varicella zoster virus

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  • Varicella-Zoster Virus

    Kaveh Haratian,Ph.D.

    Medical Virologist

    Department of Bacteriology and Virology

    School of Medicine

    Alborz University of Medical Sciences Oct 26, 2013

  • Varicella-Zoster Virus

    Varicella (chickenpox) acute, highly contagious viral disease with worldwide

    distribution majority of annual costs*

    80% to 85% of chickenpox : physician visits 85% to 90% of chickenpox : hospitalization most of which are related to productivity losses by

    caregivers mainly a childhood disease

    5 years of age : infection rate 50%

    12 years of age : infection rate 90%

    Health Canada. CCDR 1999;25(S5):1-29.

  • Varicella-Zoster Virus

    mostly a mild disorder in childhood

    tends to be more severe in adults

    It may be fatal

    Neonates

    Immunocompromised persons 4% to 13% of individuals who had previous varicella

    infection : recurrences of varicella-like rash* The risk factors

    young age (< 12 months) at first infection a milder symptoms at first infection

    *Hall S, et al. Pediatrics 2002;109:1068-73.

  • Varicella-Zoster Virus

    Fatality rates for varicella*

    adults 30 deaths/100,000 cases infants 7 deaths/100,000 cases 1-19 yr of age 1-1.5 deaths/ 100,000 cases

    In the United States

    adults account for only 5% of cases but for 55% of the approximately 100 chickenpox deaths each year

    In Canada, from 1987 to 1996

    70% of the 53 reported chickenpox deaths occurred in those > 15 years of age.

    *Meyer PM, et al. J Infect Dis 2000;182:383-90. Preblud SR. Pediatrics 1981;68:14-7.

  • The pathogen

    a double-stranded DNA virus : human herpesvirus-3 subfamily Alphaherpersvirinae

    only one serotype is known

    humans are the only reservoir VZV enters the host through the nasopharyngeal

    mucosa, and almost invariably produces clinical disease in susceptible individuals

    Following varicella, the virus persists in sensory nerve ganglia, from where it may later be reactivated to cause herpes zoster (Shingles)

  • Transmission

    The virus is transmitted by

    direct contact with the rash

    Airborne respiratory droplets

    vertical transmission (mother to baby) during pregnancy can transmit the virus for up to 48 hours before rash

    appears and remains contagious until all spots crust over little genetic variation

    no animal reservoir

    visceral dissemination of the virus has occurred in 30% and mortality in 7% to 10% of these patients*

    *Feldman S, et al. Pediatrics

    1975;56:388.

  • Signs and symptoms

    In healthy children

    the disease is generally mild.

    The illness usually appear 1416 days after exposure

    Incubation period 10-21 days

    Prodromal symptoms : particularly in older children Low-grade fever preceding skin manifestations by 1-2 D 24-48 hr before rash

    Mild abdominal pain

    Mild cough and runny nose Mild headache

    malaise or irritability

  • Signs and symptoms

    red, itchy rash appear first on the scalp, face, trunk quickly turn into clear fluid-filled vesicles 24-48 hr later, clouding and umbilication of lesions

    initial lesions are crusting, new crops form on trunk and then the extremities

    Characteristics : various stages of evolution

    oropharyngeal, vagina involvement : common

    cornial involvement and serious ocular disease : rare

    the average number of varicella lesion is about 300 lesions

    1,500 lesions Itching may range from mild to intense

  • Laboratory studies

    unnecessary for diagnosis, obvious clinically

    Immunohistochemical staining of skin lesion scrapings can confirm varicella A Tzanck smear : multinucleated giant cells

    useful for high-risk patients who require rapid confirmation

    not sufficiently sensitive or specific for varicella

    more specific immunohistochemical staining of such scrapings, if available

    Immunoglobulin M tests : not reliable, positive results indicate current or recent VZV activity

    Redbook27th Ed;2006;711-725.

  • Immune response

    Natural infection induces lifelong immunity to clinical varicella in almost all immunocompetent persons

    Newborn babies of immune mothers are protected by passively acquired antibodies during their first months of life

    Temporary protection of non-immune individuals can be obtained by injection of varicella-zoster immune globulin within 3 days of exposure

    The immunity acquired in the course of varicella prevents

    neither the establishment of a latent VZV infection, nor the possibility of subsequent reactivation as zoster.

