36  Childhood Immunization

36.1 Introduction

Childhood immunization is a cornerstone of public health, offering lifesaving protection against infectious diseases. It is one of the most cost-effective strategies for reducing morbidity and mortality in children worldwide. Immunization is vital in achieving Sustainable Development Goal (SDG) 3, which aims to reduce neonatal mortality to 12 per 1000 live births and under-five mortality to 25 per 1000 live births by 2030. Despite its effectiveness, challenges such as parental misconceptions, healthcare accessibility, vaccine hesitancy, and logistical issues persist.

36.2 Key Immunization Concepts

• Immunization: The process of artificially conferring immunity against infectious diseases.
• Vaccination: The act of introducing an antigenic material into the body to stimulate an immune response, leading to future protection upon exposure.
• Vaccine: A biological preparation that enhances active acquired immunity against specific pathogens. Vaccines can be live-attenuated, inactivated, subunit, toxoid-based, or nucleic acid-based.

36.3 Types of Vaccines

Vaccines are classified based on their composition and mechanism:

1. Live Attenuated Vaccines: Contain weakened pathogens (e.g., Measles, Mumps, Rubella, BCG, Yellow Fever, OPV).
2. Killed/Inactivated Vaccines: Pathogens are killed but retain their immunogenic properties (e.g., Hepatitis A, Rabies, IPV).
3. Toxoid-Based Vaccines: Contain inactivated toxins to generate immunity (e.g., Tetanus, Diphtheria).
4. Subunit/Conjugate Vaccines: Use fragments of pathogens for immunity (e.g., Pneumococcal, Hib, Hepatitis B).
5. Nucleic Acid-Based Vaccines: Utilize mRNA or DNA to instruct cells to produce an immune response (e.g., SARS-CoV-2 vaccines).

36.4 Expanded Programme on Immunization (EPI) in Ghana

Ghana’s routine immunization schedule includes:

• Birth: BCG, OPV (0)
• 6 Weeks: Pentavalent (DTwP/HepB/Hib), OPV (1), PCV (1), Rotavirus (1)
• 10 Weeks: Pentavalent (2), OPV (2), PCV (2), Rotavirus (2)
• 14 Weeks: Pentavalent (3), OPV (3), IPV, PCV (3), Rotavirus (3)
• 6-7 Months: RTS,S (Malaria vaccine)
• 9 Months: Measles-Rubella (MR), Yellow Fever, RTS,S (3)
• 18 Months: MR Booster, Meningococcal A, RTS,S (4)
• Adolescents: HPV vaccine for girls aged 10-13.

36.5 Principles of Immunization

• Herd Immunity: High vaccination coverage reduces disease transmission.
• Cold Chain Management: Essential for vaccine potency.
• Missed Opportunities: Ensuring timely vaccination enhances community protection.
• Vaccine Safety: Strict protocols ensure vaccines are safe and effective.

36.6 Contraindications to Vaccination

While vaccines are generally safe, contraindications exist:

• Live vaccines should be avoided in immunocompromised individuals.
• Severe allergic reactions (anaphylaxis) to vaccine components.
• Pregnancy – Certain live vaccines (e.g., Yellow Fever, Measles) are contraindicated.

36.7 Vaccine-Preventable Diseases & Control Programs

Immunization programs target several infectious diseases:

• Tuberculosis (BCG): Protects against severe TB forms in infants.
• Polio: Eradication efforts involve IPV and OPV.
• Pneumococcal Disease (PCV13): Prevents pneumonia, meningitis.
• Rotavirus: Reduces childhood diarrheal deaths.
• Measles, Rubella, Mumps (MR/MMR): Prevents severe complications.
• Meningococcal Disease (Men A): Prevents outbreaks.
• Yellow Fever: Essential for endemic regions.
• HPV: Prevents cervical cancer.

36.8 Challenges & Future Directions

• Vaccine Hesitancy: Addressing misinformation.
• New Vaccine Development: Ongoing innovations like mRNA vaccines.
• Policy & Surveillance: Strengthening disease monitoring to prevent outbreaks.

