V aricella Zoster Virus (VZV)

(Chicken pox – Shingles)

By Abelardo J. C. Campos, MD

 

 

THE ORGANISM

 

·       VZV is a DNA virus of the Herpes group.  Infecting particles can be found in secretions of the upper airways and fluid secretions from the vesicles.

 

·       Varicella: Characteristically produces vesicular pruritic disseminated lesions at varying degrees of maturity.  Most frequent in children, with prodromal malaise, pharyngitis and rhinitis, usually with fever and pruritus.  Causes more severe illness in adults.

 

·       Zoster: Most common in adults.  Lesions are localized and painful, often involving the trunk (4).

 

EPIDEMIOLOGY

 

·       VZV has a worldwide distribution:

·       80 % of children under 10 years have had varicella

·       95 % of adults are immune

·       25 % of adults with no history of varicella are susceptible

 

·       Mortality rates vary with age of onset:

·       Mortality rate in children less than 1 year is 6-8 per 100,000

·       Mortality rate in ages between 1-14 years is 0.75 per 100,000

·       Mortality rate in ages between 15-19 years is 2.72 per 100,000

·       Mortality rate in ages between 30-49 years is 25.2 per 100,000

·       Encephalitis occurs in older teenagers and adults in 1 per 3000 (4,5)

·       30 % of children with leukemia and lymphoma who acquire varicella have severe infections and the mortality is 21%

 

CLINICAL MANIFESTATIONS

 

VARICELLA

 

·       The presenting manifestations are rash, low grade fever and malaise. A prodrome may appear 1 to 2 days before in some patients.  In healthy children, illness is generally benign, lasting 3 to 5 days.  After the onset of the rash, malaise, pruritus, anorexia, or listlessness can develop.  

 

·       The skin manifestations consist of maculopapules, vesicles, and scabs in varying stages of evolution, quickly progressing from one stage to the next. Each skin vesicle appears on an erythematous base. The vesicle develops into a pustule and this into a hardened crusted papule.

 

·       The lesions appear on the trunk and face and rapidly spread centripetally to other areas of the body.

 

·       Successive crops of lesions appear over a period of 2 to 4 days. For this reason, the hallmark of the disease is the appearance of lesions at all stages. Less commonly the lesions can be found in the mucosa of the oropharynx and vagina. The crusts completely fall off within 1 to 2 weeks after the onset of the infection leaving a slightly depressed scar (4,5).

 

VARICELLA COMPLICATIONS

 

Bacterial skin superinfection:

 

·       Skin infections including cellulitis can be caused by many bacteria, including Group A streptococcus, which can be severe. Early recognition and treatment of the infection is necessary. Good hygiene can minimize this complication (5).

 

Lower Respiratory:

 

·       Bacterial superinfection of the lower respiratory tract can result in pneumonia and bronchitis. The usual pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus.

 

·       Viral pneumonia is a serious life-threatening complication, more common in adults and immunocompromised patients. It generally appears 3 to 5 days into the course of the illness and is associated with tachypnea, dyspnea, cough, and fever. In adults it can be asymptomatic. Chest radiographs demonstrate nodular or interstitial infiltrates (4,5).

 

Central nervous system:

 

·       VZV has a tropism for nervous tissue. Neurologic disease can occur before or after the acute infection. It can even occur with VZV reactivation without skin lesions (Zoster sine herpete). Neurologic abnormalities are manifested as acute cerebellar ataxia or encephalitis.

 

·       Cerebellar ataxia is a benign complication that is thought to be due to postinfection demyelination. Resolution occurs within 2 to 4 weeks.  It is estimated to occur in 1 in 4000 cases, among those younger than 15 years old.  It usually appears within one week of the exanthema but it can appear 21 days after the onset of rash. Ataxia, vomiting, altered speech, fever, vertigo and tremor are common symptoms. Cerebrospinal fluids demonstrate lymphocytosis and elevated levels of cerebrospinal fluid protein. Polymerase chain reaction (PCR) techniques demonstrate VZV DNA in the cerebral spinal fluid (CSF).

 

·       Encephalitis occurs in 0.1 to 0.2% of patients. Mortality has been estimated to range between 5 to 20% and sequelae has been detected in 15% of survivors.   Physical examination can reveal decreased level of consciousness, headaches, ataxia, vomiting, altered thought patterns, fever and seizures. The duration of the disease is at least 2 weeks.

 

·       Reye’s Syndrome is described in association with varicella, often with concomitant use of aspirin in children younger than 5 years (1,4,5). It begins in late stages of varicella, with vomiting, restlessness, irritability, and progressive decrease in the level of consciousness, associated with progressive cerebral edema. There is an association with elevated levels of ammonia, a bleeding diathesis, hyperglycemia and elevated serum transaminase levels (4,5).

