Coryza

Infection, Immunity, and Immunizations in Pediatrics

Epidemiology & Related Fields

• Encompasses public health, respiratory health, international health, vaccination, drug design, resistance, microbiology, virology, antibiotic & antiviral strategies, and understanding the microbiome.

Clinical Specialties Involved

• Includes endocrinology, neurology, gastroenterology, cardiology, autoimmunity, autoinflammation (PMIS-TS, Kawasaki disease), immunodeficiency & dysregulation, malignancy, genetics, and allergic disease.

Focus Areas

• Common infections in children.
• Appropriate antibiotic use and misuse.
• Distinguishing between infection and inflammation.
• Identifying the seriously ill child.
• Understanding primary immune deficiencies.
• The role and impact of immunizations.
• Managing imported infections.
• Addressing congenital infections.

Common Infections in Children

• Infections are a leading cause of hospital admissions for children.
• Younger children are generally more susceptible than older children.
• The respiratory tract is the most common site of infection.
• Treatment may involve antibiotics or antivirals, but often includes supportive care like oxygen and fluids.
• Rapid diagnostic tests are limited, so treatment decisions rely on clinical assessment.
• Knowing the likely bacterial cause is crucial for effective antibiotic selection.
• Mild viral infections can mimic serious bacterial infections.
• Viral illnesses can also be severe and should not be underestimated.
• Co-infections (both viral and bacterial) can occur.

Viral and Bacterial Infection Association with Invasive Disease

• The graphs presented show the correlation between viral infections (like influenza and RSV) and the incidence of pneumococcal pneumonia.
• The data suggests that viral infections can increase the risk of secondary bacterial infections.

Global Burden of Influenza in Children Under 5

• Lancet 2020 study by Nair, H et al.
• In 2018, there were an estimated 109.5 million (63.1-190.6 million) influenza episodes in children under 5.
• Influenza is attributable to 870,000 ALRI (Acute Lower Respiratory Infection) hospital admissions.
• Influenza is attributable to 15,000 ALRI-related deaths.
• Hospital admission and mortality rates have improved since 2008 due to the rollout of the pneumococcal conjugate vaccine.
• Influenza can lead to primary viral pneumonitis, co-infection with other viruses or bacteria, and secondary bacterial infections (e.g., chest, ear, brain).

Global Impact of RSV in Children Under 5

• Lancet Gill May 2022 study.
• 33 million RSV lower respiratory tract infections (LRTI).
• 3.6 million RSV hospitalizations.
• 457,000 RSV-attributable deaths, with 97% occurring in low and middle-income countries.
• Both RSV and influenza are associated with secondary bacterial infections.
• Immunization against influenza and pneumococcus has an impact on hospital admissions.
• Children serve as a source of infection for adults.
• Passive immunization with RSV antibodies is being explored for all infants, not just high-risk groups.
• Immunization during pregnancy can protect both the mother and young infants from RSV.
• JCVI (Joint Committee on Vaccination and Immunisation) in the UK recommended one or both RSV immunization options in September 2023, pending economic analysis.

Upper Respiratory Infections

• Epiglottitis
• Croup
• Bronchiolitis

Specific Respiratory Infections and Causative Agents

• Pharyngitis/Tonsillitis:
  • Group A Streptococcus (Strep)
  • Adenovirus
  • Epstein-Barr Virus (EBV)
• Epiglottitis:
  • Haemophilus influenzae type b (Hib)
• Otitis Media:
  • Pneumococcus
  • Haemophilus influenzae
  • Group A Strep
  • Moraxella catarrhalis
• Croup:
  • Parainfluenza virus (Para flu) + others
• Tracheitis:
  • Staphylococcus aureus (S. aureus)
  • Group A Strep
• Pneumonia:
  • Group A Strep
  • Pneumococcus
  • S. aureus
  • Haemophilus influenzae (non-b)
  • Tuberculosis (TB)
• Atypical Pneumonia:
  • Mycoplasma pneumoniae
  • Chlamydia pneumoniae
• Bronchiolitis:
  • Respiratory Syncytial Virus (RSV)
  • Rhinovirus
  • Influenza virus (Flu)
  • Adenovirus
  • Parainfluenza virus (Paraflu)
  • Human Metapneumovirus

Antibiotic Use and Considerations

• Choose the most appropriate antibiotic,
• Use narrow-spectrum antibiotics when possible to minimize resistance.
• Obtain microbiological and virological samples to guide and refine treatment.
• Clearly document your treatment plan, including the suspected infection.
• Adhere to local antibiotic guidelines.
• Implement infection control measures.
• Follow the "Start Smart then Focus" approach (PHE/UK.gov).
• Consider the economic impact of antimicrobial resistance (Jim O'Neil, May 2016).

