1. Immunization Infectious diseases in childhood University of Pécs Department of Paediatrics Zoltán Nyul

2. Immunization Passive immunization: Antibodies Passive immunization: Antibodies –Natural immunity: Maternal antibodies 3-6 mo –Passiv vaccination: Hepatitis, diphtheria-, varicella-, measles hyperimmunglobuline etc Active immunization: Antigen Active immunization: Antigen –Live, attenuated: BCG, MMR, Rotavirus, varicella –Inactivated: Cellular: IPV, influenza Cellular: IPV, influenza Antigen: Antigen: –Toxoid: tetanus, diphtheria –Protein: HBV, Pertussis(acellular) –Polysaccharide (meningococcus, pneumococcus) –Conjugated polysaccharide: Haemophilus infl, Pneumococcus, meningococcus

3. Vaccination schedule in Hungary AgeVaccine 0-6 wks BCG (Hepatitis active-passive*) 2 mo DTP(a)+HiB+IPV 3 mo DTP(a)+HiB+IPV 4 mo DTP(a)+HiB+IPV 15 mo MMR 18 mo DTP(a)+HiB+IPV 6 yrs DTP(a)+IPV 11 yrs Di-Te, MMR 14 yrs Hepatitis I, II DTP(a): diphtheria, acellular pertussis, tetanus. HiB: haemophilus influenzae. IPV: poliomyelitis. MMR: morbilli-mumps-rubeola * In case of maternal positive HBsAg titer

4. Recommended Immunization Schedule for Persons Aged 0 Through 6 Years United States 2009 www.cdc.gov/vaccines

5. Factors determining immunresponse Host: Host: –Genetic factors: MHC –Age, gestation, nutrition Vaccine Vaccine –Dosis –Route of vaccination Oral, intracutaneous, subcutaneous, intramuscular Oral, intracutaneous, subcutaneous, intramuscular –Adjuvants

6. Individual immunity: – –Vaccines are highly protective but their effectivity due to host factors are not 100% Population (herd) immunity: – –High immunization rate provides protection for the not vaccinated individuals through decreased circulation of the pathogen in the population. The fall of the vaccination coverage against measles under 85% (73% in London) resulted in outbreaks of morbilli epidemics in the UK.

7. Vaccine adverse events Immunization reaction: Immunization reaction: –Mild, not preventable –Vaccine-related Complication, adverse event Complication, adverse event –Severe, mostly not preventable –Host-related or host-vaccine interaction (i.e. immunodeficient host – BCG) Vaccination accident Vaccination accident –Preventable –Wrong administration, wild type vaccine

8. Morbilli, measles (1th disease) Morbillivirus (paramyxoviridae) Morbillivirus (paramyxoviridae) Epidemiology: Epidemiology: –CI: 95% –Airborne

9. Clinical manifestation Clinical manifestation –Incubation: 10 days –Prodromum (4 days): Fever, rhinorrhea, conjunctivitis, cough, pharyngitis Koplik’s spot –Stadium floritionis: malaise, high-degree fever, deep red maculopapulose exanthems developing behind the ear, spreading to the neck, face, trunk and extremities. The exanthems tend to confluate. The rash lasts 5 days –Desquamation may appear (sole, palms free)

10. Incubation 10-11 days Prodromum 3-4 days Rash 5 days Catarrhal symptoms: Cough, conjunctivitis, rhinitis Fever: Koplik’s spot: Rash: Contagiosity exposition

12. Laboratory: leukocytosis then leukopenia, eosinopenia Laboratory: leukocytosis then leukopenia, eosinopenia Complications: Complications: –Laryngitis –Otitis media, mastoiditis –Bronchopneumonia, pneumonitis (giant cell pneumonitis) –Encephalitis –SSPE Therapy: symptomatic Therapy: symptomatic

13. Scarlet fever (2nd disease) Pathogen: Streptococcus pyogenes (group A Streptococcus) strains with erythrogen toxin Pathogen: Streptococcus pyogenes (group A Streptococcus) strains with erythrogen toxin Epidemiology: winter, 2-8 yrs of age Epidemiology: winter, 2-8 yrs of age Incubation period: 2-5 days Incubation period: 2-5 days

