Hsv ppt (2)

HSV IN NEONATES

Overview

Introduction

Epidemiology

Patho-physiology

Risk Factor

Clinical features

Diagnosis

Treatment

Prognosis

Introduction - history

“Herpes” – from the Greek “to creep, crawl”

“Herpetic eruptions” were described as early as 100 AD

1960’s – HSV1 and HSV2 differentiated

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

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

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.

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

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

infants American family physician neonatal Herpes Simplex Virus Infections volume65, november6/march15,2002

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)

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)

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

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

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

VESICULAR LESIONS HSV

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.


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%)

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.

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.

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

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

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.

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

poorer outcomes


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.

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.

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

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

Hsv ppt (2)

Healthcare

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