Joint British Association for Sexual Health & HIV National UK Guideline for Herpes Simplex Virus (HSV) in Pregnancy (2024 Update) PDF

Guidelines International Journal of STD & AIDS 2024, Vol. 0(0) 1–...

Guidelines International Journal of STD & AIDS 2024, Vol. 0(0) 1–20 Joint British Association for Sexual Health © The Author(s) 2024 Article reuse guidelines: and HIV and Royal College of Obstetricians sagepub.com/journals-permissions DOI: 10.1177/09564624241280734 and Gynaecologists national UK guideline journals.sagepub.com/home/std for the management of herpes simplex virus (HSV) in pregnancy and the neonate (2024 update) Emily Clarke1,2 , Raj Patel3,4, Dyan Dickins5, Katy Fidler6, Allan Jackson7, Margaret Kingston8 , Christine Jones4,9, Hermione Lyall10, Marian Nicholson11, Emanuela Pelosi9, David Porter12, Gemma Powell13 and Elizabeth Foley3,4 Abstract This updated national UK guideline offers recommendations on the management of genital herpes simplex virus (HSV) in mothers and pregnant people during pregnancy and within 4 weeks following birth. It includes recommendations for first episode and recurrent HSV, HSV in preterm pre-labour rupture of membranes and in co-infection with HSV and HIV. Recommendations around management of the neonate are made, on prevention of postnatal transmission, management of breastfeeding, and the management of clinically discordant couples. This guideline is aimed at healthcare professionals working in sexual health clinics, maternity units, and those working on postnatal wards and neonatal units in the UK. However, the principles of the recommendations should be adopted across all services, including community care. Keywords Europe, pregnancy, antiviral, women, HSV (herpes simplex virus), viral disease Date received: 15 August 2024; accepted: 20 August 2024 What’s new in the 2024 management of · Use of ulcer panel PCR testing for herpetic lesions in genital herpes in pregnancy guideline pregnancy. · Antiviral suppressive therapy to start earlier at 32 The guidelines have been substantially revised and updates weeks of pregnancy for all mothers and pregnant in brief include: people requiring this, and at 22 weeks if there is a high risk of preterm delivery. 1 10 Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK Imperial College Healthcare NHS Trust, London, UK 2 11 University of Liverpool, Liverpool, UK Herpes Viruses Association, London, UK 3 12 Solent NHS Trust, Southampton, UK Alder Hey Children’s NHS Foundation Trust, Liverpool, UK 4 13 University of Southampton, Southampton, UK Patient and public representative, London, UK 5 Liverpool Women’s NHS Foundation Trust, Liverpool, UK 6 Brighton and Sussex Medical School, University of Sussex, Falmer, UK Corresponding author: 7 NHS Greater Glasgow and Clyde, Glasgow, UK Emily Clarke, Axess Sexual Health, Liverpool University Hospitals NHS 8 British Association for Sexual Health and HIV Clinical Excellence Group, Foundation Trust, Royal Liverpool University Hospital, Mout Vernon London, UK Street, Liverpool L7 8XP, UK. 9 University Hospital Southampton NHS Foundation Trust, Southampton, Email: [email protected] UK 2 International Journal of STD & AIDS 0(0) · Use of valaciclovir as an alternative to aciclovir for BASHH and RCOG websites for a 2-month consultation treatment and/or suppression of genital herpes in the period, with direct requests for external peer review made to pregnant woman or person. key bodies including the RCPCH. The guideline has been · A new section on the use of serology in the third trimester, reviewed by the BASHH Public Panel and piloted in and virology involvement in writing this guideline. a representative clinic. · Expansion of the neonatal management section, including The guideline writing process was overseen by the risk stratification to guide investigations and treatment. BASHH Clinical Effectiveness Group. This is the most · Increased focus on the importance of the multi- recent update of the BASHH/RCOG national guideline first disciplinary team (MDT) to include genitourinary med- written in 2014. icine (GUM) physicians, obstetricians and neonatologists with formal documentation of a birth and postnatal care plan. Search strategy · Expansion of the prevention of postnatal transmission This document was produced in accordance with the section, including a new section on breastfeeding. guidance set out in the BASHH Clinical Effectiveness · A new section on the management of clinically or se- Group’s (CEG’s) document ‘Framework for guideline de- rodiscordant couples. velopment and assessment’ (available from: https://www. bashh.org/guidelines). A literature search was performed using PubMed/ Objective and scope MEDLINE, EMBASE, Google, The Cochrane Library The first joint British Association for Sexual Health and and relevant guidelines from 2014 to 2023. A MEDLINE/ HIV (BASHH) and Royal College of Obstetricians and PubMed and EMBASE search was carried out from 2014 to Gynaecologists (RCOG) guideline on the management of 2023 using the following search terms/Medical Subject genital herpes in pregnancy was published in 2014; this Headings (MeSH): ‘HSV/herpes’, ‘genital ulcers’, ‘HSV/ updated guideline supersedes that of 2014. herpes pregnancy’, ‘neonatal HSV/herpes’, ‘HSV/herpes For more detailed information on the general manage- drugs’, ‘pregnancy complications: infectious’, ‘Herpes ment of