NAME: Herpes simplex virus
CHARACTERISTICS: HSV virus, types 1 and 2, belong to the sub family Alphaherpesviridae in the family Herpesviridae, genus SimplexvirusFootnote 2. They are 120-300 nm in diameter and consist of a linear, double stranded DNA genome (152 Kb for HSV-1 and 155 Kb for HSV-2) enclosed within an icosahedral capsid, surrounded by a phospholipid rich envelope. The lipid envelope is derived from the nuclear envelope of the infected cell.
PATHOGENICITY/TOXICITY: Although both HSV-1 and HSV-2 may infect any area, HSV-1 is associated mainly with “above the waist” infections involving the mouth, pharynx, face, eye, and central nervous system (CNS), whereas, HSV-2 is associated mainly with “below the waist” infections of the genital regionFootnote 1,Footnote 3.
Herpes labialis/cold sores: Caused mainly by HSV-1, there have been reported cases caused by HSV-2Footnote 1,Footnote 2,Footnote 4. Primary infections with HSV-1 are acquired usually in childhood and may be asymptomatic or subclinicalFootnote 1,Footnote 2,Footnote 4. Symptomatic primary infections present mainly as gingivostomatitis, with fever, sore throat, fetor oris, anorexia, cervical adenopathy, and mucosal edema and vesicular and ulcerative painful lesions involving the buccal mucosa, tongue, gums, and pharynxFootnote 1,Footnote 2,Footnote 4,Footnote 5. Ulcers heal without scarring within 2-3 weeksFootnote 1,Footnote 2. Recurrent infections have generally milder symptoms and clinical courseFootnote 2. Recurrent lesions due to HSV-1 occur mainly on a specific area of the lip (vermillion border of the lip), and are called “cold sores” or “fever blisters”Footnote 1,Footnote 4. The lesions heal in approximately 8-10 daysFootnote 4.
Herpetic whitlow: Characterized by formation of painful vesicular lesions on the nail or finger areaFootnote 1.
Infections of the eye: Characteristic dendritic ulceration occurs on conjunctiva, and corneaFootnote 1. HSV infection may cause other ocular diseases, including blepharitis/dermatitis, conjunctivitis, dendritic epithelial keratitis, and corneal ulcerationFootnote 6.
Encephalitis: Serious infections of the CNS, affecting both children and adolescentsFootnote 7. It may occur due to primary or latent infection with HSV-1 virusFootnote 1,Footnote 7. HSV encephalitis affects one temporal lobe, leading to focal neurologic signs and edema. The disease can be fatal (mortality rate of 70%), if left untreatedFootnote 1,Footnote 7.
Genital herpes: It is a sexually transmitted diseaseFootnote 1. Genital herpes is caused mainly by HSV-2, although HSV-1 has become as common as HSV-2 in primary genital infections in developed countries. Primary genital herpes is characterized by formation of multiple, bilateral, painful, and extensive genital ulcers, which heal without scarring within 12 days. Patients also present with tender enlarged lymph nodes, fever, malaise, and myalgia. Rarely, the disease may also cause aseptic meningitis with neck rigidity and severe headache. Recurrent genital herpes disease is of shorter duration, is milder and does not have systemic symptoms. The main manifestation of the disease is prodromal paresthesias in the perineum, genitalia or buttocks, followed by formation of grouped lesions on the external genital area. The lesions heal without scarring in 2-5 days.
Neonatal Herpes: Neonatal herpes is an extremely severe disease with a very high mortality rate. Neurological complications may occur in infants who survive the infectionFootnote 1. Clinical manifestations of the disease are variable and can be classified into three groups: disseminated disease, involving multiple visceral organs, such as lung, liver, adrenal glands, skin, eye, and the brain (25%); CNS disease with listlessness and seizures (~ 30% of total cases; including 60 to 75% of those cases displaying disseminated disease); and disease limited to the skin, eyes, and/or mouth (SEM) (45%)Footnote 1,Footnote 4.
EPIDEMIOLOGY: Worldwide. HSV infections occur worldwide without any specific seasonal distributionFootnote 2. The prevalence of HSV-1 infection is greater than HSV-2 infection in most geographic areasFootnote 3. HSV-1 causes mainly oral infections in children and has a seroprevalence in adults of 70% in developed countries and 100% in developing countriesFootnote 8. Orolabial herpes has an infection rate of approximately 33% in developing countries and 20% in developed countriesFootnote 3. Genital herpes, caused mainly by HSV-2, is the main cause of genital ulcers worldwideFootnote 8. Neonatal herpes is an uncommon but serious complication of genital herpes with occurrence rates ranging from 1/3,000 to 1/20,000 live births, resulting in an estimated incidence of 1,500 new cases of neonatal HSV infection annually in the United StatesFootnote 3,Footnote 4,Footnote 8. Corneal diseases due to HSV infection are an important cause of blindness, and account for an estimated 500,000 cases annually in the United StatesFootnote 6. Herpes simplex encephalitis (HSE), caused by HSV infection, is one of the most severe CNS infections, accounting for approximately 10–20% of all encephalitic viral infections of the CNS, in the United StatesFootnote 7.
HOST RANGE: HumansFootnote 1, but non-human primates in captivity can be accidentally infected. Rabbits and rodents can be infected experimentally.
INFECTIOUS DOSE: Unknown.
MODE OF TRANSMISSION: Direct contact with infected secretions or mucous membranes/skin with lesions from an asymptomatic or symptomatic patients shedding the virus, is the main mode of transmission of HSVFootnote 2,Footnote 3,Footnote 7. Transmission of HSV-1 can also occur by respiratory dropletsFootnote 7. Genital herpes is transmitted sexuallyFootnote 1,Footnote 2. Neonatal herpes can be acquired at different times: intrauterine (in utero) in 5% of the cases, peripartum (perinatal) in 85% of the cases, and postpartum (postnatal) in 10% of the casesFootnote 1,Footnote 4.
