Download MBBS Pediatric PPT 5 Intra Uterine Infections Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Pediatric PPT 5 Intra Uterine Infections Lecture Notes


INTRA UTERINE INFECTIONS

Learning Objectives
Common IU infections
When to suspect IU infection
Hep B vertical transmission, Congenital rubel a syndrome

,Congenital toxoplasmosis

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

TORCHES CLAP

To ?Toxoplasma,

C ? Chicken pox

R ? Rubel a,

L ? Lyme's

C ? Cytomegalo virus,

A ? AIDS

H ? HSV,

P ? Parvo virus B 19

E ? Enterovirus,

S - Syphilis

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

FETUS & NEONATE

CONGENITAL

PERINATAL

POSTNATAL

CMV,TOXOPLASMA

HSV

VARICELLA

PARVO B19

RUBELLA

ENTEROVIRUS, HEP- B&C,

HEP- A

Prevalence:HBV infection

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

hepatitis B

India: Prevalence rate for HBsAg seropositivity 2-7 %
Pregnant women : 0.9% and 11.2
HBeAg seropositivity of 30% -56.8%
Carrier status

90% of affected infants develop chronic infection
30-50% of under-five children and 6% of children above

five years of age .

Chronic hepatitis B infection acquired in childhood

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

Hence, it is imperative to prevent mother to child

transmission.

Pregnancies with HBV

Risk of chronic infection 1/ age( inversely proportional to

age)

90% carriage rate for neonatal infection&

40-75 % vertical transmission rate

Intrapartum route > transplecental>breastfeeding
Hep B : Strategies for prevention
Universal screening of pregnant women

Case management of HBsAg-positive mothers and their

infants

Elective LSCS, continue breastfeeding

Immunoprophylaxis : Al infants born to mothers with

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
months.

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

When to suspect?

Three strategies ?

A) Routine / universal screening
B) Women with high risk factors

a) Multiple partners

b)Repeated BT's

c) Partner with STD

C) Symptomatic women

d) Unhygienic food habits

e) Rubel a non-immune

f) Occupational exposure

Contd...
Maternal H/o
Contact with a known infected case during pregnancy
History of non vesicular rash [ Rubel a/ parvo virus ]
Vesicular rash [varicel a & herpes simplex]
History of recurrent abortions
Contd...
Neonatal manifestations
P DA in a term/ near term neonate( Rubel a)
Clinical stigmata of IU infections: SFD,

hepatosplenomegaly, blue berry muffins,
microcephaly,chorioretinits, cataracts

Late onset neonatal cholestasis

CONGENITAL

MAIN FINDINGS

INFECTION

Rubella

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

CMV

microcephaly, periventricular
calcifications,jaundice,snhl

Toxoplasma

hydrocephalus, generalized
calcifications,chorioretinitis

Syphilis

osteochondritis,periosteitis,ssnuffles,rash

Herpes

skin lesions,keratoconjunctivitis,acute
encephalitis

Varicella

limb hypoplasia,scarring, GI tract atresis

LCMV

hydrocephalus, chorioretinitis,ic calcifications
Rubella: German Measles
Rubella is also cal ed as

3 d ay Measles or
German Measles.

Family ? Togaviridae
Genus - Rubivirus
In general belong to

Togavirus group

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

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

appearance of rash. suggesting immunologic basis

for the rash

In 20 ? 50 % cases of primary infections are

subclinical
RUB

RUBELLA

Incidence (Indian scenario):

Singh et al (1999):

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

non-immune

Tarbudkar et al (IJMM 2003):

IgG seropositivity ? 67%
IgM seropositivity ? 23%

How Adults acquire Infection ??

Acquired rubel a - via airborne droplet emission -from

the upper respiratory tract of active cases.

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

No carrier state: exists entirely in active human cases.

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

Malaise
Low grade fever
Morbil iform rash
Rash starts on Face &

Extremities

Rarely lasts more than 5

days

No features of the rash

give clues to definitive

diagnosis of Rubella.

Rubella rashes
Acquisition of immunity

Antibodies appear in serum as

rash appears & and antibody

titers rise as rash fades

Rapid rise in 1 ? 3 weeks
Rash with detection of IgM

antibodies -indicates recent

infection.

IgG antibodies persist Life

long

maternal antibody protection-

for 4 ? 6 months.

Congenital rubella syndrome

Teratogenic property of the infection was documented

by an Australian opthalmologist Greeg in 1941

Charachterized by classical triad of

- cataracts,
- cardiac disease
- SNHL

MC isolated finding SNHL
TRANSMISSION IN UTERO

VIREMIA

Inapparent Rubella

Clinical

Therapeutic abortion

Infection of pregnant woman

No transplacental

infection

Infection of Embryo and Fetus

N

Still birth

Miscarriage

Infant born with CRS

Defects manifest at birth

Defects manifest later

Fetal involvement as a function of

gestation

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

infection , cardiac defects & deafness

involvement

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

defects

17-22 wks ?36%
23-30 wks- 30 %
31-36 wks -60%
>36 wks ? 100%
RUB

Transmission & risk of fetal infection

100
90
80

60
50
40
30

20

<11

11-15

15-22 22-30

31-36

>36

Manifestations:Three groups

(Gregory et al): Transient

Reflect ongoing heavy viral infection

. Hepatosplenomegaly, hepatitis

Jaundice,

? Thrombocytopenia, blue-berry muffins

EXPANDED

? Interstitial pneumonia,

RUBELLA

? Hemolytic anemia

SYNDROME

? Adenopathy, long bone growth defects

Large AF, cloudy cornea, diarrhoea
RUB

Manifestations: Permanent

from defective organogenesis &

tissue destruction

-- Deafness ? MC (80%)

-- Salt & pepper retinopathy

CRS

-- CHD(PDA,Pulm stenosis)

--CNS anomalies ? microcephaly,

mental & motor retardation,

autism (6%)

RUB

Manifestations : Developmental

& late onset:

?
-- Endocrinopathies(IDDM ?MC(20%)

Thyroid dysfunction (5%))

--deafness, vascular effects

Progressive CNS disease,

--ocular damage
Congenital rubella- blue berry muffins
Metaphyseal lucencies

Diagnosis ? maternal infection

Clinical diagnosis ? unreliable; lab.diagnosis is

essential

Techniques a) Isolation ?nose, throat

b) Serology ? more realistic

Acute primary infection ?