36.9 Specific vaccines

36.9.1 BCG Vaccine (Tuberculosis)

• Pathogen: Mycobacterium tuberculosis or M. bovis (Non-sporing, rod-shaped, acid-fast bacillus)
• Type: Live attenuated, freeze-dried
• Storage: 2°C - 8°C (Never frozen)
• Administration: Intradermal (deltoid)
• Shelf Life: 12 - 18 months
• Usage: Do not shake to mix; use within 2 hours
• Efficacy:
  • 0–80% for Pulmonary TB (PTB)
  • 75–86% for Miliary TB & TB Meningitis
• Indications:
  • Infants, health personnel, and contacts with sputum-positive cases.
  • Suspected exposure? Perform a tuberculin test before immunization.
  • In cases of contact: Tuberculin test, repeat after 6 months. If positive ⇒ Chemoprophylaxis.
• Notes:
  • Duration of immunity is uncertain; it wanes over time.
  • Protects children against meningitis & disseminated TB but does not prevent primary infection or reactivation.
  • Scar confirms vaccination but not protection. Absence of a scar may indicate the need for testing and revaccination.
  • Up to 10% scar failure rate is acceptable in properly vaccinated individuals.
  • Tuberculin test: Uses Purified Protein Derivative (PPD) for Mantoux/Heaf test.

36.9.2 Polio Vaccines

• Pathogen: Poliovirus Types I, II, III.
• Adults: More prone to inapparent paralytic infections.
• Virus Survival: Inactivated at 55°C for 30 minutes (but inhibited by Mg++, milk, ice cream)
• Types of Vaccines:
  • Inactivated Polio Vaccine (IPV) – Salk (1956)
  • Live Attenuated Oral Polio Vaccine (OPV) – Sabin (1962)
  • Variants:
  • tOPV (Trivalent OPV): Contains live strains of all three virus types.
  • bOPV (Bivalent OPV): Contains live strains of Types I & III.
  • nOPV (Novel OPV): A modified strain of Type II with enhanced stability.
• Efficacy:
  • 90% in industrialized nations.
  • 72–98% in hot climates (lower protection against Type III).
• Duration of Immunity:
  • Lifelong if boosted by wild virus, otherwise shorter.
• Vaccine-Associated Paralytic Poliomyelitis (VAPP):
• Polio Type II in tOPV linked to VAPP, undermining eradication efforts.
• Solution: Withdraw Type II from OPV ⇒ Introduce bOPV + at least one IPV dose in routine schedules.
• Ghana (since June 2018): bOPV + IPV at 14 weeks.
• nOPV introduced as a more antigenically stable next-gen Type II vaccine.

36.9.3 Pentavalent Vaccine (“PENTA”)

• Components: Diphtheria, Whole-cell Pertussis, Hepatitis B, Hib (Haemophilus influenzae type
• Introduced: 2001; used in Ghana since March 2002.
• Storage:
  • Liquid DPT-HepB: Refrigerated at 2°C - 8°C (not frozen).
  • Lyophilized Hib: Stored at -20°C or refrigerated at +2 - 8°C.
• Preservation: Contains preservatives, allowing reconstitution for extended use.

36.9.4 Tetanus Vaccine

• Pathogen: Clostridium tetani (Toxin-producing)
• Vaccine Type: Toxoid (inactivated toxin)
• Schedule:
  • Children & Adults: 3 doses (one month apart); reinforced every 10 years with two doses for lifelong immunity.
  • Boosters: Recommended at time of injury.
  • Maternal immunization: Protects against neonatal tetanus.

36.9.5 Hepatitis B Vaccine

• Pathogen: Hepadnavirus (Double-stranded DNA virus)
• Carrier Rate: 2 - 10% (higher in perinatal infections).
• Transmission: Highly infectious among carriers with HBeAg.
• Vaccine:
  • HBsAg adsorbed onto alum (adjuvant).
  • Produced via recombinant DNA in yeast cells.
• Pre-exposure Immunization
  • Universal infant immunization.
  • Catch-up vaccination for adolescents.
  • Healthcare workers, hemodialysis patients, blood recipients, drug abusers, transplant candidates.
• Post-exposure Prophylaxis:
  • HBIG (Hepatitis B Immunoglobulin): Provides passive immunity (3-6 months).
  • Best protection: HBIG + Hep B vaccine within 24 hours after exposure.
  • Routine infant vaccination: HB vaccine alone is sufficient.
  • Not needed for pre-transfusion prophylaxis due to modern blood screening.