INCUBATION PERIOD: Incubation period generally ranges from 1-26 daysFootnote 2. Incubation period for orolabial HSV infection is 2 to 12 days, with an average of 4 daysFootnote 4. Genital herpes is acquired within 5 daysFootnote 1. Oral and genital lesions appear approximately 19 and 24 days following transplantation organ of an infected organFootnote 5.
COMMUNICABILITY: HSV viruses are passed through close personal contact and mainly oral-genital or genital-genital contactFootnote 9. Vertical transmission can also occur in symptomatic and asymptomatic women. Transfer may be in utero, intrapartum, or postnatal.
DRUG SUSCEPTIBILITY: Antiviral drugs like acyclovir, foscarnet valacyclovir, famciclovir, and penciclovir can inhibit viral replicationFootnote 1. Foscarnet is used for acyclovir-resistant HSV casesFootnote 1,Footnote 2.
SUSCEPTIBILITY TO DISINFECTANTS: HSV virus is easily inactivated by lipid solventsFootnote 2. It can be inactivated by 0.5% Lysol in 5 min; by Listerine (1:1 mixtures) in 5 min; by 2,000 ppm (2,000 ul/liter) of bleach in 10 min; by rubbing alcohol (1:1 mixtures)Footnote 11. HSV is also susceptible to quaternary ammonium compoundsFootnote 12. Most herpes viruses are also susceptible to 30% ethanol and isopropanol, 0.12% orthophenyl phenol, and 0.04% glutaraldehydeFootnote 13.
PHYSICAL INACTIVATION: HSV virus is easily inactivated by exposure to PH <4, temperatures >56°C for 30 min, pasteurization (60°C for 10 h), and microwave heating for 4 minFootnote 2,Footnote 11. HSV-2 is more thermolabile than HSV-1 Footnote 11.
SURVIVAL OUTSIDE HOST: HSV virus survives for short periods of time outside the host Footnote 3. It can survive on dry inanimate surfaces (survival ranges from few hours to 8 weeks). They survive longer at lower humidityFootnote 14.
SURVEILLANCE: Monitor for symptoms, including lesions in or around the oral cavityFootnote 3. Viral culture or PCR is used to detect presence of viral infection. Culture in cells can show multinucleated giant cells, desquamated epithelial cells with intranuclear inclusions. Direct examination of virus in clinical samples can also be done using fluorescent antibody (DFA) test to detect viral antigens present within a tissue or smear specimen, Tzanck test, Enzyme immunoassay (EIA)Footnote 2,Footnote 3. PCR can be used to detect viral DNA in cerebrospinal fluid in the case of encephalitis or in blood in cases of neonatal HSV infectionFootnote 1-Footnote 4,Footnote 15.
Note: All diagnostic methods are not necessarily available in all countries.
Genital herpes: Treated with antiviral drugs such as acyclovir, valacyclovir, famciclovir, and penciclovirFootnote 2. Valacyclovir, famciclovir are approved for chronic suppression of genital herpesFootnote 1.
Herpes labialis: Primary infection in children is treated with oral acyclovir. N-docosanol, a non prescription topical medication, or topical acyclovir reduces time to healing and duration of pain by approximately half a dayFootnote 2,Footnote 4. Oral acyclovir and valacyclovir can be used for recurrent infectionsFootnote 4.
HSE: Treated with Acyclovir.
Neonatal HSV infection: Treated with intravenous acyclovir for 21 days for disseminated infection or CNS infection, and 14 days for SEM infectionFootnote 4.
PROPHYLAXIS: Acyclovir can be used as a prophylactic drug to prevent reactivation of herpes labialis after exposure to ultraviolet radiation, facial surgery, or exposure to sun and wind during skiingFootnote 4. Prophylaxis with oral acyclovir is recommended to suppress genital HSV recurrences near the end of pregnancyFootnote 4. Suppressive therapy with Valcyclovir may be used to prevent frequent recurrences of genital herpes.
LABORATORY-ACQUIRED INFECTIONS: No infections reported.
SOURCE/SPECIMENS: Virus is shed from saliva, cervix, and urethraFootnote 1.
PRIMARY HAZARDS: Direct contact with clinical material or viral isolates, inhalation of concentrated aerosolized materials, droplet exposure of mucous membranes of the eyes, nose, or mouth, ingestion, accidental parenteral inoculation are the primary hazards associated with herpes viruses including HSV 1 and 2Footnote 16.
SPECIAL HAZARDS: None.
RISK GROUP CLASSIFICATION: Risk Group 2Footnote 17.
CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures.
PROTECTIVE CLOTHING: Lab coat. Gloves when direct skin contact with infected materials or animals is unavoidable. Eye protection must be used where there is a known or potential risk of exposure to splashesFootnote 18.
OTHER PRECAUTIONS: All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC). The use of needles, syringes, and other sharp objects should be strictly limited. Additional precautions should be considered with work involving animals or large scale activitiesFootnote 18.
SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply an appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean upFootnote 19.
DISPOSAL: Decontaminate all wastes that contain or have come in contact with the infectious organism before disposing by autoclave, chemical disinfection, gamma irradiation, or incinerationFootnote 19.
STORAGE: The infectious agent should be stored in leak-proof containers that are appropriately labelled.
REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.
UPDATED: September 2011
PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada
Although the information, opinions and recommendations contained in this Pathogen Safety Data sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.
Public Health Agency of Canada, 2011