genital herpes infection in people who are not genitalis’ and ‘Herpes simplex diagnosis’, ‘HSV/herpes pregnant, please refer to the 2024 BASHH guideline on the breastfeeding’. The search was limited to humans and the management of genital herpes.1 English language. For some specific recommendations, an The scope of this guideline is the inpatient and outpatient additional MEDLINE/PubMed search was performed when management of genital herpes simplex virus infection in the necessary. antenatal, intrapartum and postnatal periods in mothers and A Google search was performed in 2023 with the search pregnant people, and neonates. This updated guideline also term ‘HSV guideline(s)’ and all relevant documents of the includes the prevention of genital herpes infection in un- first 150 search results were reviewed. A search of The infected women and people during pregnancy. The pop- Cochrane Library included the Cochrane Database of ulation covered by this guideline includes all the routine Systematic Reviews, Database of Abstracts of Reviews of antenatal and perinatal care that mothers and pregnant Effects and Cochrane Central Register of Controlled Trials. people and their babies should receive, including those The following guidelines were reviewed in detail: 2017 mothers and pregnant people with a suspected or confirmed European guideline for the management of genital herpes2; diagnosis of genital herpes simplex infection and those at 2024 BASHH guidance on the management of genital risk of acquisition in primary or secondary care. herpes.1 The members of the guideline development group This guideline is aimed at healthcare professionals selected studies relevant to the scope of the guideline. working in sexual health clinics, maternity units, and those Article titles and abstracts were reviewed and if relevant the working on postnatal wards and neonatal units in the UK. full-text article obtained. Priority was given to randomised However, the principles of the recommendations should be controlled trial and systematic review evidence and, where adopted across all services, including community care. possible, recommendations were made and graded based on the best available evidence (Appendix 1). In areas where evidence is lacking, recommendations based on consensus Stakeholder involvement opinion within the writing group have been made. This guideline has been developed by a writing group in- cluding clinicians working in the fields of genitourinary Background medicine, obstetrics, neonatology and virology, and patient and public representatives. Specific expertise was provided Neonatal herpes is a very rare but serious viral infection by members of the BASHH Herpes Simplex Advisory with a high morbidity and mortality.3 It is classified into Panel, the RCOG and the Royal College of Paediatrics and three subgroups in the infant depending on the site of in- Child Health (RCPCH). The guideline was posted on the fection: disease localised to only skin, eye and/or mouth Clarke et al. 3 (SEM), local central nervous system (CNS) disease (en- be absent. Features of dissemination are typically non- cephalitis alone or with SEM lesions) or disseminated specific with only 18% presenting with fever and 79% disease with multiple organ involvement. presenting with ‘sepsis’.5,6 Median admission CRP may not Neonatal infection occurs as the result of an infection at be significantly raised and was 20 mg/L in recent UK wide the time of birth (85%), in the immediate postnatal period surveillance.5 (10%) or, very rarely, in utero (5)% - termed congenital Prior to antiviral therapy, 85% of infants with dissemi- herpes.4 nated infection died within 1 year.8 Disseminated disease Although neonatal HSV infection is very rare, the sus- carries the worst prognosis – with appropriate antiviral picion of possible neonatal HSV infection in infants with treatment, mortality is still around 66% and more likely in compatible symptoms or risk factors for perinatal or those who are semi-comatose or comatose, have HSV postnatal exposure is much more common. Thus the de- pneumonitis, disseminated intravascular coagulopathy, are mand for diagnostic investigation of possible neonatal HSV premature, or with delayed antiviral treatment.5,7 41% of infection is significant. infants have long term morbidity and this is more likely in those with seizures, HSV-2 infection, or delayed antiviral treatment.7 Disease localised to skin, eye and/or mouth (SEM) Recent UK surveillance data has demonstrated an overall Infants who present with symptoms localised to the skin, mortality of 24% (all presentations of neonatal HSV). 