2. Congenital infections occur as a result of clinical or
subclinical maternal infection with a variety of agents.
Congenital infections can occur during pregnancy or
the peripartum period.
Primary infection of the mother results in greater risk
of consequences to the developing fetus.
Infection may result in:-
• Asymptomatic persistent infection with sequelae later in life.
• Early spontaneous abortion
• Congenital malformation
• Intrauterine growth restriction (IUGR)
• Premature birth, stillbirth
• Acute or delayed disease in the neonatal period.
2
3. The timing of infection during gestation affects the outcome.
First trimester infection may alter embryogenesis, with
resulting congenital malformations (congenital rubella)
Third trimester infection often results in active infection at
the time of delivery (toxoplasmosis, syphilis).
Infections that occur late in gestation may lead to a delay
in clinical manifestations until some time after birth
(syphilis).
Maternal immunity is effective and antibody is protective for
the fetus (rubella).
Maternal antibody may ameliorate the outcome of infection
or have no effect (CMV)
The placenta may function as an effective barrier.
3
4. Clinical Manifestations
• Clinical manifestations could vary
Asymptomatic at birth
Relatively mild non specific symptoms
Multisystem involvement with severe and life-
threatening complications.
Most congenital infections have over lapping non
specific signs and symptoms.
4
8. Congenital syphilis
• Results from transplacental transmission of T. Pallidum (a spirochete)
• Transmission can occur at any stage of pregnancy.
• The incidence of congenital infection in the offspring of untreated
infected women is high when they have primary or secondary
syphilis
• Unless treated the risk of transmission to the fetus approaches 100%
• Lack of prenatal screening for pregnant women is the most common
risk factor for congenital syphilis
Untreated maternal syphilis can result in
• Stillbirth/ peri natal death
• Premature delivery
• About half of survivors have long-term neurological sequelae.
8
9. Clinical Manifestations
• manifestations are divided into early and late stages.
• The early signs appear during the 1st 2 yr of life, and late signs
appear gradually during the 1st 2 decades.
• Early manifestations result from transplacental spirochetemia
and are analogous to the secondary stage of acquired syphilis.
• Approximately 66% of infected infants are asymptomatic at
birth (identified only during routine prenatal screening) ;
• If untreated, symptoms develop within weeks or months.
9
10. Early congenital syphilis
• Reticulo-endothelial/ haemotogical features
Generalised LAP and HSP
Haemolytic anaemia/thrombocytopenia/pancytopenia
Jaundice (unconjugated/conjugated or mixed)
• Mucosal features
Rhinitis (snuffles)
Mucous 'patches' seen on palate and lips
Peri oral and peri anal condylomata
• Cutaneous features
Maculo-papular eruption over buttocks and
lower torso, palms and soles
Bullous eruptions (pemphigus syphiliticus)
Desquamation
10
11. • Bone involvement
Osteo-chondritis, periostitis, osteitis .
Can lead to pseudo paralysis
• Neurosyphilis (rare at birth)
Meningitis
Eye involvement
Glaucoma
Chorioretinitis
uveitis
• Myocarditis
• Pneumonitis
• Renal involvement
nephritic or nephrotic
11
12. Late manifestation
• The late manifestations result primarily from chronic inflammation of
bone, teeth, and the CNS.
• Skeletal changes
– Frontal bossing (Olympian brow),
– Unilateral or bilateral thickening of the sternoclavicular third of the
Clavicle (clavicular or Higoumenaki sign),
– An anterior bowing of the midportion of the tibia (saber shins),
– Convexity along the medial border of the scapula (scaphoid scapula).
• Dental abnormalities are common and include
– Hutchinson teeth :- peg or barrel-shaped upper central incisors
– Abnormal enamel, which results in a notch along the biting surface;
– Mulberry molars, characterized by a small biting surface and an
excessive number of cusps.
– Defects in enamel formation lead to repeated caries and eventual tooth
destruction.
12
13. • A saddle nose ; a depression of the nasal root, is a result of
syphilitic rhinitis that destroys the adjacent bone and cartilage.
A perforated nasal septum may be an associated abnormality.
• Rarely
– Juvenile paresis:- an uncommon latent meningovascular
infection, typically presents during adolescence with
behavioral changes, focal seizures, or loss of intellectual
function.
– Juvenile tabes with spinal cord involvement
– Cardiovascular involvement with aortitis are extremely
rare.
