Pediatric Immunization

Public Health Impact of Pediatric Immunization

• Immunization is universally recognized as one of the greatest public health achievements of modern times.
• As a direct consequence of immunization, the annual incidences of several major infectious diseases have fallen by more than $99\%$ compared with their average annual incidences in the 20th century:
  • Diphtheria
  • Paralytic poliomyelitis
  • Measles
  • Mumps
  • Rubella
  • Haemophilus influenzae type b (Hib)

Categories of Immunizing Agents

• Immunizing agents are classified into three primary categories:
  1. Immunoglobulins
  2. Antisera
  3. Vaccines

Immunoglobulins and Passive Immunity

• Major Classes: There are 5 major classes of immunoglobulins:
  • IgM
  • IgA
  • IgG
  • IgE
  • IgD
• Preparations Available for Passive Immunization:
  • Normal human immunoglobulin
  • Specific (hyper-immune) human immunoglobulin

Antisera and Antitoxins

• Definition: Antiserum is a blood serum rich in specific antibodies derived from humans or animals. It is used to confer rapid, temporary passive immunity against specific diseases, toxins, or venoms.
• Primary Applications and Types:
  1. Antivenoms and antitoxins: Used to neutralize animal venoms (such as snakebites) and bacterial toxins.
  2. Infectious disease treatment: Used in acute management (such as rabies).
  3. Laboratory diagnostics.

Principles of Immunity and Vaccination

• Immunization: The deliberate stimulation of an immune response in a person by administering a specific agent to protect against an infectious disease.
• Active Immunity:
  • Developed in response to a stimulus by an antigen (an infecting agent or a vaccine).
  • Characterized by the production of antibodies by the host's own immune system.
• Passive Immunity:
  • Immunity conferred by an antibody produced in another host.
  • Can be acquired naturally (e.g., maternal antibodies) or artificially.
• Medical Indications for Passive Immunoglobulin Therapy:
  1. Replacement therapy in primary immune-deficiency disorders.
  2. Kawasaki disease.
  3. Hypogammaglobulinemia in chronic B-cell lymphocytic leukemia.
  4. Prevention and management of specific infections.
  5. Hepatitis B immune globulin (IM): Administered for postexposure prophylaxis against perinatal infection in infants born to HBsAg-positive ($\text{HBsAg}^{+\text{ve}}$) mothers.
  6. Palivizumab: A monoclonal antibody administered intramuscularly (IM) as prophylaxis for infants against respiratory syncytial virus (RSV).
• Key Terminology:
  • Vaccination: A method of giving an antigen to a child to stimulate an immune response through active immunization.
  • Vaccine: A substance designed to produce specific protection against a given disease. A vaccine is strictly "antigenic" but not "pathogenic".
  • Antigen: A live or inactivated substance (e.g., a protein) capable of producing an immune response.
  • Antibody: A protein molecule (immunoglobulin) produced by B lymphocytes to help eliminate an antigen.

Classification and Types of Vaccines

• Live Attenuated (Avirulent) Vaccines:
  • Virulent pathogenic organisms are treated to become attenuated and avirulent while maintaining their antigenic properties.
  • They lose the capacity to induce disease but retain full immunogenicity.
  • Contraindications for Live Attenuated Vaccines:
  1. Leukemia and lymphoma
  2. Other malignancies
  3. Patients receiving immunosuppressive therapy (e.g., corticosteroids and anti-metabolic agents)
  4. Radiotherapy
  5. Pregnancy
• Inactivated Vaccines:
  • Whole virus: Polio, Hepatitis A
  • Bacteria: Pertussis, Cholera, Typhoid
  • Protein-based subunit: Hepatitis B, Influenza, Acellular Pertussis
  • Toxoid: Diphtheria, Tetanus
  • Polysaccharide-based (known for high efficacy and safety):
  • Pure polysaccharide: Pneumococcal, Meningococcal
  • Conjugate polysaccharide: Pneumococcal, Haemophilus influenzae type b (Hib), Meningococcal

