2. An 18-month-old female presented to the emergency department with fever, a
diffuse rash (onset 5 days before), and a swollen right hand. On examination she
was irritable but alert. Her temperature was 39oC and her heart rate was increased
at 180 beats/min. She had diffuse vesiculopustular lesions over her entire body.
With some areas showing older, crusted lesions. She had cellulitis of the right
hand manifested by marked erythema, swelling, and tenderness. There were no
mouth lesions, the lungs were clear, and the liver and spleen were not enlarged.
Laboratory data were significant only for leukocytosis with a white blood cell count
of 15,800/µL with 88% neutrophils. The chest radiograph was clear. A radiograph of
the right hand showed only soft tissue swelling. The patient was treated with
intravenous cefazolin. Improvement in the condition of her right hand was notable
within 48 hours. The patient had a systemic viral infection with a complication
of bacterial superinfection (cellulitis)
Case Presentation
3. ● 18-month-old female
● chief complaint
○ fever
○ diffuse rash (onset 5 days before)
○ swollen right hand
● physical examination
○ irritable but alert
○ temperature = 39oC
○ heart rate = 180 beats/min
○ diffuse vesiculopustular lesions (entire body)
■ some areas showing older, crusted lesions
○ cellulitis of the right hand
■ marked erythema, swelling, and tenderness
○ no mouth lesions, the lungs were clear, and the liver and spleen were not
enlarged
Patient Information
4. Patient Information
● laboratory examination
○ leukocytosis
■ white blood cell count of 15,800/µL
■ 88% neutrophils
○ chest radiograph was clear
○ radiograph of the right hand showed only soft tissue swelling
● management
○ intravenous cefazolin
○ improvement in the condition of her right hand was notable within 48
hours
● The patient had a systemic viral infection with a complication of
bacterial superinfection (cellulitis)
5. 01
This patient had a characteristic rash at
various stages of evolution.
What was her underlying viral illness? What
other causes of her skin rash should be
considered in the differential diagnosis?
6. Chickenpox
● Due to primary infection with VZV (member of the
Herpesvirus family).
● Enveloped, dsDNA viruses
● Varicella lesions develop in “crops” such that lesions can be
seen in various stages of evolution, including vesicular,
pustular, and crusted.
● Incubation period: 10-21 days
● Route of infection
○ Mucosal (usually nasopharyngeal) inoculation via
infected airborne droplets or aerosolized droplets
○ Direct contact with the virus (via skin lesions)
Joson
7. IMPETIGO ENTEROVIRUSES HERPES SIMPLEX VIRUSES
nonbullous
● (+) small vesicles or pustules
● (+) extremities
● (+) crusting
● (+) erythema
● (+) multiple
● (-) coalescing
● (-) perioral or perinasal
● (?) begins with a single
erythematous macule
● (?) history of minor trauma, insect
bites, scabies, herpes simplex,
varicella, or eczema at the site of
infection
bullous
● (+) fever
● (-) bullae
● (-) diarrhea
● (-) generalized weakness
(+) fever
(-) general upper respiratory symptoms
(-) malaise
(-) myalgias
(-) conjunctivitis
(-) emesis
(-) diarrhea
● herpangina
○ (+) vesicles
○ (-) posterior pharynx and
tonsils
● hand-foot-and-mouth disease
○ (+) fever
○ (+) lesions on hands, feet,
buttocks, and genitalia
○ (+) erythema
○ (-) sore mouth/throat
○ (-) malaise
○ (-) macular lesions on
buccal mucosa, tongue,
and/or hard palate
(+) fever
(+) listlessness or irritability
(+) vesiculopustular lesions
(+) crusting
(?) lesions in genitalia (HSV-2)
(?) inability to eat and/or drink
(-) gingivitis
(-) increased drooling (in infants due to
pain on swallowing)
Mataga
8. 02 How is the diagnosis of infection with
this pathogen made?
9. Rapid centrifugation Culture
● performed by centrifuging specimens onto
susceptible cells grown on round coverslips in
flat-bottom shell vials or in multiwell plates
and then by incubating and staining for viral
antigen. The stain is usually DIF or indirect
immunofluoresence
● Advantage
○ Requires less incubation time and
includes the confirmatory test.