13
14. • A hypersensitivity phenomenon.
• unilateral or bilateral interstitial keratitis leading to corneal
opacification and complete blindness.
• Less common ocular manifestations include
• choroiditis, retinitis, vascular occlusion, and optic atrophy.
• Eighth nerve deafness may be unilateral or bilateral,
progresses to permanent deafness.
• The Clutton joint represents a unilateral or bilateral synovitis
involving the lower extremities (usually the knee), which
presents as painless joint swelling with sterile synovial fluid;
• Soft tissue gummas (identical to those of acquired disease)
14
15. Diagnosis
• Dark-field microscopy or direct fluorescent antibody– T. pallidum testing on specimens
from skin lesions, placenta, or umbilicus is diagnostic of primary syphilis
• polymerase chain reaction (PCR).
• Serologic tests for syphilis remain the principal means for diagnosis.
1.Nontreponemal tests:
Venereal Disease Research Laboratory (VDRL)
Rapid plasma reagin (RPR) tests,
Are highly sensitive in early infection.
The quantitative results of these nontreponemal tests correlate with disease
activity
Helpful in screening.
Titers increase with active disease
treatment failure or reinfection,
Decline with adequate treatment.
Usually become nonreactive within 1 yr of adequate therapy for primary syphilis
Within 2 yr of adequate treatment for secondary disease.
With congenital infection, these tests become nonreactive within a few months
after adequate treatment.
Certain conditions such as autoimmune diseases may give false-positive VDRL results
in the serum (but not in the CSF),
15
16. 2. Treponemal tests
• Measure antibody specific for T. pallidum,
• T. pallidum hem agglutination assay (TPHA),
• the fluorescent treponemal antibody absorption (FTA-ABS) test,
and
• the T. pallidum particle agglutination (TPPA) test.
• Used for confirmatory testing of positive results of the
nontreponemal antibody tests.
• Treponemal antibody titers become positive soon after initial
infection and usually remain positive for life,
• Do not correlate with disease activity and are not quantified.
• They are useful for diagnosis of a 1st episode of syphilis and for
distinguishing false-positive results of nontreponemal antibody tests
Limited usefulness in the evaluation of response to therapy and
possible reinfections.
16
17. • The interpretation of nontreponemal and treponemal serologic
tests in the newborn may be confounded by maternal IgG anti
bodies that are transferred to the fetus.
• Passively acquired antibody is suggested by neonatal titer at
least 4-fold (i.e., a 2-tube dilution) less than the maternal titer.
This can be verified by gradual decline in antibody in the
infant, usually becoming undetectable by 3–6 mo of age.
• The diagnosis of neurosyphilis is established by demonstrating
pleocytosis and increased protein in the CSF, and a positive
CSF VDRL test along with neurologic symptoms.
• The CSF VDRL test is very specific but relatively insensitive
(22–69%) for neurosyphilis
17
18. Treatment
• Adequate maternal therapy should eliminate the risk for congenital syphilis as
T.pallidum is extremely sensitive to penicillin
• For those <4 weeks
– Aqueous penicillin G (100,000–150,000 U/kg/24 hr divided every 12 hr
IV for the 1st wk of life, and every 8 hr thereafter) or
• For those alder than 4 weeks
– Aqueous crystalline penicillin G, 50,000 U/Kg /dose every 4–6 hr for 10
days
– procaine penicillin G (50,000 U/kg IM once daily) given for 10 days.
• Neurosyphilis
– Aqueous crystalline penicillin G, 200,000 to 300,000 U/kg/day, given
every 4–6 hr for 10–14 days in doses not to exceed the adult dose
• Treated infants should be followed up serologically to confirm decreasing
nontreponemal antibody titers.
18
20. Congenital toxoplasmosis
Toxoplasma gondii is a parasitic organism.
The domestic cat is the primary host.
Infection can be contracted by
• Ingesting oocytes present in faecal material of infected hosts
• Eating pseudocysts present in undercooked meat.
Most women have no symptoms.
•15% of women report acute flu-like illness with lymphadenopathy.
Sero prevalence in Ethiopians approaches 80%.
Risk of fetal infection is lowest in early pregnancy but most fetuses infected early have
severe consequences.
