IMMUNIZATIONDaniel R Hinthorn, MD, FACP

Professor of Internal Medicine, Pediatrics, and Family Medicine

Director, Infectious Diseases

KUMED

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.

Vaccine

Birth

1M

2M

4M

6M

12 - 15M

18M

24M

4-6Yr

11-12Y

Hepatitis B HB 1 HB 1 HB 2

HB 1 HB 2

HB 1 HB 2

HB 2 HB 3

HB 3

HB 3

HB 3

DTaP DTaP1

DTaP2

DTaP3

DTaP4

DTaP Td

Hib Hib Hib Hib Hib

eIPV eIPB eIPV eIPV

Pneumococcal PCV PCV PCV PCV

MMR MMR MMR

VZV VZV

Hepatitis A HAV

Recommended Childhood Immunizations

* MMWR May 19, 2000 & aafp.org/policy

HB

MMRVZV

Oval = catch up

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.

CDC Study –Infant Pertussis: Who Was the Source?

774 infant cases from 4 states

264 cases had source identified

Sources:

Bisgard, K. Bisgard, K. PIDJ.PIDJ. 2004;23:985-9. 2004;23:985-9.

Mother 32%

Father 15%

Sibling 20%

Grandparent 8%

Other 25%

Age of Pertussis Source* for Infants

*219 source-persons with known age*219 source-persons with known age

00

1010

2020

3030

4040

5050

6060

0-40-4 5-95-9 10-1910-19 20+20+

Age of Source (Years)Age of Source (Years)

% o

f In

fan

t C

ase

s%

of

Infa

nt

Ca

ses

Bisgard, K. Bisgard, K. PIDJ.PIDJ. 2004;23:985-9. 2004;23:985-9.

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;Schwenkenbecher, 1912;Kurt et al. Kurt et al. JAMA.JAMA. 1972;221(3):264-7; 1972;221(3):264-7;

Etkind et al. Etkind et al. Am J Dis Child.Am J Dis Child. 1992;146:173-6; 1992;146:173-6; Christie et al. Christie et al. Infect Control Hosp Epidemiol.Infect Control Hosp Epidemiol. 1995;16:556-63; 1995;16:556-63;

Matlow et al.Matlow et al. Infect Control Hosp Epidemiol. Infect Control Hosp Epidemiol. 1997;18:715-16; 1997;18:715-16;CDC. CDC. MMWRMMWR. 2004;54(03):67-71.. 2004;54(03):67-71.

Whitney, C. G. et al. N Engl J Med 2003;348:1737-1746

Rates of Invasive Pneumococcal Disease among Persons at Least Five Years Old, According to Age Group and Year

69% reduction in 0-69% reduction in 0-2 year olds2 year olds

32% reduction32% reduction

18% reduction18% reduction

Conjugate pneumococcal vaccine

introduced

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.

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

Vaccines possibly considered before international travel

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

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

What diseases of travel should you consider in such patients? 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

Worry about eating when you are traveling: (not protected by vaccines)

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)

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

Hepatitis A & B & C 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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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

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.

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.

College students get meningitis

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.

Meningococcal vaccine now suggested for college

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.

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

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

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

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.

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.

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

IMMUNIZATIONIMMUNIZATION