Comparison: Inactivated vs. Live Attenuated Vaccines

• Inactivated Vaccines Characteristics:
  • Contains killed or inactivated pathogen.
  • Cannot replicate within the host.
  • Minimal interference from circulating antibodies.
  • Immune response induced is mostly humoral.
  • Generally not as effective as live vaccines; requires $3\text{--}5\,\text{doses}$.
  • Antibody titer diminishes over time.
• Live Attenuated Vaccines Characteristics:
  • Contains attenuated form of virus or bacteria.
  • Must replicate within the host to be effective.
  • Interference from circulating antibody can occur.
  • Immune response induced is similar to natural infection.
  • Usually effective with a single dose.
  • Usually mild response, but severe reactions are possible.
  • Biologically/thermally unstable.

Bacterial Toxoids

• Preparation and Mechanism:
  • Prepared by detoxifying bacterial exotoxins, rendering them non-pathogenic while retaining their antigenicity.
  • Adjuvants (e.g., alum precipitation) are incorporated to increase vaccine potency.
  • Mechanism of Action: Antibodies generated in the body neutralize the toxic moiety produced during infection rather than directly acting upon the pathogen itself.
  • Efficacy: Highly efficacious and safe immunizing agents.

Vaccine Constituents and Administration Routes

• Major Constituents of Vaccines:
  • Active Immunizing Agent:
  • Single antigen (e.g., tetanus toxoid, diphtheria toxoid)
  • Complex antigens (e.g., live viruses, killed bacteria)
  • Suspending Fluid:
  • Sterile water or saline
  • Tissue culture fluid (containing egg antigens, gelatin)
  • Preservatives, Stabilizers, and Antibiotics:
  • Added to prevent bacterial growth and stabilize antigens.
  • Examples: Thiomersal (a mercurial compound), Neomycin, Streptomycin.
• Routes of Administration:
  • Deep Subcutaneous or Intramuscular (IM) route: Most standard vaccines.
  • Oral route: Sabin polio vaccine (OPV), Rotavirus.
  • Intradermal route: Bacillus Calmette-Guérin (BCG) vaccine.
  • Scarification: Smallpox vaccine.
  • Intranasal route: Live attenuated influenza vaccine.
• Schemes of Immunization:
  • Primary Vaccination:
  • Single-dose vaccines: BCG, Varicella, Measles, Mumps, Rubella, Yellow fever.
  • Multiple-dose vaccines: Polio, DPT, Hepatitis B.
  • Booster Vaccination:
  • Administered to maintain immunity level after it declines over time.

Vaccine Effectiveness Categories

• Absolutely Protective ($100\%$):
  • Yellow fever vaccine
• Almost Absolutely Protective ($99\%$):
  • Varicella vaccine
  • Measles vaccine
  • Mumps vaccine
  • Rubella vaccine
  • Diphtheria toxoid
  • Tetanus toxoid
• Highly Protective ($80\text{--}95\%$):
  • Polio vaccine
  • BCG vaccine
  • Hepatitis B vaccine
  • Pertussis vaccine
• Moderately Protective ($40\text{--}60\%$):
  • TAB vaccine (Typhoid-Paratyphoid A & B)
  • Cholera vaccine
  • Influenza killed vaccine