  • Immune response

    Antibody assays : indication of previous infection or response to vaccination less reliable as correlates of immunity, particularly to zoster failure to detect antibodies against VZV does not

    necessarily imply susceptibility, as the corresponding cell-mediated immunity may still be intact

    20% of persons aged 5565 show no measurable cell-mediated immunity to VZV in spite

    of persisting antibodies, and a history of previous varicella Zoster is closely correlated to a fall in the level of VZV-

    specific T-cells an episode of zoster will reactivate the specific T-cell

    response

  • High-risk groups

    High risks of complications Newborns and infants whose

    mothers never had chickenpox or the vaccine

    Teenagers Adults Pregnant women

    People whose immune systems are impaired by another disease or condition

    People who are taking steroid medications for another disease or condition, such as asthma

    People with the skin inflammation eczema

  • Complications of Varicella

    herpes zoster (shingles) lifetime risk 15%-20% mainly affecting the

    elderly and immunocompromised persons

    secondary bacterial skin and soft tissue infections

    otitis media bacteremia, pneumonitis osteomyelitis septic arthritis

    endocarditis necrotizing fasciitis toxic shock-like syndrome hepatitis thrombocytopenia

    hemorrhagic varicella cerebellar ataxia encephalitis severe invasive group A

    streptococcal infection increases the risk 40-60 fold*

    *Health Canada. CCDR 1999;25(S5):1-29. Davies HD, et al. N Eng J Med 1996;335:547-54.

  • Complications of Varicella

    When compared with children, adults are

    3 to 18 fold higher risk : admitted to hospital for varicella 11 to 20 fold higher : higher rates of complications such as

    pneumonia

    1.1- to 2.7-fold higher : encephalitis* The risk factors identified in adults for varicella pneumonia

    underlying chronic lung disease

    Smoking** varicella pneumonia occurring in 3.4% to 9.3% of pregnant

    women (no higher than in nonpregnant adults)*** High mortality *Choo PW, et al. J Infect Dis 1995;172:706-12

    **Ellis ME, et al. Br Med J 1987;294:1002. ***Harger JH, et al. Obstet Gynecol 2002;100(2):260-65.

  • Neonatal varicella

    can be a serious illness, depending upon

    the timing of maternal varicella and delivery

    If the mother develops varicella within 5 days before or 2 days after delivery acquires the virus transplacentally no protective antibodies

    Prophylaxis or treatment is required with varicella-zoster immune globulin (VZIG) and acyclovir

    Without these drugs, mortality rates 20% - 30%*

    The primary causes of death are severe pneumonia and

    fulminant hepatitis

    *Derrick CW Jr, et al.South Med J 1998 Nov; 91(11): 1064-6.

  • Neonatal varicella

    Onset of maternal varicella more than 5 days antepartum provides the mother sufficient time to manufacture and

    pass on antibodies along with the virus. Full-term neonates : usually have mild varicella Treatment with VZIG is not recommended, but

    acyclovir may be used, depending on individual circumstances

    Derrick CW Jr, et al.South Med J 1998 Nov; 91(11): 1064-6.

  • Congenital varicella syndrome

    gestational varicella : currently no evidence associated increase in spontaneous abortion, stillbirth, or prematurity transplacental or perinatal infection can have other serious

    outcomes.

    0.4% of live births when maternal infection occurred from conception through the 12th week of gestation

    2% when infection occurred between the 13th and 20th week of gestation*

    A smaller, prospective study of 347 women who had varicella during pregnancy found an overall congenital varicella syndrome rate of 0.4%**

    *Enders G, et al. Lancet 1994;343:1547-50. **Harger JH, et al. Obstet Gynecol 2002;100(2):260-65.

  • Congenital varicella syndrome

    maternal infection with chickenpox (maternal varicella zoster) early during pregnancy (i.e., up to 20 weeks gestation)

    The range and severity of associated symptoms and

    phy

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