Introduction: Herpes simplex virus (HSV) 1 and 2 are members of the Herpesviridae group which is a group of double-stranded, enveloped DNA viruses. The Herpesviridae group also includes Varicella Zoster Virus (VZV), Cytomegalovirus (CMV), Epstein- Barr virus (EBV) and Human Herpesvirus (HHV) 6, 7 and 8.
Classically, HSV1 causes oral infection i.e. cold sores and HSV2 causes genital infection, but this can be interchangeable. Both HSV1 and HSV2 can cause neonatal herpes simplex encephalitis, while HSV1 is the most common cause of childhood herpes disease. Spread of the virus is usually via the orolabial route and mucous membranes, and following primary infection, HSV develops latent infection in neurons. Latent infection is maintained in latency by cell mediated immune response, but the virus can reactivate and cause recurrent disease, usually near the site of within the dermatome of the affected ganglion, at times of stress, illness, immunosuppression and after UV exposure.
• Asymptomatic – in approximately two-thirds of individuals. US figures report that 50-80% of adults are seropositive for HSV1 and 20- 40% for HSV2, and European figures report a 50-80% seropositivity for HSV1 with 4-25% seropositivity for HSV2. 1, 2
• Genital herpes infection – small number of painful, clustered vesicles with an erythematous base associated with pain on rupture of lesion leaving shallow ulcers that heal without treatment. Lesions in primary infections typically last 4-10 days, with recurrent infections resolving sooner. Lesions are classically located around vaginal region including vulva, cervix, perianal region, buttocks or thighs. This occurs with or without associated dysuria or difficulty with urination secondary to pain, and with or without systemic symptoms including fever. HSV2 accounts for 70-80% of cases and HSV1 accounts for 20-30%.
• Neonatal herpes – Symptoms include fever, lethargy, poor feeding, seizures, bulging fontanelle and neurological signs and symptoms. 70% of neonatal herpes have CNS involvement or are disseminated, while 30% have localised skin/eye/mouth disease. Neonatal encephalitis presents with fever, headache, ataxia, confusion, visual disturbance, seizures, photophobia, and fluctuating consciousness.
Other HSV related infectious syndromes include herpes labialis, Mollaret’s meningitis, ocular herpes and herpetic whitlow.
HSV in pregnancy:
There are many factors associated with HSV transmission causing neonatal herpes including the type of maternal infection (primary or non-primary infection or recurrent infection), the presence of maternal antibodies (which would be expected to cross the placenta to offer neonatal protection), the duration of rupture of membranes prior to delivery, and the mode of delivery. The greatest risk of neonatal infection is when a woman acquires a new infection (i.e. primary genital herpes) in the third trimester, especially within 6 weeks of delivery as the neonate will be unlikely to have acquired protective antibodies in this time.
For these reasons, it is vital to be familiar with the important definitions of HSV infections in order to assess risk and direct management.
• First episode genital HSV infection – primary: First acquisition of HSV causing genital herpes in pregnancy. This is usually HSV2, but not always. Maternal antibodies for HSV1 and 2 should be checked; these will be negative in primary infection.
• First episode genital HSV infection – non-primary: First acquisition of genital herpes in pregnancy, but with a background history of oral herpes. The patient will usually have previous HSV1 infection i.e. cold sores and will have positive antibodies to HSV1, and then acquires HSV2 genital herpes infection during pregnancy.
• Recurrent HSV infection: The HSV type recovered from the genital lesion is the same type as pre-existing antibodies in the serum. Recurrence risk is greater with HSV2 than with HSV1, and the likelihood of recurrences reduces over time. 3
Diagnosis is based on clinical suspicion for HSV infection, including vesicular or ulcerated lesions. HSV DNA PCR from lesions is 98-100% sensitive. Viral shedding is intermittent so negative PCR does not exclude diagnosis.
Type-specific HSV serology should be used with caution and under specialist advice.