Immunization Risks and Contraindications

• Adverse Reaction Categories:
  • No immune response is entirely free from the risk of adverse reactions or remote sequelae.
  • Reaction Categories:
  1. Reactions inherent to inoculation
  2. Reactions due to faulty techniques
  3. Reactions due to hypersensitivity
  4. Neurological involvement
  5. Provocative reactions
  6. Others
• Local vs. General Reactions:
  • Local Reactions: Pain, swelling, redness, tenderness, and development of a small nodule or sterile abscess at the injection site.
  • General Reactions: Fever, malaise, headache, and other constitutional symptoms.
  • Reactogenicity Profile: Most killed bacterial vaccines (e.g., typhoid) cause some local and general reactions. Diphtheria toxoid, tetanus toxoid, and live polio vaccine produce minimal reactions.
• Absolute General Contraindications:
  • Serious allergic reaction (anaphylaxis) following a previous vaccine dose or to a vaccine component.
  • Immunocompromised states or pregnancy for live virus vaccines.
  • Moderate or severe acute illness with or without fever.
  • History of anaphylactic-like reactions to eggs is a contraindication to influenza and yellow fever vaccines.
  • Egg Allergy Exception: Current preparations of measles and mumps vaccines do not contain significant amounts of egg proteins and may be administered without prior testing in children with a history of egg allergy.
• Conditions Where Vaccines CAN Be Administered Safely:
  • Mild acute illness with or without fever.
  • Convalescent phase of illness.
  • Recent exposure to an infectious disease.
  • Current antimicrobial therapy.
  • Breastfeeding.
  • Mild to moderate local reaction or low-grade to moderate fever following a previous vaccination.
  • History of penicillin or other non-vaccine allergy, or receiving allergen extract immunotherapy.

National Immunization Schedule in Iraq

• Schedule Matrix by Age Group:
  • $0\text{--}1\,\text{week}$: BCG, OPV0, HBV1
  • $2\,\text{months}$: Penta 1 (DPT1, HIB1, HBV2) + ROTA V.1 + OPV1 + PCV13-1
  • $4\,\text{months}$: Tetra (DPT2, HIB2) + ROTA V.2 + OPV2 + PCV13-2 + IPV1
  • $6\,\text{months}$: Penta 2 (DPT3, HIB3, HBV3) + OPV3 + PCV13-3 + IPV2
  • $9\,\text{months}$: Measles + Vitamin A ($100{,}000\,\text{IU}$)
  • $12\,\text{months}$: MMR1
  • $18\,\text{months}$: MMR2 + Vitamin A ($200{,}000\,\text{IU}$) + OPV booster 1 + DPT booster 1
  • $4\text{--}6\,\text{years}$: OPV booster 2 + DPT booster 2 + Vitamin A ($200{,}000\,\text{IU}$)

Specific Vaccine Formulations and Protocols

• Bacillus Calmette-Guérin (BCG) Vaccine:

  • Dose, Route, Site: $0.05\,\text{ml}$, Intradermal, left upper arm at the insertion of the deltoid.
  • Local Reaction & Healing Progression:
  • A papule develops at the site $2\text{--}3\,\text{weeks}$ post-injection.
  • Slowly increases in size to $4\text{--}8\,\text{mm}$ in diameter by $5\,\text{weeks}$.
  • Subsides or breaks into a shallow ulcer covered by a crust.
  • Heals spontaneously within $6\text{--}12\,\text{weeks}$, leaving a permanent, tiny, round scar of $4\text{--}8\,\text{mm}$.
  • Recipient becomes Mantoux positive in $8\,\text{weeks}$.
  • Adverse Reactions: Local ulceration, discharging sinus, axillary lymphadenitis, disseminated infection, osteomyelitis.
  • Contraindications: Cellular immunodeficiency, symptomatic HIV infection.
  • Storage Conditions: Store at $2\text{--}8\,^\circ\text{C}$; sensitive to heat and light; discard unused reconstituted vaccine after $4\,\text{hours}$.

• Poliomyelitis Vaccines:

  • Oral Polio Vaccine (OPV):
  • Dose & Route: 2 drops; Oral.
  • Adverse Reactions: Vaccine-derived poliovirus.
  • Contraindications: Inherited or acquired immunodeficiency, symptomatic HIV infection.
  • Storage: Store at $2\text{--}8\,^\circ\text{C}$; sensitive to heat; utilize Vaccine Vial Monitor (VVM).
  • Inactivated Polio Vaccine (IPV):
  • Dose & Route: $0.5\,\text{ml}$; Intramuscular (IM) or Subcutaneous (SC).
  • Adverse Reactions: Local pain, swelling.
  • Contraindications: Known allergy to vaccine components.
  • Storage: Store at $2\text{--}8\,^\circ\text{C}$; sensitive to light.