14. Clinical manifestation: Clinical manifestation: –High-degree fever, headache, vomiting, sore throat –Throat: Exudative tonsillitis, pharyngitis, enanthems on the soft palate Exudative tonsillitis, pharyngitis, enanthems on the soft palate White-, then red „strawberry tongue” White-, then red „strawberry tongue” Cervical lymphadenopathy Cervical lymphadenopathy –Exanthems after 1-2 days: Face flushed, circumoral pallor Face flushed, circumoral pallor Diffuse rash with many points, „sandpaper” texture of the skin. Pastia’s line on the skin folds of elbows, knees etc Diffuse rash with many points, „sandpaper” texture of the skin. Pastia’s line on the skin folds of elbows, knees etc –Desquamation 2-3 weeks later

15. Circumoral pallor on the faceStrawberry tongue

17. Pastia’s sign

18. Desquamation

19. Laboratory: Laboratory: –Leukocytosis (neutrophils, „toxic” granulocytes), eosinophilia, urobilinogenuria Complications: Complications: –Suppurative complications –Glomerulonephritis, acute rheumatic fever

20. Diagnosis: Diagnosis: –Throat culture, rapid antigen test Dd: mononucleosis infectiosa, Kawasaki disease, toxic shock syndrome Dd: mononucleosis infectiosa, Kawasaki disease, toxic shock syndrome Therapy: Therapy: –Antibiotics: Penicillin

21. Rubella (3rd disease) Rubella virus (rubivirus, RNS) Rubella virus (rubivirus, RNS) Infection via droplets, CI: 20-80% Infection via droplets, CI: 20-80% Clinical picture: Clinical picture: –Incubation 18 days (12-23 days) –Generally subclinical –Prodromum: occipital, cervical, retroauricular lymphadenopathy (Theodor-Klatsch sign) occipital, cervical, retroauricular lymphadenopathy (Theodor-Klatsch sign) Mild catarrhale, low-grade fever, conjunctivitis Mild catarrhale, low-grade fever, conjunctivitis –Exanthems: Maculopapular rash from the face down, confluent on the face, disappears in 3-4 days, desquamation may be.

22. Incubation 14-21 days Prodromum 1-2 days Exanthema 3 days Prodromum: Mild or missing catarrhal symptomes, mild fever Rash: Contagiosity Nuchal, retroauricular lymphadenomegaly:

23. rashNuchal lymphadenomegaly

24. Complication is rare Complication is rare –Encephalitis, thrombocytopenia, arthritis Congenital rubella syndrome (CRS): Congenital rubella syndrome (CRS): Depends on gestation age at exposition: Depends on gestation age at exposition: –< 2 mo: Chance for infektion 65-85%, multiple defects –In 3. mo: 30-35%, single defects Permanent manifestation: Cataract, vitium, deafness (Gregg-triad) Permanent manifestation: Cataract, vitium, deafness (Gregg-triad) Temporary symptoms: HSM, tctpenia, anemia, osteopathy, pneumonitis, exanthems Temporary symptoms: HSM, tctpenia, anemia, osteopathy, pneumonitis, exanthems Late manifestation: Diabetes mellitus, hyper-, hypothyreosis, SSPE Late manifestation: Diabetes mellitus, hyper-, hypothyreosis, SSPE

25. Erythema infectiosum (megalerythema, fifth disease) Parvovírus B19 (erythrovirus, DNA) Parvovírus B19 (erythrovirus, DNA) –Target: haemopoietic precursors –immuncomplexes, often subclinical Clinical picture Clinical picture –Incubation 4-14 days –Mild prodromal symptoms during viremia –Exanthems: rash on the face („slapped cheek”), then second stage rash on the trunk, maculopapular exanthems –Arthritis in women

27. Complication: Complication: –Transitoric aplastic crisis (TAC) in chronic haemolytic anaemias –Pure red cell anemia in immunocompromised patients –Non-immune hydrops fetalis –Haemophagocytosis syndrome –Glove-socks syndrome –Vasculitis, myocarditis, encephalitis, nephritis

