Download MBBS Pediatric PPT 5 Intra Uterine Infections Lecture Notes

INTRA UTERINE INFECTIONS

Learning Objectives
Common IU infections

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When to suspect IU infection
Hep B vertical transmission, Congenital rubel a syndrome

,Congenital toxoplasmosis

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Diagnosis , management & prevention
TORCH-Coined by Nahmias in 1974, now

TORCHES CLAP

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To ?Toxoplasma,

C ? Chicken pox

R ? Rubel a,

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L ? Lyme's

C ? Cytomegalo virus,

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A ? AIDS

H ? HSV,

P ? Parvo virus B 19

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E ? Enterovirus,

S - Syphilis

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What are common IU infections?
Two major categories: congenital& perinatal
congenital: transmitted to the fetus in utero
Perinatal :acquired intrapartum / in the post natal period
ROUTES OF VIRAL INFECTIONS OF

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FETUS & NEONATE

CONGENITAL

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PERINATAL

POSTNATAL

CMV,TOXOPLASMA

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HSV

VARICELLA

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PARVO B19

RUBELLA

ENTEROVIRUS, HEP- B&C,

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HEP- A

Prevalence:HBV infection

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5% of the world's population is chronical y infected with

hepatitis B

India: Prevalence rate for HBsAg seropositivity 2-7 %

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Pregnant women : 0.9% and 11.2
HBeAg seropositivity of 30% -56.8%
Carrier status

90% of affected infants develop chronic infection

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30-50% of under-five children and 6% of children above

five years of age .

Chronic hepatitis B infection acquired in childhood

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carries a 25% risk for development of chronic liver
disease, cirrhosis or hepatocel ular carcinoma .

Hence, it is imperative to prevent mother to child

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transmission.

Pregnancies with HBV

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Risk of chronic infection 1/ age( inversely proportional to

age)

90% carriage rate for neonatal infection&

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40-75 % vertical transmission rate

Intrapartum route > transplecental>breastfeeding
Hep B : Strategies for prevention

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Universal screening of pregnant women

Case management of HBsAg-positive mothers and their

infants

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Elective LSCS, continue breastfeeding

Immunoprophylaxis : Al infants born to mothers with

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positive HBsAg , should receive HBIG (within 12-24 hrs

of birth)(0.5ml)+ Hep B vaccine(0.5ml=10?gm)(within

few hrs of birth) & Repeat Hep B vaccine @ 1& 6

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months.

Universal immunization : 2 course (6 doses)
Identification in a pregnant women

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When to suspect?

Three strategies ?

A) Routine / universal screening

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B) Women with high risk factors

a) Multiple partners

b)Repeated BT's

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c) Partner with STD

C) Symptomatic women

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d) Unhygienic food habits

e) Rubel a non-immune

f) Occupational exposure

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Contd...
Maternal H/o
Contact with a known infected case during pregnancy
History of non vesicular rash [ Rubel a/ parvo virus ]

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Vesicular rash [varicel a & herpes simplex]
History of recurrent abortions
Contd...
Neonatal manifestations
P DA in a term/ near term neonate( Rubel a)

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Clinical stigmata of IU infections: SFD,

hepatosplenomegaly, blue berry muffins,
microcephaly,chorioretinits, cataracts

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Late onset neonatal cholestasis

CONGENITAL

MAIN FINDINGS

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INFECTION

Rubella

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cataracts, cloudy cornea, blue berry muffins,
PDA, PPS

CMV

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microcephaly, periventricular
calcifications,jaundice,snhl

Toxoplasma

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hydrocephalus, generalized
calcifications,chorioretinitis

Syphilis

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osteochondritis,periosteitis,ssnuffles,rash

Herpes

skin lesions,keratoconjunctivitis,acute

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encephalitis

Varicella

limb hypoplasia,scarring, GI tract atresis

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LCMV

hydrocephalus, chorioretinitis,ic calcifications
Rubella: German Measles

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Rubella is also cal ed as

3 d ay Measles or
German Measles.

