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Varicella zoster virus infections
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- 3. • Varicella-zoster virus(VZV) causes primary, latent, and recurrent infections. • The primary infection is manifested as varicella (chickenpox) • morbidity and mortality • it predisposes to severe group A streptococcus and Staphylococcus aureus infections
- 4. Etiology • VZV isa neurotropic human herpesvirus • virus is enveloped with double-stranded DNA genomes • encode more than 70 proteins
- 5. • transmission ofVZV to susceptible individuals occurs at a rate of 65-86% • contagious 24-48 hr before the rash is evident and until vesicles are crusted • Varicella vaccine is introduced in 1995
- 6. Herpes zoster • reactivationof latent VZV. • uncommon in childhood • Zoster is not caused by exposure to a patient with varicella • The lifetime risk for herpes zoster for individuals with a history of varicella is 10-20% • 75% of cases occurring after 45 yr of age. • Herpes zoster is very rare in healthy children <10 yr of age
- 7. • Herpes zosterin children tends to be milder than disease in adults • It occurs more frequently & disease is more severe if- – Children is on immunosuppressive therapy – HIV infected children.
- 8. Pathogenesis • VZV istransmitted in – by airborne spread - oropharyngeal secretion – through direct contact - fluid of skin lesions
- 10. • Primary infection(varicella) results from - • inoculation of the virus onto the mucosa of the URT and tonsillar lymphoid tissue. • virus replicates in the local lymphoid tissue • brief subclinical viremia(First) • spreads the virus to the reticuloendothelial system • Widespread cutaneous lesions occur (during a second viremic). • VZV is also transported back to the mucosa of the upper respiratory tract and oropharynx
- 11. • Virus istransported in a retrograde manner through sensory axons dorsal root ganglia throughout the spinal cord virus establishes latent infection in the neurons and satellite cells Subsequent reactivation of latent virus herpes zoster
- 12. –vesicular rash thatusually is dermatomal in distribution. –necrotic changes may be produced in the associated ganglia. –The skin lesions of varicella and herpes zoster have identical histopathology –infectious VZV is present in both.
- 13. Clinical Manifestation • Varicella(Chicken pox) • Varicella Zoster • Breakthrough varicella • Progressive varicella • Neonatal varicella • Congenital varicella syndrome
- 14. Varicella(Chickenpox) • incubation periodis 10 -21 days. • Subclinical varicella is rare • Prodromal symptoms – Fever – malaise – anorexia – headache – mild abdominal pain
- 15. • Varicella lesions –appear first on the scalp, face, or trunk. – The initial exanthem consists of intensely pruritic – erythematous macules – papular stage – fluid-filled vesicles. – Clouding and umbilication of the lesions begin in 24-48 hr.
- 16. • simultaneous presenceof lesions in various stages of evolution is characteristic of varicella • The distribution of the rash is predominantly central or centripetal • The number of varicella lesions 10 to 1,500 • Ulcerative lesions involving the mucosa of oropharynx and vagina
- 17. • vesicular lesionson the eyelids and conjunctivae • The exanthem may be much more extensive in children with skin disorders • Hypopigmentation or hyperpigmentation of lesion sites persists for days to weeks.
- 21. differential diagnosis • vesicularrashes caused by other infectious agents :- – enterovirus – monkey pox – rickettsial pox – S. aureus – drug reactions – disseminated herpes zoster – contact dermatitis – insect bites
- 22. Varicella in VaccinatedIndividuals (“Breakthrough Varicella”) • One dose of varicella vaccine is >97% effective in preventing severe varicella • 85% effective in preventing all disease after exposure to wild-type VZV. • Breakthrough disease is varicella that occurs in a person vaccinated >42 days before rash onset and is caused by wild-type VZV
- 23. • rash occurring< 14 days after vaccination was most commonly wild-type VZV • Rash occurring 14-42 days after vaccination was due to either – Wild-type VZV-------- breakthrough varicella – vaccine strains---------vaccine-associated rash
- 24. • The Breakthroughvaricella rashes are – atypical – predominantly maculopapular – vesicles are seen less commonly – illness is most commonly mild with <50 lesions – shorter duration of rash – Less contagious – Complications are less – little or no fever
- 26. Progressive Varicella • Progressivevaricella, is a severe complication of primary VZV infection. • visceral organ involvement • coagulopathy • severe hemorrhage • Continued new vesicular lesion development • Severe abdominal pain
- 27. • appearance ofhemorrhagic vesicles • the risk for progressive varicella – congenital cellular immune deficiency disorders – Malignancy – organ transplantation – Pt. is on steroid therapy • Unusual clinical findings – develop a unique hyperkeratotic appearance – continued new lesion formation for weeks or months
- 28. Neonatal Varicella Infants whosemothers demonstrate varicella in the period from 5 days prior to delivery to 2 days afterward are at high risk for severe varicella.