Antimicrobial Stewardship

• Treatment Algorithm:

  • Start Smart, Then Focus
  • Do not start antibiotics without clinical evidence of bacterial infection.
  • Clinical review and decision at 48-72 hours.

• Start Smart:

  1. Take a thorough drug allergy history.
  2. Initiate prompt, effective antibiotic treatment within one hour of diagnosis for severe sepsis or life-threatening infections.
  3. Comply with local antimicrobial prescribing guidance.
  4. Document clinical indication, disease severity, dose, and route of administration on the drug chart and in clinical notes.
  5. Include a review/stop date or duration.
  6. Obtain cultures before starting therapy when possible (but do not delay therapy).

• Then Focus:

  1. Stop antibiotics if indicated.
  2. Switch from IV to oral antibiotics when appropriate.
  3. Change antibiotic based on review and microbiology results.
  4. Continue antibiotics if necessary.
  5. Consider OPAT (Outpatient Parenteral Antibiotic Therapy).

• Document all decisions.

• Refer to local formulary or BNFC (British National Formulary for Children) for weight/age-appropriate dosing.

Antimicrobial Resistance

• Antimicrobial resistance is a significant global public health risk, driven by antibiotic misuse.
• Few new antibiotic classes have been identified since the early 2000s.

Challenges with New Antimicrobials in Children

• Tolerability, formulation, toxicity, and pharmacokinetics of drugs can differ in children.
• Studies in children are more difficult to conduct.
• Pediatric access to new drugs may lag behind adult availability by up to 10 years.
• There is a need for parallel pediatric trials.

VZV & Other Infections

• Varicella-Zoster Virus (VZV) infection is usually self-limiting but can have mortality if there is secondary infection with Staph or Strep.
• Significant national increase in VZV & Group A Strep infections in 2022-23.
• Differentiate impetigo (Staph/Strep) from HSV stomatitis . HSV can be severe if eczema is present, sometimes causing encephalitis.
• Enterovirus may mimic hand, foot, and mouth disease.
• Other conditions include Meningococcal sepsis, HSP (Henoch-Schönlein Purpura), and Kawasaki disease (KD).
• Kawasaki disease can lead to coronary artery aneurysms if untreated, resulting in long-term cardiac disease risk.

Kawasaki Disease (KD) and Similar Conditions

• Kawasaki disease was clinically described in 1967.
• Differential diagnosis includes PIMS-TS/MIS-C, adenovirus infection, measles, and Group A Strep infections.
• Diagnostic criteria involve typical features present for 5 days with fever.
• Treatment includes ECHO (Echocardiogram), IVIG (Intravenous Immunoglobulin), Aspirin, and possibly steroids.
• Incomplete/atypical KD presents with fewer typical features and requires additional laboratory findings.
• KD is more common in infants.

PIMS-TS/MIS-C and COVID-19

• PIMS-TS (Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2) / MIS-C (Multisystem Inflammatory Syndrome in Children) is a KD-like inflammatory disease associated with myocardial dysfunction.
• Seen in initial COVID waves but no longer as prevalent.
• Diagnostic tests for SARS-CoV-2 include PCR and antibody detection.
• PCR is likely positive early in the illness but may become negative later.
• Antibody detection increases over time.

Fever Dilemmas

• Fever poses diagnostic and management challenges.
• Antimicrobial stewardship is crucial.
• Limited hospital beds can complicate management.
• Important to consult NICE (National Institute for Health and Care Excellence) guidelines on sepsis, the febrile child, Kawasaki disease, HLH/MAS (Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome), JIA/autoimmunity (Juvenile Idiopathic Arthritis), malignancy, travel-related illnesses, PIMS-TS/MISC, Toxic shock syndrome, and Meningitis/sepsis.

