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Varicella-Zoster Virus
Varicella-Zoster Virus (VZV)
• Causes primary, latent, and recurrent infections.
• The primary infection: varicella (chick...
ETIOLOGY
VZV
• Neurotropic human α-herpesvirus
EPIDEMIOLOGY
• Vaccine started in 1995
• Most children were infected by 15 yr.
• < 5% of adults remaining susceptible.
• E...
• More serious in infants, adults, and
immunocompromised.
• Households transmission 65–86%;
• Contagious period from 2days...
PATHOGENESIS
• VZV is transmitted in respiratory secretions and in the
fluid of skin lesions either by airborne spread or ...
• During viremia the mononuclear cells carry the virus
to form new crops of vesicles.
• Also goes back to upper respirator...
PATHOGENESIS
• Virus is transported through sensory axons to the dorsal root ganglia
throughout the spinal cord, causing l...
CLINICAL MANIFESTATIONS
• usually self-limited.
• may be associated with severe complications:
 bacterial superinfection
...
Varicella (Chicken pox)
• I.P: 10 to 21 days
• The illness usually begins 14–16 days after exposure.
• Prodromal symptoms ...
• lesions appear first on the scalp, face, or trunk.
• Initially: pruritic erythematous macules then papular
stage to form...
• The rash is predominantly centripetal.
• Ulcerative lesions involving the mucosa of oropharynx,
eyelids and conjunctivae...
The differential diagnosis
• herpes simplex virus,
• enterovirus,
• monkey pox,
• rickettsial pox
• S. aureus;
• drug reac...
Varicella in Vaccinated Individuals
• Vaccine is effective in;
- >95% preventing severe disease
- 80% preventing all disea...
Progressive Varicella
• visceral organ involvement,
• coagulopathy,
• severe hemorrhage, and
• continued vesicular lesions...
Risk factors for progressive varicella
1. congenital cellular immune deficiency.
2. malignancy, particularly on chemothera...
Neonatal Chickenpox
• Newborns have high mortality in susceptible mother
contracting varicella around the time of delivery...
Neonatal Chickenpox
• Because the mother has not yet developed a significant
antibody response, the infant receives a larg...
Neonatal Chickenpox ttt
• human varicella-zoster immune globulin (VariZIG) is indicated.
• Newborns whose mothers develop ...
Congenital Varicella Syndrome
• up to 2% of fetuses whose mothers had varicella in the 1st 20
wk of pregnancy may have a V...
Stigmata of Varicella-Zoster Virus Fetopathy
DAMAGE TO SENSORY NERVES
• Cicatricial skin lesions
• Hypopigmentation
DAMAGE...
DAMAGE TO BRAIN/ENCEPHALITIS
• Microcephaly
• Hydrocephaly
• Calcifications
• Aplasia of brain
DAMAGE TO CERVICAL OR LUMBO...
Diagnosis of VZV embryopathy
• The history.
• chickenpox stigmata seen in the fetus.
• Viral DNA may be detected in tissue...
• Although varicella immune globulin to exposed
mother may not modify infection in the fetus.
• Similarly, acyclovir treat...
Herpes Zoster
• vesicular lesions clustered within 1 or less commonly
2 adjacent dermatomes
In the elderly:
• begins with ...
In children:
• rash is mild
• lesions appearing for a few days
• symptoms of acute neuritis are minimal
• complete resolut...
Herpes Zoster
in immunocompromised children
• more severe, similar to adults, including postherpetic neuralgia.
• dissemin...
DIAGNOSIS of Chicken pox
DIAGNOSIS of Chicken pox
• Leukopenia is typical during the 1st 72 hr; it is
followed by
• lymphocytosis.
• liver function...
• Quick direct fluorescence assay of cells from
cutaneous lesions,
• PCR.
• tissue culture.
• VZV IgG antibodies: 4-fold r...
TREATMENT
• Antiviral modifies the course of both varicella
and herpes zoster (acyclovir).
• foscarnet is the only drug av...
• acyclovir therapy is not recommended routinely for treatment of
uncomplicated varicella in healthy child
• Oral therapy ...