Risk of fetal infection Severe consequences of infection
1st trimester 17% 70%
3rd trimester 65% <1%
20
21. Clinical Manifestation
Infants congenitally infected with Toxoplasmosis can be
•completely asymptomatic
•unaffected at birth and manifest problems later
•severely affected in-utero and at birth
. The classical tetrad described by Sabin in 1942 includes
•hydrocephalus/microcephaly
•chorioretinitis
•convulsions (link)
•calcification
• usually intracerebral
Haemopoietic manifestations include
•hydrops due to anaemia
•rash due to thrombocytopenic purpura
• blueberry muffin appearance
•lymphadenopathy
•hepatosplenomegaly
21
22. Neurological manifestations include
• convulsions
• hydrocephalus with bulging fontanels
• microcephaly
• chorioretinitis can be present early or develop later
Generalised features include
• lethargy and malaise
• poor feeding
• Jaundice
Diagnosis
• Mainly serologic :- IgM specific
IgG
• PCR from CSF
• CT Scan
22
23. Management
• Loading dose of Pyrimethamine 2mg/kg/24hrs for 2 days
followed by: 1mg/day for 2-6mo then 3x/wk for total of 1 year +
• Sulfadiazine (100 mg/kg/day divided bid PO), +
• Leukovorin (5–10 mg given Every other day PO).
• Prednisone (1 mg/kg/day divided bid PO)
• Active chorioretinitis involves the macula or otherwise
threatens vision
• CSF protein is >1,000 mg/dL at birth,
• Ongoing opthalmological and developmental follow up.
Prevention
• Avoid eating raw meat
• Avoid contact with cats feaces
• Screening of pregnant women
• Early treatment of infected pregnant mothers
23
24. Congenital rubella syndrome
• Most people develop immunity (if not immunised)
during childhood. In non-immunised populations, 10-
20% of women of child bearing age are susceptible.
• Re-infection occurs in around 2% of people but is
generally subclinical.
• Rubella vaccination is effective in almost totally
eliminating congenital rubella infection - provided
coverage remains high.
• Clinical features
• Most congenital infection is the result of primary
maternal infection.
24
25. Onset of Maternal infection and Fetal out come
Onset of maternal
infection
Fetal Complications
<12 weeks Congenital rubella syndrome (>90%)
12-18 weeks Sensorineural deafness (20%)
>18 weeks Rare
25
26. Congenital rubella syndrome is a severe, disabling condition
• Eye disorders (cloudy cornea/cataracts, chorioretinitis,
microphthalmia)
• Sensorineural deafness
• Cardiovascular (PDA and /or pulmonary stenosis )
• Microcephaly
• Growth restriction
• Haemopoietic disorders
• Hepatosplenomegaly
• Lymphadenopathy
• Thrombocytopenia
• Anaemia
• Extramedullary haematopoiesis (blueberry muffin skin
rashes)
• Long bones radiolucencies seen on X-ray
• Pneumonitis with associated respiratory signs
26
27. Investigations
Fetal diagnosis is possible from
• Cord blood IgM
• Rubella PCR of amniotic fluid
Postnatal diagnosis is by
• Detection of rubella-specific IgM antibody can be helpful in
diagnosing recent postnatal infection or congenital infection in the
newborn
•rubella-specific IgG serum concentrations that are increasing also
suggest congenital infection
• Isolation of rubella virus from body secretions
Other investigations that provide clue to the complications of CRS.
27
28. Management
• The best therapy for CRS is prevention
• The treatment of a newborn with CRS is supportive.
• Rubella immunization is given for all children with
measles and mumps (MMR)
• This vaccine is not available in our country
• It is said to be rare in our country reason being most
women acquire the virus during child hood
28
29. Congenital CMV infection
• CMV is a ubiquitous herpes virus that usually causes only mild
disease.
• It is commonly acquired in infancy and childhood through saliva
sharing
• Around 1% of non-immune women develop primary CMV in
pregnancy,
• approximately 50% of their fetuses become infected.
• Congenital CMV can develop from maternal primary infection or re-
activation
• Perinatal and postnatal infection can occur through birth canal
secretions,breast milk or blood.
• primary infection more likely to result in sequelae.
• Risk for sequelae is highest after fetal infection during the first
trimester.