● Disadvantage
○ All viruses stain the same color, since all
of the currently available culture
confirmation reagents use the same
fluorochrome: Fluorescein isothiocyanate
(FITC)
Direct fluorescent-antibody
staining
● a technique used in the laboratory to
diagnose diseases of the skin, kidney, and
other organ systems. It is also called the
direct immune fluorescent test or primary
immunofluorescence.
● rapid test that can be performed on
respiratory samples and tissue and
requires only 2-4 hours for results
● detects the presence of a particular
antigen (typically a specific protein on the
surface of a virus, bacterium or other
microbe).
Garcia
10. Nucleic Acid Amplification Test
● Novel nucleic acid amplification method which
can amplify RNA
● “Self-sustained sequence
replication”/transcription mediated amplification
● Sensitive, isothermal, transcription-based
amplification system specifically designed for the
detection of RNA targets
● Uses a battery of 3 enzymes
○ Avian myeloblastosis virus reverse
transcriptase
○ RNase H RNA polymerase
○ T7 RNA polymerase
● Leads to main amplification product of single-
stranded RNA
● Suited for RNA analytes (mRNA, rRNA, genomic
RNA)
Virus culture
● Traditional tube culture
○ Inoculating specimens onto cultured cell
monolayers
○ Periodic observation for cytopathic effect
Nebit
12. Epidemiology
Varicella-zoster virus
● Worldwide distribution
● More common in temperate regions
○ Annual epidemics in the late winter and spring in areas with low vaccination rates
● Mode of transmission:
○ Airborne
○ Direct contact
■ With skin lesions and fomites
● Varicella vaccine introduced in 1995
○ Live attenuated vaccine was approved in US
■ In the first 5 years, the incidence dropped 76% to 87%
○ In pre-vaccine era, there were 4 million cases of varicella annually in US
Hermida
13. What complications other than bacterial superinfection
(as seen in this case) can occur as a result of this viral
infection?
04
14. Complications
● Causes more severe illness in adults than children
● Immunocompromised children & nonimmune, pregnant women - more prone
● Other complications:
○ Hepatitis
○ Arthritis
○ Glomerulonephritis
○ Myocarditis
● Multiorgan involvement - high mortality
● Primary varicella during pregnancy
○ Intrauterine infection → fetal loss or infant with congenital varicella syndrome
○ Dermatomal scarring, limb hypoplasia, ocular defects, low birth weight and
mental retardation
○ Pericarditis
○ Pancreatitis
○ Encephalitis
○ Cerebellar ataxia
Morales
15. Complications
● Secondary bacterial infections of the skin lesions
○ Streptococcus pyogenes
○ Staphylococcus aureus
● VZV Infections
○ associated with S. Pyogenes-induced necrotizing fasciitis
○ Fever, malaise, headache, and abdominal pain
● Reye’s syndrome with encephalopathy
○ Elevated transaminase level
○ Elevated serum ammonia level
○ Can occur in children with varicella or influenza who take aspirin
Jacinto
16. After acute primary infection with this
virus, latent infection develops. What
illness may occur years later as a result of
viral reactivation? How do the clinical
manifestations of this reactivation
infection differ from those of primary
infection?
05
17. Herpes Zoster (Shingles)
● Reactivation of a latent VZV infection
● Dorsal root ganglia are latently infected following primary infections
● Cell-mediated-immunity (CMI) is necessary to maintain latency
○ Loss in CMI is associated with reactivation
● Other risk factors:
○ CMI dysfunction
○ Diabetes
○ Physiologic stress
Hayudini
20. 06 What specific antiviral therapy has been
shown to be efficacious? Are there any
concerns about resistance?
21. ● Acyclovir
○ Varicella, Herpes Zoster
○ <50 years old
■ antivirals are not necessary
■ shorten the duration of illness
○ ≥50 years of age
■ analgesics + antivirals is recommended
■ (+) ocular involvement
○ May be taken with or without food
■ May be taken w/ meals to reduce GI discomfort.
○ Monitor urinalysis, BUN, serum creatinine, urine
output, liver enzymes, CBC.
○ Assess for neurotoxicity and nephrotoxicity in
pediatric patients receiving high doses.