33% eye or mouth alone have the best prognosis. They represent of preterm infants died in comparison with 19% of term approximately 32% of neonatal herpes cases, with median infants. Mortality was more frequent in those with HSV-2 presentation at 8 days of life.5 They typically present with than those with HSV-1 infection (68% versus 29%), al- vesicular lesions or ulcers on the skin, eye or mouth and though previous studies have suggested that mortality may have no CNS or visceral organ involvement.6 be higher in those with HSV-1 infection.5,7 With appropriate antiviral treatment to prevent pro- gression, mortality is 0% and neurological and/or ocular Incidence morbidity is around 6% and more likely in those with at least 3 lesions or HSV-2.7 However such infants are at risk Neonatal herpes is very rare in the UK, but surveillance data of recurrent SEM disease during childhood, which may suggests that the incidence may be rising. Active surveil- disrupt childcare and schooling, and may be misdiagnosed, lance by the British Paediatric Surveillance Unit (BPSU) for example, as recurrent varicella. between 1986 and 1991 found 76 cases over the five-and-a- half-year surveillance period with an incidence of 1.65/100 000 live births annually (95% CI 1.3–2.0).9 Subsequent Central nervous system disease/meningoencephalitis surveillance from 2004 to 2006 showed an approximate In the UK, 35% have CNS disease with a median pre- doubling of incidence with 86 cases seen over the three-year sentation of 14 days.5 They may present with a variety of surveillance period, incidence 3.58/100,000.10 A single signs including lethargy, poor feeding, or seizures and may centre study in Nottingham in 2006–2013 found an in- not have skin, eye and/or mouth lesions.6 Median admission cidence of 17.5/100 000 live births, suggesting an increase CRP may not be raised and was 3.9 mg/L in recent UK wide in neonatal herpes of almost 5 times the UK wide incidence surveillance.5 previously published.11 Further surveillance by the BPSU Prior to antiviral therapy, 50% of infants with CNS between 2019 and 2022 reported 118 confirmed cases with disease died within 1 year.8 With antiviral treatment, 4 still pending and estimated incidence as 6.9/100,000 live mortality from CNS disease is around 15% and more likely births.5 in those who are semi-comatose or comatose, in premature The incidence in the UK is around 50% of that reported infants, and in those with delayed time to treatment.7 from other European countries and the USA.12,13 In the Neurological morbidity (including developmental delay, USA, the average reported incidence is 10/100,000 or 1 in epilepsy, blindness and cognitive disabilities) is common at 10,000, but there is considerable variation between pop- 64%, and more frequent in those with seizures, HSV-2 ulations and rates of up to 1 in 7,500 have been reported in infection, and those with delayed time to antiviral certain deprived inner-city populations, and 1 in 3,000 in treatment.6,7 Florida.14–16 Data from the USA and Europe (as in the UK) suggest that incidence of neonatal herpes may be increasing over time.13,17,18 Disseminated infection Recent data on seroprevalence of antibodies to HSV-1 In the UK, 33% of infants with neonatal herpes have dis- and/or HSV-2 in mothers and pregnant people in the UK are seminated disease with a median presentation of 6 days.5 lacking. However, studies in the USA and Europe suggest Multiple organs are involved and may include the liver, that antibodies to HSV-1 and -2 may be declining over time, lungs and brain, and skin, eye and/or mouth symptoms may rendering an increased number of mothers and pregnant 4 International Journal of STD & AIDS 0(0) people vulnerable to primary herpes acquisition during infection (primary genital herpes) in the third trimester, pregnancy.14,19,20 Over the last decade the incidence of particularly within 6 weeks of delivery, as viral shedding primary genital herpes in women in the UK has remained may persist and the baby is likely to be born before the fairly static, but reporting has been significantly affected by development of protective maternal antibodies.25,26 the impact of COVID-19 on sexual health clinics.21 Rarely, congenital herpes may occur because of trans- placental intrauterine infection. Case reports suggest that the skin, eyes and CNS may be affected and there may be fetal Aetiology growth restriction or fetal death.4,27–29 Neonatal herpes may be caused by herpes simplex virus type 1 Although recurrent genital herpes is associated with (HSV-1) or herpes simplex virus type 2 (HSV-2) as either viral a very low risk of neonatal herpes, recurrent herpes at the type can cause genital herpes in mothers and pregnant people, time of delivery, which is commonly asymptomatic or and HSV-1 may also be acquired due to post-natal contact. In unrecognised, may cause neonatal herpes. HSV-2 type- recent UK surveillance, approximately 52% of neonatal herpes specific antibody correlates with protection from severe is due to HSV-1 and 48% due to HSV-2.5 neonatal HSV-2 in infants exposed to HSV-2 at birth.30 Most cases of neonatal herpes occur as a result of either Data from the USA suggest that around 2% of women direct contact with infected vaginal secretions at birth (75– acquire genital HSV infection in pregnancy and most of 85%) or postnatal acquisition (10–25%) which may occur as these maternal infections are asymptomatic or a result of exposure to oro-labial herpes infection, usually unrecognised.3,26 However, acquisition in the UK in from a close relative, friend of the parents or possibly pregnancy may vary markedly given differing rates of a health care worker.4,9,10,22 Trans-placental spread in vir- neonatal herpes between the UK and USA. It is difficult to aemic mothers may very rarely cause in utero congenital distinguish clinically between recurrent and primary genital herpes (5%).4 HSV infections, as many first noted episodes of HSV are not true primary infections.24 Transmission Transmission associated with prematurity. In the UK, 7.4% of Genital herpes infection is classified as follows1: live births are preterm (