis: 3x daily 3 MIU or 3x1 gr for 3 weeks than repeat after 2 weeks interval until labor

• Remington:– Acute toxoplasmosis in pregnant women:

Spiramycin 3gr/day for 3 weeks, 2 weeks interval until labor

– Pregnancy ≥ 24 weeks: sulfadiazin 50-100 mg/kg + pyrimethamine 0,5-1 mg/kg/day every 2-4 days until labor

RUBELLARUBELLA

Rubella

• 1941 associated with congenital disease (Gregg)

• Today vaccination in developed countries. – Very rare to see cong rubella

• In developing countries - Without vaccination 70 - 80% of women are already infected by childbearing age.

Yes: 110 countries: 57%No 52 countries 43%

Epidemiology• Epidemics every 5 - 7 years

• Risk of infection.• During epidemics:

very high of nonimmune women

Epidemic: Infection risk : 1 % in 3 months

Nonepidemic: Infection risk : 0.1 % in 3 months

Rubella infection in Indonesia 1996

Center No IgG IgM % pos % pos

Jakarta 73 67.1 1.4 Bandung 102 77.5 0Semarang 100 78.0 0Yogya 92 79.3 0Surabaya 101 77.2 0.9Denpasar 100 78.0 3.0

Total 568 76.6 0. 9

T Rachimhadhi 1997

Source of infectionSource of infection

Nasopharyngeal infectionNasopharyngeal infection

Infected pregnant womanInfected pregnant woman

How is the transmission ?How is the transmission ?

Through airway

Through placenta, from mother to fetus

Rubella

Mother Child

Before conception

Onset of rash < 11 d. after LMP No risk

Maternal reinfection I trim 8 %

Maternal vaccination Theoretical risk never proven

Prevention

vaccination

Rubella

Mother Child

First trimester 20% Miscarriage

Congenital defects

Symptomatic 90 % Ear affectionAsymptomatic 90 % Heart /eye defects

After first trimester

13-16 weeks 17 % Retinopathy17-20 weeks 6 % Learning defect

> 20 weeks NoLate sequelae >17yrs

Diabetes, encephalitis

Congenital Rubella SyndromeIncidence of Fetal Infection

• In 1st trimester → occurred in 81% at 0-12 weeks based on LMP

• In 2nd trimester → decresed from 67% at 13-14 weeks to 25% at 23-26 weeks

• In 3rd trimester → 35% at 27-30 weeks 60% at 31-36 weeks 100% in 8 infants exposed > 36

weeks

• The term Congenital Rubella Syndrome (CRS) is used to denote any combination of the findings known to result from gestasional rubella

• Birth defects almost exclusively result from infection in the first 16 weeks of gestation

• The main defects :

– Deafness

– Eye defects (cataracts),

– Cardiovascular defects (Patent Ductus Arteriosus)

– CNS damage leading to mental retardation

Congenital rubella syndrome

1. Developmental defects ( permanent damage)

• Deafness,• Ocular defects: cataract, glaucoma, microphthalmia• Cardiac abnormalities: septal defects, pulm stenosis• CNS defects: mental retardation, microcephaly

2. On going viral infection at birth (not permanent damage)

• Low birthweight, trombocytopenia,• hepato-splenomegaly,

3. Delayed defects• Insulin dependent diabetes, thyroid disorder, mental retardation

Pathogenesis of Fetal defects

• Many of defects are at the interface of malformations and disruptions

• Placental involvement

– During the period of maternal viremia, the placental may become infected → damaged endothelial cells → the virus entered the fetal circulation by embolic transport

• Heart Defects– Once the virus has entered the early embryo, a

chronic nonlytic infection is established → the virus can infect virtually any organ

– Cardiac malformations occur after infection at any time in the first 12 weeks of gestation but rare after this time

• Eye Defects– Lenses from 1st trimester rubella-infected

abortuses showed pyknotic nuclei, cytoplasmic vacuoles, and inclusion bodies in the primary lens cells and retardation of lens development

– For the cataract formation → the virus reach the lens from the amniotic fluid → gain access to the lens as long as the invagination and detachment of the lens vesicle from the surface ectoderm was incomplete

• Deafness– Sensorineural deafness is the most common

defect and mainly result when infection occurs in the first 16 weeks gestation

– It can progress after birth

– It is caused by direct viral damage of the epithelium of the cochlear duct or to the stria vascularis → causing changes of the endolymph and structure of cochlear duct

Congenital rubella

Outcome of Congenital Rubella syndrome

• 1/3 will lead normal independent lives

• 1/3 will live with parents

• 1/3 will be institutionalised

The only effective way to prevent cong.rubella is to

- detect infection in I trimester- terminate pregnancy

The effects to fetus :The effects to fetus :

Fetal death abortion

Still birth

Heart, eye, and hearing disorder, with/without mental retardation andmicrocephaly

What are the symptoms ?What are the symptoms ?

