Congenital Viral Infection.

 

Definition: Congenital viral infection is defined as mental or physical traits,          anomalies, malformations, diseases occurring in a neonate due to a viral influence occurring during gestation up to the moment of birth.

 

Teratogenesis: It is the production or induction of malformation especially of a developing embryo or a foetus.

 

      The principles for a virus to cause a congenital infection are:

 

• Ability of the virus to infect the pregnant women and transmit it to the foetus.
  
  
• The stage of gestation at which the infection occur.
  
  
• The ability of the virus to cause damage to the foetus:
  
  a. Directly
  b. Indirectly- By altering the foetal environment.
  
  

Pathogenesis of congenital viral infections:-

 

 

 

 

 

Common congenitally transmitted viral infection

 

Virus	Incidence(per 1000 live births)
Rubella	0.1-0.7
Cytomegalovirus (CMV)	5-25
Herpes simplex virus (HSV)	0.03-0.5
Varicella zoster virus (VZV)	Rare
Hepatitis B virus (HBV)	0-7
Enterovirus	Rare
Parvovirus B 19	Rare
Human Papilloma Virus (HPV)	Rare
Human Immunodeficiency Virus(HIV)	Variable

 

Of these Rubella and CMV are teratogenic. The others are not known to be teratogenic.

 

1. Cytomegalovirus:-  It is a beta-Herpesvirinae, also called as human herpes virus-5

  

• Incidence- 5-25/1000 live births
• Mode of transmission: While birth is the most common mode. However transplacental and through breast milk also transmission is possible.
• 80 % of the newborns with CMV infection are asymptomatic.
• In 10 % the infection causes severe hearing loss and deafness.
• In 5-10 % of the neonates it can cause a grave disease called Congenital CMV inclusion disease.
•  Clinical features:
1. IUGR
2. Jaundice
3. Hepatosplenomegaly
4. Thrombocytopenia
5. Microcephaly
6. Intracranial calcification
7. Retinitis
   
   

• Mortality rate is 30 %.
• Prenatal diagnosis:

1.      Ultrasonography of abdomen to look for foetal defects like microcephaly, cerebral calcification.

2.      Previously amniotic fluid culture was done and cytopathic effect of typical owl eye appearance was looked for.

3.       Now amniocentesis and cordocentesis is done and IgM detection is done.

4.      Recently PCR has also been used and is very sensitive and specific

 

2. Herpes simplex virus:-  It is a alpha-Herpesvirinae, also called HHV1, 2.

 

• Congenital herpes infection is almost always caused by HHV-2.
• Incidence – 0.03-0.5/1000 live births
• Mode of transmission: Mostly during birth.
• Almost always symptomatic.
• Disease presents in 3 different ways:

 

1. Localized disease of the skin, eye, and mouth.
2. Encephalitis with or without localized lesions.
3. Disseminated disease with multi-organ involvement. Has mortality as high as 80 %.

• Prenatal diagnosis: -
  Clinically lesions may be visible; PCR of foetal blood obtained by cordocentesis may be done.

 

 

3. Varicella Zoster Infection:  It is an alpha Herpesvirinae. It is also called HHV-3

 

• Incidence is rare
• The features of the disease vary with the time during gestation when the primary VZV infection took place.
• Maternal chickenpox during the 1^st half of pregnancy may cause congenital malformations like: Chorioretinitis, Cerebellar cortical atrophy, Hydronephrosis and cutaneous, body, leg defects.
  
  
• Later in pregnancy the foetus expresses congenital varicella lesions which gradually fade away.
  
  
• Rarely if the mother develops VZV infection in the last few days of pregnancy and the baby gets exposed just before or during the birth with the absence of antibodies in maternal blood then there is a chance of a very serious disseminated form of the disease with a short incubation period less than 2 weeks and is generally fatal. Presenting with severe lesions on the skin and organ damage and failure.
  
  
• Lab Diagnosis: Tzanck smear of the lesions can be used.
• Treatment: VZIG or ZIG is given to the neonate or mother as and when detected. Vaccination is contraindicated in pregnancy.
  
