Download Herpes virus infection and prophylaxis

Herpes virus infection and prophylaxis
Introduction
Clinical neonatal herpes is uncommon in Australia. Data from the Australian Paediatric Surveillance Unit
(APSU) gives an incidence of 3.4 - 8 /100,000 live births. In the USA the incidence is higher, between 15 48 /100, 000 1 . In the UK the incidence is 1.7/100,000 2 . A 3 year prospective Canadian study reported an
incidence of 5.9/100,000 with the majority of cases (62%) being due to Herpes Simplex type 1 3 . This is
also the case in Australia 4 . In the prospective Canadian study 40% of the cases of neonatal herpes had
no history of genital herpes before delivery 3 .
The following table summarises the risk by maternal presentation 5 . Note that a primary infection includes
first infection by type 1 or type 2 virus in a woman who has seroconverted to the other type.
Maternal infection
Risk of neonatal
infection
Primary infection (no seroconversion)
30-50%
Primary infection (seroconversion before 34
weeks)
<3%
Recurrent infection with visible vesicles
< 1%
Recurrent infection without visible vesicles
0.02 - 3%
These data are also available on-line. http://www.asid.net.au/downloads/Management-of-PerinatalInfections-ASID-2002-rev-2007.pdf
Nosocomial infection and infection by a primary caregiver are well recognised 6,7,8 . Neonates are therefore
at risk of herpes infection if they come into contact with herpes labialis, or an herpetic whitlow.
Consequences:
There are four presentations [time of presentation].
localised to skin or mucous membranes
generalised multiorgan involvement [week 1; range 0-2 weeks]
localised to lung (pneumonitis) [3-7 days]
meningoencephalitis [7-30 days]
80 % of untreated localised disease will progress to disseminated +/- CNS disease if untreated.
Despite treatment the mortality rate in disseminated disease is 15-20%.
50% of the survivors of CNS disease and 86 % of the survivors of disseminated disease have sequelae 2 .
Diagnosis:
Virus culture takes 1-4 days 2 . Since delay in diagnosis contributes to worse outcomes 9 , rapid screening
with PCR for herpes DNA should be requested in surface vesicle swabs (if present) , nasopharyngeal
swabs, blood and CSF. Delay in diagnosis is also contributed to by the absence of vesicles in 30% of
file:///Volumes/neonatal/html/Newprot/herpes.html[15/10/13 11:54:58 AM]
cases, and up to 70% of CNS / disseminated disease 9 . In neonates with a non specific septic illness, and
with negative bacterial cultures, features such as elevated transaminases, thrombocytopenia, DIC,
respiratory distress and CSF pleocytosis are associated with herpes infection 1, 10 . CNS disease can,
however, be present in the absence of pleocytosis and a negative PCR 1 .
Maternal presentation
RANZCOG does not have a guideline on intervention for maternal herpes but supports the
recommendations 1,5 of the Australasian Society for Infectious Diseases (ASID)
http://www.asid.net.au/downloads/Management-of-Perinatal-Infections-ASID-2002-rev-2007.pdf
The UK Royal College of Obstetricians and Gynaecologists (RCOG) has a published Green-top guideline
11 (no 30) http://www.rcog.org.uk/resources/Public/pdf/greentop30_genital_herpes0907.pdf . Also from the
UK, the British Association for Sexual Health and HIV (BASHH) have published guidelines. 12 These can
be accessed through the National Guideline Clearinghouse (NCG)
http://www.guidelines.gov/summary/summary.aspx?doc_id=12214
Caesarean section is effective in preventing neonatal herpes infection 13 . Prophylactic aciclovir beginning at
36 weeks for recurrent infection is also effective at reducing clinical recurrence at delivery, HSV detection,
asymptomatic shedding and C/S for clinical recurrence 14 .
The following table summarises the main recommendations of these resources. All three sources stipulate
that the neonatologist be informed of the birth.
