review

1. HSV IN NEONATES

2. Overview
 Introduction
 Epidemiology
 Patho-physiology
 Risk Factor
 Clinical features
 Diagnosis
 Treatment
 Prognosis

3. Introduction - history
 “Herpes” – from the Greek “to creep, crawl”
 “Herpetic eruptions” were described as early as 100 AD
 1960’s – HSV1 and HSV2 differentiated

4. Introduction
 Herpes simplex virus(HSV) -ubiquitous, enveloped &
Ds- DNA virus
 belongs to Herpesvirdae family
 Man is the only Host
 Two types HSV -1, 2
HSV-1- oral infections (gingivo-stomatitis and
pharyngitis)
HSV-2- genital herpes
- predominant cause of neonatal herpes
AVERY’S DISEASES
OF THE NEWBORN 19th
edition

5. HSV
 Alfa-herpesviruses : eg Herpes Simplex Virus, Varicella
Zoster virus
 Beta-herpesviruses : eg. Cytomegaloviruses
 Gama-herpesviruses: eg. Epstein-Barr virus
Textbook of Microbiology 8th Edition Ananthanarayan and Paniker’s

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. Nelson 20th
edition
 uncommon but potentially fatal
 >90% cases- maternal-fetal transmission
 Incidence-1/ 3,000-5,000 live births, higher than
syphilis,rubella,toxoplasmosis and rubella
 30% of mothers of affected infant - history of genital
herpes
Neonatal herpes

8. Epidemiology
 worldwide prevalence of HSV 2 seropositivity- high (25% in
US)
 Antibodies to HSV-2 -approximately 20% of pregnant women
 5 % report a history of symptomatic infection
 Infection Rate during pregnancy similar to non-pregnant
women,
 often asymptomatic
 Seroconversion rate in pregnant women- 2-3%
 Transmission occur from asymptomatic patients shedding the
virus
 Symptomatic and asymptomatic primary genital HSV
infections are associated with the preterm labor and LBW
infantsAmerican family physician neonatal Herpes Simplex Virus Infections volume65, november6/march15,2002

9. Factors influencing transmission of HSV to
neonate:-
 type of maternal infection (higher for primary i.e.30% vs 2%)
 maternal antibody status
 mode of delivery(vaginal/caesarean section)
 duration of rupture of membranes
 type of HSV(1 or 2)

10. Pathophsiology
 Viral infection begins at a cutaneous portal of entry.
 Virus replicates locally, resulting in the death of the cell
inflammatory response herpetic vesicles and ulcers
 Virus also enters nerve endings and spreads beyond the
portal of entry to sensory ganglia by intra-neuronal
transport
 Many sensory neurons infected during initial infection
(latent infection)

11. Pathophysiology
 Virus replicates in some sensory neurons
progeny virions send back to periphery
released from nerve endings
replicate further in skin or mucosal surface
 Viremia, does not appear to play an important role in HSV
infections
in the immunocompetent host but can occur in neonates,
 can result in dissemination of the virus to visceral organs
 Pathogenesis of HSV infection in newborns – complicated, not well
understood

12. Risk factors
 Transmission generally occurs during delivery, (may
even occur with LSCS with intact fetal membranes)
 The most common portals of entry - conjunctiva,
mucosal epithelium of the nose and mouth, and breaks
or abrasions in the skin that occur with scalp electrode
use or forceps delivery.
 Intraneuronal transport to the central nervous system -
cause encephalitis
 Hematogenous spread- to visceral organs and the brain
 May occur intra- partum or post-natally
American family physician neonatal Herpes Simplex Virus Infections volume65, november6/march15,2002

13. Salient features of HSV
infection
The hallmarks of HSV infections are skin vesicles and
shallow ulcers
 Acute oropharegeal infections
 Herpes labialis
 Cutaneous infestations genital herpes
 Ocular infestation
 CNS manifestations
 Infection in immunocopromised persons
 Perinatal infection

14. VESICULAR LESIONS HSV

15. Clinical Features In Neonates
 Pre term delivery, LBW
 Congenital HSV infection (4%) 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.
American family physician neonatal Herpes Simplex Virus Infections volume65, november6/march15,2002

17. CLINICAL FEATURES
 Presentation non specific
 Three subtypes-
1) Disease localize to the skin, eye or
mouth; (50%)
2) Encephalitis, with or without skin, eye or
mouth involvement; (33%)
3) Disseminated infection that involves
multiple sites, including the CNS, lung,
liver, adrenals, skin, eye or mouth (17%)

19. Ocular manifestation
 broad spectrum- ranging from mild superficial lesions involving the
external eye, to severe sight-threatening diseases of the inner eye-
 Primary HSV keratitis – dendritic ulcers
 Recurrent HSV keratitis
 HSV conjunctivitis
 Iridocyclitis, chorioretinitis and cataract
COMPLICATIONS-
 Corneal complications range from epitheliopathy to frank
neurotrophic or metaherptic ulcers.
 Long standing disciform keratitis- bullous keratopathy.
 deep vascular stromal scarring include secondary lipid
keratopathy.
 Finally, stromal inflammation may lead to visually significant
corneal scarring and irregular astigmatism.