Usually mild fever, headache, Fatigue and feeling not well,Sore throat, cough

30-50% asymptomatic

Rash 16 to 18 days after exposed

In adult, usually accompanied by pain

on joints

Laboratory exam.Laboratory exam.

Viral isolation on tissue culture Viral isolation on tissue culture (urine, (urine, Nasopharyngeal secretionNasopharyngeal secretion))

RNA detection (PCR)RNA detection (PCR)

Antibody detection serologic exam.)Antibody detection serologic exam.) : IgM, IgG, IgA of : IgM, IgG, IgA of Rubella and IgG avidityRubella and IgG avidity

IgMIgM

Appear 2 -3 days after rashAppear 2 -3 days after rash

Peak level after 1 to 4 weeksPeak level after 1 to 4 weeks

can be detected on the 3can be detected on the 3rdrd to 8 to 8thth week week

remain until 6 - 12 monthremain until 6 - 12 month

Immune responseImmune response

IgGDetected 5 to 10 days after the rash Detected 5 to 10 days after the rash (can appear earlier)(can appear earlier)

Peak level after 15 to 30 daysPeak level after 15 to 30 days

Slowly decreases until a few yearsSlowly decreases until a few years until a low level and constantuntil a low level and constant

Immune responseImmune response

Prevention

Antenatal screening / postpartum vaccination

• All pregnant women should be tested for rubella immune status IgG

• Non-immune women – Should be offered rubella vaccination

in the immediate post partum period.

Recommendation of today :

Serologic testing for antibodies of women of childbearing age

Vaccination of nonimmune( seronegative) womenYoung women caring for children:

teachers, health care providers etc

Infertility patients (part of routine examination)

Pre pregnancy counseling

Vaccination by accident in first trimester:– No indication for medical termination

Primary infection is harmful to the fetus before 17 th week of pregnancyAbortion is today only option


Serological Monitoring of Rubella in Pregnant WomenPrenatal Screening (first half of Pregnancy)

IgM detection

Not infected

Non Immune patientsecond sample should be collected at 17-20 th

week of pregnancy

Determination of IgG

Seroconversion

IgM - (?)

Testing should be repeated

IgM +

recent primaryinfection

IgG + IgG -

IgG -IgG +

Immune Patient

Is immunity after vaccination canIs immunity after vaccination canRemain for a lifetime ?Remain for a lifetime ?

Adult : remain > 8 years (if the titer is high)

children : 25% will lose the antibody after 5 years

So need to be reexaminedIgG Rubella when the woman have a plan to pregnant (3 to 6 months before)

Who need to be examined ?Who need to be examined ?

The woman before pregnant (ideally)

In early gestation on 20 weeks

gestation (for the seronegative

woman)

Neonates whose mother primarily

infected when she was pregnant

Suspected patient

After vaccination

C M VC M V

CMV

• Population Survey → CMV may be found in 40-100% of people, depending on socioeconomic conditions

• In developing countries → infection earlier in life → 50% young adults are

seronegative

CMVMother Infant

Primary infection 40-50% Viral excretion 0,5-2%

Recurrent infection 1-2% 10%

asymptomatic Congenital disease < 0,2%1 10% Symptomatic 90% sequelae

Seropositivity: 90% Asympt 15% sequelae

20 -100% cervix

urine Brain / ear / eyebreastmilk 35% 10% 10%

Prevention• Hygienic measures Ganciclovir• Prenatal screening ?

Mother Infant

Primary infection 40-50% Viral excretion 0,5-2%

Recurrent infection 1-2% 10%

asymptomatic Congenital disease < 0,2%1 10% Symptomatic 90% sequelae

Seropositivity: 90% Asympt 15% sequelae

20 -100% cervix

urine Brain / ear / eyebreastmilk 35% 10% 10%

Prevention• Hygienic measures Ganciclovir• Prenatal screening ?