- 29. • The infantacquires the infection transplacentally • The infant's rash usually occurs toward the end of the 1st week to the early part of the 2nd week of life • maternal immunoglobulin G (IgG) is able to cross the placenta if delivery occurs after 30 wk of gestation
- 31. • Newborns whosemothers demonstrate varicella 5 days before to 2 days after delivery should receive 1 vial of VariZIG as soon as possible.
- 32. • All prematureinfants born <28 wk gestation to a mother with active varicella at delivery (even if the maternal rash has been present for >1 wk) should receive VariZIG
- 33. • intravenous immuneglobulin (IGIV) may provide some protection • the infant should be treated with acyclovir (10 mg/kg every 8 hr IV) when lesions develop. • prognosis is good if pt. receive prompt antiviral therapy
- 35. Congenital Varicella Syndrome •Risk of infection (No disease) – Early part of pregnency- 25% • Risk of CVS – Before 13 wks of gestation – 0.4% – In between 13 – 20 wks - 2%
- 42. skin cicatricial skinscarring Limb limb hypoplasia Neurologic microcephaly, cortical atrophy, seizures, and mental retardation Eye chorioretinitis, microphthalmia, and cataracts Renal hydroureter and hydronephrosis autonomic nervous system neurogenic bladder, swallowing dysfunction, and aspiration pneumonia
- 43. • The diagnosisof VZV fetopathy is based mainly on the – history of gestational varicella – presence of characteristic abnormalities in the newborn infant – viral DNA may be detected in tissue samples by PCR. – VZV-specific IgM antibody is detectable in the cord blood – Chorionic villus sampling
- 44. Herpes Zoster • manifestsas vesicular lesions clustered within 1 or 2 adjacent dermatomes • rash is mild, with new lesions appearing for a few days • symptoms of acute neuritis are minimal • postherpetic neuralgia is very unusual in children. • Transverse myelitis with transient paralysis is a rare complication of herpes zoster
- 45. Herpes zoster involvingthe lumbar dermatome.
- 47. • Immunocompromised children –moresevere herpes zoster – postherpetic neuralgia is common. –disseminated cutaneous disease – visceral dissemination with pneumonia, hepatitis encephalitis, and DIC –retinitis.
- 48. Diagnosis of varicella •Laboratory evaluation has not been considered necessary • Leukopenia • relative and absolute lymphocytosis. • liver function tests are mildly elevated • CSF in CNS complication – mild lymphocytic pleocytosis – moderate increase in protein content
- 49. • Rapid laboratorydiagnosis – direct fluorescence assay – rapid culture with specific immunofluorescence staining – PCR amplification testing – multinucleated giant cells can be detected with nonspecific stains Tzanck smear • VZV IgG antibodies:- Rise > 4 fold • Testing for VZV IgM antibodies is not useful
- 50. Treatment in Varicella •Acyclovir therapy is not recommended routinely for treatment of uncomplicated varicella in the otherwise healthy child – the marginal benefit – the cost of the drug – low risk for complications of varicella.
- 51. • Oral acyclovirin children >12 mo of age with – chronic cutaneous or – pulmonary disorders – Pt. Is on corticosteroid therapy – individuals receiving long-term salicylate therapy • Nonpregnant individuals > 13 years of age
- 52. Intravenous Acyclovir therapy •Varicella with severe disease – pneumonia – severe hepatitis – thrombocytopenia – encephalitis • varicella in immunocompromised patients • Dose:- IV acyclovir (500 mg/m2 every 8 hr IV) continued for 7–10 days • Other molecules – famciclovir – Valacyclovir • Acyclovir-resistant VZV:- intravenous foscarnet
- 53. Treatment in HerpesZoster • uncomplicated HZ - antiviral agent may not always be necessary • herpes zoster in immunocompromised – Acyclovir (500 mg/m2 or 10 mg/kg every 8 hr IV). • Use of corticosteroids in the treatment of herpes zoster in children is not recommended.