36.9.6 Yellow Fever Vaccine

• Pathogen: Flavivirus (RNA virus); spread by Aedes aegypti mosquitoes.
• Vaccine: Live attenuated, freeze-dried (17D strain, grown in chick embryo).
• Contains: Neomycin, polymyxin.
• Contraindications: Allergy to components.

36.9.7 Measles-Rubella (MR) & MMR Vaccine

• Viruses:
  • Measles, Mumps (Paramyxoviruses, RNA)
  • Rubella (Togavirus, single-stranded RNA)
• Purpose: Prevent congenital rubella infection.
• Variants
  • MR (Measles-Rubella) – Used in Ghana.
  • MMR (Measles-Mumps-Rubella).
• Presentation: Freeze-dried.
• Administration: Subcutaneous injection.

36.9.8 Pneumococcal Disease & Vaccines

• Pathogen: Streptococcus pneumoniae (Gram-positive diplococcus).
• Common Diseases:
  • Non-Invasive: Otitis media, sinusitis, bronchitis.
  • Invasive (IPD): Pneumonia, Bacteraemia, Meningitis.

• Vaccines

  • Polysaccharide (PPV23): Short-lived immunity, recommended for high-risk individuals ≥2 years.
  • Conjugate (PCV13): Provides longer-lasting immunity and is effective against pneumonia. Ghana uses PCV13 (“Prevenar”)

36.9.9 Rotavirus Vaccine

• Disease Impact: Severe diarrheal illness in young children; major cause of dehydration.
• Transmission: Ubiquitous (water and sanitation improvements do not prevent infection).
• Vaccine Options in Ghana:
• Rotavac (May 2021): 3 doses (6, 10, 14 weeks).
• Rotarix (GSK): Monovalent, given orally in two doses (by 16 weeks, no later than 24 weeks).
• Rotateq: Bovine-human reassortant vaccine; three doses at 2, 4, 6 months.
• RotaShield (Wyeth): Withdrawn due to risk of intussusception.

36.9.10 Human Papillomavirus (HPV) Vaccine

• Virus Type: Small, double-stranded DNA virus.
• High-Risk Oncogenic Strains: Types 16 & 18 (cause 70% of cervical cancers).
• Vaccines:
  • Quadrivalent (HPV 6, 11, 16, 18) – Produced in yeast.
  • Bivalent (HPV 16, 18).
• Target Age Group: 10-13-year-old girls (not a standard vaccination group).
• Catch-up Vaccination: Not recommended in public health programs.

36.9.11 Malaria Vaccines and Immunization Strategy

Malaria remains a significant global health challenge, particularly in endemic regions. The Plasmodium falciparum life cycle involves two distinct stages:

1. Asexual Stage (Human Host) – Sporozoites enter the bloodstream through mosquito bites, travel to the liver, and mature into merozoites before infecting red blood cells.
2. Sexual Stage (Mosquito Vector) – Gametocytes ingested by mosquitoes undergo development, enabling transmission.

RTS,S/AS01 Malaria Vaccine

The RTS,S/AS01 malaria vaccine provides partial protection against Plasmodium falciparum infection.

• Mechanism of Action:
  • Induces antibody production to block sporozoite entry into liver cells.
  • Activates T-cell responses to eliminate sporozoites that reach the liver.
• Administration:

  • Four-dose series:

    • 1st dose at 5 months (not recommended for infants
    • 2nd and 3rd doses administered at 4-week intervals.
    • 4th dose given between 15–18 months

  • Can be co-administered with other vaccines in national immunization programs

• Efficacy: Less than 50%, but beneficial for reducing severe cases and mortality.
• Recommendations: Targeted for high-malaria-burden African countries with existing control programs.

36.9.12 Rabies Vaccines and Post-Exposure Prophylaxis

Rabies is a fatal viral zoonosis transmitted through the bite of infected animals (mainly carnivores and bats).