21. Herpes simplex virus type 2 mediated acute retinal necrosis in a
pediatric population: case series and review
( Ruwan et al, Graefes Arch Clin Exp Ophthalmo (2013)
 Retrospective, observational case series
 CASES- patients (15 eyes) all aged upto21 years with ARN
resulting from HSV-2 and examined between 1995 and 2009. Mean
age of presentation was 11.7 years . Mean initial vision was 20/200
 DIAGNOSIS- (PCR) of aqueous, vitreous, and serum, antibody
determination of serum and intraocular fluids, fundoscopic exam,
therapeutic trial of antivirals active against HSV-2, or a combination
thereof.
 INTERVENTION- 11 pts received steroids, 14 received antiviral
therapy
 RESULTS- mean final visual acuity 20/400, worsen in 5 eyes
-Anatomically, 14 of 15 eyes had healed or improved retinal
appearance.
 CONCLUSIONS-In a pediatric population with ARN, HSV-2 should
be considered as the prime candidate. Prompt diagnosis may lead
to appropriate anti-viral therapy.

22. DIAGNOSIS
 Hallmark of primary genital Herpes- multiple painful
vesicles in clusters on inflamed surface ass with pruritis,
dysuria, vaginal discharge and tender regional
lymphadenopathy
 Clinical diagnosis should be confirmed by laboratory
test
 Isolation of virus or viral DNA detection by polymerase
chain reaction (PCR) in CSF/blood
 Viral culture –GOLD STANDARD
 should include cultures of suspicious lesions as well as
eye and mouth swabs
AVERY’S DISEASES OF THE NEWBORN 19th edition

23. Diagnosis
 When to suspect HSV in an infant??
 all neonates who present in 1st mth of life with non- sp.
Symptoms
 any vesicular rash upto 8 wks of age
 body fluids – culture for HSV

24. Clinical and laboratory features of neonatal HSV
infection : A. chantel Caviness et al, Pediatric Infectious Disease Journal, 2008
 Case control study to identify clinical and laboratory features of
neonates with and without HSV infection admitted to Texas
Children's Hospital during a 14-year period.
 Univariate and multivariate analyses were performed to identify
clinical and laboratory factors associated with neonatal HSV
infection.
 Forty cases and 160 comparison subjects were identified.
 maternal primary HSV infection, maternal fever, vaginal delivery,
prematurity, postnatal HSV contact, vesicular rash, hypothermia,
lethargy, seizures, severe respiratory distress, hepatosplenomegaly,
thrombocytopenia, elevated hepatic enzymes, and cerebrospinal
fluid (CSF) pleocyosis and proteinosis, were found to be associated
with neonatal herpes infection
 Factors not associated were fever, total peripheral white blood cell
count, and red blood cells in the CSF.
 For neonates presenting without vesicular rash, maternal fever,
respiratory distress requiring mechanical ventilation, and CSF
pleocytosis were independently associated with HSV infection.

25. Treatment
 The cornerstone of the treatment of neonatal HSV-
Parental Acyclovir
 Dosage- 60 mg/kg/d in 3 div. doses iv x14 d for skin,
eyes, and mucous membrane inv.
-same dose for 21 days- CNS/ Disseminated
disease
 High safety profile- non teratogenic
 Selective against HSV infected cells
 At the end of therapy CSF PCR should be done in all
the neonates, If 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
American family physician neonatal Herpes Simplex Virus Infections volume65, november6/march15,20

26. Treatment
 Topical Trifluorothymidine, Vidarabine, and Idoxuridine-
herpes keratitis. Steroids - contraindicated
 All primary episodes of genital HSV infections should be
treated (Aciclovir, Famciclovir, Valacyclovir) (ACOG)
 MOA- inhibits viral replication
 Prophylactic Acyclovir- considered in the third trimester
for women who have a primary episode of genital HSV
 LSCS does not completely remove the risk of
transmission
 Rupture of membranes for more than 4 to 6 hours
before delivery increases the risk.

27. 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.

28. Prognosis
 MORTALITY- skin, eyes and mouth- no mortality
- Encephalitis- 15%
-Disseminated disease-57%, even with
antiviral therapy
 Long term morbidity is common in survivors and
includes -seizure, psychomotor retardation, spasticity,
blindness or learning disabilities

29. Take Home Message
 HSV infection common in women of reproductive age
 Can transmit infection even if asymptomatic
 Can be contracted and transmitted to the fetus during
pregnancy/ postnatally
 Varied presentation- mortality, morbidity varies