Transcript Varicella zoster virus

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"I learned not to scratch "When I had chickenpox it was really boring
chickenpox because it
because I had no one to play with. It was
really itchy and not nice at all."
can make things worse."
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"I got
chickenpox
when I was 7."
• Varicella Zoster virus
• Chickenpox and herpes zoster
 Pathophysiology
 Complications
 Diagnosis
 Treatment
• Vaccination
• Case scenario
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• Varicella-zoster virus (VZV) is a DNA virus
belongs to the herpes virus family
• It is the cause of chickenpox and herpes
zoster
• Chickenpox follows initial exposure to the
virus and is typically mild, self-limited
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Maternal infection during the first 28 weeks of
pregnancy may result in transmission of VZV
to the fetus and cause congenital varicella
syndrome
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Chickenpox (varicella)
Direct
contact
Airborne
spread
Incubation period
10-21 day
2 days
Fever
Malaise
URTI
Rash
Macules
Vesicles
VZV
Pustules
Scab
Advanced age
Unilateral
blister
&
Vesicles
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Herpes
zoster
Swelling
Redness
Lymphoma
AIDS
Sensory ganglia
Pain
Flu-like
Cell-mediated immunity
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Chickenpox
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Aseptic meningitis
Cerebellar ataxia
Encephalitis
Arterial ischemic strokes
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• Incidence
1/4000 cases of varicella
• Presentation
Ataxia usually begins with rash accompanied by Headache,
vomiting, lethargy, fever, nuchal rigidity, nystagmus
• Prognosis
Self-limited disease, most patients improve in 1-3 weeks virtually
all recover without complications
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• Incidence
1-2/10,000 cases of varicella
• Presentation
 Symptoms usually appear about one week after rash
 Fever, headache, vomiting, altered mental status, focal
neurologic findings, hemiparesis, sensory changes and
seizures
• Prognosis
 Mortality about 5-10%
 10-20% of survivors will have neurologic complication
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Immunocompetent children (median age = 5 yr) present
with acute hemiplegia
Median interval between varicella and onset of
hemiplegia = 2 months
Ref: Moriuchi et al. Pediatr Infect Dis J.2000; 19:648
Post-varicella angiopathy may account for 1/3 of all
childhood strokes
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Ref: Askalan et al Stroke.2001; 32:1257
DeVerber et al Sem Ped Neurol.2000; 7:309
Herpes Zoster
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Chickenpox
Postherpetic neuralgia
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Most common complications of zoster, which is pain that persists
more than six weeks after the development of rash
TCA
Amitriptyline 25 - 75 mg daily
Anticonvulsant
Carbamazepine 400 - 1200 mg daily
Phenytoin 300 - 400 mg daily
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Relieve pain
in some
patients
• Molecular Methods:
PCR assays for VZV are use in the diagnosis of
VZV meningoencephalitis from CSF samples
• Detection of VZV specific IgM:
VZV IgM is produced in primary varicella and
herpes zoster and it is not possible to
distinguish between the two conditions
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PCR: Polymerase Chain Reaction
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Thymidine kinase (TK)
Acyclovir
Acyclovir monophosphate
cellular kinases
Acyclovir diphosphate
Acyclovir triphosphate
Competitive inhibition of viral DNA polymerase
Incorporation into and termination of the growing viral DNA chain
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Inactivation of the viral DNA polymerase
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Treatment with Acyclovir
Shortened the time to 50% healing
Decreased fever, anorexia, and
lethargy by day 2
Reduced the maximum number of
lesions and vesicles
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20-30 mg/kg per dose PO QID (80 mg/kg/day) for 5 days
Treatment was begun within 48
hours of rash onset
Reduced the duration of new lesion
formation
Reduced the prevalence of localized
zoster-associated neurologic symptoms
Shortened the times to complete lesion
scabbing, healing, and cessation of pain
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Nausea, vomiting and diarrhea
Headache and malaise
Thrombocytopenia
Renal failure and hepatitis
Stevens-Johnson syndrome
Coadministration of probenecid with
acyclovir has been shown to increase
the mean acyclovir half-life
• Patients should be advised to maintain adequate
hydration
• Dosage adjustment is recommended when
administering in renal impairment
• Caution should also be exercised when administering
to patients receiving potentially nephrotoxic agents
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Drug Name
Valacyclovir (Valtrex), Famciclovir (Famvir)
Description
Prodrug rapidly converted to the active drug.
More expensive but has a more convenient dosing regimen
than acyclovir
Contraindications
Documented hypersensitivity
Interactions
Probenecid, zidovudine, or cimetidine coadministration
prolongs half-life and increases CNS toxicity of valacyclovir
Precautions
Caution in renal failure and coadministration of nephrotoxic
drugs; associated with onset of hemolytic uremic syndrome
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• A live attenuated varicella virus vaccine
(VARIVAX ®) was licensed in 1995 in the United
States and is manufactured by Merck & Co.,
Inc
• The vaccine contains more than 1,350 plaque
forming units of Oka/Merck VZV in each
0.5 ml dose
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• The vaccine has proven to be effective for
more than 10 years in preventing varicella.
However, breakthrough infection (i.e., cases
of chickenpox after vaccination) can occur
(less than 1%-4.4%), usually resulting in mild
illness
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• VARIVAX® is a highly heat sensitive vaccine
• To maintain potency, the vaccine must be kept
frozen at or below -15oC
• Vaccine efficacy will be reduced if the vaccine is
not handled and transported as recommended.