• DPT Vaccine (Diphtheria Toxoid, Tetanus Toxoid & Killed Whole Cell or Acellular Pertussis):

  • Dose, Route, Site: $0.5\,\text{ml}$; IM; anterolateral aspect of mid-thigh.
  • Adverse Reactions: Local pain, swelling, fever.
  • Absolute Contraindications: Progressive neurological disease, anaphylaxis after a previous dose, encephalopathy within $7\,\text{days}$ of a previous dose.
  • Precautions (Re-evaluate if previous dose caused):
  1. Fever $> 40.5\,^\circ\text{C}$ within $48\,\text{hours}$
  2. Collapse within $48\,\text{hours}$
  3. Persistent inconsolable crying for more than $3\,\text{hours}$ within $48\,\text{hours}$
  4. Seizures within $72\,\text{hours}$
  • Storage: Store at $2\text{--}8\,^\circ\text{C}$; sensitive to light.

• Measles Vaccine:

  • Dose, Route, Site: $0.5\,\text{ml}$; SC; right upper arm or anterolateral thigh.
  • Adverse Reactions: Fever, transient macular rash $5\text{--}10\,\text{days}$ later.
  • Absolute Contraindications:
  1. Immunosuppressive therapy (e.g., alkylating agents, high-dose corticosteroids)
  2. Malignancy
  3. Immunodeficiency (e.g., advanced HIV)
  4. Untreated tuberculosis (TB)
  • Storage: Store at $2\text{--}8\,^\circ\text{C}$; sensitive to heat and light; use within $4\text{--}6\,\text{hours}$ of reconstitution.

• Measles, Mumps, Rubella (MMR) Vaccine:

  • Dose, Route, Site: $0.5\,\text{ml}$; SC; right upper arm or anterolateral thigh.
  • Adverse Reactions: Fever, transient rash, arthralgia, aseptic meningitis, lymphadenopathy.
  • Absolute Contraindications:
  1. Immunosuppressive therapy (e.g., alkylating agents, high-dose corticosteroids)
  2. Malignancy
  3. Severe immunodeficiency (e.g., advanced HIV)
  4. Untreated tuberculosis (TB)

• Hepatitis B Vaccine:

  • Dose, Route, Site: $0.5\,\text{ml}$; IM; anterolateral thigh (gluteal region must be avoided).
  • Dosing Schedule: Birth, $6\,\text{weeks}$, and $6\,\text{months}$.
  • Interval Rules:
  • Doses 1 and 2 must be $\ge 4\,\text{weeks}$ apart.
  • Doses 2 and 3 must be $\ge 8\,\text{weeks}$ apart.
  • Final dose must be given at $\ge 6\,\text{months}$ of age AND $\ge 16\,\text{weeks}$ beyond the 1st dose.
  • Adverse Reactions: Local soreness, fever, fatigue.
  • Contraindications: Anaphylaxis after a previous dose.
  • Storage: Store at $2\text{--}8\,^\circ\text{C}$; do not freeze.

• Rotavirus Vaccine:

  • Dose Formulations & Route:
  • RV1: $1\,\text{ml}$ (lyophilized) or $1.5\,\text{ml}$ (liquid); Oral.
  • RV5: $2\,\text{ml}$ (liquid); Oral.
  • Dosing Schedule:
  • RV1: 2-dose series.
  • RV5: 3-dose series.
  • Administered at $6\text{--}14\,\text{weeks}$ of age, with doses $\ge 4\,\text{weeks}$ apart; observe maximum age limit.
  • Adverse Reactions: Intussusception.
  • Contraindications: History of intussusception, severe immunodeficiency.
  • Precautions: Postpone vaccination during ongoing diarrhea or moderate illness.
  • Storage: Store at $2\text{--}8\,^\circ\text{C}$; do not freeze; protect from light; use immediately after reconstitution or opening.

Axiom of Preventive Medicine

• Hippocrates: "The greatest medicine of all is teaching people how not to need it."