28. Roseola infantum (exanthem subitum, sixth disease) HHV-6B (herpesviridae) HHV-6B (herpesviridae) Infects almost all humans by age 2 Infects almost all humans by age 2 Clinical manifestation: Clinical manifestation: –Incubation 10-15 days –3 days high degree fever, occasionally other mild symptoms (adenopathy, diarrhea) –As the fever resolves, diffuse maculopapular rash emerges. –Febrile seizure is common

30. Varicella (chickenpox) Varicella zoster virus (herpesviridae, double-stranded DNS) Varicella zoster virus (herpesviridae, double-stranded DNS) Epidemiology: Epidemiology: –CI: 99-100% –Mortality: 2/100 000 –airborne, winter, early spring Incubation: 2-3 wks Incubation: 2-3 wks

31. –Fever, headache, malaise –Small round maculopapules, vesicles, pustules, scabs with erythematous base –The lesions appear on the trunk and spread centrifugally to the other part of the body (even to the mucosa) –Crusts fall off in 1-2 weeks

34. Complications: Complications: –Bacterial superinfection –Meningoencephalitis 1-2/1000 –Pneumonitis 1/400 –Acut postinfectios cerebellitis 1/4000 –Reye syndrome (salicylat) Dd: strophulus, pytiriasis rosea, pytiriasis lichenoides, vesicobullose diseases Dd: strophulus, pytiriasis rosea, pytiriasis lichenoides, vesicobullose diseases

35. Treatment Treatment –acyclovir (4x20mg/kg/die p.o., 3x500mg/m2 i.v.) Atypical varicella Atypical varicella Complications Complications Immunocompromized patients Immunocompromized patients –Symptomatic, hygiene, antihistamines –Bacterial superinfection: antibiotics –Congenital varicella, immunocompromized patients: VZIG

36. Pertussis (whooping cough) Pathogen: Bordetella pertussis, parapertussis Pathogen: Bordetella pertussis, parapertussis Incubation period: 2 wks (1-3) Incubation period: 2 wks (1-3) No transplacentar immunity No transplacentar immunity High contagiosity High contagiosity –Transmission via droplets –Infectivity: from the beginning of the symptoms 6-8 wks long

37. Clinical manifestation: Clinical manifestation: –Stadium catarrhale (2 wks) Pharyngitis, rhinorrhea, dry, non-productive cough –Stadium convulsivum (2 wks) Cough paroxysms (>30/day) Vomiting, epistaxis, ulceration of lingual frenulum, conjunctivitis Apnoe, hypoxia –Stadium decrementi (2 wks) Gradual decrease in frequency and intensity of paroxysms

38. Conjunctival haemorrhage Ulceration of the frenulum linguae

39. Pneumonia „Görgényi-Götche” triangle

40. Diagnosis Diagnosis –Laboratory: Leukocytosis Leukocytosis lymphocytosis (60-80%) (lymphocyta promoting factor/pertussis toxin) lymphocytosis (60-80%) (lymphocyta promoting factor/pertussis toxin) PCR PCR Complications: Complications: –Bronchopneumonia, Encephalopathy Treatment: Treatment: –Supportive care Monitoring vital signs, hydration, oxygen Monitoring vital signs, hydration, oxygen –Specific therapy: erythromycin, other macrolids, TMP/SMX early

41. Diphtheria Corynebacterium diphtheriae Corynebacterium diphtheriae –Gram positive bacillus –Toxin: cardiotoxic, nephrotoxic Incubation: 1-3 days Incubation: 1-3 days

42. Faucial diphtheria Faucial diphtheria –Abrupt onset with low-grade fever, malaise, sore throat –Development of a white, later dirty gray colored membrane on one or both tonsils, spreading to the soft palate, uvula, oropharynx –„Malignant diphtheria”: toxic appearance, extent membrane with tissue edema („collum proconsulare”)

43. Laryngeal diphtheria (croup) Laryngeal diphtheria (croup) –Primary or faucial diphtheria spreading downward –Stadium catarrhale: dry, brassy cough, aphonia –Stadium stenoticum: inspiratoric dyspnea –Stadium asphycticum: cyanosis, inspiratory retraction of intercostal, substernal tissue Anterior nasal diphtheria Anterior nasal diphtheria

44. „collum proconsulare”