Antiviral Therapy
Parado
22. Resistance
Resistance to Acyclovir
● Acyclovir resistance is usually suspected in patients with persistent lesions
or recurrence in patient treatments
● Not common but occurs at higher rates in immunocompromised patients
● Acyclovir resistance can be attributed to thymidine kinase mutations
● Confers cross-resistance among antiviral nucleoside analogs
Gabriel
23. What are the infection control issues related to this
patient’s illness?
07
24. 1. Patients must be placed in isolation
2. Implement a strict infection control
measures
○ Hand washing
○ Gloves
○ Gowns
1. Individuals who are nonimmune need to
wear mask
Grecia
25. Grecia
4. Seronegative healthcare personnel who
come in contact with the infected patients
should not have contact with other patients
- minimum of 2 weeks after exposure
26. 1. Post exposure vaccine should be administered within
120 hours of exposure.
2. Exposed individuals who cannot receive the live
vaccine
● Varicella-zoster immune globulin preparation
should be administered within 96 hours.
○ Immunocompromised individuals
○ Infants
○ Pregnant women
Montoya
27. Two different vaccines exist against this agent. How do
they differ in terms of vaccine composition, target
population, and efficacy?
08
28. ● A live attenuated varicella vaccine was approved in 1995
for general use in the United States. A similar vaccine has
been used successfully in Japan for about 30 years.
○ A single dose of the vaccine is highly
effective at inducing protection from
varicella in children (80–85% effective) but
less so in adults(70%).
○ The vaccine is about 95% effective in
preventing severe disease. About 5% of
individuals develop a mild vaccine
associated rash 1 month after
immunization.
○ In 2006, two doses of the vaccine were
recommended for children, and that
schedule is reportedly more than 98%
effective in preventing varicella disease.
Malicdem
29. ● A herpes zoster (shingles) vaccine was licensed in the United States
in 2006.
○ It is a 14 times more potent version of the
varicella vaccine.
○ It has been shown to be effective in older adults
at reducing both the frequency of outbreaks of
zoster and the severity of disease that does
occur.
○ The zoster vaccine is recommended for those
with chronic medical conditions and for persons
older than 60 years of age.
○ Shingrix is a recombinant subunit vaccine which
has been used in many countries since 2017.
Zostavax is an attenuated vaccine which
basically consists of a larger-than-normal dose
of chickenpox vaccine.
Hosena
18-month-old female
chief complaint
fever
diffuse rash (onset 5 days before)
swollen right hand
physical examination
irritable but alert
temperature = 39oC
heart rate = 180 beats/min
diffuse vesiculopustular lesions (entire body)
some areas showing older, crusted lesions
cellulitis of the right hand
marked erythema, swelling, and tenderness
no mouth lesions, the lungs were clear, and the liver and spleen were not enlarged
laboratory examination
leukocytosis
white blood cell count of 15,800/µL
88% neutrophils
chest radiograph was clear
radiograph of the right hand showed only soft tissue swelling
management
intravenous cefazolin
improvement in the condition of her right hand was notable within 48 hours
The patient had a systemic viral infection with a complication of bacterial superinfection (cellulitis)
Acyclovir is beneficial in treating Varicella-zoster virus VZV (both varicella and herpes zoster). In immunocompetent adults ≥50 years of age, treatment with both analgesics and antivirals is recommended, particularly in patients with ocular involvement. In immunocompetent patients <50 years old, antivirals are not necessary but can shorten the duration of illness. Because of its cost, acyclovir is often not used in uncomplicated cases.
Aciclovir is converted to aciclovir monophosphate by virus-specific thymidine kinase then further converted to aciclovir triphosphate by other cellular enzymes. Aciclovir triphosphate competes with deoxyguanosine triphosphate for viral DNA polymerase and incorporates into viral DNA to block DNA synthesis and viral replication.
Pharmacokinetics:
Absorption: Poorly absorbed from the gastrointestinal tract. Penetrates into the skin. Bioavailability: 10-20% (oral).
Distribution: Widely distributed to body tissues including CSF (approx 50% of plasma levels). Crosses the placenta and enters the breast milk. Volume of distribution: 0.7 L/kg. Plasma protein binding: 9-33%.
Metabolism: Converted by viral enzymes to aciclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes.
Excretion: Via urine (62-91% as unchanged drug and 9-14% as metabolites). Elimination half-life: Approx 2-3 hours.