29
30. Symptomatic babies can be variously affected including
•Growth restriction
•Haematological problems
•Thrombocytopenia and purpura are common
•Anaemia, neutropenia, lymphocytosis are occasional
•Hepatosplenomegaly
•Lymphandenopathy
•Neurological problems
•Poor tone and poor suck
•Seizures
•Microcephaly
•Chorio-retinitis
•Cerebral calcification (classically peri ventricular)
•Deafness (can be a late manifestation and is the most common cause of
sensory-neural hearing loss)
• Pneumonitis
• Colitis
• Hepatitis
• Dental defects
Clinical features
30
31. Investigations
A high index of suspicion is needed.
Investigation is warranted in
• Babies whose mothers have developed primary infection in
pregnancy or have 're-activated'
• Growth restricted infants with low platelet count
Tests performed include
• IgM assayed from cord/baby blood ( tests have poor sensitivity)
• Viral culture from urine (the test of choice)
• Throat/saliva swab sent for PCR can give a more rapid answer.
• Culture and PCR should be performed as soon as possible in the
first 2 weeks of life as CMV detected after this time can
indicate peri/post natal infectionon
31
32. Management
General measures include management of
• Nutritional problems
• Haematological disturbances (low platelets)
• Respiratory disease
Specific treatment
• Foscarnet or ganciclovir (long-term benefits in congenital infection is
not established).
• Used for life-threatening CMV infection (particularly post-natal
disease in preterm babies)
• Chorio-retinitis (will not reverse damage that has already occurred).
Long-term follow-up is essential with attention to
• Management of neurological sequelae
• Hearing testing, continued for the first 2 to 5 years of life, due to the
risk of late-onset deafness
32
33. Prevention
Use of standard precautions is important.
– Prevention of transfusion acquired infection
• use leukocyte filtered or CMV negative blood
– Aseptic measures
• hand-washing,
–especially after nappy changing
• prevents nosocomial spread of infection
33
34. Herpes Simplex Virus (HSV)
• Neonatal infection is usually the result of HSV 2
• Associated with genital infection.
• many women (and men) remain asymptomatic
• HSV can remain latent for long periods, with shedding or re-activation
occurring at any time.
• In cases of neonatal infection, most women do not give a history of active
genital herpes at the time of delivery.
• Babies born to mothers with a primary genital infection at the time of
delivery have a 50% risk of developing infection, compared with <5% in
cases of recurrent infection present at the time of delivery.
• 90% are acquired during passage through the birth canal or through
ascending infection
• 5% have 'congenital' HSV infection
• 5% have post-natally acquired infection
34
35. Clinical features
Usual clinical presentations are
Skin/eye/mouth (SEM) localised disease
• Isolated vesicles or 'crops
• Other skin reactions including zoster-like eruptions
• Keratoconjuncitivitis with dendritic ulcers
• Choriodoretinitis
• Single of multiple oral vesicular lesions can be present
Disseminated disease
•poor prognosis, with over 70%mortality untreated
•Non-specific presentation with
Lethargy , poor feeding ,fever ,convulsion ,apnoea ,respiratory distress
hepatosplenomegaly ,jaundice ,DIC
Pneumonitis
Meningo-encephalitis
35
36. Investigations
Immunoflourescence staining of specimens
Viral culture can take 5 days to demonstrate typical cytopathic changes.
Lumbar puncture with CSF sent for PCR and culture.
• However, negative PCR testing on CSF does not completely rule out
HSV infection,
EEG and brain imaging are useful adjuncts in cases where diagnosis of
CNS infection is in doubt.
Serological studies are of little value early on as
• IgM may take 2 weeks to appear
• IgG titres may not rise in babies and may reflect maternal antibody
status.
36
37. Management
Specific early treatment is with
• Acyclovir 10mg/kg IV three times daily for a total of 14 to 21 days
• Vidarabine 15mg/kg 12 hourly, IV is also effective but is more cumbersome
Supportive care as always is vitally important with attention to general care.
Eye lesions require topical treatment (Acyclovir eye ointment)
• ophthalmological referral is essential.
Prognosis
• Mortality and morbidity rates for disseminated and CNS disease are very high,
• Even in the setting of localised SEM disease, 10% have long-term neurological
sequelae.
• Recurrent skin and eye eruptions can occur.
Oral acyclovir has a role in this setting.
37
38. Prevention
Early detection and management of genital herpes in all
pregnant mothers
LUSCS should be performed in mothers with active genital
herpes, particularly primary infection,
Swabs from the baby's eyes and throat should be sent and if
positive, the baby treated with acyclovir systemically
Babies born vaginally in the face of active genital lesions should be
treated systemically.
.
38