• Reconstituted vaccine must be discarded if not
used within 30 minutes, because of possible loss
of potency
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• Healthy vaccinated persons have a minimal
risk for transmitting vaccine virus to their
contacts; this may be higher in vaccinees in
whom a varicella-like rash develops following
vaccination
• The incidence of herpes zoster after
vaccination among otherwise healthy children
is 18 per 100,000 person years of follow-up
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A six-year-old male was admitted to the
hospital complaining of:
• Vomiting
• Headache
• Decreased level of consciousness
• Convulsion two days ago
History of present illness:
Chickenpox seven days ago
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Samah & Manar
Vital signs:
• Temp 36.8 oC
• BP
85/53 mmHg
• Pulse 95 beats/min
• RR
28 breath/min
• Height 120 cm
• Weight 21 kg
• IBW
23.75 kg
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Samah & Manar
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WBC
15.4 X 109/L
Hb
126 g/L
Na
139 mmol/L
K
3.8 mmol/L
Glucose 6 mmol/L
Bilirubin 5 umol/L
Samah & Manar
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MRI was negative
CSF was negative for all
EEG showed Parietal epileptic activity
Encephalitis
CBC showed
Left Shift
Kering was positive
Brudzinski was positive
CBC showed Left Shift
Kering was positive
Brudzinski was positive
Stop
Culture
vancomycin
Varicella
PCR was
positive
PCR
for
varicella
and
ceftriaxone
Varicella
Encephalitis
Empirically start on
Acyclovir IV 30 mg/kg/day
Vancomycin IV 40mg/kg/day
Ceftriaxone IV 100 mg/kg/day
Vomiting
Ondansetron 2.4 mg IV stat
Omeprazole 10 mg PO BID
Rectal Domperidone
10
mgimprove
TID
Not
improved
Not
Clonazepam 0.2mg TID
EEG showed Parietal
epileptic activity
Carbamazepine 200 mg PO
BID
Switch to phenytoin
LDBradycardia
: 100
mg IV
Vomited
MD : 50 mg IV BID
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Dopamine
Antagonists
(metoclopramide)
Antihistamines
(diphenhydramine)
Cannabinoids
(nabilone)
Treat post-operative
and cytotoxic drug
nausea & vomiting
Neoplastic disease,
radiation sickness,
Metoclopramide 6
opioids, cytotoxic
mg IV every 8 hours
drugs and general
anaesthetics
Motion sickness
Diphenhydramine
and severe morning
15 mg IV every 8
sickness in
hours
pregnancy
Cytotoxic nausea,
and vomiting, or
vomiting
unresponsive to
other agents
Benzodiazepines
(lorazepam)
Anticholinergics
(hyoscine)
Steroids
(dexamethasone)
NK1 Receptor
Antagonists
(aprepitant)
Post-operative
nausea and vomiting
Radiation and
chemotherapy
induced nausea and
vomiting
Chemotherapy
induced nausea and
vomiting
5HT3 Receptor
Antagonist
(ondansetraon)
Clonazepam
Post-operative
0.2 mg
nausea
PO every
and 8vomiting
hours
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• Phenytoin follows zero order kinetics
• TOXICITY
– Dose Related: drowsiness, confusion, nystagmus,
ataxia, slurred speech, nausea, unusual behavior,
mental changes
– Non-Dose Related: hirsutism, acne, gingival
hyperplasia, folate deficiency, osteomalacia,
hypersensitivity reactions
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Samah & Manar
• Phenytoin Serum Levels: (10-20 mg/L)
– Loading Dose:
– 2-4 hours post IV or 24 hours post PO load
– Maintenance Dose:
– Steady state trough levels (5-10 days)
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Samah & Manar
On 25/4/2008
• Acyclovir 400 mg PO QID
• Clonazepam 0.2 mg PO TID
• Phenytoin Sodium 50 mg PO BID
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• Varicella-zoster virus (VZV) is a DNA virus
belongs to the herpes virus family that may
cause chickenpox and herpes zoster
• Aseptic meningitis, cerebellar ataxia,
encephalitis and arterial ischemic strokes are
the main complications of chickenpox
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Samah & Manar
• Postherpetic neuralgia is the main
complication of herpes zoster
• Acyclovir remains the treatment of choice of
varicella zoster virus
• Immunization against the virsu helps in
preventing varicella
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Samah & Manar
• Helms R, Quan D, Herfindal E eds. Textbook of therapeutics. Drug and
disease management. Eighth Edition. Philadelphia, PA. Lippincott Williams
& Wilkins; 2006: 451-471
• Nahata M, Mara N, Benavide S. Viral infections. In: Koda-Kimble M, Young
L, Kradjan W eds. Applied therapeutics. The clinical use of drugs. Eighth
Edition. Philadelphia, PA. Lippincott Williams & Wilkins; 2006: 721-739
• Anderson P, Knoben J, Troutman W. Handbook of clinical drug data. Tenth
Edition. New York, NY. McGraw Hill; 2002: 553-557
• Askalan et al. Stroke. 2001; 32:1257
• Moriuchi et al. Pediatr Infect Dis J 19:648, 2000
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