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Family ? Togaviridae
Genus - Rubivirus
In general belong to

Togavirus group

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Post natal Rubella
Occurs in Neonates and Childhood
Adult infection - through mucosa of the upper

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respiratory tract ----cervical& occipital lymphnodes

Viremia - after 7 ? 9 days& Lasts for 13 ? 15 days
Leads to development of antibodies
The appearance of antibodies coincides the

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appearance of rash. suggesting immunologic basis

for the rash

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In 20 ? 50 % cases of primary infections are

subclinical
RUB

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RUBELLA

Incidence (Indian scenario):

Singh et al (1999):

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Seroprevalence of Rubel a 90-95% (IgG) and only 5-10% are

non-immune

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Tarbudkar et al (IJMM 2003):

IgG seropositivity ? 67%
IgM seropositivity ? 23%

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How Adults acquire Infection ?

Acquired rubel a - via airborne droplet emission -from

the upper respiratory tract of active cases.

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Virus ? also present in urine, feces and on the skin.

No carrier state: exists entirely in active human cases.

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The disease has an incubation period of 2 to 3 weeks.
Clinical manifestations

Malaise
Low grade fever

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Morbil iform rash
Rash starts on Face &

Extremities

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Rarely lasts more than 5

days

No features of the rash

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give clues to definitive

diagnosis of Rubella.

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Rubella rashes
Acquisition of immunity

Antibodies appear in serum as

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rash appears & and antibody

titers rise as rash fades

Rapid rise in 1 ? 3 weeks

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Rash with detection of IgM

antibodies -indicates recent

infection.

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IgG antibodies persist Life

long

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maternal antibody protection-

for 4 ? 6 months.

Congenital rubella syndrome

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Teratogenic property of the infection was documented

by an Australian opthalmologist Greeg in 1941

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Charachterized by classical triad of

- cataracts,
- cardiac disease
- SNHL

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MC isolated finding SNHL
TRANSMISSION IN UTERO

VIREMIA

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Inapparent Rubella

Clinical

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Therapeutic abortion

Infection of pregnant woman

No transplacental

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infection

Infection of Embryo and Fetus

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N

Still birth

Miscarriage

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Infant born with CRS

Defects manifest at birth

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Defects manifest later

Fetal involvement as a function of

gestation

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Maternal infection
<12 wks [period of organogenesis]: 81 % fetal

infection , cardiac defects & deafness

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involvement

13-16 wks ? 54%- retinopathy, hearing loss , CNS

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defects

17-22 wks ?36%
23-30 wks- 30 %
31-36 wks -60%

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>36 wks ? 100%
RUB

Transmission & risk of fetal infection

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100
90
80

60

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50
40
30

20

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<11

11-15

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15-22 22-30

31-36

>36

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Manifestations:Three groups

(Gregory et al): Transient

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Reflect ongoing heavy viral infection

. Hepatosplenomegaly, hepatitis

Jaundice,

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? Thrombocytopenia, blue-berry muffins

EXPANDED

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? Interstitial pneumonia,

RUBELLA

? Hemolytic anemia

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SYNDROME

? Adenopathy, long bone growth defects

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Large AF, cloudy cornea, diarrhoea
RUB

Manifestations: Permanent

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from defective organogenesis &

tissue destruction

-- Deafness ? MC (80%)

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-- Salt & pepper retinopathy

CRS

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-- CHD(PDA,Pulm stenosis)

--CNS anomalies ? microcephaly,

mental & motor retardation,

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autism (6%)

RUB

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Manifestations : Developmental

& late onset:

?

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-- Endocrinopathies(IDDM ?MC(20%)

Thyroid dysfunction (5%))

--deafness, vascular effects

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Progressive CNS disease,

--ocular damage
Congenital rubella- blue berry muffins

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Metaphyseal lucencies

Diagnosis ? maternal infection

Clinical diagnosis ? unreliable; lab.diagnosis is

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essential

Techniques a) Isolation ?nose, throat

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b) Serology ? more realistic

Acute primary infection ?