• Disease Determinants:
  • Severity of wound and viral inoculation.
  • Proximity of bite to central nervous system (higher risk if near head).
  • Timeliness of post-exposure prophylaxis (PEP).
• Rabies Virus (RABV) Presence in Humans:
  • Found in saliva, tears, urine, and nervous tissues.
  • Not detected in blood.
• Incubation Period: 1-3 months, but may extend up to 1 year

Post-Exposure Prophylaxis (PEP)

• Immediate wound cleansing.
• Rabies vaccine series initiation.
• Rabies immunoglobulin (Rabies IG) infiltration around the wound (if indicated).

Rabies Vaccine Types

• Cell Culture or Embryonated Egg Vaccines (CCEECV):
  • Live attenuated, freeze-dried (propagated in human diploid or chick embryo).
  • Administered intramuscularly (IM) or intradermally (ID) on Days 0, 3, 7, 14, and 28.
  • Preferred site of administration: Deltoid (adults) or anterolateral thigh (children)
• Nerve Tissue Vaccines (NTV) (Obsolete):
• Derived from animal brain tissue.
• Associated with Guillain-Barré Syndrome, encephalitis.
• Not recommended by WHO.

Note: Chloroquine prophylaxis suppresses rabies vaccine antibody response, particularly when given intradermally.

36.9.13 Influenza and COVID-19 Vaccines

36.9.13.1 Influenza Virus and Vaccine Development

Influenza viruses undergo continuous genetic variations, requiring annual vaccine updates.

• Antigenic Drift – Small mutations producing minor variants (Influenza A, B) → epidemics.
• Antigenic Shift – Major genetic reassortments (Influenza A only) → pandemics.

36.9.13.2 COVID-19 Vaccine Technologies

• Inactivated or Weakened Virus – Uses killed virus components.
• Protein-Based Vaccines – Uses harmless protein fragments to generate immunity.
• Viral Vector Vaccines – Genetically engineered virus produces spike proteins.
• RNA/DNA Vaccines – Uses mRNA/DNA encoding spike proteins (e.g., Moderna, Pfizer).

36.10 Vaccine Reactions and Adverse Events Following Immunization (AEFI)

36.10.1 Minor Vaccine Reactions

• Common reactions occur as part of the immune response:
  • Fever, injection-site swelling/pain, malaise.
  • Most frequent with DPT vaccines.
  • Symptoms self-resolve.
• Parents should be educated on symptom management.

36.10.2 Severe Reactions (Rare)

• Anaphylaxis (1 per million doses) – Requires urgent medical intervention (e.g., adrenaline).
• BCG Osteitis – Rare, vaccine-specific reaction.
• Vaccine-Induced Fainting – Common in adolescents, often misinterpreted as anaphylaxis.

36.10.3 AEFI Classification

1. Vaccine Reaction – Direct response to vaccine components.
2. Program Error – Due to improper vaccine handling/administration
3. Coincidental – Occurs post-immunization but is unrelated to vaccination.
4. Injection Reaction – Pain/anxiety linked to the injection process.
5. Unknown Cause – Unresolved cases

36.11 Vaccine Storage and Multidose Vial Policy

• Cold Chain Maintenance: Essential for vaccine efficacy and stability.
• Heat Sensitivity:
  • BCG, Measles, Polio can be frozen.
  • Diluent-containing vaccines (DPT, TT, HepB) must NOT be frozen.
  • Frozen vaccines may cause reduced immune response
• Shelf Life: Max 2 years under ideal storage.
• Vaccine Vial Monitors (VVM):
• Monitor vaccine exposure to heat.
• Discard if VVM reaches critical stages.

36.11.1 Multidose Vial Policy (Current Guidelines)

• Vaccines usable for up to 4 weeks if:
  • Stored at 2–8°C.
  • Aseptic techniques are used for administration.
  • VVM remains intact.
• Reconstituted vaccines (BCG, Measles, Yellow Fever):
• Must be discarded after 6 hours or at the end of the session.

Contraindications to Vaccination

• Live vaccines contraindicated in:
  • Immunocompromised individuals (HIV, malignancies).
  • Pregnant women (risk of teratogenicity).
  • Neurological disorders (avoid DPT in uncontrolled epilepsy).
• Egg allergy: Avoid Yellow Fever, Influenza, but alternative fibroblast-derived vaccines may be used.

36.12 Vaccination in Special Populations

36.12.1 Preterm Infant Immunization

• Immunization response similar to term infants.
• Start immunization at 2 months, irrespective of prematurity.
• OPV delayed until discharge (reduces nursery transmission risks).