Clinical symtoms:Clinical symtoms: Ptechie (71%)Ptechie (71%) Icteric (67%)Icteric (67%) Microcephaly (53%)Microcephaly (53%) Small for gestational age (50%)Small for gestational age (50%)Most deafness in children caused by Most deafness in children caused by CMV infectionCMV infection

Congenital CMV infectionCongenital CMV infection

Abnormal laboratory result:Abnormal laboratory result: Hyperbilirubinemia (81%)Hyperbilirubinemia (81%) Elevated transaminase (83%)Elevated transaminase (83%) Trombositopenia (77%)Trombositopenia (77%) Elevation of CSF protein level (77%)Elevation of CSF protein level (77%)

Congenital CMV infectionCongenital CMV infection

SalivaSaliva UrineUrine Cervix/Vagina secretionCervix/Vagina secretion SpermSperm Breast milkBreast milk Infected blood/donor’s organ Infected blood/donor’s organ Infected pregnant womanInfected pregnant woman


The way of transmissionThe way of transmission

• Respiratory dropletsRespiratory droplets• contact with source of infection (saliva, contact with source of infection (saliva, urine, cervix and vaginal secretion, urine, cervix and vaginal secretion, sperm, breast milk, tears)sperm, breast milk, tears)• Transfusion & organ transplantationTransfusion & organ transplantation• Vertically from mother to fetus:Vertically from mother to fetus: * * prenatal prenatal (placenta)(placenta) * * perinatalperinatal (in labor) (in labor) * * postnatal postnatal (breast milk, direct contact)(breast milk, direct contact)

If the mother If the mother primarilyprimarily infected, infected, in pregnancy, transmission to fetus is in pregnancy, transmission to fetus is 40%40%

If the mother If the mother secondarysecondary infected infected(have been infected before pregnancy), (have been infected before pregnancy), So the risk of transmission to fetus So the risk of transmission to fetus 1 to 2%1 to 2%

The risk of transmission fromThe risk of transmission fromMother to fetusMother to fetus

Prevalence of CMV infection

Newborn: 1 - 2% ---------> 1 year: 15- 40%

Women working small children: annual acquisition rate 8- 20%

General population: annual acquisition rate 3- 5%

Pregnant population

Europe Other

England: 25% Canada 44%

Denmark 52% USA 50-80%

Norway 70% Chile 98%

Finland 85% Africa 98-100%

Russian 70% Asia 98-100%

Congenital infection : 0.5 - 2 %

Identification of Primary CMV in pregnancy

MotherSerologic testing

CMV - IgG pos.Iow IgG avidity

CMV - IgM pos.or seroconverter

Fetus Amniocentesis Viral / antigen detection CMV - PCR

Viral load Viral load : Severe infection: Severe infection

UltrasoundUltrasound

NewbornNewborn CMV-IgM posCMV-IgM pos

Virus / PCR pos in body fluids (urin)CMV – IgG pos at 1 year

CMV: Ultrasonographic Findings

Best diagnostic clue:

• Calcification

– Intracranial

– Hepatic • Hepato spleno megaly• Amniotic fluid volume disorder

CMV

Liver Brain

Calcifications

CMV

Ascites and Echogenic bowel

Ascites

23 gest week 37 gest week

CMV- amniocentesis

• At least 6-7 weeks after maternal infection– Mat.viremia: 2-3 weeks post infection

– Fetal infection 4-6 weeks later

• After 21-23 gest week– Fetal diuresis >21 week

Lisnard et al, Obst Gynecol 2000,95,881

Gouarin et al, J Clin Micr 2002 ,1767

CMV Recommendation

• App 90 % IgG positivity– 10% of pregnant women can acquire the

primary infection in this high risk area.

– Testing of pregnant women working with children may be justified

– Give hygienic advise

1st Sample

Preventive measures to be given For women at high risk : - Retesting later in pregnancy for IgG to identify primary maternal infection


IgG +, IgM +, IgG Avidity low

Primary infection

Confirmatory test :

Serological Monitoring of CMV Infection in Pregnant Women

IgG - IgG +

no more testingOld infection

Determination of IgG

Not infected

IgG - IgG +

CMV TreatmentMedical Care

• Ganciclovir treatment– The drug of choice for CMV disease– Nucleoside analogue that inhibits DNA synthesis

in the same manner as acyclovir– The length of treatment is variable and depends

on the disease and the host– Induction dose: 5mg/ kg twice daily.

Later, the dose is decreased from twice daily to once daily and continued as maintenance therapy

• Ganciclovir treatment– Also been used to treat CNS disease, including

encephalitis and neuropathy

– For pregnancy → CSafety for use during pregnancy has not been established

Prognosis

• Symptomatic neonates

→ Mortality rate up to 30%

→ 70- 90% have some neurologic impairment,

including hearing loss, mental retardation, and

visual disturbances

• Asymptomatic neonates

→ 10% develop neurologic sequele

Prevention

• Nonimmune pregnant women should attempt to limit exposure to the virus

• Pregnant women should always wash hands after exposure to urine and respiratory secretions from children

• Development of a vaccine against CMV is under investigation

The 5th children diseaseButterfly rash in children

Mild febrile illness

Upper respiratory symptoms

Adults

Often asymptomatic

macupapular rash

Polyarthritis

Main reservoir: School aged children

Fatal foetal hydrops due to B19 Parvo virus. The fulminant ascites is typical

Parvovirus

What is the symptoms ?What is the symptoms ?