Note that the following is given for information only. This may not reflect the obstetric practice within RPAH
presentation
ASID
RCOG
Caesarean section (Level of
Evidence III, Grade of
Recommendation B)
Primary
infection at or
near term
(membrane
rupture < 6
hours)
Secondary
infection with no
lesions at
delivery
Secondary
infection with
active lesions at
If vaginal delivery avoid invasive
Caesarean procedures and membrane
rupture. Consider IV aciclovir to
section
mother and infant. (Level of
Consider
Evidence III, Grade of
suppresive Recommendation C)
aciclovir
Insufficient evidence to
recommend continuous aciclovir
in the last 4 weeks (Level of
Evidence III, Grade of
Recommendation B)
Vaginal
delivery
BASHH
Caesarean section (Grade of
Recommendation B)
If vaginal delivery avoid invasive
procedures and membrane
rupture. Consider IV aciclovir to
mother and infant. (Level of
evidence IV Grade of
recommendation C)
Continuous aciclovir in the last 4
weeks. (Level of Evidence Ib,
Grade of Recommendation B)
Caesarean section not indicated
(Level of Evidence III, Grade of
Recommendation B)
Vaginal delivery (Level of
Evidence III, Grade of
Recommendation B)
Continuous aciclovir in the last 4
weeks reduces recurrence and
C/S. (Level of Evidence IV,
Grade of Recommendation A)
Continuous aciclovir in the last 4
weeks reduces recurrence and
C/S. (Level of Evidence Ia,
Grade of Recommendation A)
Caesarean Caesarean section not routinely
section if
recommended. (Level of
ROM < 6
Evidence III, Grade of
file:///Volumes/neonatal/html/Newprot/herpes.html[15/10/13 11:54:58 AM]
Caesarean section should be
considered. (Level of Evidence
III, Grade of Recommendation
B)
delivery
hours
Recommendation B)
Continuous aciclovir in the last 4
weeks reduces recurrence and
C/S. ( Grade of
Recommendation A)
Baby
The ASID resource has an algorithm for treating babies born to mothers with a history of genital herpes in
5.
Clinical signs of Herpes Infection
Full investigations should be performed including lumbar puncture, and iv aciclovir started at 60 mg/kg/day
in 3 divided doses 15 .
High risk
The baby should have surface swabs and investigations, and commenced on aciclovir. If the baby then
develops symptoms then lumbar puncture and CNS imaging should be added.
Low risk
Collect surface swabs at 24 hours and review clinically. If the baby develops clinical signs or the swabs are
positive then iv aciclovir is started.
Investigations
HSV PCR on swabs, blood, CSF (if performed), FBC, LFT's, viral culture on CSF (if performed).
Neither the RCOG or BASHH guidelines specify recommendations for the newborn apart from "informing
the neonatologist" 11,12
Duration of therapy 15
14 days for localised disease ie skin, oral or ocular.
21 days for disseminated or CNS disease.
Nosocomial infection
The BASHH guidelines state that mothers, staff and friends/relatives with active HSV infection such as
orolabial or an hereptic whitlow should avoid contact between the lesions and neonate (Level of evidence
IV grade of Recommendation C) 12 . The RCOG guideline states that "mothers, family members and
healthcare workers should take measures to avoid transmission of the virus to the neonate (Level of
evidence IV grade of Recommendation C). 11 . Breast feeding should continue unless there is active herpes
infection around the nipple area.
If a mother develops herpes infection in the perinatal period she should have her immune status to HSV 1
and 2 determined.
Staff with active herpes infection should not come to work until the lesion has dried. Staff who have no
clinical contact with babies may, however, fulfil administrative duties, teaching, research etc.
file:///Volumes/neonatal/html/Newprot/herpes.html[15/10/13 11:54:58 AM]
Meta-analysis of RCTs of topical aciclovir has found that this reduces healing time but the effect is small,
about one day 16 .
