varicella zoster virus *** chicken pox
DESCRIPTION
Varicella zoster virus in kidsTRANSCRIPT
Varicella-Zoster Virus Done by : Mohammed A Qazzaz
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.
ETIOLOGY VZV
• Neurotropic human α-herpesvirus
EPIDEMIOLOGY
• Vaccine started in 1995
• Most children were infected by 15 yr. • < 5% of adults remaining susceptible. • Epidemics occurred in winter and spring,
• 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
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.
• 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.
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
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.
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.
• 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
• 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
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.
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.
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.
Risk factors for progressive varicella
1. congenital cellular immune deficiency.2. malignancy, particularly on chemotherapy.3. after organ transplantation4. 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.
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.
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.
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.
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.
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
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
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
• 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.
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.
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
Herpes Zosterin 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.
DIAGNOSIS of Chicken pox
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.
• Quick direct fluorescence assay of cells from cutaneous lesions,
• PCR.• tissue culture.• VZV IgG antibodies: 4-fold rise • VZV-specific IgM assays
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
• 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
• 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
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 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
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.
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.
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
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%
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.
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.
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,
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.
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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