Herpes simplex viruses (HSV) are members of the herpes virus family. HSV is a large virus (2nd only to Pox Virus) with a core containing double-stranded DNA within a coat, an icosahedron with 162 capsomeres.
The envelope which surrounds the ‘naked’ particle is partly nuclear membrane-derived, partly virally coded, with glycoprotein spikes. The diameter of a complete particle is 120–200 nm. The ‘naked’ virion measures about 100 nm. The virus enters the cells through cellular membrane fusion after being attached to specific receptors through an envelope glycoprotein. The capsid is transported to nuclear pores where DNA circularizes after uncoating and enters the nucleus.
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Clinical Feature of Herpes Simplex Virus
SYMPTOMS AND SIGNS
HSV-1 infections usually affect the oral cavity, lips, or face, and occasionally genital region, and HSV-2 infections are confined to genital region. In HSV 1, labial herpes (‘cold sore’) is the most common manifestation.
The primary infection is symptomless in most cases but may present as fever, enlarged submandibular lymph nodes, sore throat, gingivostomatitis with ulcers or vesicles, edema, with associated anorexia, pain, and malaise. This condition usually lasts for 10–21 days and may be accompanied by an inability to eat or drink. Dehydration may be a problem, especially in small children.
Symptomatic primary infection is most common in children of 1–5 years of age, with an incubation time of 2–12 days (mean about 4 days). There may be a prodrome of burning, itching, or tingling pain for some hours followed by groups of vesicles usually on the external borders of the lips. Lesions may also be present in the skin surrounding the lips; chin, cheeks, or nose. Within a few days, the vesicles progress to pustules or ulcers with brownish-yellow crusts. Pain is most severe in the beginning and resolves during the next 4–5 days.
The Herpes 2 infection usually affects the genital regions. The primary genital infection may be severe, with illness usually lasting up to about 3 weeks (sometimes longer) with a shedding period of virus usually terminating shortly before or at the time of healing. The lesions are vesicles or ulcers localized to the genital tracts of both males and females. The lesions are painful and may be associated with inguinal lymphadenopathy and dysuria. Systemic complaints, including fever and malaise, usually occur.
Complicating extragenital infections, including aseptic meningitis, have been observed in about 10–20% of cases. Paraesthesia or dysesthesia may occur after the genital affection. Especially in women, the severity of the primary infection may be associated with a high number of complications and frequent recurrences. Previous HSV1 infection reduces the severity and duration of primary HSV2 infection.
The recurrent genital affection is usually milder, with fewer vesicles or ulcers, and with a duration of 7–10 days. The recurrent lesions seldom last more than 10 days, and the shedding of the virus may terminate sooner. Sometimes, virus excretion can occur between active periods.
Infection in the newborn may be acquired in utero, at or just after birth. The newborn has low resistance to this infection and usually develops a severe disease. The mortality rate of untreated disease is about 50%. Babies with neonatal herpes infection may develop:
- A disseminated generalized form with many affected organs, including the central nervous system (CNS).
- Encephalitis with or without herpetic lesions of the skin.
- Herpetic lesions localized to skin, mouth and eyes.
The generalized form is especially serious, and is often combined with intravascular coagulopathy, hepatic and adrenal necrosis, pneumonitis and/or encephalitis followed by permanent neurological sequelae if the patient survives. The congenital infection may induce malformations such as microcephaly or microphthalmia, or other symptoms such as jaundice, hepatosplenomegaly, bleeding diathesis, seizures, irritability, chorioretinitisand herpetic vesicles of the skin.
In the USA HSV1 is considered the most common viral strain of fatal encephalitis. The lesion is usually a local process in the brain, consisting of hemorrhagic necrosis and edema, mimicking a brain tumor. The localization is usually one of the temporal lobes. At later stages, however, the expansion retracts leaving scar tissue and midline structures deviating to the affecting side.
In immunocompromised patients, the HSV infection may be severe, especially in cases of reduced cellular immunity. This is true both in patients with a disease affecting the immune system, e.g. AIDS, and in patients under immunosuppressive treatment. Especially bone marrow, renal and cardiac transplant recipients are at risk for severe herpes infections.
The lesions may be progressive, and involve unusual sites such as the respiratory tract, esophagus, liver, and intestinal mucosa, or occur as a disseminated infection in severely immunocompromised patients. The severity of the disease is directly related to the degree of immunosuppression, and will also last longer than usual, about 6 weeks. Malnourishment, especially in children, seems to aggravate symptoms. Even immunocompromised patients may discharge the virus asymptomatically.
The initial infection with herpesvirus may be located in the eye, with severe keratoconjunctivitis as a result. Recurrent infections of the eye may appear as ulcers of the cornea, sometimes dendritic ulcers, or as vesicles on the eyelids. Later chorioretinitis may develop. The cornea may develop opacifications after recurrence, indicating a progressive involvement. Blindness may be the consequence. Even herpetic necrosis of the retina has been observed as a very rare consequence of the infection.
Laboratory Diagnosis of Herpes Simplex Virus
- stain scrapings obtained from the base of vesicles (Giemsa stain)
- presence of multinucleated giant cells indicate HSV-1, HSV-2, or VZV.
Isolation and identification of the virus
- The virus is isolated from lesions; also from throat washings, CSF, and stool.
- Inoculation of tissue cultures ( human diploid fibroblast).
- Identification by neutralization test or immunofluorescence staining with specific antiserum.
- typing is done by using monoclonal antibodies or by RE analysis of viral DNA
PCR (Polymerase Chain Reaction): most sensitive/specific
- It helps in detection of amplified viral DNA by PCR in CSF or other samples
- typing is done by using type-specific primers or using common primers followed by RE analysis or hybridization probes.
- Serology is of no use in recurrences except in cases of encephalitis. antibody appears in 4-7 days after infection, reach a peak in 2-4 weeks.
- The complement fixation test (CFT) measures total antibodies, not differentiating type-specific antibodies.
- EIA more efficient than CFT; type-specific antigen (Ag) used to detect type-specific antibodies. diagnostic valve limited by multiple Ag shared by HSV-1 and HSV.
- It also gives heterotypic anamnestic responses to VZV in HSV infection and vice-versa.
Interpretation of Diagnostic Test for Herpes Simplex Virus (HSV)
|Cultures of Vesicles or Ulcers||Positive||Active Infection||Confirm by staining with specific monoclonal antibodies establishes the diagnosis. Culture from current late disease is much less sensitive.|
|ELISA (Serology)||Positive||Prior exposure or active infection||Distinguishes HSV-1 and HSV-2.|
|Direct Cytologic exam||Positive||Active Infection||Use right-Giemsa stain followed by Tzanck smear (see multinucleated giant cells. Negative test does not rule out the diagnosis. Does not differentiate HSV-1 and HSV-2).|
|Polymerase chain reaction (PCR)||Positive||Active Infection||Detects HSV in tissue, CSF, or cell samples. Sensitive, specific and rapid. Distinguishes HSV-1 and HSV-2|
|Western Blot or|
No prior exposure
|Detects glycoprotein-G; distinguishes HSV-1 and HSV-2. Western blot is gold standard for antibody detection (IgM and IgG).|