Cootie Shots! (Vaccinology for Internists)

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

2. Outline • Teeny bit of historical perspective • Immunological basis for vaccines • You’re the consultant… • Case-based details

4. 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

5. 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) Passive vs Active Immunization

9. 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?

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

12. Influenza pandemics ? 1918 H1N1 “Spanish” flu 1977 H1N1 2009 Novel H1N1 1957 H2N2 “Asian” flu ? Each pandemic represents an antigenic shift in influenza A 1968 H3N2 “Hong Kong” flu

15. 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

16. 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?

17. Streptococcus pneumoniae

18. 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

19. 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?

20. 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

21. 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

22. 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…”

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

24. 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

25. 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.”

26. 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?”

27. 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?”

28. 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…

29. Does our friend need a rabies shot?

30. 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…

31. Is it too late for our homeless friend to reconsider?

32. Rabies 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

35. 80% furious/encephalitic 20% dumb/paralytic Coma, death within 14d (faster with furious rabies)

36. 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

37. 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

39. 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.

40. 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?

41. 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

43. 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

44. 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) • Requires calculation of attack rates, deciding how big the vaccine target population is (e.g., coworkers vs community)

45. 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?

47. 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

48. 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.”

49. 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?

50. 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) • HIV: CD4 must be >200 (15%)