- 54. Complications • more commonin immunocompromised patients • In healthy child, mild varicella hepatitis is relatively common • Mild thrombocytopenia occurs in 1-2%
- 55. Bacterial Infections • Secondarybacterial infections of the skin – group A streptococci and S. aureus – occur in up to 5% of children – impetigo – cellulitis – lymphadenitis – subcutaneous abscesses. • manifestation of secondary bacterial infection – erythema of the base of a new vesicle. – Recrudescence of fever 3-4 days after the initial exanthem
- 56. • Other invasivecomplications – varicella gangrenosa – bacterial sepsis – pneumonia – arthritis – osteomyelitis – cellulitis – necrotizing fasciitis – toxic shock syndrome
- 57. Encephalitis and CerebellarAtaxia • morbidity from CNS complications is highest among patients < 5 yr • Nuchal rigidity • altered consciousness • seizures • gait disturbance • nystagmus, and slurred speech • Neurologic symptoms usually begin 2-6 days after the onset of the rash. • Clinical recovery is rapid and is usually complete
- 58. Pneumonia • Respiratory symptoms,which may include – cough – dyspnea – cyanosis – pleuritic chest pain – hemoptysis
- 59. EVIDENCE OF IMMUNITYTO VARICELLA Evidence of immunity to varicella consists of any of the following: 1. Documentation of age-appropriate vaccination with a varicella vaccine: • Preschool-aged children (i.e., aged >12 mo): 1 dose • School-aged children, adolescents, and adults: 2 doses
- 60. 2. Laboratory evidenceof immunity or laboratory confirmation of disease 3. Diagnosis or verification of a history of varicella disease by a health-care provider 4. Diagnosis or verification of a history of herpes zoster by a health-care provider
- 61. Postexposure Prophylaxis 1) Vaccine:-given to healthy children within 3-5 days after exposure 2) High-titer anti-VZV immune globulin is recommended - immunocompromised children - pregnant women - newborns exposed to varicella
- 62.
Editor's Notes
- #4 Varicella-zoster virus (VZV) causes primary, latent, and recurrent infections. The primary infection is manifested as varicella (chickenpox) and results in establishment of a lifelong latent infection of sensory ganglion neurons. Reactivation of the latent infection causes herpes zoster (shingles). morbidity and mortality in immunocompetent infants, adolescents, adults, as well as in immunocompromised persons; it predisposes to severe group A streptococcus and Staphylococcus aureus infections
- #5 VZV is a neurotropic human herpesvirus with similarities to herpes simplex virus, which is also α-herpesvirus. These viruses are enveloped with double-stranded DNA genomes that encode more than 70 proteins, including proteins that are targets of cellular and humoral immunity
- #6 contagious 24-48 hr before the rash is evident and until vesicles are crusted, usually 3-7 days after onset of rash. Susceptible persons may also acquire varicella after close, direct contact with adults or children who have herpes zoster# By 2005, vaccination coverage had increased to 90% and varicella cases had declined 90-91% from those in 1995 in sites where active surveillance was being conducted. By 2002, varicella-related hospitalizations had declined 88% from 1994 and 1995.
- #7 # Zoster is not caused by exposure to a patient with varicella; exposures to varicella boost the cell-mediated immune response to VZV in individuals with prior infection, decreasing the likelihood of reactivation of latent virus.# Herpes zoster is very rare in healthy children <10 yr of age, with the exception of infants who were infected in utero or in the 1st year of life, who have an increased risk for development of zoster in the first years of life. Herpes zoster in children tends to be milder than disease in adults and is less frequently associated with postherpetic neuralgia
- #8 The zoster vaccine, recommended for adults 60 yr of age and older, reduces both the frequency of herpes zoster and its most frequent complication, postherpetic neuralgia.
- #11 # inoculation of the virus onto the mucosa of the upper respiratory tract and tonsillar lymphoid tissue. During the early part of the 10- to 21-day incubation period# VZV is also transported back to the mucosa of the upper respiratory tract and oropharynx during the late incubation period, permitting spread to susceptible contacts 1-2 days before the appearance of rash.