4 fold rise in the AB level (between acute &

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convalescent phase) (or)

Presence of rubel a specific IgM
Diagnosis - Interpretation

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Rubel a vaccine 1 yr. age ---> immune; no risk
Exposed & seropositive ---> Fetus not at risk
Exposed & seronegative ---> serum 3-4 weeks

after exposure ---> infected if positive --->

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fetus at risk

Exposed & uncertain ---> serum with in 7 days

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---> positive ---> immune, no risk

Diagnosis - neonate
Guidelines:
Any one of the fol owing (to label as congenital

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rubel a infection)
A) Isolation of virus
B) Rubel a specific IgM ? cord/neonatal serum
C) Persistent/rising IgG titers

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Above + congenital defects = CRS
Isolation and Identification of virus

Nasopharyngeal / throat

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swabs taken 6 days prior or
after appearance of rash is a
good source of Rubel a
virus

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Using cel culture antigens

can be detected by
immunofluresecent

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Management

Antenatal infection:

Counselling

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Termination of pregnancy ? infection before 20

wks

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Congenital infection:

I/V/O Chronicity

Managed as a dynamic state rather than a static

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disease state

MGT. CONTD.

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Multidisciplinary approach
Med, Surg, Edu, & rehabilitative
Complete Ped, Cardiologic, Neuro, Ophthal &

Audiologic examn.

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complemented by CBC, Radiology & CSF evaluation

in asymptomatic patients

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Hearing & Visual Aids, Contact lens, Occ. & Physio.

therapy
RUB

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Role of `Ig'

Current recommendation:
Pregnant women known to have been exposed

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to rubel a, who do not want to terminate

pregnancy under any circumstances ? large

doses (20ml) should be administered

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Patient should be advised ? protection from

fetal infection cannot be guaranteed

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Prevention

Isolation key role in prevention of infection
Infected patients can shed the virus even up to

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12- 15 months of age & can be infective

Vaccination two approaches---Childhood

immunization with MMR vaccine at 15 months&

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post pubertal vaccination of adolescent girls
Congenital toxoplasmosis

Congenital toxoplasmosis

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Classic triad ? chorioretinitis, hydrocephalus,intracranial

calcifications

85 % - asymptomatic at birth

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Pathogen

Toxoplasma gondi --obligate, intra cel ular protozoan

parasite, important pathogen for fetus, neonate &

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immunocompromized patient
Pathophysiology

Cat- only definitive host- sheds mil ions of oocysts in the

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stool, for 2wks / more

Children & adults- susceptible if not immune,
Transmission by direct ingestion of oocysts, from

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uncooked meat

Congenital infection- parasites from maternal circulation

invade & multiply with in placental cel s before reaching

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the fetus

Contd...
Transmission from placenta to fetus - < 4wks to 16 wks
Transmission rate - 1st trimester -15 %

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- 3rd trimester -60%

- term ? 90 %

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Fetal disease severity ? inversely proportional to
gestational age
Outcome as a function of gestation

st

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Fetus infected in 1 trimester-die in utero/ neonatal

period, or have severe CNS disease & eye involvement

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nd

Fetuses infected in 2 & 3rd trimester: mild / sub clinical

disease in newborn period.

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Congenital infections after -Maternal chronic infections

are rare, can occur when mother is HIV infected

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Outcome Vs gestation

3rd

Ist trimester

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2nd trimester

trimester

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IUD

CNS/ eye disease

Post natal

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death

Subclinical/ mild disease
Toxoplasma clinical diagnosis

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Four recognized patterns

Subclinical

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infection

Neonatal

symptomatic

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disease

Symptomatic

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Sequelae /relapse

in first 3

in infancy/

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months of life

adolescence

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Specific clinical manifestations
Neurologic-microcephaly/ hydrocephalus, seizures,

opisthotonus, paralysis, swal owing difficulties,deafness,
encephalitis, intra cranial calcifications, endocrine

