IMMUNIZATION

1. IMMUNIZATION Daniel R Hinthorn, MD, FACP Professor of Internal Medicine, Pediatrics, and Family Medicine Director, Infectious Diseases KUMED

2. Early Vaccine Uses • Earliest use was smallpox vaccinations. • 1950s and 60s, vaccines were thought to hold great promise for better lives. • Polio vaccines • Salk, killed polio vaccine, 1955. • Sabin, live OPV, 1961. • The Cutter vaccine caused paralytic polio. • Measles vaccine licensed, 1963. • Rubella vaccine use was widespread, 1968. • Mumps vaccine was cautiously started, 1969. • Swine flu disease 1918, & vaccine 1976. • Guillain Barre syndrome occurred.

3. Recommended Childhood Immunizations HB MMR VZV Oval = catch up * MMWR May 19, 2000 & aafp.org/policy

4. New vaccines recently released • Menamune • Conjugate vaccine for meningococcal disease • Bound to protein of diphtheria toxin • Activates T lymphocytes • Longer lasting antibody responses • Adacel • Conjugate vaccine for pertussis • Now approved for use in children, adolescents, and for adults up to age 64 years.

5. CDC Study –Infant Pertussis: Who Was the Source? • 774 infant cases from 4 states • 264 cases had source identified • Sources: Other 25% Mother 32% Grandparent 8% Father 15% Sibling 20% Bisgard, K. PIDJ. 2004;23:985-9.

6. Age of Pertussis Source* for Infants 60 50 40 % of Infant Cases 30 20 10 0 0-4 5-9 10-19 20+ Age of Source (Years) *219 source-persons with known age Bisgard, K. PIDJ. 2004;23:985-9.

7. Healthcare Professionals Involvedin Transmission of Pertussis • Physicians 1912 Schwenkenbecher • Nurses 1972 Kurt et al • Physicians 1992 Etkind et al • Nurses 1995 Christie et al • Nurses 1997 Matlow et al • Nurses and Physicians 2005 CDC Schwenkenbecher, 1912;Kurt et al. JAMA. 1972;221(3):264-7;Etkind et al. Am J Dis Child. 1992;146:173-6; Christie et al. Infect Control Hosp Epidemiol. 1995;16:556-63; Matlow et al. Infect Control Hosp Epidemiol. 1997;18:715-16; CDC. MMWR. 2004;54(03):67-71.

8. Rates of Invasive Pneumococcal Disease among Persons at Least Five Years Old, According to Age Group and Year Conjugate pneumococcal vaccine introduced 18% reduction 69% reduction in 0-2 year olds 32% reduction Whitney, C. G. et al. N Engl J Med 2003;348:1737-1746

9. FluMist: live virus vaccine recently approved for influenza • Temperature adapted influenza vaccine made. • This is the first live virus influenza vaccine and should be available this fall, for age 5-50. • First dose in peds 5-8 years, give two doses 6 wks apart. Prevention of spread is the idea. • Healthy adults age 8-49 should get one dose. • Each dose has 3 influenza strains rec by the USPHS for the 2003-4 season. • Efficacy was 87% in children in 30,000 pts during the trials. • For older adults, the inactivacted vaccine looked better.

10. Currently suggested adult re-immunizations • Hepatitis A: If at risk, travel out of US, highly endemic areas, job exposures. • Hepatits B: If IVDA, not monogamous. • Tetanus: Td every 5-10 y or after tetanus prone wound. • Varicella: if never had chickenpox. • Pneumovax • Influenza Atkinson et al, 6th ed, CDC, 2000

11. Yellow fever Polio Varicella Tetanus-diphtheria Measles Typhoid *Rabies Meningococcus Japenese B encephalitis *Plague Hepatits A Hepatitis B *Typhus *Calmette-Guerin BCG *Tick-borne encephalitis Vaccines possibly considered before international travel

12. Do your patients know they should see a physician before travel? • Worries about diseases during or after travel? • 1 million people travel between developed and developing countries each week. • 60-70% chance each will develop a health complaint related to travel. • Surveys at 14 major airport, 8000 travelers. • Leisure 70%, visiting 20%, work 10%. • >50% planned > 4 wks in advance, others less. • 40% had not sought medical advice. • IDN July 2003

13. Flying problems with motion sickness Acclimatization Water Food & beverages Sunstroke Insects Schistosomiasis Sleeping sickness Malaria prophylaxis Traveler’s diarrhea Problems with meds and prophylaxis Insurance overseas Return of bodies to the US What diseases of travel should you consider in such patients?