Key NICE Guidance Documents

• Feverish illness in children.
• Bacterial meningitis & meningococcal septicaemia.
• Sepsis.
• Antimicrobial prescribing for common infections.
• Antimicrobial stewardship.
• Urinary tract infection in children.
• Diarrhoea and vomiting illness in children.
• Early neonatal infection.
• TB.
• Also, refer to BSAC.org (British Society for Antimicrobial Chemotherapy) pediatric pathways.

Sepsis

• Defined as an "overwhelming life-threatening response to an infection resulting in tissue damage, organ failure, and death."
• Characterized by the body’s overactive toxic response to infection.
• Management involves the UK Sepsis 6 bundle/ NICE Sepsis guidelines:
  • Prompt antibiotic treatment.
  • Oxygen administration.
  • Fluid resuscitation.

NICE Traffic Light System for Identifying Risk of Serious Illness

• A traffic light system is used to categorize risk based on clinical signs.

• Green (Low Risk):

  • Normal skin colour.
  • Responds normally to social cues.
  • Content/smiles.
  • Stays awake or awakens quickly.
  • Strong, normal cry/not crying.
  • Normal skin and eyes.
  • Moist mucous membranes.
  • Absence of amber or red symptoms/signs.

• Amber (Intermediate Risk):

  • Pallor reported by parent/carer.
  • Not responding normally to social cues.
  • No smile.
  • Wakes only with prolonged stimulation.
  • Decreased activity.
  • Nasal flaring.
  • Tachypnoea (RR >50 breaths/minute for ages 6-12 months; RR >40 breaths/minute for ages >12 months).
  • Oxygen saturation $≤95$ in air.
  • Crackles in the chest.
  • Tachycardia (>160 beats/minute for age
  • Capillary refill time (CRT) $≥3$ seconds.
  • Dry mucous membranes.
  • Poor feeding in infants.
  • Reduced urine output.
  • Age 3-6 months with temperature $≥39°C$.
  • Fever for $≥5$ days.
  • Rigors.
  • Swelling of a limb or joint.
  • Non-weight-bearing limb/not using an extremity.

• Red (High Risk):

  • No response to social cues.
  • Appears ill to a healthcare professional.
  • Does not wake or, if roused, does not stay awake.
  • Weak, high-pitched, or continuous cry.
  • Grunting.
  • Tachypnoea (RR >60 breaths/minute).
  • Moderate or severe chest indrawing.
  • Reduced skin turgor.
  • Age <3 months with temperature $≥38°C$.
  • Non-blanching rash.
  • Bulging fontanelle.
  • Neck stiffness.
  • Status epilepticus.
  • Focal neurological signs.
  • Focal seizures.

Investigations Based on Risk

• Under 3 months:

  • FBC (Full Blood Count).
  • Blood culture.
  • CRP (C-reactive protein).
  • Urine culture.
  • Other investigations as indicated.

• Under 1 month:

  • As above, plus Lumbar puncture (LP).

• 1-3 months:

  • LP if unwell or WBC
  • IV antibiotics for all infants under 1 month and those 1-3 months if unwell or WBC

• Child over 3 months with Red features:

  • FBC.
  • Blood culture.
  • CRP.
  • Urine culture.
  • LP if clinical features or unwell.
  • CXR (Chest X-ray) if clinical features.

• Amber features:

  • As for red unless experienced pediatrician reviews.
  • CXR if WBC >20 and temp >39.

• Green features:

  • Urine test.
  • No blood tests.

Screening Tools in Febrile Children

• Waterfield et al. Arch Dis Child 2022 reviewed screening tools in febrile children < 90 days in A&E.
• Study involved 555 infants.
• 81% had blood tests, 76% received IV antibiotics.
• 5 cases of meningitis, 7 of bacteremia, 66 UTIs were identified.
• Sensitivity and specificity of NICE & BSAC pathways were reviewed.

Case Study 1: 2-Week-Old Infant

• 2-week-old infant.
• Fever for 24 hours at home.
• Not feeding well.
• Crying constantly when awake and waking less often for feeds.
• Temperature 38.5°C.
• Pale, cool peripheries.

Lab Results for Case Study 1

• WBC 4 (normal 5-10).
• Neutrophils 1.0 (low), lymphocytes 3.0 (normal).
• CRP 50.
• U&E normal.
• LFT deranged.

