Cootie Shots! (Vaccinology for Internists) Christopher Hurt, MD Division of Infectious Diseases December 2009.

Cootie Shots!(Vaccinology for Internists)

Christopher Hurt, MDDivision of Infectious Diseases

December 2009

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OutlineOutline

• Teeny bit of historical perspective• Immunological basis for vaccines• You’re the consultant…

» Case-based details

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Edward JennerEdward 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 ImmunizationPassive vs Active Immunization

Passive• Preformed Abs• MtCT• Antisera/antitoxins

» Clostridium tetani» Clostridium botulinum» Corynebacterium

diphtheriae» Hepatitis B virus» Rabies virus» Measles virus

Active

• Natural infection

• 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?

NEJM 360(25):2605-2615. June 18, 2009.

1918H1N1 “Spanish” flu

1977H1N1

2009Novel H1N1

1957H2N2 “Asian” flu

1968H3N2 “Hong Kong” flu

Influenza pandemicsInfluenza pandemics

Each pandemic represents anantigenic shift in influenza A

?

?

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Who should Who should notnot get LAIV / intranasal 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?”

What’s Grandma talking about?

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Streptococcus pneumoniaeStreptococcus pneumoniae

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Epidemiology of pneumococcusEpidemiology 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.pneumoS.pneumo and HIV 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 vaccinesPneumococcal 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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RecommendationsRecommendations

• 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 something…”

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Does a positive TST mean you’ve been Does a positive TST mean you’ve been exposed exposed to TB, or to TB, or infected infected with TB?with TB?

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Bacille Calmette-Guérin (BCG)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 recipientsInterpreting 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 virusRabies virus• Rhabdovirus; (-)ssRNA• Binds to ACh receptors in

muscles, gangliosides in nerves» Internalized by receptor-mediated

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/encephalitic20% dumb/paralytic

Coma, death within 14d(faster with furious rabies)

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Post-Exposure Treatment (PET)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

• 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)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 meningitidisNeisseria 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 RecommendationsCDC 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 RecommendationsCDC 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)

• 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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RecommendationsRecommendations

• 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 recommendationsSpecific 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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RecommendationsRecommendations

• 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)

• 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 hepatitis viruses are possible?

Which ones are likely?Which ones are likely?(Considering this is a vaccine talk…)(Considering this is a vaccine talk…)

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Hepatitis BHepatitis B• Prototype hepadnavirus• Dane particles

» 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

Dane particle(infectious)

Filamentsof HBsAg

Spheres ofHBsAg

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Hepatitis BHepatitis B• “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 non-replicative + – IgG – +

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Diagnosis sAg sAb cAb eAg eAb

Acute hepatitis + – IgM + –

Window period – – IgM +/ – +/ –

Recovery – + IgG – +/ –

Immunized – + – – –

Chronic replicative + – IgG + –

Chronic non-replicative + – IgG – +

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Hepatitis AHepatitis A

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RecommendationsRecommendations

• 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?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?Which vaccines are safe in HIV?• If CD4 is ≥200 (or 15%),

everything is safe• If CD4 <200 (or 15%), no live

virus vaccines» No LAIV

» No varicella

» No zoster

» No MMR

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And what if my spleen’s gone missing?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