- #15 # Subclinical varicella is rare; almost all exposed, susceptible persons experience a rash# Prodromal symptoms may be present, particularly in older children and adults#Temperature elevation is usually moderate, usually 100-102?F, but may be as high as 106?F; fever and other systemic symptoms usually resolve within 2-4 days after the onset of the rash.
- #16 While the initial lesions are crusting, new crops form on the trunk and then the extremities
- #18 # many children have vesicular lesions on the eyelids and conjunctivae, but corneal involvement and serious ocular disease are rare# The exanthem may be much more extensive in children with skin disorders, such as eczema or recent sunburn. # Hypopigmentation or hyperpigmentation of lesion sites persists for days to weeks in some children, but severe scarring is unusual unless the lesions were secondarily infected.
- #23 rash occurring within the 1st 2 weeks after vaccination was most commonly wild-type VZV, reflecting exposure to varicella before vaccination could provide protection
- #25 # approximately 25-30% of breakthrough cases are not mild, with clinical features more similar to those of wild-type infection. # contagiousness varies proportionally with the number of lesions: typical breakthrough cases (<50 lesions) are about a third as contagious as unvaccinated cases, whereas breakthrough cases with ≥50 lesions are as contagious as wild-type cases
- #26 illness is most commonly mild with <50 lesions approximately 25-30% of breakthrough cases are not mild
- #27 Severe abdominal pain, which may reflect involvement of mesenteric lymph nodes or the liver# appearance of hemorrhagic vesicles in otherwise healthy adolescents and adults, immunocompromised children, pregnant women, and newborns, may herald severe disease
- #28 @ malignancy, particularly if chemotherapy was given during the incubation period and the absolute lymphocyte count is <500 cells/mm3. The mortality rate for children who acquired varicella while undergoing treatment for malignancy and who were not treated with antiviral therapy approaches 7%; varicella-related deaths usually occur within 3 days after the diagnosis of varicellapneumonia#@ High risk of progressive varicellapatients receiving high-dose corticosteroidspatients receiving inhaled corticosteroids asthmatic persons receiving multiple short courses of systemic corticosteroid therapy
- #29 # Mortality is particularly high in neonates born to susceptible mothers who contracted varicella around the time of delivery.# The infant acquires the infection transplacentally as a result of maternal viremia, which may occur up to 48 hr prior to onset of maternal rash# The infant's rash usually occurs toward the end of the 1st week to the early part of the 2nd week of life (although it may be as soon as 2 days). 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 demonstrates varicella >5 days prior to delivery, she still may pass virus to the soon-to-be-born child, but infection is attenuated because of transmission of maternal VZV-specific antibody across the placenta
- #30 The infant's rash usually occurs toward the end of the 1st week to the early part of the 2nd week of life
- #32 @ Newborns whose mothers demonstrate varicella 5 days before to 2 days after delivery should receive 1 vial of VariZIG as soon as possible. Although neonatal varicella may occur in about half of these infants despite administration of VariZIG, it is usually mild
- #36 Fortunately, clinically apparent disease in the infant is uncommon
- #43 Most of the stigmata can be attributed to virus-induced injury to the nervous system, although there is no obvious explanation why certain regions of the body are preferentially infected during fetal VZV infection. The characteristic cutaneous lesion has been called a cicatrix, a zigzag scarring, in a dermatomal distribution
- #44 Chorionic villus sampling and fetal blood collection for the detection of viral DNA, virus, or antibody have been used in an attempt to diagnose fetal infection and embryopathy@ Varicella immune globulin has often been administered to the susceptible mother exposed to varicella, but whether this step modifies infection in the fetus is uncertain. Similarly, acyclovir treatment may be given to the mother with severe varicella
- #45 # In the elderly, herpes zoster typically begins with burning pain followed by clusters of skin lesions in a dermatomal pattern. Almost half of the elderly with herpes zoster experience complications; the most frequent complication is postherpetic neuralgia, a painful condition that affects the nerves despite resolution of the shingles skin lesions.# Approximately 4% of patients suffer a 2nd episode of herpes zoster; 3 or more episodes are rare. # . An increased risk for herpes zoster early in childhood has been described in children who acquire infection with VZV in utero or in the 1st year of life
- #48 immunocompromised children, particularly those with advanced HIV infection, may have unusual, chronic or relapsing cutaneous disease, retinitis, or central nervous system (CNS) disease without rash. The finding of a lower risk for herpes zoster among vaccinated children with leukemia than in those who have had varicella disease suggests that varicella vaccine virus reactivates less commonly than wild-type VZV. The risk for herpes zoster in healthy vaccinated children may be lower than in children who had wild-type varicella disease, although many more years of follow-up will be needed to determine that this is the case.
