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Cootie Shots!
(Vaccinology for Internists)
Christopher Hurt, MD
Division of Infectious Diseases
December 2009
Outline
• Teeny bit of historical perspective
• Immunological basis for vaccines
• You’re the consultant…
» Case-based details
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Edward Jenner
• Notices milkmaids don’t
get smallpox
» Cowpox virus (actually not
Vaccinia)
• 1796 – Blossom, Sarah
Nelmes, and James
Phipps make history
• 1980 – WHO declares
smallpox eradicated
» Last naturally acquired
case in Oct 1977
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Passive vs Active Immunization
Passive
Active
• Preformed Abs
• MtCT
• Antisera/antitoxins
• Natural infection
» Clostridium tetani
» Clostridium botulinum
» Corynebacterium
diphtheriae
» Hepatitis B virus
» Rabies virus
» Measles virus
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• Artificial infection
» Attenuated (measles)
» Inactivated (influenza)
» Purified components
(tetanus toxoid, H.flu
type b polysaccharide)
» Cloned recombinant
antigens (HBsAg)
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An oncology fellow calls to ask about the intranasal flu
vaccine (FluMist) – she heard something about it not
being as good for H1N1 as the flu shot. Is that true?
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NEJM 360(25):2605-2615. June 18, 2009.
Influenza pandemics
?
1918
H1N1 “Spanish” flu
1977
H1N1
1957
H2N2 “Asian” flu
Each pandemic
represents an
antigenic shift
in influenza A
2009
Novel H1N1
?
1968
H3N2 “Hong Kong” flu
Who should not get LAIV / intranasal
• Close-contacts to persons with severely
compromised immune systems (e.g., BMT)
• Persons aged 50+, or between 6 months – 2 yrs
• Asthmatics
• Pregnant women
• Neurologic problems causing impaired breathing
or swallowing
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Your grandmother calls and says, “My friend Mabel
told me there’s a vaccine event at the Harris Teeter
next week. Should I get that pneumonia shot?”
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What’s Grandma talking about?
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Streptococcus pneumoniae
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Epidemiology of pneumococcus
• Often colonizes
nasopharynx (5-10% of
adults)
» Seasonal variation in
colonization
• Incidence may be higher
in specific populations
» Blacks, Alaskans,
Aborigines
• Yearly estimate = 25
pneumonia cases:100K
young adults; 280:100K
elderly
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S.pneumo and HIV
• Defective Ab production likely mechanism for
predisposition – Ab falls off as CD4 declines
• Incidence 10:1000 per year – 200x higher than
age-matched group
» 1:25 HIV-infected patients expected to have
pneumococcal pneumonia annually
» Search for HIV in pneumococcal pneumonia in
young pt?
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Pneumococcal vaccines
• Two vaccines available:
» Prevnar – infants to 2yo
• 7-valent, non-pathogenic diphtheria toxin conjugate vaccine
» Pneumovax – age 2+
• 23-valent polysaccharide vaccine
• Vaccine effective for preventing pneumococcal
bacteremia (invasive pneumococcal disease), not
pneumonia itself
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Recommendations
• Administer to:
» Adults @ high risk from respiratory infections (CV, pulm dz)
» Anatomic/functional asplenics, immunocompromised (HIV)
» Pts with problems opsonizing (cirrhotics, alcoholics)
» Pts with heme malignancies (Hodgkin’s, myeloma)
» CSF leaks, cochlear implants
» Otherwise healthy elderly, aged 65+
• Revaccinate once after 5 years:
» 65+ yo if received first dose prior to age 65
» Anatomic or functional asplenics, immunocompromised
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Student Health calls you (always fun!). “We planted a PPD
on one of our students 48h ago. He came back today and
it’s very positive. He said, I was told this would happen,
see? And lifted up his shirt sleeve to show me
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something…”
Does a positive TST mean you’ve been
exposed to TB, or infected with TB?
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Bacille Calmette-Guérin (BCG)
• Attenuated strain of Mycobacterium bovis (part of
MTB complex)
• Efficacy in preventing disseminated TB among
children – especially tuberculous meningitis
• In US, used only under extraordinary circumstances
» Child without TST conversion but close, intimate contact to
untreated, ineffectively treated, or drug-resistant active TB
• Immunocompromised should not receive vaccine, due to
increased risk of disseminated BCG disease
• One-third of recipients develop hypertrophic scar
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Interpreting TST/PPD in BCG recipients
• BCG-related TST reactivity generally wanes w/time
• Repeated TSTs may boost/prolong reactivity
• No reliable method exists to distinguish BCG from TB
• Quantiferon-TB Gold… maybe
• “TST reactions should be interpreted regardless
of BCG vaccination history.”
