vzv infections
TRANSCRIPT
Human Herpesviruses Varicella-zoster virus infection
(VZV/HHV-3)
Herpes Zoster
Associated Professor Lali Sharvadze, MD, PhD
Infectious Diseases, AIDS & Clinical Immunology Research Center
• Herpes simplex type I (HHV-1)• Herpes simplex type II (HHV-2)• Varicella-zoster virus (VZV/HHV-3)• Epstein-Barr virus (EBV/HHV-4)• Cytomegalovirus (CMV/HHV-5)• Human herpesvirus type 6 (HBLV/HHV-6)• Human herpesvirus type 7 (HHV-7)• Kaposi's sarcoma herpesvirus (KSHV/HHV-8)
HERPESVIRUS TYPES
• HSV-1 causes Oral-facial infections, Gingivostomatitis and pharyngitis
• HSV-2 is a sexually transmitted infection that causes genital herpes
• Varicella-zoster virus causes Shingles (herpes zoster) and Chickenpox
• Epstein-Barr virus causes Infectious mononucleosis• Cytomegalovirus causes CMV mononucleosis and
immunocompromised host infections• Human herpesvirus type 6 causes childhood illness known
as roseola infantum or sixth disease.• Human herpesvirus type 7 cause a skin condition in infants
known as exanthema subitum,• Human herpesvirus type 8 cause Sarcoma Kaposi's
Human Herpesviruses
Varicella-zoster virus causes two diseases
Shingles (herpes zoster)
and Chickenpox
Human Herpesviruses
Herpes Zoster also known
as Zona
or
Shingles
Zoster comes from Greek zōstēr, meaning "belt" or "girdle", after the characteristic belt-like dermatomal rash.
The common name for the disease, shingles, derives from the Latin cingulus, a variant of Latin cingulum meaning "girdle".
Etymology (origin)
Varicella-zoster virus (VZV) causes two distinct clinical diseases:varicella (chickenpox) and herpes zoster (shingles).
Chickenpox, a ubiquitous and extremely contagious infection, is usually a benign illness of childhood characterized by an exanthematous vesicular rash.
Herpes Zoster: With reactivation of latent VZV (which is most common after the sixth decade of life), Herpes zoster presents as a dermatomal vesicular rash, usually associated with severe pain.
Human herpesvirusisDEFINITION
ETIOLOGY
Herpes Zoster is caused by Varicella Zoster Virus
VZV is a member of the family Herpesviridae, sharing with other members such structural characteristics as a lipid envelope surrounding a nucleocapsid with icosahedral symmetry, a total diameter of ~180–200 nm, and centrally located double-stranded DNA that is ~125,000 bp in length.
The family of Herpesviridae.The genus of varicellovirus
Etiology
Electron micrograph of Varivella Zoster virus
Epidemiology
Herpes zoster (shingles) is a sporadic disease that results from reactivation of latent VZV infection.
Herpes zoster occurs at all ages, but its incidence is highest (5–10 cases per 1000 persons) among individuals in the sixth decade of life and beyond.
Data suggest that 1.2 million cases occur annually in the United States.
The incidence rate of shingles ranges from 1.2 to 3.4 per 1,000 person/years among younger healthy individuals, increasing to 3.9–11.8 per 1,000 person/years among those older than 65 years,
The incidence rates worldwide are similar.
This relationship with age has been demonstrated in many countries, and is attributed to the fact that cellular immunity declines as people grow older.
Recurrent herpes zoster is very rare except in immunocompromised hosts, especially those with AIDS.
Shingles has no relationship to season and does not occur in epidemics.
There is, however, a strong relationship with increasing age
Pathogenesis
Transmission of the virus occurs readily by the respiratory route
Transmission occurs mainly through respiratory droplets which contains virus.
Direct person to person contact with lesions also spread the virus.
During chickenpox, (Presumably) , the virus infects dorsal root gangliawhere it remains latent and establishes lifelong residence (latent infection) until reactivated.