14. At home. Chicken, turkey, and other meats. Contamination with Campylobacter, occasionally with Salmonella. Wash the cutting boards. Hands after touching it. Food left at room temperature esp overnight to serve later. Eating out. Same as at home plus… *Hepatitis A Ameba Neurocyticercosis Internationally Eat only foods that are served hot. No ice, no leafy, no fruit unless you peel it yourself. (*typhoid) Worry about eating when you are traveling: (not protected by vaccines)

15. Hepatitis A vaccination has reduced rates of hepatitis A • Hepatitis - 85% of kids infected have no sx. • Case fatality is 3/1000 overall, more in older. • 10% of people with HAV relapse to Sx & infective • Kids traveling account for most of 10% Hep A • U.S. born children returning to Mexico with parents to the villages of birth is a big risk factor. • States with mandated HepA vaccine • 83% decline in hepatitis A, especially in kids. • IDN July 2003

16. Hepatitis A *Fresh food fussed over with fecaled fingers. Food, water, *feces, *urine transmission. Zoo transmission. Military example. No therapy. Prevention: vaccine, 2 doses. Gammaglobulin. Hepatitis B Blood, needles, sexual transmission. Vaccine 3 doses for full protection. Therapy. Hepatitis C Blood transmission. Cocaine straws are biggest risk. No vaccine. Therapy - depression for a year. Hepatitis A & B & C

17. A salade for military doctors • A recruit reported to sick-call for fatigue. • Dx was non-medical and he was assigned to kitchen police duty. • Making salad for a banquet. • Felt bad, felt not listened to, so he spiked the salade with body secretions. • 30 days later a high percent of those attending became ill with hepatitis A. • All ate the salade. • He confessed.

18. Hepatitis B infection • 2 billion people affected & 350 Africans/Asians are carriers • USA 1.25 million & .35% population are chronic carriers. • Maternal transmission HBeAg positive is 85%, but 10-30% if HBeAg negative • 85% of these newborns bec chr carriers. • Blood & sexual transmission are most important mechanisms otherwise.

19. Who needs HBV vaccine? • Infants not vaccinated. • Persons who have increased risks of hep B • Individuals who have multiple sex partners • Partner of HBV positive persons • Household contact has hepatitis B • MSM, IVDA • Travelers to endemic areas of the world • Job exposure to body fluids • Work with intellectually disabeled persons • CRF pts, clotting factor recipients • Persons who have chronic hepatitis C

20. Special notes: hepatitis B • Hepatitis B vaccine • Mother is HB neg • 1st dose by 2 mo, 2nd at least 1 mo later. • 3rd dose at least 4 mo after 1st, 2 mo after 2nd. • Never before 6 months. • Mother is HB pos • 1st dose by 12 hrs, & HBIG at separate site. • 2nd dose 1-2 mo, 3rd dose at 6 mo. • Mother HB unkown status • 1st dose by 12 hrs. Test mother. • If pos, give neonate HBIG by 7 days. • MMWR May 19, 2000.

21. Impact of HCV Infection • Prevalence • 170 million affected worldwide • USA, 4 million or 1.8% population have HCV RNA (indicating active disease). • 1% of US deaths due to ESLD (40% HCV) • 65% are ages 30-49 years. • Risk factors • Drug abuse, risky sexual behavior. • Course • May be clinically silent, but end in ESLD.

22. Newly approved vaccine for influenza: FluMist • Temperature adapted influenza vaccine made. • This is the first live virus influenza vaccine and should be available this fall, for age 5-50. • First dose in peds 5-8 years, give two doses 6 wks apart. Prevention of spread is the idea. • Healthy adults age 8-49 should get one dose. • Each dose has 3 influenza strains rec by the USPHS for the 2003-4 season. • Efficacy was 87% in children in 30,000 pts during the trials. • For older adults, the inactivacted vaccine looked better.

23. More on FluMist • The vaccine made by crossing • a master donor strain with wild virulent strains • to give the desired hemagglutinins and neuraminadase. • Grown in chickens. • Temp sensitive allows growth in nose but not the lower respiratory tract. • Avoid giving to immune suppressed, or those with chronic medical problems who might get disease. • Probably protects against some strains not in the vaccine too unlike the inactivated vaccines.

24. Immunizations and the illnesses they prevent: staying healthy • Influenza A or B. • Fever, runny nose, muscle aching, sore throat, cough. • Who should take the influenza (inactivated) vaccine? • Those with other illnesses: heart, lung, diabetes. • Who should use the live virus FluMist? • Ages 5-49. Temperature sensitive strain. • Are there rapid diagnostic tests and therapies if someone doesn’t take it in time? • Relenza & Tamiflu, amantadine & rimantadine.

25. Pneumovax (the pneumonia shot) • Of the dozens of causes of pneumonia, this is the most lethal. The first 7 days are critical. • Symptoms are cough, pleurisy, sputum, high fever, aching. • Deaths more often in under age 5 and over 60. • Vaccine for kids has 7 types. For adults 23 types. • Both are inactive, not live organisms. • Diabetes, other illnesses as for influenza. • Repeat it every 5 years.