90 % primary infection on 90 % primary infection on

Immunocompetent adult and children areImmunocompetent adult and children are

asymptomaticasymptomatic

Laboratory examinationLaboratory examination

Direct Direct • HistopathologyHistopathology• Tissue cultureTissue culture• PCRPCR

Indirect Indirect • Serologic exam. Serologic exam. IgM, IgG and IgM, IgG and IgG AvidityIgG Avidity

When and who need to beWhen and who need to beexamined ?examined ?

Blood / tissue donorBlood / tissue donor

Transplanted tissue recipientTransplanted tissue recipient

Woman, before pregnant (ideal),Woman, before pregnant (ideal),

If negative, exam. on early pregnancy,If negative, exam. on early pregnancy,

And on late pregnancyAnd on late pregnancy

Neonates of iNeonates of infected mothernfected mother

H S VH S V

Herpes Simplex Virus (HSV)• Both HSV types, HSV-1 dan HSV-2 can cause

oral and genital infection

• HSV-1 → cause gingivostomatitis, herpes labialis, and herpes keratitis

• HSV-2 → cause genital lesion• After initial infectio → HSV dormant in ganglia

nerve and can cause periodic symptoms

• Recurrent herpes eruption precipitated by– Excessive exposure to the light– Disease accompanying with fever– Physic and physical stress– Immunosuppresion– Unknown stimulation

• Recurrent erruption usually not too sever, and didn’t usuallny appear

Neonatal and Congenital HSV

Type of Infection Timing of acquisition

Mode of acquisition

Congenital In Utero( antepartum)

Transplasental

Neonatal At or near birth (intrapartum)

Genital exposure

Neonatal Postnatal Nosocomial (staff or family direct skin contact)

Epidemiology• The incidence of Genital HSV infection rise in

developing county

• From the study in Canada, seropositive HSV-2 in pregnant women about 17 %

• Canada → Neonatal HSV 1 : 17.000 newborn• US → Neonatal HSV 1 : 3500 newborn

Clinical Manifestation

• Manifestation of congenital and neonates HSV classified into 3 levels:1. Infection of skin, eye, and mouth (38% can cause

neurological sequale)

2. Central nervous system disorder ( ensephalitis with or without infection of skin, eye, and mouth)

3. Systemic spreading (in serious infection, mortality rate can reach 90% if didn’t get therapy)

HSV in pregnancy

• Primary infection in 1st and 2nd trimester infection → increase the risk of abortion, premature, and small for gestational age

• Primary infection in the 3rd trimester → Ig G hasn’t completely developed → fetus didn’t get protection →30-50% risk of neonates herpes infection

SalivaSaliva Vesicle liquidVesicle liquid Infected pregnant womanInfected pregnant woman


• contact with lesioncontact with lesion• Indirect contactIndirect contact• Vertically from mother to fetusVertically from mother to fetus * Prenatal (placental * Prenatal (placental rare rare 1 : 200.000 pregnancy)1 : 200.000 pregnancy) * Perinatal* Perinatal * Postnatal* Postnatal

HSV transmissionHSV transmission

What are the symptoms ?What are the symptoms ?

Primary infection Fever, headache, malaise, neuralgia broad lesion lymphadenopaty asymptomatic (8%)

Recurrent infection The symptoms are milder and healing time is shorter

Laboratory DiagnosisLaboratory Diagnosis

Tissue culture Tissue culture

Serology examination IgG and IgM Serology examination IgG and IgM (HSV-1 and HSV-2)(HSV-1 and HSV-2)

Who and when, we need Who and when, we need to exam.?to exam.?

Suspected patientSuspected patient

Woman before pregnantWoman before pregnantIf (-), examine in early pregnancyIf (-), examine in early pregnancy* If (-), examine her couple* If (-), examine her couple* If (-), her couple (+) with previous* If (-), her couple (+) with previous Herpes Genital, examined his wife Herpes Genital, examined his wife toward the end of pregnancytoward the end of pregnancy

Infected mother’s neonatesInfected mother’s neonates

Prevention strategyPrevention strategy

Don’t do sexual intercourse during Don’t do sexual intercourse during

Active lesions are presentActive lesions are present

Better use condomBetter use condom

Born by Born by Caesarean section, Caesarean section,

If there are lesions If there are lesions

(prevent mother to fetus transmission)(prevent mother to fetus transmission)

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*

Thank you Thank you & &

Success Success foreverforever

Thank you Thank you & &

Success Success foreverforever

TORCH in Pregnancy

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