Lumbar Puncture and CSF Analysis

• Lumbar puncture is performed to obtain cerebrospinal fluid (CSF).
• CSF is analyzed for protein levels.
• CSF WBC 200.
• Glucose reduced.
• Protein elevated.

CSF Findings in Meningitis (NICE Guidelines)

• Bacterial Meningitis:

  • Raised cell count (neutrophils).
  • Raised protein.
  • Low glucose.
  • Bacteria identified in blood or CSF culture or PCR.

• Viral Meningitis:

  • Raised cell count (lymphocytes).
  • Normal protein.
  • Normal glucose.
  • Virus identified in CSF, stool, throat, or blood.

• HSV encephalitis is also considered.

Causes of Meningitis/Encephalitis

• • Group B Strep (GBS).
  • E. coli.
  • Listeria.
  • Pneumococcus.
  • Meningococcus.
  • Treatment: Cefotaxime (or ceftriaxone) & amoxicillin.

• Herpes simplex and Enterovirus also considered, treat with Aciclovir.

• Over 3 months:

  • Meningococcus.
  • Pneumococcus
  • Haemophilus influenzae (non-b).
  • Treatment: Cefotaxime / ceftriaxone.

• Herpes simplex and Enterovirus also considered, treat with Aciclovir.

Case Study 2: 8-Year-Old

• 8-year-old child.
• Cold the previous week.
• New fever.
• Complaining of headache before going to bed.
• Sleepy, confused when woken.
• Neck stiff when examined.
• Cool peripheries.
• Poor Capillary return.

Meningococcal Septicemia

• Caused by meningococcus, usually Group B in the UK.
• Group C previously common, Group A common in Africa/Middle East, with W&Y increasing in the UK.
• Serogroup is defined by the polysaccharide capsule of the organism, with no cross-protection between strains.
• May or may not have associated meningitis.
• Clinical presentation involves a rapid onset of septic shock.
• Management includes cefotaxime/ceftriaxone and early PICU admission.
• Septicemia with other organisms may mimic meningococcal disease.

Symptoms of Meningitis/Septicemia

• Meningitis:
  • Neck stiffness.
  • Sensitivity to light (not reliable in young children).
  • Drowsiness/irritability.
  • Vomiting.
  • Headache.
  • Full fontanelle.
• Septicemia:
  • Red/purple non-blanching rash.
  • Cold hands and feet.
  • Tachypnoea.
  • Flu-like symptoms.

Case Study 3: 4-Month-Old

• 4-month-old infant.
• No previous health problems.
• Recurrent cough and noisy breathing for the past 3 days.
• Mild indrawing, RR 60, nasal flaring, alert, well-perfused.
• Temperature 37.8°C.
• Bilateral crackles and wheezes.

Bronchiolitis Pathogens

• RSV (Respiratory Syncytial Virus).
• Paraflu (Parainfluenza Virus).
• Influenza A/B.
• Rhinovirus.
• Adenovirus.
• Human Metapneumovirus.
• Coronavirus ( various strains).

Case Study 4: 6-Week-Old Follow-Up

• 6 weeks later.
• Never really got better.
• Not feeding well.
• Clearly lost weight since last admission.
• RR 60.
• Widespread crackles & respiratory distress.
• Temperature 38.2°C.
• PICU team alerted.

Immunodeficiency

• WBC 4 (neutrophils 3.0, lymphocytes 1.0 (2.5-4)).
• CRP 23.
• Blood culture, urine culture no growth.
• Still RSV +ve and now para flu +ve.
• IgG 1.5 (2.5-6).
• IgA < 0.04.
• IgM <0.08(0.5 – 1.5).

Infant Immunity

• Normal Newborn infants makes IgM & some IgA, but most of their IgG is maternal.
• Maternal immunization can protect infants.

Pneumocystis Pneumonia

• Bronchial secretions may show PCP (pneumocystis pneumonia/jirovecii), an opportunistic infection.

Immune Deficiency

• Infection is common in children.
• Immune deficiency is rare.
• Severe Combined Immune Deficiency (SCID) occurs in approximately 1 in 50,000-60,000 births.
• SCID presents with severe disease in neonates/infants and is an immunological emergency.
• Presentations may not be solely infectious; look for failure to thrive, skin problems, chronic chest problems, organomegaly/adenopathy.
• Normal infant lymphocyte count is >2.5.
• Newborn screening for SCID involves TRECs (T-cell receptor excision circles) on neonatal dry blood spots, indicating thymic output, since September 2021.
• Genetic immune defects may present in older children/adults.