• To be most effective, treatment should be initiated as
early as possible, preferably within 24 hr of the onset
of the ex...
Herpes Zoster ttt
• Antiviral drugs are effective for treatment of herpes
zoster.
COMPLICATIONS of Chicken pox
• mild varicella hepatitis is relatively common but rarely
clinically symptomatic.
• Mild thr...
Bacterial Infections
• 2ry group A streptococci and S. aureus, in up to 5%.
• serious invasive infections caused by group ...
Encephalitis and Cerebellar Ataxia
• Encephalitis: 1/50,000
• acute cerebellar ataxia: 1/4000
• morbidity more in < 5 yr o...
Encephalitis and Cerebellar Ataxia
• Clinical recovery is typically rapid, occurring within
24–72 hr, and is usually compl...
PROGNOSIS of Chicken pox
• mortality rate of 3 per 100,000 cases.
• lowest fatality 1–9 yr.
• infants have a 4 times great...
PREVENTION
• VZV transmission is difficult to prevent
because the infection is contagious for 24–48
hr before the rash app...
Vaccine
• Live virus varicella vaccine: alone or combined with
MMR (MMRV).
• Administration of varicella vaccine within 4 ...
Vaccine
• Varicella vaccine is recommended for routine
administration to children at 12–18 mo and at
4–6 yr of age.
• Vacc...
Vaccine contraindication
• Varicella vaccine is contraindicated in children
with cell-mediated immune deficiencies,
• Can ...
Post-exposure Prophylaxis
• Vaccine given to normal children within 3–5 days
after exposure is effective in preventing or ...
Varicella zoster virus *** chicken pox
Varicella zoster virus *** chicken pox
Varicella zoster virus *** chicken pox
Varicella zoster virus *** chicken pox
Varicella zoster virus *** chicken pox
Varicella zoster virus *** chicken pox
Varicella zoster virus *** chicken pox
Varicella zoster virus *** chicken pox
Varicella zoster virus *** chicken pox
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Varicella zoster virus *** chicken pox

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Varicella zoster virus *** chicken pox

  1. 1. Varicella-Zoster Virus
  2. 2. Varicella-Zoster Virus (VZV) • Causes primary, latent, and recurrent infections. • The primary infection: varicella (chickenpox) • Followed by: lifelong latent infection of sensory ganglion neurons. • Reactivation causes herpes zoster (shingles). • Chickenpox causes morbidity and mortality which is more in: - adolescents, adults - immunocompromised • Can be treated with antiviral drugs. • Can be prevented by immunization.
  3. 3. ETIOLOGY VZV • Neurotropic human α-herpesvirus
  4. 4. EPIDEMIOLOGY • Vaccine started in 1995 • Most children were infected by 15 yr. • < 5% of adults remaining susceptible. • Epidemics occurred in winter and spring,
  5. 5. • More serious in infants, adults, and immunocompromised. • Households transmission 65–86%; • Contagious period from 2days before rash until vesicles are crusted, usually 3–7 days after onset of rash. • Chicken pox can be acquired after close contact with cases having herpes zoster
  6. 6. PATHOGENESIS • VZV is transmitted in respiratory secretions and in the fluid of skin lesions either by airborne spread or through direct contact. • Primary infection (varicella) results from inoculation of the virus onto the mucosa of the upper respiratory tract and tonsillar lymphoid tissue. • virus replicates in the local lymphoid tissue then by viremia spreads to the reticuloendothelial system.
  7. 7. • During viremia the mononuclear cells carry the virus to form new crops of vesicles. • Also goes back to upper respiratory mucosa during the late incubation period, becoming infectious before rash(2d). • Host immune responses limit viral replication. • In the immunocompromised continued viral replication cause disseminated infection with complications in the lungs, liver, brain, and other organs.
