Herpes simplex
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Background
Herpes simplex virus (HSV) is a common DNA virus belonging to the Herpesviridae family. There are two types:- HSV-1 typically causes orolabial (cold sore) infections.
- HSV-2 more commonly causes genital infections.
Epidemiology in the UK
HSV-1 is widely prevalent, with most infections acquired in childhood. HSV-2 is primarily sexually transmitted and is more common in adults. The overall seroprevalence of HSV-1 in UK adults is approximately 60–80%, while for HSV-2 it is around 5–10%.
Mode of transmission
Transmission occurs through:- Direct contact with infected skin or mucosal surfaces.
- Asymptomatic viral shedding is common and can contribute to spread.
- Vertical transmission from mother to neonate can occur, particularly during delivery if the mother has active genital lesions.
Pathogenesis
HSV is primarily transmitted via direct contact with infected mucosal surfaces or skin lesions. Upon entry, it infects epithelial cells, where it replicates and causes cell lysis, resulting in vesicular lesions. This local replication may also lead to systemic symptoms during primary infection.
The virus then enters nearby peripheral sensory nerves and travels retrogradely to sensory ganglia (e.g., trigeminal or sacral), where it establishes lifelong latency. Reactivation can occur in response to:
- Fever
- UV light exposure
- Stress
- Hormonal changes
- Immunosuppression
During reactivation, the virus travels back to the skin or mucosa, causing recurrent lesions.
Cytotoxic T-cell responses and natural killer cells are critical in controlling infection. Individuals with T-cell immunodeficiency (e.g., HIV, chemotherapy) are at higher risk for reactivation, disseminated disease, or encephalitis.
Problems in immunocompromised patients
- Increased frequency and severity of reactivations.
- Atypical, chronic ulcerative lesions.
- Risk of disseminated HSV infection or visceral involvement (e.g. pneumonitis, hepatitis).
- Higher risk of herpes simplex encephalitis.
Herpes simplex virus (HSV) infections are controlled primarily by cell-mediated immunity, particularly cytotoxic T-cells. Individuals with T-cell deficiencies (e.g., advanced HIV infection, post-transplant immunosuppression, congenital T-cell immunodeficiencies) are at higher risk for severe and recurrent HSV infections, including disseminated disease and encephalitis
Clinical features
- HSV-1 typically causes orolabial lesions (cold sores), gingivostomatitis, or herpes labialis.
- HSV-2 more often causes genital ulcers, dysuria, and inguinal lymphadenopathy.
- Primary infection may be asymptomatic or present with fever, malaise, and painful vesicles.
- Recurrent infection is usually milder and shorter in duration.
- Rare complications include herpetic whitlow, herpes gladiatorum, ocular herpes, and herpes encephalitis.
Diagnosis
- Clinical presentation is often sufficient for diagnosis in typical cases.
- PCR is the gold standard for detecting HSV DNA in vesicle swabs or CSF (in suspected encephalitis).
- HSV serology can help in determining prior exposure.
- Neuroimaging (MRI) may support diagnosis of herpes simplex encephalitis by showing temporal lobe involvement with sparing of the basal ganglia.
Treatment options
- First-line: Oral or intravenous aciclovir, which inhibits viral DNA replication.
- Alternatives: Valaciclovir or famciclovir (prodrugs with better oral bioavailability).
- Recurrent infections: Suppressive therapy may be considered in frequent relapses.
- Herpes simplex encephalitis: Requires urgent IV aciclovir (10–14 days or longer depending on severity).
- Immunocompromised patients may need longer or higher-dose antiviral treatment and monitoring for resistance.