  

4. Hepatitis B virus infection: It is an orthohepadnavirinae member.

 

 

• Incidence is 0-7/1000 live births.
• It may occur anytime during perinatal life but more common during the birth process and the risk is higher when the acute maternal disease occurs during the last trimester of pregnancy.
• Most cases are acquired from mothers who are asymptomatic carries of Hepatitis B.
• Foetal acquisition risks are greater if the mother is :
  
  
1. HepBe Antigen positive and HepBe antibody negative.
2. Has detectable levels of serum specific HepB DNA Polymerase.

 

• Most of the congenitally acquired Hepatitis B neonates develop progressive chronic disease or about 10-20% become carriers for life. These carriers are at a higher risk of developing hepatocellular carcinoma.
• Lab diagnosis: detection of hepatitis B serum markers in maternal serum followed by screening of the child for the disease.
• Treatment: All infants born to mothers who are HBs Antigen positive should be given Hepatitis B immunoglobulin and Hepatitis B vaccine immediately within 24 hrs of birth followed by vaccination at 1 and 6 months of age.
• WHO has recommended for hepatitis B vaccination being included in national immunization programme.
  
  

 

 

5. Enterovirus:

 

• Polio virus: - Transplacental transmission possible but is rare.
                         Intrauterine death and abortions have occurred.
  
  
• Coxsackie B virus: - Mode of transmission is mainly during birth but transplacental and postnatal transmission is also possible.
                                     Severe Myocarditis, Encephalitis, Sepsis like infection can occur.
  
  
•   Echovirus: - Usually gives rise to respiratory and GIT diseases.
  
  
• Incidences of all the conditions are rare.
  
  

 

 

 

 

 

6.  HIV Infection:-

 

• Paediatric AIDS: - In the neonates the immune system is yet to develop fully hence HIV congenital infection has a devastating effect.
• Clinical symptoms appear by 2 years of age and death follows in another 2 years.
• Incidence of HIV is variable from place to place.
• Mode of transmission to foetus may be transplacental during birth or after birth. During and after birth are more common.
• Clinical features:-
  
  

1.      Lymphoid interstitial pneumonitis.

2.      Severe oral candidiasis.

3.      Encephalitis.

4.      Generalized lymphadenopathy.

5.      Bacterial sepsis.

6.      Hepatosplenomegaly.

7.      Diarrhoea

8.      Growth retardation

• Prognosis is poor.
• If HIV in mother is detected as early as in the 1st trimester of pregnancy the rate of transmission of the disease to the child can be reduced considerably with the use of anti-retroviral drugs.

 

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7. Parvovirus B19:- 

 

• It is an erythrovirus.
• It may cause hydrops fetalis.
• Foetal death may occur due to severe anaemia.
• Teratogenicity is not known.
• Death before 20^th week of pregnancy.

 

8. Human papilloma virus:

 

• HPV 6, 11 may give rise to benign laryngeal papillomas in later life.
• Most common route of transmission is during birth.
• Most of the cases children are chronic carriers.

 

 
 

  

Common viruses and their Modes of transmission

 

Virus	Terato-genicity	Modes of transmission
		Transplacental	During birth	Post-natal
Rubella	Present	+	-	Rare
CMV	Present	+	++	+
HSV	?	+	++	+
VZV	?	+	Rare	Rare
HBV	?	+	++	+
Enterovirus	?	+	++	+
HIV	?	+	++	+
ParvovirusB19	?	+	-	Rare
HPV	?	-	++	-

 

 

The outcome of viral diseases

 

 

Virus	Death of foetus and abortion	Clinically apparent disease soon after birth	Long term persistence of active infection or as a carrier
Rubella	+	+	+
CMV	+/-	+	+
HSV	+	+	+
VZV	+	+	+
HBV	-	-	+
Enterovirus	+	-	+/-
HIV	-	+	++
ParvovirusB19	++	-	-
HPV	-	-	++