Immune System Components and Defects

• Cells:
  • Lymphocytes (IgG, A & M).
  • Neutrophils.
• Defects:
  • Inadequate cell number: X-linked agammaglobulinemia/SCID/congenital neutropenia.
  • Defect in cell function: chronic granulomatous disease, neutrophil function defect.
  • Defect in cytokine production/intracellular messaging.

Distribution of Primary Immunodeficiencies

• Antibody deficiencies are most common (65%).
• Combined cellular and antibody deficiencies (15%).
• Phagocytic cell deficiencies (10%).
• Cellular deficiencies (5%).
• Complement deficiencies (5%).

Presenting Symptoms of Immunodeficiencies

• Most common presenting symptom is infection without dysregulation (68.3%).
• Dysregulation without infection (8.9%).
• Infection and dysregulation (9.0%).
• Other symptoms (9.0%).
• Family history only (1.6%).
• Lab abnormalities only (3.3%).

How Antibodies Help

• Neutralization: Antibodies bind to and inactivate viruses and toxins, preventing them from infecting cells.
• Complement Recruitment: Antibody-antigen complexes activate the complement system, triggering antibacterial activity.
• Opsonization: Phagocytic cells grab antibodies bound to foreign substances, facilitating efficient phagocytosis.

T Cell and B Cell Cooperation

• T helper cells
• Macrophages
• B cells

Warning Signs of Primary Immunodeficiency

1. Four or more new ear infections within one year.
2. Two or more serious sinus infections within one year.
3. Two or more pneumonias within one year.
4. Two or more months on antibiotics with little effect.
5. Recurrent, deep skin or organ abscesses.
6. Persistent thrush in mouth or fungal infection on skin.
7. Failure of an infant to gain weight or grow normally.
8. Need for intravenous antibiotics to clear infections.
9. Two or more deep-seated infections, including septicemia.
10. A family history of PI.

Recognizing Primary Immune Deficiencies

• Patient-centered screening for primary immunodeficiency.
• Initial presenting manifestations in inborn errors of immunity include infections and noninfectious manifestations.
• Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert committee.

SCID and Newborn Screening

• Infants with SCID will be identified through Newborn screening with improved outcome from BMT.
• 8-week-old with underweight, hepatosplenomegaly, and severe eczema; T/B cell numbers often low/absent or occasionally normal.
• 8-month-old from a consanguineous family, sibling died at 4 weeks, cough for 2 months, poor weight gain; never had lymphocyte count > 1.5, IgG low, IgA absent, IgM low.

TRECs and Newborn Screening

• TREC’s (T Cell receptor excision circles) are DNA by-products of TCR gene rearrangements.
• Marker of thymic output of naive T cells.
• Numbers fall with Age.
• Measured on NBS blood spot.

US Experience with TREC Screening

• US Experience 2010-2013
• 11 programmes, > 3 million births
• 52 SCID, 1:58000 births
• 411 non SCID lymphopenia: Di George, Trisomy 21 CHARGE, Trisomy 18, Ataxia telangiectasia
• False positive more likely in preterm infants
• UK estimates annually: 266 false positive, 31 Lymphopenic not SCID, 17 SCIDs.
• Prevent 6.3 SCID deaths annually
• Neonatal BCG: plan to delay to 6 weeks

Who to Investigate for Immunodeficiency

• Frequent or unusually severe infections.
• Infection with unusual organism.
• Family history.
• Unusual inflammatory/autoimmune or malignancy phenotype.
• Low threshold in children with underlying syndromic/chromosomal problems with infection.

Tests for Immunodeficiency

• FBC: low total WBC, neutrophil, or lymphocytes.
• Total Ig GAM +/-E.
• Responses to routine immunisations.
• Lymphocyte subsets: numbers of T and B cells.
• Lymphocyte function.
• Genetic panels.

Treatment of Immunodeficiency

• Antibiotic / antiviral prophylaxis.
• Prompt treatment of infections.
• Replacement immunoglobulin (usually subcutaneous infusion at home weekly).
• Bone marrow transplant.
• Close Collaboration with other specialties: respiratory, rheumatology, gastroenterology, hematology, genetics.