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dysfunction

Ophthalmologic-

MC cause for chorioretinitis & visual impairment

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Focal necrotizing retinitis- usually bilateral, yel ow white cotton

whool patches

macular involvement- macular scars

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Diagnosis - newborn

Serology:

A) Investigation of choice ? IgM assay in the cord or

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neonatal serum

B) Method of choice ? ISAGA (acceptable-IgM DS-

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capture ELISA)

IgA anti P30 antibodies by ELISA : Encouraging

IgE ELISA ? upcoming modality

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Prenatal diagnosis

Options

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a) Isolation

b) Serology

c) Non-specific tests

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Cordocentesis

PCR - AF

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a) Risk of fetal loss 0.3/1000

b) Isolation -72% sensitive

c) IgM serology ? 28% sensitive

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d) <24 wks. not useful

Method of Choice

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if available

(a study of 746 pregnancies)
Guidelines for evaluation

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A) History & physical examination

B) Ophthalmology & neurological assessment

C) CBC, LFT, G6PD assessment, cranial CT

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D) CSF ? cytology, biochem, IgG & IgM AB

E) Serological tests, isolation

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F) ABER

Contd...
Ig G Avidity testing : differentiates acute Vs remote

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infection

PCR ? can detect Toxoplasma in peripheral blood buffy

coat, CSF & amniotic fluid

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sensitivity is >90% -between 17-21 wks gestation
50-60%- after 21 wks
Other diagnostic testing
PBC- leukocytosis/ leukopenia,lymphocytopenia,

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monocytosis, eosinophilia [ >30%] & thrombocytopenia

LFT& Renal function tests

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G6pd screen- before starting sulfadiazine

Quantitative Igs

CSF analysis

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Contd...

BERA-
CT head [plain]: calcifications scattered in white matter,

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basal ganglia, periventricular, Hydrocephalus: peri
aqueductal obstruction, Cortical atrophy & porencephalic
cysts

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Acute toxoplasmosis- tachyzoites
Acute & Chronic toxoplasmosis-cysts in tissues & body

fluids

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Tissue / mouse culture:from peripheral blood buffy coat/

placenta- takes 1- 6 wks
Management Of mother & infant

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Mother: spiramycin- before 18 wks- til term, If fetus is

not infected by 18 wk (AF PCR)

Sulfadiazine alone : Fetal infections before 17 wks

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Pyrimethamine,sulfadiazine& folinic acid-

Confirmed fetal infections after 18 wks
Amniocentesis couldnot be performed

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All acute maternal infections after 24 wk

Management

In all acute infections during pregnancy ? amniotic fluid PCR

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should be performed

Ultrasonographic monitoring of ventricular size is also

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important
Contd...
Therapeutic abortion & patient education
Neonatal management-therapy is recommended

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regardless of symptoms
To prevent sequele
To resolve acute symptoms
To improve outcomes
Drugs act against tachyzoites only--so extended therapy ?up

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to 1 yr

Neonatal management
Pyrimethamine-

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- first 2 days- 1mg/kg, 12th hrly
- 2-6 months- 1mg/kg/day
- Til 1yr-1mg/kg thrice weekly
- symptom resolution ? first few weeks
Prednisone- 0.5mg/kg/dose, 12th hrly

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-active CNS disease & active chorioretinitis, til acute

symptoms resolve
Contd...

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Ventricular shunting- for hydrocephalus
Multidisciplinary approach
Co-existing HIV infection--treat similar y, add anti retro

viral drugs, watch for bone marrow toxicity

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Thank you
MCQs
Which of the following confer(s) passive

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immunity:

Hepatitis B vaccine
MMR vaccine
Hepatitis B immunoglobulin

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Infection with measles virus

Immunoglobulins are made:
In a laboratory from deactivated viruses and bacteria
From the plasma of a person in the acute phase of an

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infectious Disease

From the pooled plasma of blood donors
From protein produced artificially in a laboratory

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The most suitable site for intramuscular

vaccination is:
Anterolateral aspect of the thigh
Deltoid area of the upper arm

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Fatty area of buttock
Anywhere in buttock