4 fold rise in the AB level (between acute &

convalescent phase) (or)

Presence of rubel a specific IgM
Diagnosis - Interpretation
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 --->

fetus at risk

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

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

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

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

Above + congenital defects = CRS
Isolation and Identification of virus

Nasopharyngeal / throat

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

Using cel culture antigens

can be detected by
immunofluresecent
Management

Antenatal infection:

Counselling

Termination of pregnancy ? infection before 20

wks

Congenital infection:

I/V/O Chronicity

Managed as a dynamic state rather than a static

disease state

MGT. CONTD.

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

Audiologic examn.

complemented by CBC, Radiology & CSF evaluation

in asymptomatic patients

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

therapy
RUB

Role of `Ig'

Current recommendation:
Pregnant women known to have been exposed

to rubel a, who do not want to terminate

pregnancy under any circumstances ? large

doses (20ml) should be administered

Patient should be advised ? protection from

fetal infection cannot be guaranteed

Prevention

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

12- 15 months of age & can be infective

Vaccination two approaches---Childhood

immunization with MMR vaccine at 15 months&

post pubertal vaccination of adolescent girls
Congenital toxoplasmosis

Congenital toxoplasmosis
Classic triad ? chorioretinitis, hydrocephalus,intracranial

calcifications

85 % - asymptomatic at birth
Pathogen

Toxoplasma gondi --obligate, intra cel ular protozoan

parasite, important pathogen for fetus, neonate &
immunocompromized patient
Pathophysiology

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

stool, for 2wks / more

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

uncooked meat

Congenital infection- parasites from maternal circulation

invade & multiply with in placental cel s before reaching
the fetus

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

- 3rd trimester -60%

- term ? 90 %

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

st

Fetus infected in 1 trimester-die in utero/ neonatal

period, or have severe CNS disease & eye involvement

nd

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

disease in newborn period.

Congenital infections after -Maternal chronic infections

are rare, can occur when mother is HIV infected

Outcome Vs gestation

3rd

Ist trimester

2nd trimester

trimester

IUD

CNS/ eye disease

Post natal

death

Subclinical/ mild disease
Toxoplasma clinical diagnosis

Four recognized patterns

Subclinical

infection

Neonatal

symptomatic

disease

Symptomatic

Sequelae /relapse

in first 3

in infancy/

months of life

adolescence

Specific clinical manifestations
Neurologic-microcephaly/ hydrocephalus, seizures,

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

Ophthalmologic-

MC cause for chorioretinitis & visual impairment
Focal necrotizing retinitis- usually bilateral, yel ow white cotton

whool patches

macular involvement- macular scars
Diagnosis - newborn

Serology:

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

neonatal serum

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

capture ELISA)

IgA anti P30 antibodies by ELISA : Encouraging

IgE ELISA ? upcoming modality

Prenatal diagnosis

Options

a) Isolation

b) Serology

c) Non-specific tests

Cordocentesis

PCR - AF

a) Risk of fetal loss 0.3/1000

b) Isolation -72% sensitive

c) IgM serology ? 28% sensitive

d) <24 wks. not useful

Method of Choice

if available

(a study of 746 pregnancies)
Guidelines for evaluation

A) History & physical examination

B) Ophthalmology & neurological assessment

C) CBC, LFT, G6PD assessment, cranial CT

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

E) Serological tests, isolation

F) ABER

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

infection

PCR ? can detect Toxoplasma in peripheral blood buffy

coat, CSF & amniotic fluid

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

monocytosis, eosinophilia [ >30%] & thrombocytopenia

LFT& Renal function tests

G6pd screen- before starting sulfadiazine

Quantitative Igs

CSF analysis

Contd...

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

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

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

fluids

Tissue / mouse culture:from peripheral blood buffy coat/

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

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

not infected by 18 wk (AF PCR)

Sulfadiazine alone : Fetal infections before 17 wks

Pyrimethamine,sulfadiazine& folinic acid-

Confirmed fetal infections after 18 wks
Amniocentesis couldnot be performed
All acute maternal infections after 24 wk

Management

In all acute infections during pregnancy ? amniotic fluid PCR

should be performed

Ultrasonographic monitoring of ventricular size is also

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

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

to 1 yr

Neonatal management
Pyrimethamine-
- 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

-active CNS disease & active chorioretinitis, til acute

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

viral drugs, watch for bone marrow toxicity

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

immunity:

Hepatitis B vaccine
MMR vaccine
Hepatitis B immunoglobulin
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

infectious Disease

From the pooled plasma of blood donors
From protein produced artificially in a laboratory
The most suitable site for intramuscular

vaccination is:
Anterolateral aspect of the thigh
Deltoid area of the upper arm
Fatty area of buttock
Anywhere in buttock


This post was last modified on 07 April 2022