For women presenting with first episode genital herpes in the third trimester, particularly within 6 weeks of expected delivery, type-specific HSV antibody testing (immunoglobulin G [IgG] antibodies to HSV1 and HSV2) may be helpful. For these women, characterising the infection will influence the advice given regarding mode of delivery and risk of neonatal herpes infection. The presence of antibodies of the same type as the HSV isolated from genital swabs would confirm this episode to be a recurrence rather than a primary infection and elective caesarean section would not be indicated to prevent neonatal transmission.
Management of HSV in pregnancy is divided into the treatment of infection during pregnancy, decisions regarding delivery, and management of the neonate (Table 1). Pregnant patients with a history of HSV should inform their obstetrician and a referral to GUM clinic should be considered. Genital HSV is a notifiable disease and should be reported via the HPSC (https:// www.hpsc.ie/notifiablediseases/ notifyinginfectiousdiseases/).
Aciclovir is first line antiviral therapy for managing HSV in pregnancy. Aciclovir is well tolerated and does not require clinical or laboratory monitoring. Aciclovir is appropriate to use in all trimesters of pregnancy. The use of aciclovir is associated with a reduction in the duration and severity of symptoms and a decrease in the duration of viral shedding. Oral paracetamol and topical lidocaine 2% gel can be offered as symptomatic relief for patients with HSV.
Patients should be advised to avoid sexual contact when they have symptoms of HSV and should be offered testing for other STIs including HIV, hepatitis B, syphilis, chlamydia and gonorrhoea.
Labour management 4
Patients who have a primary infection at the onset of labour should be given IV aciclovir (Table 2).
Neonatal HSV is rare but has been associated with high morbidity and mortality. It is defined as HSV infection in any infant ≤42 days of age. A confirmed case is a laboratory confirmed infection, a probable case is a clinically compatible illness without another known cause of infection. 50% of neonatal herpes infection is due to HSV1 and 50% due to HSV2. Neonatal infection is classified into three subgroups depending on site of infection – disease localised to skin/eye/ mouth, local central nervous system disease (encephalitis) and disseminated infection with multi-organ involvement. Infants with disease localised to the skin/eye/mouth have the best prognosis, and represent 30% of neonatal herpes infections. Most cases of neonatal herpes occur as a result of direct contact with infected maternal secretions, and vertical transmission is most likely to occur during passage through the birth canal among women with active lesions. The highest risk for neonatal infection occurs in women with a primary genital HSV infection, which may be asymptomatic, acquired near the time of delivery. Congenital infection, i.e. transfer of infection in utero, is extremely rare. Post-natal acquisition from another person can also occur in approximately 10% of cases. Aside from timing (within 6 weeks of delivery) and type of (primary/ non-primary) infection, other factors that increase the risk of neonatal transmission include the use of foetal scalp electrodes and duration of membrane rupture. Neonatal HSV became a notifiable disease in Ireland in 2018.
The neonatal team should be informed of all babies born to mothers who have HSV during their pregnancy. If a baby is born via SVD to a woman who has third trimester primary genital herpes, the baby should be commenced on aciclovir 20mg/kg TDS for 10 days (Table 3) while awaiting results if well, and if baby is unwell to perform lumbar puncture. Breastfeeding is recommended unless there are herpetic lesions around the nipples.
Parents and other caregivers with active lesions, regardless of site, should be careful when handling the infant: lesions should be covered and hands should be washed before touching the baby. Parents should be advised to monitor the baby and look for; skin, eye and mucous membrane lesions, lethargy/ irritability and poor feeding. If the baby develops any of these, parents should be advised to seek medical help.
Many thanks to Dr Susan Knowles, Consultant Microbiologist and Dr Niamh Lynn, Consultant GU/HIV Medicine for their input with this article.
References available on request
Written by Dr Elaine Houlihan, Microbiology Specialist Registrar, The National Maternity Hospital and Louise Delany, Antimicrobial Pharmacist, The National Maternity Hospital
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