 

Varicella in the immunocompromised host:

 

·       Immunocompromised patients may develop severe skin eruption with or without hemorrhage. Healing of the cutaneous lesions takes three times longer than in the general population. Patients develop high fever.  Virus spreads to visceral organs causing hepatitis, pneumonitis, pancreatitis, small bowel obstruction and encephalitis. Bacterial superinfections including bacteremia can develop.  Antiviral therapy significantly reduces morbidity and can reduce mortality. (4)

 

Varicella in pregnancy:

 

·       A rare complication in the United States (US), because most adults are immune. Rarely, varicella in early pregnancy (first 20 weeks) may result in congenital varicella syndrome (CVS).  CVS occurs in 2% of infections in pregnancy and is characterized by unusual cutaneous defects, cicatricial skin scars, and atrophy of the extremities. The patients often have microcephaly, cortical atrophy, seizures, mental retardation, chorioretinitis, microphthalmia, or cataracts.

 

·       Newborns whose mothers develop varicella close to term are at risk of neonatal varicella.  These babies can be born with varicella lesions or develop lesions after birth, but they will not have serious complications.

 

·       Full-term infants born from seropositive mothers exposed to non-maternal varicella are passively protected by maternally acquired antibodies to VZV.  Premature infants 24-25 weeks do not acquire maternal VZV antibodies.

 

·       Herpes zoster in pregnancy does not result in CVS. (2,5)

 

HERPES ZOSTER

 

·       Zoster is a unilateral vesicular eruption with dermatomal distribution. Thoracic and lumbar dermatomes are the most commonly involved, presumably because this is the area of greatest VZV infection in the primary infection. The onset of the disease is preceded by pain 48 to 72 hours before the rash develops in the affected dermatome. The rash appears as erythematous, maculopapular lesions that rapidly evolve into vesicles. The vesicles may coalesce and form bullous lesions. The lesions continue to form for 3 to 5 days, with a total duration of the disease of 10 to 15 days. However it can take as long as 1 month before the skin returns to normal (4).

 

 

HERPES ZOSTER COMPLICATIONS

 

Ophthalmologic:

 

·       Herpes zoster can affect the cornea and be followed by iridocyclitis, secondary glaucoma. This condition is known as herpes zoster ophthalmicus and is sight – threatening.

 

Postherpetic neuralgia:

 

·       Postherpetic neuralgia may cause constant or intermittent stabbing pain in the affected dermatome.  The pain can be very intense in adults and may be worse at night or with exposure to temperature changes. It may occur in as many as 25 to 50% of patients older than 50 years old.  Fifty percent of persons older than 50 will suffer debilitating pain for more than 1 month.

 

Meningoencephalitis and encephalitis:

 

·       The clinical manifestations are similar to other viral infections of the central nervous system. Frequently there are no clinical symptoms. After central nervous system zoster, granulomatous cerebral angitis can be found.

 

·       The involvement of the dorsal root ganglia is classic. Motor paralysis and excruciating pain can occur as a consequence of the involvement of the anterior horn cells.

 

Zoster in the immunocompromised host:

 

·       Immunocompromised patients can experience a more severe form of the disease. Lesions form for up to 2 weeks after infection and scabbing occurs until 3 to 4 weeks into the course of the disease.

 

·       Patients with lymphoproliferative malignancies are at risk of cutaneous dissemination and visceral involvement, including pneumonitis, hepatitis, and meningoencephalitis.

 

·       Eight to 11 % of patients with Human Immunodeficiency Virus can be infected with Herpes Zoster Virus. These patients can develop chronic herpes zoster, with formation of new lesions without the healing of the already existing ones. (4)

 

 

DIAGNOSIS

 

·       The diagnosis of VZV infection is usually based on clinical findings.  However, in some situations, eg. immunocompromised patients, this can be difficult. In these patients, it is necessary to use laboratory exams to confirm the diagnosis.

 

·       History of exposure to varicella or zoster in the past 3 weeks.

 

·       Physical examination of the rash:

·       varicella: lesions in all stages of evolution, from vesicle over exanthema to pustule to crusted lesion

·       zoster: dermatome distribution of lesions (4,5).

 

Laboratory diagnosis

 

·       Serologic test: Enzyme immunoassay (EIA), latex agglutination (LA), Indirect fluorescent antibody (IFA) and fluorescent antibody to membrane antigen assay (FAMA) are reliable in the immunocompetent patient but not necessarily in immunocompromised patients. The complement fixation (CF) test is insufficiently sensitive in either case. Specific diagnosis can also be made by DNA hybridization and PCR techniques. For confirmation of diagnosis, to obtain the virus strain for epidemiologic analysis, or to test drug resistance, a cell culture can be done (4,5).

 

TRANSMISSION

 

·       Direct Contact: Direct contact with respiratory secretions and/or fluids from the vesicles of patients.  (primary zoster)

 

·       Airborne: Inhalation of small particle aerosols from nasopharyngeal secretions from infected individuals followed by localized replication at an undefined site, which lead to the seeding of the reticuloendothelial system and viremia. After this, localization and replication of the viral particles in the skin produces the onset of the classic rash. Usually this takes about 14 days, but it can range from 10 to 21 days.  (varicella or disseminated zoster [greater than 2 dermatones] in immunocompromised hosts) 

 

·       Incubation Period: 10 to 21 days. If Varicella-Zoster immune globulin (VZIG) was administered, 28 days.