Consequently, the dorsal root and cranial sensory ganglia of everyone who has had Chickenpox are latently infected with VZV. They contain genomic NDA of VZV, but not infectious virus.
The mechanism of reactivation is unknown;
Pathogenesis
The latent VZV eventually reactivates. The reactivated virus multiplies and spreads within the ganglion, infecting many additional neurons and supporting cells-a process that causes intense inflammation.
The virus than travel from the sensory ganglion back down the nerve to the skin, where it produces the characteristic rash of herpes zoster.
The mechanism of reactivation of the virus is unknown;
Pathogenesis
Viral Viral reactivation reactivation
Vesicular Rash
Pathogenesis
Viral Viral latencylatency
mononuclear cells
skin
Unless the immune system is compromised, it suppresses reactivation of the virus and prevents shingles outbreaks.
Why this suppression sometimes fails is poorly understood, but shingles is more likely to occur in people whose immune systems are impaired due to aging, immunosuppressive therapy, psychological stress, or other factors
1) A cluster of small bumps 2) turns into blisters
3) The blisters fill with lymph, break open 4) crust over
Clinical Manifestations of Herpes Zoster
Patients with herpes zoster can transmit infection to seronegative individuals, with consequent chickenpox.
Someone can not catch shingles, However someone catch chickenpox through direct contact with someone who has shingles
• Unilateral vesicular dermatomal eruption, (rash), • Severe pain
The Main symptoms of Herpes Zoster
In the prodromal stage of herpes zoster, the diagnosis can be exceedingly difficult and may be made only after lesions have appeared or by retrospective serologic assessment.
The earliest symptoms of shingles, which include Headache, fever, and malaise are nonspecific, and may result in an incorrect diagnosis.
These symptoms are commonly followed by sensations of burning pain, itching, hyperesthesia (oversensitivity), or parenthesis ("pins and needles": tingling, pricking, or numbness).
Pain can be mild to extreme in the affected dermatome, with sensations that are often described as stinging, tingling, aching, numbing or throbbing,
and can be intersperses with quick stabs of agonizing pain.Shingles in children is often painless, but people are more likely to get shingles as they age, and the disease tends to be more severe.
The pain and rash most commonly occurs on the torso, but can appear on the face, eyes or other parts of the body.
At first the rash appears similar to the first appearance of hives (urticaria); however, unlike hives, shingles causes skin changes limited to a dermatome, normally resulting in a stripe or belt-like pattern that is limited to one side of the body and does not cross the midline.
Localization of the rash
The onset of disease is heralded by pain within the dermatome, which may precede lesions by 48–72 h;an erythematous maculopapular rash evolves rapidly into vesicular lesions. Sometimes pre eruptive period and pain lasts as long as three weeks, and is followed by the appearance of the characteristic skin rash.
Later the rash becomes vesicular, forming small blisters filled with a serous exudates, as the fever and general malaise continue.
The painful vesicles eventually become cloudy or darkened as they fill with blood, and crust over within seven to ten days; usually the crusts fall off and the skin heals, but sometimes, after severe blistering, scarring and discolored skin remain.
Development of the shingles rash
Day 2
Day 1 Day 5
Day 6
Development of the shingles rash
In the normal host, these lesions may remainfew in number and continue to form for only 3–5 days.
The total duration of disease is generally 7–10 days; However, it may take as long as 2–4 weeks for the skin to return to normal.
Zoster sine herpete ("zoster without herpes") describes a person who has all of the symptoms of shingles except this characteristic rash.
In a few patients, characteristic localization of pain to a dermatome with serologic evidence of herpes zoster has been reported in the absence of skin lesions, an entity known as
Zoster sine herpetica
Herpes zoster is characterized by a unilateral vesicular dermatomal eruption, often associated with severe pain.
The dermatomes from T3 to L3 are most frequently involved.
The factors responsible for the reactivation of VZV are not known. In children, reactivation is usually benign; in adults, it can be debilitating because of severe pain.
When branches of the trigeminal nerve are involved, lesions may appear on the face, in the mouth, in the eye, or on the tongue.