- #49 @ Leukopenia is typical during the 1st 72 hours after onset of rash# Laboratory evaluation has not been considered necessary for the diagnosis or management of healthy children with varicella or herpes zoster# The atypical nature of breakthrough varicella, with a higher proportion of rashes being papular rather than vesicular, will pose diagnostic challenges# Leukopenia is typical during the 1st 72 hours after onset of rash; it is followed by a relative and absolute lymphocytosis
- #50 #Rapid laboratory diagnosis of VZV is often important in high-risk patients and can be important for infection control# VZV can be identified quickly by direct fluorescence assay (DFA) of cells from cutaneous lesions (vesicular fluid) in 15-20 min, by rapid culture with specific immunofluorescence staining (shell vial technique) in 48-72 hr, and by PCR amplification testing (vesicular fluid, crusts) in 2 hr to days#VZV IgG antibodies can be detected by several methods, and a fourfold or greater rise in IgG antibodies is confirmatory of acute infection. VZV IgG antibody tests can also be valuable to determine the immune status of individuals whose clinical history of varicella is unknown or equivocal. Testing for VZV IgM antibodies is not useful for clinical diagnosis because commercially available methods are unreliable and the kinetics of the IgM response is not well defined
- #51 # The only antiviral drug available in liquid formulation that is licensed for pediatric use is acyclovir. Given the safety profile of acyclovir and its demonstrated efficacy in the treatment of varicella, treatment of all children, adolescents, and adults with varicella is acceptable# acyclovir therapy is not recommended routinely by the American Academy of Pediatrics for treatment of uncomplicated varicella in the otherwise healthy child because of the marginal benefit, the cost of the drug, and the low risk for complications of varicella
- #52 Oral therapy with acyclovir (20 mg/kg/dose, maximum 800 mg/dose) given as 4 doses/day for 5 days can be used to treat uncomplicated varicella in: nonpregnant individuals >13 yr of age and children >12 mo of age with chronic cutaneous or pulmonary disorders, individuals receiving short-term, intermittent#Acyclovir therapy does not interfere with the induction of VZV immunity@ To be most effective, treatment should be initiated as early as possible, preferably within 24 hr of the onset of the exanthem. There is less clinical benefit if treatment is initiated more than 72 hr after onset of the exanthem
- #53 ). Acyclovir has been used to treat varicella in pregnant women; its safety for the fetus has not been established# Dose:- IV acyclovir (500 mg/m2 every 8 hr IV) therapy initiated within 72 hr of development of initial symptoms decreases the likelihood of progressive varicella and visceral dissemination in high-risk patients. Treatment is continued for 7–10 days or until no new lesions have appeared for 48 hr.
- #54 Antiviral drugs are effective for treatment of herpes zoster. In healthy adults, acyclovir (800 mg 5 times a day PO for 5 days), famciclovir (500 mg tid PO for 7 days), and valacyclovir (1,000 mg tid PO for 7 days) reduce the duration of the illness and the risk for development of postherpetic neuralgia; concomitant corticosteroid use improves the quality of life in the elderly. In otherwise healthy children, herpes zoster is a less severe disease, and postherpetic neuralgia is rare# herpes zoster in immunocompromised children can be severe, and disseminated disease may be life threatening
- #55 In healthy child, 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.
- #58 gait disturbance ,nystagmus, and slurred speech are the features of cerebellar ataxia
- #59 Varicella pneumonia is a severe complication that accounts for most of the increased morbidity and mortality in adults and other high-risk populations, but pneumonia may also complicate varicella in young children
- #62 Newborns whose mothers demonstrate varicella 5 days before to 2 days after delivery should receive 1 vial of VariZIG. VariZIG is also indicated for: pregnant women without evidence of immunitypremature infants born at <28 wks of gestation (or weight <1,000 g) who were exposed to varicella during the neonatal period, regardless of maternal immunitypremature infants born at >28 wks of gestation who were exposed to varicella and whose mothers have no evidence of varicella immunity