 

·       Infectious Period: 24 to 48 hours before onset of lesions until the lesions crust completely.

 

·       Patients infected with Zoster should be placed on contact isolation for a minimum of five days after onset of rash.  Patients with varicella should be placed in strict or airborne isolation, depending on the classification nomenclature of the institution, in negative pressure rooms, if available (1).  Immunocompromised hosts with disseminated zoster should also be placed in strict isolation.  Several well described outbreaks have occurred in healthcare settings.  Transmission has occurred through the ventilation system. (6,7)

 

EXPOSURE

 

·       Criteria for exposure: Close contact by susceptible individuals with an infected source. 

Household Contact: Close, indoor contact (in the same room) for more than one hour or face to face contact with the infected source for more than 5 minutes.

 

Hospital contact: contact with an infected source in the same ward, room or nursery or newborn exposure to a maternal varicella (5).

 

TREATMENT

 

General measures:

·       Adequate general hygiene measures are important. Bathing, astringent soaks, and closely cropped fingernails to avoid scratching of the pruritic lesions. Topical dressings and administration of antipruritic drugs can be useful to control the pruritus. Control of fever with acetaminophen. CHILDREN SHOULD NEVER RECEIVE SALICYLATES (1,4,5).

 

Specific treatment:

·       CONSIDER administering Acyclovir orally when treating severe varicella, for example:

·       Children older than 12 years.

·       Persons with chronic cutaneous or pulmonary diseases

·       Persons on chronic salicylate therapy or corticosteroids

·       Persons at high risk of developing complications

·       Pregnant females

·       Acyclovir is NOT recommended for the treatment of uncomplicated varicella in healthy patients. Consider administering Acyclovir intravenously to immunocompromised patients.

 

PREVENTION AND CONTROL

 

Vaccine:

·       There is a live attenuated varicella vaccine. It induces protection against 95% of household contact and has high seroconversion rates (above 95%) with persistence of VZV IgG antibodies after 1 year of immunization. Adults need two doses separated by 4 weeks. Seventy percent of adults have VZV IgG antibodies after 2 to 6 years. However, immunized adults will have a less severe illness if they develop a breakthrough infection with wild virus.

·       Children with vaccine induced immunity develop mild breakthrough infections after exposure to the natural virus, but the illness is less severe. The household transmission from these patients was 12% versus 80% for wild type virus.

·       Children with leukemia in remission have an attack rate of 13% after household exposure to varicella. They will require two doses of the vaccine to obtain an appropriate level of protection.

·       Vaccination of healthy, elderly, susceptible patients may reduce the incidence of zoster and subsequent complications in these patients, especially post-herpetic neuralgia (1,3,4,5).

·       Vaccine usually used as post-exposure follow up. (5)

 

Indications

·       Ages 12 months to 13 years: one dose.

·       Ages 13 years to young adult: two doses with a 4 to 8 week interval.

(IF SUSCEPTIBLE)

·       Consider in healthcare workers without natural immunity

·       Contraindications to vaccination should be considered prior to administration of vaccine.  These include: neomycin allergy, blood dyscrasias, acute leukemia, lymphomas or other malignant neoplasms, HIV infection or AIDS, and anyone receiving immunosuppressive medication (5).

·       VZIG is indicated in immunocompromised susceptible hosts who are exposed to zoster, neonates whose mothers develop varicella from 2 days prior to birth to 5 days after birth, exposed premies, and otherwise high risk individuals. 

 

REFERENCES

 

1.     American Academy of Pediatrics. (1994).  Varicella zoster infections.  In Red book: Report of the committee on infectious diseases.  (23^rd ed. , pp. 511-517).  Elk Grove Village, IL: Author.

2.     Gershan, A. A. (1990).  Chickenpox, measles, and mumps.  In J. S. Remington & J. O. Klein (Eds.). Infectious Diseases Of The Fetus And Newborn Infant  (3^rd ed. pp. 398-411).  Philadelphia, PA: W.B. Saunders Company.

3.     Takahashi, M. (2000).  Development of live varicella vaccine: Past and future.  Japanese Journal of Infectious Diseases, 53, 47-55.

4.     Whitley, R. J. (2000).  Varicella zoster virus.  In G. C. Mandell J. E. Bennett, & R. Dolin (Eds.).  Principles and practice of infectious diseases (5th ed, pp. 1580-1585).   Philadelphia, PA: Churchill Livingstone.

5.     Zaia, J. A. (1999).  Varicella zoster virus.  In G. C. Mayhall (Ed.).  Hospital epidemiology and infection control (2^nd ed., pp. 544-551).   Philadelphia, PA: Lippincott, Williams, & Wilkins.

6.     Sawyer, M.H., Chamberline, C.J., Wu, Y., et al. (1994).  Detection of varicella-zoster virus DNA in air samples from hospital rooms.  The Journal of Infections Diseases,1, 169:91-4.

7.     Josephson, A., Gombert, M.E. (1988). Airborne transmission of nosocomial varicella from localized zoster.  The Journal of Infectious Diseases, 1, 158: 238-41.