  8. 8. PATHOGENESIS • Virus is transported through sensory axons to the dorsal root ganglia throughout the spinal cord, causing latent infection in the neurons. • Subsequent reactivation of latent virus causes herpes zoster. • The skin lesions of varicella and herpes zoster have identical histopathology, and infectious VZV is present in both. • Varicella causes humoral and cell-mediated immunity that is highly protective against symptomatic reinfection. • Suppression of cell-mediated immunity to VZV correlates with an increased risk for VZV reactivation as herpes zoster
  9. 9. CLINICAL MANIFESTATIONS • usually self-limited. • may be associated with severe complications:  bacterial superinfection  Pneumonia  Encephalitis  bleeding disorders  congenital infection  life-threatening perinatal infection. • Herpes zoster, uncommon in children, causes localized cutaneous symptoms, but may disseminate in immunocompromised patients.
  10. 10. Varicella (Chicken pox) • I.P: 10 to 21 days • The illness usually begins 14–16 days after exposure. • Prodromal symptoms 24–48 hr before rash: - Fever: moderate - malaise - anorexia - headache - mild abdominal pain (occasional). • symptoms persist 1st 2–4 days after rash onset.
  11. 11. • lesions appear first on the scalp, face, or trunk. • Initially: pruritic erythematous macules then papular stage to form clear, fluid-filled vesicles. • umbilication of the lesions begin in 24–48 hr. • While the initial lesions are crusting, new crops form on the trunk and then the extremities. • presence of various stages at a time is characteristic of varicella
  12. 12. • The rash is predominantly centripetal. • Ulcerative lesions involving the mucosa of oropharynx, eyelids and conjunctivae. • The average lesions is 300, but healthy children(10-1500) • The rash is more extensive with eczema. • Hypopigmentation or hyperpigmentation of lesion sites persists for days to weeks. • severe scarring is unusual unless the lesions were secondarily infected
  13. 13. The differential diagnosis • herpes simplex virus, • enterovirus, • monkey pox, • rickettsial pox • S. aureus; • drug reactions; • contact dermatitis; • insect bites. Severe varicella was the most common illness confused with smallpox before the eradication of smallpox.
  14. 14. Varicella in Vaccinated Individuals • Vaccine is effective in; - >95% preventing severe disease - 80% preventing all disease. • 1 of every 5 vaccinated children may develop varicella in school outbreak. • Mild disease with mild or no fever. • The rash is atypical: - maculopapular - vesicles - <50 lesions • less contagious.
  15. 15. Progressive Varicella • visceral organ involvement, • coagulopathy, • severe hemorrhage, and • continued vesicular lesions, hemorrhagic vesicles . • Severe abdominal pain, • The mortality rate is 7%; within 3 days after the diagnosis of varicella pneumonia.
  16. 16. Risk factors for progressive varicella 1. congenital cellular immune deficiency. 2. malignancy, particularly on chemotherapy. 3. after organ transplantation 4. high-dose corticosteroids • Immunization of the following gp helps to reduce the problem: - HIV-infected children who have a CD4 count > 15% - children with leukemia and solid organ tumors who are stable on maintenance chemotherapy.
  17. 17. Neonatal Chickenpox • Newborns have high mortality in susceptible mother contracting varicella around the time of delivery. • Infants whose mothers develop varicella in the period from 5 days prior to delivery to 2 days afterward are at high risk for severe varicella. • The infant acquires the infection transplacentally as a result of maternal viremia, which may occur up to 48 hr prior to the maternal rash. • Rash appears at the end of the 1st week.
  18. 18. Neonatal Chickenpox • Because the mother has not yet developed a significant antibody response, the infant receives a large dose of virus without the moderating effect of maternal anti-VZV antibody. • If the mother develops varicella > 5 days prior to delivery, she still may pass virus to the soon-to-be-born child, but infection is attenuated due to transmission of maternal antibody across the placenta.
  19. 19. Neonatal Chickenpox ttt • human varicella-zoster immune globulin (VariZIG) is indicated. • Newborns whose mothers develop varicella 5 days before to 2 days after delivery should receive 1 vial. • Although neonatal varicella may occur in about half of these infants despite administration of VariZIG, it is usually mild.
  20. 20. Congenital Varicella Syndrome • up to 2% of fetuses whose mothers had varicella in the 1st 20 wk of pregnancy may have a VZV embryopathy. • Fetuses infected at 6–12 wk of gestation appear to have maximal interruption with limb development; • fetuses infected at 16–20 wk may have eye and brain involvement. • The organs involved mainly the skin, extremities, eyes, and brain • The characteristic cutaneous lesion has been called a cicatrix, a zigzag scarring, in a dermatomal distribution, often associated with atrophy of the affected limb.
