1. NEONATAL HERPES SIMPLEX VIRUS
INFECTIONS
PCNA,APRIL 2013 ISSUE
BY
MAHISHMA.K

2. • “Herpes” – from the Greek “to creep, crawl”
• “Herpetic eruptions” were described as early
as 100 AD
• 1960’s – HSV1 and HSV2 differentiated

3. • VIRUS :-
• Herpes Simplex Viruses(HSV-1 &HSV-2) belong
to alphaherpesviridae family
• They are large and encapsulated with a
icosahedral necleocapsid arranged around a
linear double stranded DNA core.

4. VIRAL STRUCTURE
Core: Consists of a single linear molecule
of dsDNa in the form of a torus
Capsid: Surrounding the core w/ a
100 nm diameter and 162 capsomeres
Tegument: Consists of viral enzymes
Envelope: Outer layer composed of
altered host membrane and a dozen
of viral glycoproteins

5. VIRAL STRUCTURE
• There is considerable cross-reactivity between
HSV-1 and HSV-2 glycoproteins
• Unique antigenic determinants exist for each
virus
• Eleven glycoproteins have been identified
which mediate attachment, penetration and
provoke immune responses

6. • TERMINOLOGY
• Primary infection:- acquisition of HSV-1 or 2
without prior exposure to either virus.No
preformed antibodies.
• Nonprimary infection:- acquisition of HSV 2
infection in an individual with prior HSV-1
antibodies or vice-versa.
• Reactivation:-it is the isolation of same type of
virus from genital lesions as that of pre-existing
antibodies.

7. • Symptomatic shedding:- presence of genital
lesions charecteristic of HSV and isolation of
HSV 1 or 2 from the lesions.
• Subclinical shedding:-isolation of HSV-1 or 2
from the genital mucosa in the absence of
lesions.

8. • Genital infections during pregnancy:-
• Genital herpes infections are caused by HSV1 & 2 and
are mostly asymptomatic both in pregnant(two-third)
&non pregnant women.
• Study states that,
HSV 2 seroprevalance among pregnant women is
estimated to be between 20 to 30% and around 10%
of seronegative women are living with a seropositive
partner, thus increasing the risk of transmission.
Women with history of genital herpes prior to herpes
have higher risk of recurrence during pregnancy(75%)
or prodromal symptoms or active lesions(14%).

9. • For neonatal transmission, women must be shedding
virus symptomatically or asymptomatically around the
time of delivery.
• The risk of transmission of HSV to neonate is higher
with primary infection acquired closer to the time of
delivery and less risk with recurrant infections.
• This is explained possibly by:-
(1).decreased transplacentally acquired antibody levels
in the neonate
(2)exposure to increased quantities of virus.

10. • However the risk of neonatal transmission
through a recurrence of infection during
pregnancy is low.

11. NEONATAL HERPES
• HSV infection in a newnate is uncommon with an
incidence of 1 in 3200 deliveries.
• However,when compared with other infections like
syphilis,rubella,toxoplasmosis and rubella its
incidence is higher.

12. • Factors influencing transmission of HSV to neonate:-
• (1)type of maternal infection(primary/secondary)
• (2)maternal antibody status
• (3)mode of delivery(vaginal/caesarean section)
• (4)duration of rupture of membranes
• (5)type of HSV(1 or 2)

13. • Type of infection:-
neonatal transmission is higher with primary or non
primary infections of the mother and less with
recurrent infections.
• Maternal antibody status:-
risk of transmission is higher with primary infection
and less with reactivation.
• Type of HSV:-
studies have shown an higher incidence of transmission
of HSV 1 to neonate irrespective of primary or
recurrent infection.

14. • Caesarian delivery has been proved to be effective in
preventing the transmission.
• Longer duration of rupture of membranes increases
the risk of transmission
• Study also points that instrumentation during delivery
and use of fetal scalp electrodes(FSE) leading to
disruption of the barrier also increases the risk
significantly.

15. • PREMATURITY:-
prematurity as a risk factor for acquisition of HSV is not
well established.
However, the incidence of HSV is more in preterms than
that of term babies and is associated with significant
mortality & morbidity.