26. Vaccination combinations • The mega-combo vaccine with multiple components rejected by FDA panel in a close 5-4 vote • Reasons: InfanrixDTaP-HepB-IPV • Fever in a few children • 200,000 calculated among 4 million kids • Tested on mostly white children in Germany with small USA studies. • How will it work with Prevnar added? • Twinrix (hepatitis A&B) approved. • IDC 14:1, 2001

27. Vaccine use questioned • The concern as each disease is decreased in frequency: • Should we keep immunizing for a rare disease? • Number of adverse problems equals diseased. • Common concerns today (some valid, some not): • Influenza vaccine: Guillain Barre Syndrome. • DPT: seizures & brain damage. • DPT: linked to autism (IOM found no evidence) • OPV believed to be too risky to use routinely. • MMR: Wakefield & regressive autism + lymphoid nodular hyperplasia. • Thimerosal and CNS development.

28. Special concerns: eIPV & MMR • Enhanced inactivated polio vaccine • Anaphylaxis to neomycin, streptomycin, or polymyxin B has been reported. • Precaution in pregnancy. • No data to support reducing eIPV to 3 doses. • MMR (live viral components) • Neomycin or gelatin anaphylaxis • Pregnancy: avoid • Immunodeficiency: avoid • Precautions: Recent IG, decreased platelet counts, history of purpura from low platelets.

29. Meningococcal vaccine now suggested for college College students getmeningitis • 23 year-old woman, K-State student Found comatose in her apartment. In February the student had URI 5 days later, she had myalgia, arthralgia The next day, nausea, vomiting, headache. Spoke to her mother on the phone. She didn’t answer phone, so parents went to Manhattan and found her. She was stuporous on arrival in the emergency department.

30. Meningococcal vaccines • Epidemiology changing • 1998-99, 88 cases and 8 deaths in college students among 2,300 US cases • Increase in vaccine-preventable cases • Now inform students & parents re: • disease & quadrivalent ACYW135 for dormitory entering freshman. • No group B vaccine available (1/3 cases) • Repeat dose in 3-5 yrs if freshman/dorms. • To prevent most cases, immunize starting at 17 y/o. • CID 2000;30:648, MMWR 2000:49(RR07):1-10, JAMA 1999;281, 1906.

31. Contraindication to immunization • Hypersensitivity to components: read labeling! • Most common are egg proteins (MMR, Influenza, yellow fever) • If patient can eat egg containing foods, it’s OK. • Antibiotics: neomycin (MMR), streptomycin, thiomerosol • Congenital immunodeficiency • Avoid oral polio vaccine (patient or family) • MMR not shed (only patient avoid) • Systemic prednisone may alter response

32. Febrile illness and vaccination • All vaccines can be administered to persons with minor illness such as diarrhea,URI with or without low-grade fever, or other low-grade febrile illness • Minor illness will not affect the seroconversion rate of vaccines • Persons with moderate or severe febrile illness should be vaccinated as soon as they have recovered from the acute phase of the illness

33. Real problems with Immunizations • Contents of vaccines • Presence of thiomerisol • Large amounts of mercury exposure • RotaShield rotavirus vaccine • Intussusception • Vaccine causing problems • Oral polio vaccine • Paralysis • Measles & MMR • Argued, not well studied pre-release

34. Preservatives in vaccines • 1997, FDA assessed the health risk of mercury in foods and drugs. • Drug companies asked to give data on thimerosal in products. • Use began in 1930s. • Prevents bacterial growth in mulit use vials. • Was used in over 30 vaccines: DPT, hepB, flu. • Metabolized to thiosalicylate and ethyl Hg. • Latter has T 1/2 of 9 days. Urinary excretion. • Accumulation occurs if intake exceeds excretion. • Minimata Bay neuromotor disability of infants. • Spasticity, muscle wasting, joint pains. • Due to industrial dumping.

35. Large study of 2% of US peds • HMO study of children <age 7 years • No association between MMR and IBD or autism. • But children who had MMR after 18 months had a reduced incidence of IBD, called a protective effect. • (Beware the association here too) • Recall the child who drove up with his parents to his burning house. • The child wanted to know why the firemen had set his house on fire. • Arch Ped Adol Med 2001;155:355.

36. Rubella vaccine • Was licensed in 1969, • live attenuated RA27/3 strain, • grown in human diploid cell culture • Induces protective antibody in about 95% of susceptible persons • Immunity appears to be long lasting • Route: subcutaneous injection, dose-0.5ml • Storage: 20 to 80C and protect from light • Side effects: fever, rash, arthralgia and arthritis

37. IMMUNIZATION