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