What is the mortality and morbidity associated with herpes simplex virus (HSV) infection?

Updated: Mar 17, 2020
  • Author: Sean P McGregor, DO, PharmD; Chief Editor: William D James, MD  more...
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Severe complications may be associated with herpes simplex. This is especially true in females who are pregnant and in individuals with immunosuppression, who may develop disseminated infection and encephalitis.

Complications of HSV-1 infections vary based on the site of involvement and whether the patient is immunocompromised. HSV-1 infections of the oral mucosa result in gingivostomatitis in children and pharyngitis in adults. Reactivation of infections of the oral mucosa present as herpes labialis and are less severe than the primary infection. HSV-1 can also infect any cutaneous surface. Patients with Darier disease, atopic dermatitis, or mycosis fungoides may develop life-threatening eczema herpeticum (Kaposi varicelliform eruption). Organ transplant recipients and patients with HIV/AIDS may develop herpetic lesions that exhibit an unusual morphology. Additionally, HSV DNA has been associated with erythema multiforme in approximately 43% of cases. [24]

Ocular and neurologic sequelae of HSV-1 infection include conjunctivitis, blepharitis, keratitis, acute retinal necrosis, Bell palsy, and encephalitis. Herpes simplex keratitis is characterized by ocular pain and is a common infectious cause of unilateral vision loss. [25] Clinical manifestations of HSV-1 encephalitis include fever, headache, nausea, vomiting, seizures, confusion, and focal deficits. [26] Approximately 15% of hospitalized patients die from HSV encephalitis, and survivors have long-term disability affecting cognitive function. [26]

The most common complication of primary HSV-2 genital infection is bacterial superinfection. Extragenital complications such as urinary retention, aseptic meningitis, and proctitis can occur in patients with HSV-2. Urinary retention and aseptic meningitis occur more frequently in women. Proctitis due to HSV-2 occurs more commonly in men who have sex with men and accounts for approximately 15% of cases. [27] Additionally, HSV-1 and HSV-2 are more common in men with proctitis and HIV infection than in those without HIV infection. [28]

Individuals co-infected with HSV and HIV and who have herpetic mucosal lesions are more likely to transmit HIV during sexual contact. In studies, despite being compliant with highly active antiretroviral therapy (HAART) for treatment of HIV-1 infection, 30-50% of women co-infected with HSV-2 and HIV-1 were shown to have genital HIV-1 shedding at least once in a 3-month period. Studies also suggest that co-infection with HSV-2 may accelerate HIV disease progression by elevating the HIV viral load. A 2008 study by Baeten et al found that HSV suppressive therapy decreased genital and plasma HIV levels in women with HSV-2/HIV co-infection. [29]

Another serious consequence of HSV infection is transmission of the virus to a neonate by a mother who is infected. [30] Asymptomatic maternal shedding occurs approximately 7% of the time and is responsible for most neonatal HSV infections. The risk of HSV transmission to the newborn is as high as 30-50% from a mother who acquired a new HSV infection near the time of delivery. Among women who have acquired HSV infection before their third trimester of pregnancy, the risk of transmission is less than 1%. HSV infections in neonates are most commonly due to HSV-2 and most are acquired peripartum from exposure to lesions (or shedding virus) in the birth canal, although in utero and postpartum transmission can rarely occur. Transmission is estimated to occur at a rate of 1 case in 3500-5000 deliveries in the United States. Neonatal infection can cause long-term sequelae and even death.

Reported in 2019, HSV-1 has been implicated in the pathogenesis of Alzheimer disease. HSV-1 has been shown to cause intracellular accumulation of amyloid-β protein (Aβ), which is involved in the pathogenesis of Alzheimer disease. [31] Additionally, patients that are apolipoprotein E carriers who had IgM or high-IgG titers against HSV-1 have an increased risk of Alzheimer disease. [32]

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