Herpes Simplex Virus Infections
HSV is a member of the herpes virus family, which includes varicella zoster virus, Epstein-Barr virus, and cytomegalovirus. Like all herpes viruses,HSV tends to establish latent infection and eventually it reactivates and becomes infectious. Most HSV-infected patients have asymptomatic infections or the symptoms are only mildly uncomfortable. However, a substantial number of patients experience frequent painful recurrences or severe or life-threatening illnesses.
1. Virology and pathogenesis
Two types of HSV exist
Both types can infect any anatomic site.
HSV-1 may cause asymptomatic infection, oral lesions, non oral or non-genital skin lesions, encephalitis, neonatal disease, and genital lesions.
HSV-2 may cause asymptomatic infection, genital lesions, neonatal disease, nonoral, nongenital skin lesions, meningitis, and oral lesions.
HSV-1 and HSV-2 are transmitted from person to person through contact with infected skin lesions, mucous membranes, and secretions. The incubation period is 1 to 26 days, and both types may be transmitted in utero or perinatally.
Asymptomatic virus shedding may transmit the disease.
Oral/facial HSV infections
HSV-1 infection is extremely common in infants and children. The most common clinical manifestation of primary HSV-1 infection is gingivostomatitis, characterized by fever,malaise, myalgia, pharyngitis, irritability, and cervical adenopathy. The illness is self-limited and usually of short duration.
Recurrent HSV-1 infections are most frequently characterized by oral and lip lesions. Many individuals who have oral HSV lesions have no known history of prior gingivostomatitis.
HSV-2 also may cause oral lesions and pharyngitis, particularly in sexually active individuals.
Genital HSV infections
Many HSV infections are asymptomatic, but they can also cause papular, vesicular, or ulcerative lesions with pain,itching, urethral or vaginal discharge, and dysuria.
Primary infections cause more severe symptoms and signs, including extensive skin lesions, tender inguinal adenopathy, and extragenital lesions. Primary infections are often associated with fever, headache, malaise, abdominal pain, and aseptic meningitis.
Eighty percent of persons who have a first episode of HSV-2 genital infection will experience a recurrence in the first year. Most patients who have genital HSVinfection have few symptomatic recurrences.
HSV encephalitis is the most common viral infection of the CNS. The incidence peaks at 5 to 30 years and at more than 50 years. Ninety-five percent of cases are caused by HSV-1. HSV encephalitis is characterized by acute fever, altered mental status, and focal neurologic symptoms and signs.
Routine CSF findings are not diagnostic.Polymerase chain reaction (PCR) can detect HSV DNA in CSF. HSV is rarely isolated by culture of the CSF.
Electro encephalographic (EEG) findings can be diagnostic, with spike and slow wave activity localized to the temporal region.
The prognosis for HSV encephalitis without treatment is poor, and even with antiviral therapy, substantial morbidity and mortality occurs. Prompt institution of empiric therapy is essential when the clinical diagnosis is suspected.
Neonatal HSV infections
Infection in neonates results from vertical transmission during the peripartum period. Seventy percent of untreated infants will progress to disseminated or CNS disease. Most neonatal infections are caused by HSV-2.
Skin, eye, mouth (SEM) disease accounts for 45% of peripartum infections. SEM disease most commonly presents in the first or second weeks of life with vesicular skin lesions which may occur anywhere on the body. Skin lesions have an erythematous base with clear or cloudy fluid. If the infection does not progress to involve the CNS or viscera, SEM disease has a low mortality.
Central nervous system disease is manifest as encephalitis, and it accounts for peripartum infections.
Neonatal HSV CNS disease most commonly presents in the second to third week of life. The diagnosis must be considered in any infant who presents with encephalitis,seizures,apnea, bradycardia, or cranial nerve abnormalities.
Cerebrospinal fluid findings are nonspecific and include pleocytosis and increased protein. Early initiation of therapy is critical when the diagnosis is suspected.
Disseminated disease is characterized by hepatitis, pneumonitis, and disseminated intravascular coagulation, and it also accounts for peripartum infections.
HSV disseminated disease presents in the first week of life. Bilateral patchy infiltrates are indicative of pneumonitis. Skin lesions may not be present initially.
Disseminated HSV disease should be considered in any infant presenting with sepsis that is unresponsive to antibiotic therapy, or who has both pneumonitis and hepatitis.
HSV is the most common cause of corneal blindness. HSV keratitis is characterized by conjunctivitis and dendritic lesions of the cornea.
Topical steroids are contraindicated because they may facilitate spread of infection to the deep structures of the eyes.
3. Management of perinatal HSV infection
The most reliable predictor of the risk of perinatal transmission is whether a woman has active genital lesions at the time of delivery.
A thorough physical examination, including vaginal speculum exam, at the onset of labor should exclude the presence of active genital lesions. If HSV lesions are found during labor, prompt cesarean section is recommended.
Management of infants exposed to HSV at delivery
Virus cultures of the infantís conjunctivae, pharynx, skin folds, CSF, and rectum at 24-48 hours can indicate whether HSV has been transmitted. Infants who are culture positive for HSV from any site after 24 hours of life are given acyclovir.
During the time when HSV-exposed infants are in the hospital, they should be placed in contact isolation. Circumcision is deferred.
4. Diagnosis of HSV infection
HSV-1 and HSV-2 can be isolated by virus culture from active skin, eye, and genital lesions. In cases of recurrent disease, virus shedding may be too brief to be detected by virus culture. Herpes simplex is rarely is recovered from CSF by culture.
Although less sensitive and specific than culture, staining for virus antigens with fluorescent antibodies detects HSV more rapidly.
5. Therapy for HSV infections
Parenteral acyclovir is indicated for severe or potentially severe infections, such as neonatal HSV infection, HSV encephalitis, and non-localized infections in immuno compromised patients. Oral acyclovir decreases new lesion formation and improves symptoms in first episode genital HSV. Oral acyclovir has limited effect on the resolution of recurrent HSV disease.
Topical acyclovir is not effective for skin or oral lesions. The ophthalmic solution is useful for HSV keratitis, in combination with IV acyclovir.
Sexually active individuals known to have genital HSV infection should be advised to use latex condoms even during asymptomatic periods.