  21. 21. Stigmata of Varicella-Zoster Virus Fetopathy DAMAGE TO SENSORY NERVES • Cicatricial skin lesions • Hypopigmentation DAMAGE TO OPTIC STALK AND LENS VESICLE • Microphthalmia • Cataracts • Chorioretinitis • Optic atrophy
  22. 22. DAMAGE TO BRAIN/ENCEPHALITIS • Microcephaly • Hydrocephaly • Calcifications • Aplasia of brain DAMAGE TO CERVICAL OR LUMBOSACRAL CORD • Hypoplasia of an extremity • Motor and sensory deficits • Absent deep tendon reflexes • Anisocoria (difference in pupil size) • Horner syndrome • Anal/urinary sphincter dysfunction
  23. 23. Diagnosis of VZV embryopathy • The history. • chickenpox stigmata seen in the fetus. • Viral DNA may be detected in tissue samples by (PCR). • VZV-specific IgM antibody in the cord blood. • Chorionic villus sampling
  24. 24. • Although varicella immune globulin to exposed mother may not modify infection in the fetus. • Similarly, acyclovir treatment may be given to the mother with severe varicella. • Acyclovir when the benefit to the mother outweighs the potential risk to the fetus (effect is uncertain). • antiviral treatment of infants with congenital VZV syndrome is not indicated because it is not progressive.
  25. 25. Herpes Zoster • vesicular lesions clustered within 1 or less commonly 2 adjacent dermatomes In the elderly: • begins with burning pain, with clusters of skin lesions in a dermatomal pattern. • Almost half of the elderly with herpes zoster develop complications; • the most frequent complication is postherpetic neuralgia, a painful condition that affects the nerves despite resolution of the shingles skin lesions.
  26. 26. In children: • rash is mild • lesions appearing for a few days • symptoms of acute neuritis are minimal • complete resolution usually occurs within 1–2 wk. • postherpetic neuralgia is very unusual in children. • Approximately 4% of patients suffer a 2nd episode of herpes zoster. ( 3 or more episodes are rare ) • Transverse myelitis with transient paralysis is a rare. Risk factors: • children who acquire varicella in the 1st year of life • whose mothers have a varicella infection in the 3rd trimester of pregnancy
  27. 27. Herpes Zoster in immunocompromised children • more severe, similar to adults, including postherpetic neuralgia. • disseminated cutaneous disease like chicken pox. • visceral dissemination with pneumonia, hepatitis, encephalitis, and disseminated intravascular coagulopathy. Patients with HIV: • chronic or relapsing cutaneous disease • Retinitis • CNS disease without rash. • A lower risk for herpes zoster in vaccinated children with leukemia.
  28. 28. DIAGNOSIS of Chicken pox
  29. 29. DIAGNOSIS of Chicken pox • Leukopenia is typical during the 1st 72 hr; it is followed by • lymphocytosis. • liver function tests usually (75%) mildly elevated. • CSF: in CNS complications: - lymphocytic pleocytosis - increase in protein - glucose concentration is usually normal.
  30. 30. • Quick direct fluorescence assay of cells from cutaneous lesions, • PCR. • tissue culture. • VZV IgG antibodies: 4-fold rise • VZV-specific IgM assays
  31. 31. TREATMENT • Antiviral modifies the course of both varicella and herpes zoster (acyclovir). • foscarnet is the only drug available for the treatment of acyclovir-resistant VZV infections (in HIV) Acyclovir Therapy
  32. 32. • acyclovir therapy is not recommended routinely for treatment of uncomplicated varicella in healthy child • Oral therapy with acyclovir (20 mg/kg/dose, maximum 800 mg/dose) given as 4 doses/day for 5 days should be used to treat uncomplicated varicella in: (Indication of oral therapy) : - nonpregnant individuals >13 yr - children >12 mo with chronic skin or pulmonary disorders - on steroids: short-term, intermittent, or aerosolized - children receiving long-term salicylate therapy - 2nd cases in household contacts. Acyclovir Therapy
  33. 33. • To be most effective, treatment should be initiated as early as possible, preferably within 24 hr of the onset of the exanthem. • There is clinical benefit if initiation of treatment is delayed more than 72 hr after onset of the exanthem. • Acyclovir does not interfere with VZV immunity. • Intravenous therapy is indicated for severe disease and for varicella in immunocompromised patients (even after 72 hr duration of rash). Acyclovir Therapy
  34. 34. Herpes Zoster ttt • Antiviral drugs are effective for treatment of herpes zoster.
