Core Tutorial in Pediatric Infectious Diseases for Third Year Medical Students Immunizations

? A fifteen-month-old child is seen for “routine care”. He is due to receive his MMR. On exam he has a temperature of 99 F and a runny nose. Should he still be immunized? What are the contraindications to immunization?

? A twelve-month-old child has been taking 2 mg/kg/day of oral prednisone for the past two weeks for asthma. He is due for his routine immunizations. Would you modify his immunization schedule and if so, why?

Learning Objectives Understand the role of vaccine components in the development of the immune response Be able to differentiate active from passive immunization and know the indications for each Know the principles of vaccine safety including side effects and contraindications

PASSIVE vs. ACTIVE Immunization Passive: Administration of preformed antibody (immune globulin = IG) either nonspecific or specific Active: Administration of antigen that stimulates protective antibody

Indications for PASSIVE Immunization Active immunization unavailable or contraindicated Immunodeficient persons High likelihood of exposure No time for active immunity to develop When disease is present, to ameliorate or aid in suppression of toxin effects or inflammatory response

Non-specific Immune Globulin 2 types of nonspecific IG: –Intramuscular –Intravenous Both derived from pooled plasma of adults 95% IgG, with trace IgA, IgM Levels of antibodies in IVIG reflect those of general population (and must have minimum concentration of measles, diphtheria, polio and hepatitis A)

Specific Immune Globulin Specific IG is available for: –Hepatitis B –Rabies –Tetanus –Varicella Zoster –Cytomegalovirus –Respiratory Syncytial Virus

Side Effects of Immune Globulin Pain, discomfort at injection site Flushing, headache, chills, nausea Chest pain, dyspnea, anaphylaxis Development of antibodies against heterologous IgG Development of anti-IgA antibodies in patients with IgA deficiency Need to delay active immunization

ACTIVE Immunization Administering all or part of microorganism or modified product (e.g. toxoid, purified antigen or antigen produced by genetic engineering) to evoke immunologic response mimicking that of natural infection. Protection is measured indirectly as antibody titers

Vaccine Constituents Intact infectious agent (all or part of organism): can be live-attenuated or killed (inactivated) Toxoids (modified product of organism): These are bacterial toxins that are modified to make them non-toxic. They induce formation of antibodies against toxin to protect against toxin- mediated illness (e.g. tetanus, diphtheria).

Other Vaccine Constituents Suspending Fluid - sterile water or saline, possibly with proteins or other components e.g. egg antigens, gelatin Preservatives, Stabilizers, Antibiotics - Mercurials, such as thimerosal, and antibiotics, such as neomycin and streptomycin, are often added to prevent bacterial growth or stabilize the antigen. May be implicated in allergic reactions.

Other Constituents, con’t. Adjuvants - Substances (e.g. aluminum salt) added to increase immunogenicity and prolong the stimulatory effect, especially for inactivated microorganisms or their modified products

Routes of Administration There is no single preferred site for all injectable vaccines Most vaccines are given by the intramuscular or subcutaneous routes Other routes include intradermal and nasal Will depend on active constituents

Routes of Administration, con’t. Intramuscular: DTaP, Influenza, Hepatitis B, Hib, Pneumococcal conjugate Subcutaneous: MMR, IPV, Varicella Intradermal: BCG Nasal: influenza (under investigation)

Vaccine Schedules Based on age-specific attack rates of disease, disease risks, and age-specific immune responses Based on vaccine product type Based on trials which determine immune titer after vaccine is administered

Schedule of Required Childhood Vaccines Depends on type of vaccine, immunity that develops, duration of immunity, age at initial immunization, level of exposure to disease –5 DTaP (diphtheria, tetanus and acellular pertussis) –4 Hib (Haemophilis influenzae type B) and IPV (inactivated poliovirus) –3 Hepatitis B –2 MMR –1 VZV (varicella zoster virus)

Current Schedule

Other Vaccines (recommended for certain groups) Influenza vaccine –chronic illness, ?all children Hepatitis A vaccine –certain areas of U.S., travelers Meningococcal vaccine –travelers, ?college students Typhoid –travelers

Common Side Effects Usually mild to moderate and self-limited Local inflammation at the site of injection Fever, irritability, lethargy Sterile abscesses usually occur after killed vaccines due to irritation by vaccine or adjuvant, or because of inadvertent injection of an intramuscular vaccine subcutaneously

Rare Side Effects Tend to have permanent sequelae or even be life-threatening –Paralytic polio after administration of OPV vaccine. Severe hypersensitivity reactions such as anaphylaxis; often due to vaccine components such as egg antigens, thimerosal, neomycin, or infectious agent

MMR Vaccine & Autism 1998, Great Britain: 12 children with developmental disorders and gastrointestinal disturbances ?link between MMR vaccine and subtype of autism that includes bowel symptoms 2001, Institute of Medicine: concluded that there was no evidence that the MMR vaccine leads to autism 2001, British Public Health Laboratory Service: “No epidemiology could prove that a vaccine never causes autism…proof of a negative is impossible”

Contraindications Hypersensitivity to the (previously administered) vaccine or its components Immunocompromised state or pregnancy (for live vaccines) Undefined illness, moderate to severe febrile illness, or progressive neurological conditions until stabilized

Contraindications for Specific Vaccines DTaP/DTP: encephalopathy within 7 days of previous DTaP or DTP MMR: pregnancy, immunodeficiency, long-term immunosuppressive therapy, severe HIV disease Varicella: pregnancy, immunodeficiency, long-term immunosuppressive therapy, HIV Hepatitis B: anaphylactic reaction to baker’s yeast

Not Contraindications Current or recent mild illness with or without a low grade fever. Current or recent antibiotic therapy. Previous mild to moderate local tenderness, redness, swelling. Fever <40.5 C after any vaccine. Family history of seizure disorder. Breastfeeding.

Impact of Vaccination Programs

References Active and Passive Immunization. Red Book 2000, 25 th ed. American Academy of Pediatrics, 2000; Chapter 1. Marchant CD, Kumar ML. Immunizations. In: Pediatric Infectious Diseases, Principles and Practice. HB Jensen and RS Baltimore, eds. 1995; pp

? Questions for Discussion A fifteen-month-old child is seen for “routine care”. He is due to receive his MMR. On exam he has a temperature of 99 F and a runny nose. Should he still be immunized? What are the contraindications to immunization? 1 of 5

? Questions, con’t A twelve-month-old child has been taking 2 mg/kg/day of oral prednisone for the past two weeks for asthma. He is due for his routine immunizations. Would you modify his immunization schedule and if so, why? 2 of 5

? Questions, con’t A two-month-old girl is brought to the office for a well child examination. The mother is concerned about the potential complications of immunizing her child. How would you address this issue with the mother? 3 of 5

? Questions, con’t A four-month-old boy is seen for a well child examination. Following his first set of immunizations he had a temperature of 103 for a day and extreme irritability. The parents are concerned about giving the second set of immunizations. How would you address their concerns? Can he be immunized today? 4 of 5

? Questions, con’t The parents of a two-month-old girl want to know why their child has to be immunized. None of their friends, family members, or neighbors has ever had hepatitis B virus infection, tetanus, diphtheria, or polio. What would be your response? 5 of 5