The trigeminal nerve is the most commonly involved nerve.
The ophthalmic division of the trigeminal nerve is most commonly involved branch.
When the virus is reactivated in this nerve branch it is termed Zoster Ophtalmicus. The skin of the forehead, upper eyelid and orbit of the eye may be involved.
Zoster ophthalmicus occurs in approximately 10% to 25% of cases.
In some people, symptoms may include conjunctivitis, keratitis, uveitis and optic nervepalsies that can sometimes cause chronic ocular inflammation, loss of vision, and debilitating pain.
Trigeminal shingles with uveitis and keratitis
If the ophthalmic branch of the trigeminal nerve is involved, zoster ophthalmicus results.
In the Ramsay Hunt syndrome (herpes zoster oticus), pain and vesicles appear in the external auditory canal, and patients lose their sense of taste in the anterior two-thirds of the tongue while developing ipsilateral facial palsy.
The geniculate ganglion of the sensory branch of the facial nerve is involved.
Complications
Shingles oticus, also known as Ramsay Hunt syndrome type IIinvolves the ear.
It is thought to result from the virus spreading from the facial nerve to the vestibulocochlear nerve.
Symptoms include hearing loss and vertigo (rotational dizziness).
Ramsay Hunt syndrome
In both normal and immunocompromised hosts, the most debilitating complication of herpes zoster is pain associated with acute neuritis and postherpetic neuralgia.
Postherpetic neuralgia is uncommon in young individuals; However, at least 50% of zoster patients over age 50 report some degree of pain in the involved dermatome months after the resolution of cutaneous disease. Changes in sensation in the dermatome, resulting in either hypo- or hyperesthesia, are common.
Postherpetic neuralgia
CNS involvement may follow localized herpes zoster. Many patients without signs of meningeal irritation have CSF pleocytosis and moderately elevated levels of CSF protein. Symptomatic meningoencephalitis is characterized by headache, fever, photophobia, meningitis, and vomiting. A rare manifestation of CNS involvementis granulomatous angiitis with contralateral hemiplegia, which can be diagnosed by cerebral arteriography. Other neurologic manifestationsinclude transverse myelitis with or without motor paralysis.
CNS complications
herpes zoster is more severe in immunocompromisedthan immunocompetent individuals. Lesions continue toform for >1 week, and scabbing is not complete in most cases until 3 weeks into the illness. Patients with Hodgkin’s disease and non- Hodgkin’s lymphoma are at greatest risk for progressive herpes zoster.
Cutaneous dissemination develops in ~40% of these patients. Among patients with cutaneous dissemination, therisk of pneumonitis, meningoencephalitis, hepatitis, and other serious complications is increased by 5–10%. However, even in immunocompromisedpatients, disseminated zoster is rarely fatal.
Herpes Zoster in HIV/AIDS patients
Recipients of hematopoietic stem cell transplants are at particularly high risk of VZV infection. Of all cases of posttransplantation.
VZV infection, 30% occur within 1 year (50% of thesewithin 9 months); 45% of the patients involved have cutaneous or visceral dissemination. The mortality rate in this situation is 10%.Postherpetic neuralgia, scarring, and bacterial superinfection are especially common in VZV infections occurring within 9 months of transplantation. Among infected patients, concomitant graft versus-host disease increases the chance of dissemination and/or death.
A case of shingles that demonstrates the typical dermatomal distribution, in this case C8/T1
Diagnoses
The diagnosis of herpes Zoster is not difficult.The characteristic dermatomal localization of the vesicular rash and pain should lead to a prompt diagnosis.
Clinical symptoms
When the rash is absent (early or late in the disease, or in the case of zoster sine herpete), shingles can be difficult to diagnose. Apart from the rash, most symptoms can occur also in other conditions.
Serology is the most common method of laboratory diagnosis.
The detection of VZV –specific IgM is considered diagnostic of acute infection.
Also, a fourfold or greater increase in VZV specific IgG antibody levels between acute- and convalescent-phase serum specimens.