  35. 35. COMPLICATIONS of Chicken pox • mild varicella hepatitis is relatively common but rarely clinically symptomatic. • Mild thrombocytopenia occurs in 1–2% of children with varicella and may be associated with transient petechiae. • Purpura, hemorrhagic vesicles, hematuria, and gastrointestinal bleeding . • Cerebellar ataxia occurs in 1 in every 4,000 cases. • Other: include encephalitis, pneumonia, nephritis, nephrotic syndrome, hemolytic-uremic syndrome, arthritis, myocarditis, pericarditis, pancreatitis, and orchitis
  36. 36. Bacterial Infections • 2ry group A streptococci and S. aureus, in up to 5%. • serious invasive infections caused by group A streptococcus, which can have a fatal outcome • The more invasive infections, such as varicella gangrenosa, bacterial sepsis, pneumonia, arthritis, • toxic shock syndrome.
  37. 37. Encephalitis and Cerebellar Ataxia • Encephalitis: 1/50,000 • acute cerebellar ataxia: 1/4000 • morbidity more in < 5 yr or > 20 yr • meningoencephalitis Encephalitis: neck rigidity, altered consciousness, and seizures characterize. • cerebellar ataxia: gradual gait disturbance, nystagmus, and slurred speech. • Neurologic symptoms usually begin 2–6 days after onset of rash.
  38. 38. Encephalitis and Cerebellar Ataxia • Clinical recovery is typically rapid, occurring within 24–72 hr, and is usually complete. • severe hemorrhagic encephalitis is very rare. • Reye syndrome of encephalopathy and hepatic dysfunction associated with varicella has become rare since salicylates are no longer routinely used as antipyretics
  39. 39. PROGNOSIS of Chicken pox • mortality rate of 3 per 100,000 cases. • lowest fatality 1–9 yr. • infants have a 4 times greater risk of dying • adults have a 25 times greater high risk of dying. • the most common complications among people who died from varicella were pneumonia, CNS complications, secondary infections, and hemorrhagic conditions. • mortality in immunocompromised children: 7–14%, • mortality in immunocompromised adults: 50%
  40. 40. PREVENTION • VZV transmission is difficult to prevent because the infection is contagious for 24–48 hr before the rash appears. • All health care workers should have documented VZV immunization.
  41. 41. Vaccine • Live virus varicella vaccine: alone or combined with MMR (MMRV). • Administration of varicella vaccine within 4 wk of MMR vaccine has been associated with a higher risk for severe disease; • therefore, it is recommended that the vaccines either be administered simultaneously at different sites or be given at least 4 wk apart.
  42. 42. Vaccine • Varicella vaccine is recommended for routine administration to children at 12–18 mo and at 4–6 yr of age. • Vaccination with 2 doses, separated by at least 4 wk,
  43. 43. Vaccine contraindication • Varicella vaccine is contraindicated in children with cell-mediated immune deficiencies, • Can be given to children with acute lymphoblastic leukemia who are in remission, and for HIV-infected children with specific guidelines. • Children with isolated humoral immune deficiencies may receive VZV vaccine.
  44. 44. Post-exposure Prophylaxis • Vaccine given to normal children within 3–5 days after exposure is effective in preventing or modifying varicella. • Oral acyclovir administered late in the incubation period may modify varicella. • High-titer anti-VZV immune globulin as postexposure prophylaxis is recommended for: - immunocompromised children, - pregnant women, and - newborns exposed to maternal varicella.

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