16. • NEONATAL HSV DISEASE CLASSIFICATION:-
• It is acquired during:
(1)in utero – 5%
(2)peripartum – 85%
(3)postnatal – 10%
It is classified as:-
(1)Disseminated disease – 25%
(2)CNS disease – 30%
(3)skin.eye & mouth disease – 45%

17. • In utero:-
• It is a rare entity and occurs approximately in 1 in
300,000 deliveries.
• Affected babies present with a triad :-
• (1)cutaneous- scarring,rash,pigmentation,aplasia
cutis
• (2)opthalmologic-micropthalmia,chororetinitis,optic
atrophy
• (3)neurologic-microcephaly,neurologic calcifications
and encephalomalacia.

18. Archival Photo:
HSV “In Utero”
Healed by Tim e
O f Birth – W ith
M icrocephally

19. • Disseminated disease:-
• Prior to antiviral therapy,it accounted for ½ to 1/3 rd the
neonatal HSV disease.
• Now incidence has reduced to 25% of all HSV infections.
• Usually presents around 10-12 days of life.
• It involves multiple organs including
CNS,lungs,liver,adrenal along with SEM
• Vesicular rash may be present but is not seen in around
20% of cases with disseminated disease.
• They present with viral sepis including respiratory
failure,hepatic failure and DIC.
• Death may occur due to severe coagulopathy.

21. • CNS DISEASE:-
• 1/3rd of neonatal herpes disease present as
encephalitis and are categorized as CNS disease.
• Present lately at 16-19 days of life.
• Clinical features include:-
• seizures-focal/generalized
• lethargy
• irritability,poor feeding
• temperature instability and bulging anterior
fontonalle
• Skin lesions are seen in 60 to 70% of the babies

22. • In the absence of skin lesions,presentation is very
similar to other causes of encephalitis.
• Unlike herpes encephalitis in older age group which
shows a higher prediliction to temporal lobe,
neonatal herpes involves multiple areas of brain.

23. • Skin,Eye,Mouth disease:-
• It accounts to 45%of the cases.
• Vesicular rash is seen in 80% of the cases with SEM
disease.
• It is usually seen around 10 to 12 days of life.
• Disease is limited to skin,eye,mouth/mucus membranes.
• It is associated with a good outcome without any
disabilities after 1 year of treatment.

24. CUTANEOUS LESIONS

25. VESICULAR LESIONS HSV

26. HSV 2 Arm Lesions
9 Days of Life
Presenting Lim b in a 34 W eek
Prem ature Infant

27. • Evaluation of a neonate with suspected HSV
infection:
• Viral culture:-
• isolation of HSV by culture is a definitive diagnostic
method.
• Conjunctiva,nasopharynx,mouth and anus are
swabbed to get the samples.
• CSF and blood can also be used for culture.

28. • PCR:-
• CSF can be subjected to PCR for identification of
Herpes infection.
• Study shows that overall sensitivity of the test is about
75% to 100% and specificity is 71% to 100%.
• A negative PCR doesnot rule out the disease as it may
be negative in early stages of the diasease where the
viral load is low.

29. • Serological testing:-
• It is not recommended,as there is transplacentally
acquired maternal Ig G antibodies.
• Hence,there is no role for serology in neonatal HSV
diagnosis

30. • Specimens to be obtained before starting antiviral
therapy:-
• CSF analysis(culture & DNA PCR)
• Swab for viral culture from vesicles,suspicious areas and
mucus membrane lesions for viral culture or PCR.
• Swab from mouth,conjunctiva,nasopharynx and
rectum(surface cultures) or PCR
• Whole blood for HSV DNA PCR
• Blood to determine alanine aminotransferase(ALT)

31. • TREATMENT OF NEONATAL HSV DISEASE:-
• ACYCLOVIR is the drug of choice because of its safety
profile.
• Current recommendation states that:-
acyclovir 60mg/kg/day q8th hrly
14 days in SEM
21 days in
CNS/disseminated

32. • At the end of therapy CSF PCR should be done in all the
neonates.
• It should be done to document a negative result.
• If it is positive, the therapy is continued till the PCR
comes negative.
• Study states that detection of HSV in CSF after
completion of treatment has been associated with
poorer outcomes.
• The significance of blood DNA PCR is not studied
well,hence serial measurements of BLOOD DNA PCR is
not recommended.