References
1. Freedman E, Mindel A, Jones CA. Epidemiological, clinical and laboratory aids for the diagnosis of
neonatal herpes -- an Australian perspective. Herpes. 2004 Aug;11(2):38-44.
2. Isaacs D and Moxon ER. Handbook of Neonatal Infections; a practical guide. (1999) WB Saunders,
London
3. Kropp RY, Wong T, Cormier L, Ringrose A, Burton S, Embree JE, Steben M. Neonatal herpes simplex
virus infections in Canada: results of a 3-year national prospective study. Pediatrics. 2006 Jun;117(6):195562.
4. Jones CA, McIntyre P, Isaacs D, Members of the Neonatal HSV study team. Epidemiology of neonatal
herpes simplex virus infection in Australia: preliminary report on the Australian Paediatric Surveillance Unit
study (1997-1999). Journal of Paediatrics and Child Health 36(3), A15. 2000
5. Jones CA. Herpes simplex virus infections in pregnancy. In: Management of Perinatal Infections
(Palasanthiran P, Starr M, Jones CA,eds). Australasian Society for Infectious Disease 2002:pp16–18.
6. Sakaoka H, Saheki Y, Uzuki K, Nakakita T, Saito H, Sekine K, Fujinaga K. Two outbreaks of herpes
simplex virus type 1 nosocomial infection among newborns. J Clin Microbiol. 1986 Jul;24(1):36-40.
7. Douglas J, Schmidt O, Corey L. Acquisition of neonatal HSV-1 infection from a paternal source contact. J
Pediatr 1983;103:
908–10.
8. Hammerberg O, Watts J, Chernesky M, Luchsinger I, Rawls W. An outbreak of herpes simplex virus type
1 in an intensive care
nursery. Pediatr Infect Dis 1983;2:290–4.
9. Kimberlin et al Natural History of Neonatal Herpes Simplex Virus Infections in the Acyclovir Era.
Pediatrics 2001;108;223-229
10. Caviness AC, Demmler GJ, Selwyn BJ. Clinical and laboratory features of neonatal herpes simplex
virus infection: a case-control study. Pediatr Infect Dis J. 2008 May;27(5):425-30
11. http://www.rcog.org.uk/resources/Public/pdf/greentop30_genital_herpes0907.pdf
12. Clinical Effectiveness Group. 2007 national guideline for the management of genital herpes. London
(UK): British Association for Sexual Health and HIV (BASHH); 2007.
13. Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L. Effect of serologic status and cesarean
delivery on transmission rates of herpes simplex virus from mother to infant JAMA. 2003;289:203-9
14. Hollier LM, Wendel GD. Third trimester antiviral prophylaxis for preventing maternal genital herpes
simplex virus (HSV) recurrences and neonatal infection. Cochrane Database of Systematic Reviews 2008,
Issue 1. Art. No.: CD004946. DOI: 10.1002/14651858.CD004946.pub2.
15. Kimberlin et al. Safety and Efficacy of High-Dose Intravenous Acyclovir in the Management of Neonatal
Herpes Simplex Virus Infections Pediatrics 2001 (108 ) 2 , pp. 230-238
16. Worrall G. Clin Evid. 2004 Dec;(12):2312-20.
back
file:///Volumes/neonatal/html/Newprot/herpes.html[15/10/13 11:54:58 AM]
file:///Volumes/neonatal/html/Newprot/herpes.html[15/10/13 11:54:58 AM]
file:///Volumes/neonatal/html/Newprot/herpes.html[15/10/13 11:54:58 AM]
Revised: December 2008: Dr Girvan Malcolm
Reproduced by kind permission of the authors:
Jones CA. Herpes simplex virus infections in pregnancy. In:" Management of Perinatal Infections".
Palasanthiran P, Starr M , Jones CA, Eds. Australasian Society for Infectious Diseases. Book House,
Sydney, 2002. p 16-18.
Note that an updated version is in preparation which will include further recommendations
file:///Volumes/neonatal/html/Newprot/herpes.html[15/10/13 11:54:58 AM]