Chickenpox also can be diagnosed by detection of
VZV DNA by reverse-transcriptase polymerase chain reaction (RT-PCR) from clinical specimens
Isolation of VZV in culture also is possible but it is very expensive
Differential Diagnoses
• Herpes Simplex• Dermatitis Herpetiformis • Impetigo • Contact dermatitis • Candidiasis • certain drugs reaction• insect bites.
Shingles can be confused with
Treatment
Patients with herpes zoster benefit from oral antiviral therapy:
Antiviral therapy accelerates healing of lesions and resolution of zoster-associated pain
The following antiviral drugs are used:
acyclovir, valacyclovir, famciclovir.
Treatment regimens: Acyclovir
is administered at a dosage of 800 mg five times daily for 7–10 days.
Famciclovir is administered at a dosage of
500 mg three times daily for 7 days
Valacyclovir is administered at a dosage of
1 g by mouth three times daily for 5–7 days. Antiviral therapy should be started as soon as possible (within
24-48 h of symptoms)
In severely immunocompromised hosts (e.g., transplant recipients, patients with lymphoproliferative malignancies), Herpes Zoster (including disseminated disease) should be treated, with IV acyclovir, which reduces the occurrence of visceral complications.
The dose is 10 mg/kg every 8 h for 7 days.
For low-risk immunocompromised hosts, oral therapy with valacyclovir or famciclovir appears beneficial.
If medically feasible, it is desirable to decrease immunosuppressive treatment concomitant with the administration of IV acyclovir.
For immunocompromised hosts:
Persons with zoster ophthalmicus should be referredimmediately to an ophthalmologist.
Therapy for this condition consists of the administration of analgesics for severe pain and the use of atropine. Acyclovir, valacyclovir, and famciclovir all accelerate healing.
Decisions about the use of glucocorticoidsshould be made by the ophthalmologist.The management of acute neuritis and/or postherpetic neuralgia
Treatment of zoster ophthalmicus
The management of postherpetic neuralgia is particularly difficult.
along with routine analgesic agents can be given the narcoticderivatives, drugs such as:
• gabapentin, • pregabalin, • amitriptyline• hydrochloride, • lidocaine (patches), • fluphenazine hydrochloride
These drugs are reportedly beneficial for pain relief.
Treatment of postherpetic neuralgia
Glucocorticoid therapy can accelerate quality-of-life improvements including a return to usual activity.
The dose of prednisone:
Orally: 60 mg/d on days 1–7, 30 mg/d on days 8–14, and 15 mg/d on days 15–21.
This regimen is appropriate only for relatively healthy elderly persons with moderate or severe pain at presentation. Patients with osteoporosis, diabetes mellitus glycosuria, or hypertension may not be appropriate candidates.Glucocorticoids should not be used without concomitant antiviraltherapy.
Treatment of postherpetic neuralgia
CNS involvement may follow localized herpes zoster.
Many patients without signs of meningeal irritation have CSF pleocytosis and moderately elevated levels of CSF protein.
Symptomatic meningoencephalitis is characterized by headache, fever, photophobia, meningitis, and vomiting.
A rare manifestation of CNS involvement is granulomatous angiitis with contralateral hemiplegia, which can be diagnosed by cerebral arteriography.
Other neurologic manifestations include transverse myelitis with or without motor paralysis.
CNS involvement
Preventionof
Herpes Zoster
Active Immunization by Vaccine
Prophylaxis
Zoster vaccine (trade name Zostavax) is used fpr prevention of Herpes Zoster.
Zostavax is a live vaccine developed by Merck & Co.
The zoster vaccine is, essentially, a larger-than-normal dose of the chickenpox vaccine (with 18 times the viral content).
In individuals >60 years of age, a VZV vaccine decreased the incidence of shingles by 51%, the burden ofillness by 61%, and the incidence of postherpetic neuralgia by 66%.
The Advisory Committee on Immunization Practices has therefore recommended that persons in this age group be offered this vaccine in order to reduce the frequency of shingles and the severity of postherpetic neuralgia.A second approach is to administer varicella
THENKS FOR ATTENTION