33. • SUPPRESSIVE THERAPY AFTER TREATMENT:-
• Trials on the use of antiviral suppressive therpay after
standard treatment of HSV has shown decreased
incidence of morbidities and neurological sequale.
• Current recommendation for suppressive therapy is :-
Oral acyclovir : 300mg/m2/dose TID for 6 months
• Absolute neutrophil count should be monitored at 2
and 4 weeks, later on every month.

34. • Approach to a infant exposed to HSV during maternal
genital HSV infection:-
• Recommendations on management of neonate
exposed to HSV takes into consideration:-
• maternal serological status
• presence of genital lesions at the time of delivery and
• mode of delivery.

35. • TESTING OF WOMEN IN LABOR:-
• All women with genital lesions charecteristic of HSV at
the time of delivery should be assessed for:
• Status of infection – primary/recurrent
• Maternal serology – HSV1/HSV 2
• PCR for viral culture from genital lesion swabs.

36. • Management of neonate born to mother with lesions
at delivery and a prior history of genital herpes before
pregnancy:-
• For women with previous history- the chances of
lesions at the time of delivery being recurrent is high
,the risk of transmission to the infant is low.

37. After 24hrs of delivery,collect surface cultures and
blood DNA PCR is done.
If clinically well at 48hrs tests are positive
Negative results
send for
CSF for culture &
Baby can be discharged HSV PCR
Further evaluation only if
There are any signs start iv acyclovir

38. • CSF culture and PCR
Negative positive
(HSV infection)
Preemptive treatment for treat as neonatal
10 days with i.v acyclovir HSV disease

39. • Management of a neonate born to mother with lesions
at the time of delivery and no prior history of genital
herpes:-
• After 24 hrs birth surface cultures and CSF PCR and viral
culture is sent as the risk of transmission to infant is
high.
• Simultaneous intravenous acyclovir is started.

40. • If maternal infections are suggestive discontinue
of reurrent infection and acyclovir
neonate asymptomatic re evaluation
only if
symptomatic
• If maternal studies are S/O
Primary infection & neonate asymptomatic preempitive
But negative CSF analysis treatment -
10days
i.v acyclovir

41. • If mother - primary infection
Neonate surface cultures are positive treat as HSV
CSF PCR positive disease
If mother – primary infection
Surface culture positive in neonate treat as HSV
But CSF PCR is negative infection

42. • Strategies for prevention of neonatal herpes:-
• Caserian delivery:-
• delivery of the baby by C-section in women with active
genital lesions can reduce the infant’s risk of acquiring
HSV.
• it is more effective if performed before the rupture of
membranes.
• However,C-section is not recommened if there are no
active lesions or prodromal symptoms at the time of
delivery in a women with history prior to pregnancy.

43. • Antiviral suppressive therapy:-
• In women with active recurrent genital herpes ,antiviral
therapy with acyclovir initiated at 36 wks of gestation
has been associated with decreased genital lesions at
the time of delivery and decreased viral detection by
culture or PCR .
• This also thus reduces the need for C-section.
• The use of acyclovir in pregnancy has not been
associated with any adverse fetal outcomes or birth
defects.

44. • Study however states that suppressive therpay
reduces the risk of genital lesions and viral load ,but
the extent to which the therapy prevents neonatal
acqusition of disease is still unknown.

45. • HSV vaccine:-
HSV 2 vaccine has been developed,but its efficacy
in previously sero positive individuals is not reported.
Currently no vaccine has proved to be effective.
• Prevention of maternal HSV acquisition during
pregnancy:-
To screen all couples for HSV serology at 14 to 18 weeks
of gestation.
Abstain from sexual contact in third trimester.

46. • Prevention of postnatal acquisition:-
• Although most neonatal HSV infections are acquired in
the peripartum period,10% of cases are acquired in
the postpartum period.
• It is caused due to exposure of virus from open lesions
of the care takers.
• It is recommended that infected contacts avoid
contact with the newborn.

47. • KEY POINTS:-
• Three major forms of herpes infections are :-
(1)disseminated disease – 25%
(2)CNS disease – 30%
(3)skin,eye & mouth disease – 45%
• Mortality rate is high in
disseminated(29%) > CNS(4%)
• Disabilities of chronic duration(morbidity) is more in CNS
disease(69%) & less in disseminated(17%)
• Neonates with HSV disease should receive oral acyclovir
suppressive therapy for 6months after completion of i.v
therapy.

48. THANK YOU