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On Saturday, you get a call to the consult pager. “We were
at a picnic, and my son went to put something in the trash
can, and this squirrel was scared and leaped out and
scratched his face. Does he need a rabies shot?”
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Another caller: “I woke up this morning and there was a
bat in my bedroom. Animal control came and took care of
it, and said it looked okay, just dehydrated.
Do you think I need a rabies shot?”
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A homeless man sees a forlorn dog off by itself at the end
of an alleyway. He felt badly for the dog, and went to go
try to give it some food. Unfortunately, Fluffy didn’t want to
be bothered…
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Does our friend need a rabies shot?
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Our friend refuses the rabies shot and leaves AMA.
Fluffy wasn’t particularly unhappy about being taken into
custody by Animal Control, and was put into quarantine.
Over the next 12h, he becomes progressively obtunded
and dies. At necropsy, they find…
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Is it too late for our homeless friend to reconsider?
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Rabies virus
• Rhabdovirus; (-)ssRNA
• Binds to ACh receptors in
muscles, gangliosides in nerves
» Internalized by receptormediated endocytosis
• Centripetal spread from
peripheral nerves to the CNS,
proliferation, and centrifugal
spread back out to tissues
» Virus in dorsal root ganglia
within 72h of infection
• Saliva is critical; aerosolized
virus can cause disease
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80% furious/encephalitic
20% dumb/paralytic
Coma, death within 14d
(faster with furious rabies)
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Post-Exposure Treatment (PET)
•
Immediate wound care (if available, povidone/iodine)
•
If animal can be captured and observed for 10d
»
If animal dies, begin PET while necropsy and slides made
•
»
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If DFA for rabies is negative, stop PET
If animal healthy and doesn’t become ill, no PET
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Post-Exposure Treatment (PET)
•
•
If animal cannot be captured and observed, or highly
suspect animal exposure, and not previously
vaccinated, begin PET:
»
HRIG (human) 20 IU/kg or ERIG (equine) 40 IU/kg
»
Infiltrate ENTIRE dose into the wound (not ½ there, ½ IM)
»
Human diploid cell vax (HDCV) 1.0 mL in deltoid as close
to exposure day as possible, then on day +3, +7, +14, +28
If previously vaccinated, different PET given:
»
No RIG
»
Human diploid cell vax (HDCV) 1.0 mL in deltoid as close
to exposure day as possible, then on day +3 only
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A Muslim student is excited about making his first Hajj to
Mecca, and calls the clinic because his parents told him
he needed to get some kind of vaccine before he goes.
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A 19yo college freshman
whose 3 roommates brought
her in after she was found
febrile and hallucinating. An
LP shows cloudy CSF with
Gram negative diplococci.
Over the next several days,
4 additional cases are
diagnosed.
Is there a role for “ring”
vaccination?
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Neisseria meningitidis
• Gram-negative diplococcus
• Of 13 capsular serogroups, 8
cause human disease
» A, B, C1+, C1, X, Y, W-135, L
• Two quadrivalent vaccines
available in US
» A, C, Y, W-135
» Menomune (MPSV4) =
polysaccharide
» Menactra (MCV4) =
conjugate to diphtheria toxoid
• Superior immunogenicity,
longer sustained titers
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CDC Recommendations
• Menactra (MCV4) is preferred for ages 11-55
» Single dose induces protective Ab titers in ≥90% age 2+
» MPSV4 can be used if MCV4 is not available
• MPSV4 must be used for children 2-10, adults >55
• College freshmen, microbiologists, US military recruits,
asplenics (anatomical or functional), terminal
complement defc’y, travelers to countries/regions with
outbreaks
• Takes 7-10 days to develop antibody response
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CDC Recommendations
• For those exposed
» Chemoprophylaxis with rifampin, ciprofloxacin, or ceftriaxone
• Household contacts, oral secretion exposures, day care
• Quinolone-resistant meningococcus reported, MN & ND 07/08
» Group B (not in vaccine) – accounts for 35% of US cases
• Azithromycin may work, but is not recommended for prophy
» Ring vaccinations based on public health guidance
• Adjunct to chemoprophylaxis for close & intimate contacts
• Data strong for serogroup C outbreaks; assumed to be true for
other 3 (A, W-135, Y)
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• Requires calculation of attack rates, deciding how big the
vaccine target population is (e.g., coworkers vs community)
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A 26yo man presents to the ED for evaluation of a new,
painful rash. The attending calls you because the patient’s
28yo wife, who suffers from RA, says she’s never had
chicken pox before. What should you do?
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Recommendations
• Varicella vaccine (Varivax) is not the same as shingles
vaccine (Zostavax)
» Both are live Oka strain, but “concentration” differs
» Varivax: 1350 PFUs of Oka/Merck; Zostavax: 19,400 PFUs
• Varicella vaccine should be given to susceptible, high-risk
adult patients (consider serologic testing):
» Environments where varicella transmission likely
» Close contacts with impaired immune systems
» Anyone living with children
» International travelers
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Specific recommendations
• “For healthy adolescents and adults (13 yo +) without
evidence of immunity, vaccination within 3-5 days of
exposure to rash is beneficial in preventing or modifying
varicella.”
