Varicella-zoster virus

Etiology

Taxonomy

| Order = Herpesvirales | Family = Herpesviridae | Genus = Varicellovirus | Species = Human herpesvirus 3

Description

The earliest reports of the rashes caused by the varicella-zoster virus can be dated back to ancient civilizations. However, it was not until 1888 that a link between the varicella-zoster virus and chickenpox was suggested. Since there was no animal host, much of the evidence needed to be obtained through clinical and epidemiological observations. Developments in the understanding of the varicella-zoster virus were made throughout the second half of the twentieth century with the link being proven in the 1950s, the introduction of the live attenuated vaccine virus in 1974, and treatment with the drug aciclovir in the 1980s. In 1986, the complete DNA sequence of VZV was established. [1]

The varicella-zoster virus has the potential to cause two diseases: chickenpox (varicella) and shingles (herpes zoster). Before the development of a varicella vaccine in 1994, chickenpox was a common contagious childhood illness. It would produce itchy blisters throughout the body but rarely led to any serious problems. Once an individual has had chickenpox, the varicella-virus is able to lay dormant in the nerves and can reemerge as shingles. Although shingles is not life threatening, it is characterized by a painful rash of blisters. Some people that have acquired shingles can develop a condition called postherpetic neuralgia which results in pain in the skin even after the rash is gone. Shingles is most common in people over 60 and in those with a weakened immune system. A herpes zoster vaccine is available to reduce the risk of developing shingles.[2]

Genome

Varicella-zoster virus is an alphaherpesvirus that is in the same subfamily as herpes simplex virus 1 and 2. The varicella-zoster virus genome contains at least 70 genes, and all but 6 have homologs in the herpes simplex virus. The complete sequence of the varicella-zoster virus was determined in 1986, and the prototype strand, VZV Dumas, is 124,884 base pairs in length. The genome consists of a unique long region which is bound by terminal long and internal long repeats and a unique short region which is bound by internal short and terminal short repeats. The unique short region is able to orientate in either of two directions, while the unique long region is rarely able to change its orientation. Therefore, there are usually two isomers of the genome in an infected cell. The genome is linear in virions, and there is an unpaired nucleotide at each end. In cells infected with the virus, the ends pair and the genome circularizes. There are five repeat regions in the genome. Repeat region 1 is located in open reading frame 11, R2 is in open reading frame 14 (glycoprotein C), R3 is in open reading frame 22, R4 is between open reading frame 62 and the origin of viral replication, and R5 is found between open reading frame 60 and 61. The length of the repeat regions vary among strains and can be used to distinguish different strains of the virus [3].

Pathogenesis

Transmission

The virus can be spread through direct contact with blisters, saliva, or mucus of a person infected with chickenpox and spread through the air by coughing and sneezing. It can also be spread indirectly through contact with contaminated, freshly soiled items, such as clothing, of an infected individual. A person infected with chickenpox is contagious from 2 days before the rash appears until all of the blisters have crusted over. Direct contact with the blisters of a person with shingles can cause the virus to spread and lead to chickenpox in a person that has never been infected with the virus or not been vaccinated. Dry and crusted blisters are no longer capable of spreading the virus. [1] [4]

Epidemiology

Chickenpox is a highly contagious, mild disease that is endemic in the population. It becomes epidemic among susceptible individuals mainly in the winter and early spring. Over 90% of the cases are in children under the age of 15. The highest age-specific at risk group is children between the ages of 1-4 which accounted for 39% of all cases. Shingles occurs in 20% of people, most of which are elderly, due to the reactivation of the latent virus from the dorsal root ganglia. [5] [6]

Clinical Features

Symptoms

Susceptible individuals initially infected with the varicella-zoster virus develop chickenpox. This is characterized by a generalized and pruritic rash that progresses rapidly from macules to papules to vesicular lesions before crusting. The rash usually first appears on the head, then the trunk, then the extremities with the highest concentration being on the trunk. The vesicles are superficial, delicate, and contain clear fluid. The vesicles may rupture before becoming dry and crusted. Successive crops appear over several days with lesions being present in several stages of development. Because of this, it is possible for macular lesions to be observed in the same area of the skin as mature vesicles. Children typically have 200 to 400 lesions in 2 to 4 successive crops. The clinical course in healthy children is usually fairly mild with malaise, itching, and a temperature up to 102°F for 2 to 3 days. Adults may have more sever symptoms and a higher incidence of complication. [6]

Shingles is characterized by an area of skin that may burn, itch, tingle or feel very sensitive on one side of the body which can come and go or be constant. A rash then appears in the same area, and the rash then turns into groups of clear blisters. The blisters turn yellow or bloody before they crust over and heal. The blisters typically last 2-3 weeks. The blisters are typically painful, and the pain can last for months after the blisters clear. Flu-like symptoms can also occur, such as a fever or headache. [7]

Morbidity/Mortality

Before the availability of the varicella vaccine, about 11,000 people required hospitalizations each year due to varicella with a hospitalization rate of approximately 2-3 per 1,000 cases among healthy children and 8 per 1,000 cases among adults in the US. Death would occur in about 1 in 60,000 cases. However, since 1996, hospitalizations and deaths due to varicella have declined 70% and 88% respectively. Almost 1 in every 3 people in the United States will develop shingles during their lifetime with approximately 1-4% of cases resulting in hospitalizations. Each year, about 96 shingles related deaths occur in the US. [6] [8]

Diagnosis

Laboratory testing can be done to confirm or rule out varicella. Varicella-zoster virus PCR is the method of choice for diagnosing varicella. The virus may also be isolated in tissue cultures, although this requires several days to obtain a result. [6]

Treatment

Treatment for varicella typically can be done at home with the use of acetaminophen, soothing baths, lotions, antihistamines, and preventing scratching. However, for more serious cases, the antiviral drug acyclovir can be used. Home treatments for shingles include applying cold to the area of infection, antihistamines, and over-the-counter pain relievers. More serious cases may require antiviral drugs such as Acyclovir, Famciclovir, and Valacyclovir. [2]

Prevention

The varicella vaccine is an active immunizing agent that is able to protect against the varicella-zoster virus. It causes the body to produce its own antibodies against the virus. Immunization is recommended for anyone 12 months of age or older who has not had chickenpox. In order to be considered immune to chickenpox without having the infection at some point, an individual must have received 1 dose of the vaccination if between 12 months and 12 years of age or 2 doses if 13 years of age or older. Zostavax® is used for protection against herpes zoster (commonly known as shingles) in people of age 50 and over [9].

References

1 Wood MJ. History of Varicella Zoster Virus. Oct. 2000
2 University of Maryland Medical Center. Varicella-zoster virus
3 Cohen, Jeffrey. The Varicella-Zoster Virus Genome. 7 Aug 2012
4 New York State Department of Health. Chickenpox (varicella zoster infection)
5 State Government Victoria. Chicken pox or shingles (varicella / herpes zoster)
6 Center for Disease Control. Varicella
7 American Academy of Dermatology. Shingles: signs and symptoms
8 Center for Disease Control. Shingles (Herpes Zoster)
9 Mayo Clinic. Varicella Virus Vaccine (Subcutaneous Route)