36.12.2 Adolescent Immunization

• HPV vaccine for girls aged 10–13.
• Booster doses for waning childhood immunity (e.g., Tetanus).
• Catch-up vaccination for missed/incomplete schedules.

36.12.3 Pregnancy and Vaccination

• Live viral vaccines generally avoided due to potential fetal risks.
• Tdap recommended in the third trimester to protect against pertussis.

36.13 Conclusion

Immunization remains a cornerstone of preventive healthcare, reducing the infectious disease burden globally. Maintaining vaccine quality, storage protocols, and surveillance systems enhances safety and efficacy. Addressing vaccine hesitancy, logistical challenges, and misinformation remains crucial for improving immunization coverage. Future advancements, including next-generation vaccines, aim to strengthen global disease prevention efforts. This detailed narrative is tailored for a professional audience and integrates key immunization strategies, vaccine science, and best practices in public health. Let me know if you need further elaboration on any aspect!

References

1. https://www.who.int/teams/immunization-vaccines-and-biologicals/policies/position-papers
2. WHO Vaccine safety course: www.vaccine-safety-training.org
3. Immunization in Practice
4. Pollard AJ, Bijker EM. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol. 2021 Feb;21(2):83-100. doi: 10.1038/s41577-020-00479-7. Epub 2020 Dec 22.PMID: 33353987
5. Bangura JB, Xiao S, Qiu D, Ouyang F, Chen L. Barriers to childhood immunization in sub-Saharan Africa: A systematic review. BMC Public Health. 2020 Jul 14;20(1):1108. doi: 10.1186/s12889-020-09169-4.

36.14 Practical work

36.14.1 Question

A 4-month-old baby is presented with fever, cough, and rhinorrhoea of 2 days duration. O/E:  Active, healthy-looking child with occasional smiles; axillary temp 37.8 °C.  The baby is treated for the common cold.  Baby has no scar over the Left deltoid area and on enquiry has visited the immunization clinic two times since birth, but has misplaced the weighing card.

• Which vaccinations will the child require at that age?
• Which vaccinations are contraindicated?
• Which ones should the child receive before going home?
• When should the child be returned for follow-up vaccinations? And for which vaccines?
• What if the baby’s mother is HIV-positive?
• What if there is a parental history of SCD?

36.14.2 Answers

The baby should have received several routine vaccinations at four months old according to Ghana’s Expanded Programme on Immunisation (EPI). Based on the standard schedule, the following vaccines are typically required at this age:

Vaccinations Required at Four Months

• Oral Polio Vaccine (OPV) – Third dose
• Pentavalent Vaccine (DPT/HiB/HepB) – Third dose (protects against diphtheria, pertussis, tetanus, Haemophilus influenzae type B, and hepatitis B)
• Pneumococcal Conjugate Vaccine (PCV) – Third dose
• Rotavirus Vaccine – Second dose

Contraindicated Vaccines

• Live vaccines such as BCG (for tuberculosis) and Measles-Rubella (MR) may be contraindicated if the child has certain immunodeficiencies, such as HIV/AIDS, or other medical conditions. However, specific contraindications should be assessed by a healthcare provider.

Vaccines to Receive Before Going Home

• Since the baby has visited the immunization clinic only twice and has no visible BCG scar, verifying which vaccines have been missed is crucial. Before discharge, the baby should receive any missed doses of the routine vaccines, particularly BCG if it was not previously administered.

Follow-up Vaccinations and Schedule

The baby should return for the next scheduled vaccinations:

• At 6 months – Vitamin A supplementation
• At 9 months – Measles-Rubella (MR) and Yellow Fever vaccines
• At 12 months – Meningococcal vaccine (Men A) and second dose of Measles-Rubella (MR)

Considerations for Special Cases

• If the mother is HIV-positive: The baby may require additional monitoring and possible adjustments to the vaccination schedule. BCG may be contraindicated if the baby is symptomatic or severely immunocompromised.
• If there is a parental history of Sickle Cell Disease (SCD): The baby should be screened for sickle cell status. Additional precautions may be needed if diagnosed with SCD, including early pneumococcal and meningococcal vaccines to prevent infections.