» Vax within 3 days of exposure to rash ≥ 90% effective in
preventing varicella. Vax within 5 days of exposure ~70% effective
in preventing varicella and 100% effective in modifying severe
disease.
• “For persons without evidence of immunity who have
contraindications for vaccination but are at risk for severe
disease and complications, use of varicella zoster immune
globulin (VZIG) is recommended for PEP.”
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A 62yo otherwise healthy
woman has heard about
the shingles vaccine.
She’s never had an
episode of shingles, but
her sister did, and it was
awful. She herself had
chicken pox twice as a
child, she says.
What do you recommend?
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Recommendations
• All persons age >60 should receive a single dose
» Especially if at risk for future immunosuppression
• Safe to give, even if had case of zoster previously – unless
comorbid medical conditions pose risk of vaccine disease
• Not indicated for:
» treating acute zoster
» preventing or treating post-herpetic neuralgia
» persons who received varicella (Varivax) vaccine as their
only varicella infection (i.e., not naturally infected)
» primary or acquired immune deficiencies (esp. CMI)
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• HIV: CD4 must be >200 (15%)
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A 34yo HIV+ MSM presents with his 34yo HIV- partner to
clinic with a week’s worth of fatigue, nausea, diarrhea,
anorexia, and fevers. His CD4 count is 582. He does not
take atazanavir. A month ago, he traveled to Mexico on
business and had sex with two different partners.
Should his partner be evaluated and/or treated?
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Which hepatitis viruses are possible?
Which ones are likely?
(Considering this is a vaccine talk…)
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Hepatitis B
Dane particle
(infectious)
•
•
Prototype hepadnavirus
Dane particles
»
»
Filaments
of HBsAg
Spheres of
HBsAg
»
»
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Double-shelled particles
Host-derived outer
lipoprotein envelope with
three related glycoproteins
– the surface antigens
(HBsAg)
Viral nucleocapsid also
called the core (HBcAg)
Core contains partially
duplex DNA and
polymerase
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Hepatitis B
•
•
•
•
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“e” Antigen (HBeAg)
By-product of HBcAg
production
Secreted into blood
No role in viral assembly
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Diagnosis
sAg
sAb
cAb
eAg
eAb
Acute hepatitis
+
–
IgM
+
–
Window period
–
–
IgM
+/ –
+/ –
Recovery
–
+
IgG
–
+/ –
Immunized
–
+
–
–
–
Chronic replicative
+
–
IgG
+
–
Chronic nonreplicative
+
–
IgG
–
+
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Diagnosis
sAg
sAb
cAb
eAg
eAb
Acute hepatitis
+
–
IgM
+
–
Window period
–
–
IgM
+/ –
+/ –
Recovery
–
+
IgG
–
+/ –
Immunized
–
+
–
–
–
Chronic replicative
+
–
IgG
+
–
Chronic nonreplicative
+
–
IgG
–
+
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Hepatitis A
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Recommendations
• As soon as possible, within 2 weeks after exposure:
» For contacts aged 1-40, single dose of single-antigen
hepatitis A vaccine (Havrix, VAQTA), -or» Hepatitis A Ig
• For healthy people, vaccine preferred, due to long-term
protection afforded and ease of administration
• If >40yo, Ig is preferred because of absence of data re:
vaccine performance in the age group, and because
hepatitis A clinically is much more severe at older ages
» Vaccine may be used, if Ig not available
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Which vaccines are safe in pregnancy?
• Probably a lot – but we don’t know for sure
• No live virus vaccines except yellow fever, if risk for
exposure is great
• Definitely okay:
» Tetanus toxoid (as Td)
» Influenza (inactivated vaccine ONLY) if beyond 1st trimester
during influenza season
• Probably okay:
» Meningococcal, pneumococcal, hepatitis A and B
• Never okay:
» No live virus vaccines! (varicella, zoster, MMR, LAIV)
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Which vaccines are safe in HIV?
• If CD4 is ≥200 (or 15%),
everything is safe
• If CD4 <200 (or 15%), no live
virus vaccines
»
»
»
»
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No LAIV
No varicella
No zoster
No MMR
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And what if my spleen’s gone missing?
• For elective splenectomy,
administer as far in advance of
the time of surgery as possible
• Functional or anatomic asplenia
warrants:
» Encapsulated bugs
• Haemophilus influenzae type b
• Pneumococcus
• Meningococcus
» Influenza (due to increased risk
of bacterial superinfection)
• Not LAIV
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