How Vaccines Work

• Generate immune response: T (cell mediated) and B cells (antibody) for organism.
• Antibody against toxin.
• Induce immunological memory.
• Protein antigens = stronger stimulation.
• Antibodies (B cell memory): easily measured.
• Specific T cell memory (more difficult to measure).
• Herd immunity.
• Protective not harmful immune response.

Types of Immunity

• Passive immunity: HBIG, ,VZIG, Rabies Ig, HNIG RSV.
• Active:
  • Live attenuated : MMR, BCG, nasal flu, rotavirus.
  • Inactivated: whole cell pertussis.
  • Inactivated toxin: Diptheria, Tetanus.
  • Recombinant components: acellular pertussis.
  • Conjugate vaccine: Bacterial Polysaccharide+protein carrier.
  • Cell wall/ envelope components: Flu, MenB.
  • DNA /RNA vaccines *.
  • Viral vector / viral-like particles *.

Herd Immunity

• If no one's immunized, contagious diseases spread throughout the population.
• If some are immunized contagious disease spread through some of the population.
• If most of the population gets immunized, the spread of contagious disease is contained.

Population Impact of Immunization

• Improved if vaccine reduces disease and carriage.

UK Vaccine Preventable Diseases

• Tetanus.
• Diptheria.
• Whooping cough.
• Polio.
• Measles.
• Mumps.
• Rubella.
• Hib.
• Men C.
• Prevnar 13 (pneumococcal).
• Pneumovax*.
• Meningococcus ACWY.
• Varicella*.
• TB*.
• Hepatitis B.
• Influenza*.
• Rotavirus.
• HPV.
• Men B.

UK Immunization Schedule

• 2 months: Tet *, Dip *, Per *, HepB *, IPV *, HiB *, Prev 13, Men B, Rota (PO).
• 3 months: Tet *, Dip *, Per *, IPV *, HiB *, Prev 13, Men B, Rota (PO).
• 4 months: Tet *, Dip *, Per *, IPV *, HiB *, Prev 13.
• 12-13 months: Men C, MMR, Hib/MenC.
• 3-4 years: MMR, IPV, Flu (2-12+).
• Over 13: Td/IPV, Men ACWY, HPV

Impact of MenC Vaccine

• Conjugate Men C vaccine introduced 2000, reduced invasive C disease and carriage.

Other Meningitis Vaccines

• Group B meningococcus (OMP vesicle): Introduced Sept 2015, impact on carriage unclear.
• Group ACWY meningococcus: Summer 2015 (teens).
• Haemophilus influenza B: Meningitis, epiglotitis Vaccine introduced 1992, disease virtually disappeared.
• Pneumococcus: 100+ different serotypes, most invasive disease UK caused by (was caused by?) 13 serotypes in Prevnar 13 (conjugate, immunogenic in infants 2010), meningitis, pneumonia, empyema, bactaremia, otitis media still occur. Problems with serotype replacement. Pneumovax: 23 serotype, non immunogenic in infants, poor immune memory.

Serotype Replacement After Pneumococcal Vaccination

• Following the introduction of infant pneumococcal vaccination, there has been a serotype replacement.

Impact of Pertussis Immunization

• *Vaccine introduced 1957.
• Scare in 1970s reduced vaccine uptake
• wP vaccine replaced with less reactogenic vaccine acellular pertussis 2000
• 2012 14 infants died in UK
• Unrecognized burden of disease in adults / older children
• September 2012 pertussis immunization offered to pregnant women
• 2013 3 Uk infant deaths all to infants of unimmunized mothers
• Now routine dTaP, Flu and COVID offered in pregnancy.
• 250% increase in whooping cough 2023 ? Reduced pregnancy immunisation & reduced population immunity.

Immunization Challenges

• Waning vaccine-induced immunity.
• Achieving herd immunity.
• Maintaining immunological memory.
• Infectious disease epidemiology.
• Vaccine strategy adjustments.
• Addressing antivaccine campaigns and vaccine hesitancy.
• Ensuring access to immunization.
• Managing the impact of conflict, famine, and widening health inequalities.
• Addressing challenges posed by COVID-19.
• UNICEF Apr 2023: 67 million children missed out on vaccines past 3 years.

Measles