45. Complications Complications –Cardiac toxicity 10-25% First-degree heart block – AV dissociation First-degree heart block – AV dissociation Congestive myocarditis Congestive myocarditis –Nephrosis sy. –Neurologic toxicity Local paralysis of soft palate, cranial neuropathies, peripheral neuritis (motor defects mainly of the lower extremities) Local paralysis of soft palate, cranial neuropathies, peripheral neuritis (motor defects mainly of the lower extremities) Sow, total resolution after 1-2 wks Sow, total resolution after 1-2 wks Treatment Treatment –Antibiotics: penicillin, erythromycin –Antitoxin –Supportive care

46. Parotitis epidemica, mumps Mumps virus (paramyxoviridae, RNA) Mumps virus (paramyxoviridae, RNA) Incubation: 18 days (2-3 wks) Incubation: 18 days (2-3 wks) Clinical manifestation: Clinical manifestation: –1-2 days prodromum with fever –Earache, uni-, or bilateral enlargement of the parotids, obscuring the angle of the mandible. –Fever may range from normal to 40C, lasts 3 days, the parotid returns to normal size within a weeks

47. Laboratory: leukopenia, elevated se-amylase Laboratory: leukopenia, elevated se-amylase Complications: Complications: –Meningitis (1-10%) –Encephalitis (1/400) –After puberty: orchitis, rarely oophoritis –Pancreatitis –Mild renal function abnormalities Treatment: symptomatic Treatment: symptomatic

49. Infectious mononucleosis EBV (herpesvirus 4, double stranded DNA) EBV (herpesvirus 4, double stranded DNA) Incubation: 2-8 wks Incubation: 2-8 wks Transmission: „kissing disease” Transmission: „kissing disease” Receptor: CD21 Receptor: CD21 –Nasopharyngeal epithelium (lytic infection) Main source of viral load Main source of viral load –B-lymphocytes (latent infection) Activation, polyclonal proliferation, immortalization – autoimmunity during infection Activation, polyclonal proliferation, immortalization – autoimmunity during infection Viral DNA incorporation in the human genom – source of reactivation, malignity Viral DNA incorporation in the human genom – source of reactivation, malignity

51. „Atypical monocytes” = activated (T) lymphocytes

52. Symptoms: Symptoms: –Fever 2-3 wks long, sore throat, exudativ tonsillitis –Lymphadenopathy –Splenomegaly, hepatomegaly –Antibiotic-related rash (ampicillin, cefalexin) on 8-9. day

53. Antibiotic rash Exudative tonsillitis

54. Laboratory: Laboratory: –Lymphocytosis, atypical lymphocytes in peripheral smear –Moderate elevation of ALAT, ASAT –Heterophile antibodies –EBV associated antibodies: Virus capsid antigen IgM, IgG Virus capsid antigen IgM, IgG EBNA EBNA (Anti EA) (Anti EA)

55. Complications Complications –Haematologic: haemolytic anemia, thrombocytopenia, neutropenia –Neurologic: meningoencephalitis, cerebellar ataxy, mononeuritis, polyradiculitis, psychotic phenomena –Airway obstructions –Carditis –Splenic rupture –X-linked lymphoproliferative syndrome –EBV malignancies (Burkitt, nasopharyngeal cc, etc)

56. Global challenges in immunization Globally, 20% of children have no access to the basic vaccination, such as diphtheria, pertussis etc Even in developed countries, the immunization coverage is suboptimal, and maintaining a high rate has been becoming difficult Appendix

57. Parental decision making on vaccination A decisional scenario: Factors promoting vaccination: – –Severity of the preventable disease – –Trust in health care professionals – –Informative campaigns, leaflets, brochures – –Social responsibility – –The level of sanctions by mandatory immunizations Appendix VaccinationDisease Own experience, factDistant Possible adverse eventsDangerous but unknown, unlikely Emotional engagementRational approach

58. Misconceptions about vaccination Because of better hygiene and sanitation, diseases had already begun to disappear before vaccines were introduced The majority of people who get the disease have been immunized Vaccines cause many harmful side effects, and even death—and may cause long-term effects we don't even know about DTP vaccine causes sudden infant death syndrome (SIDS) Vaccine-preventable diseases have been virtually eliminated, so there is no need for my child to be vaccinated Giving a child more than one vaccine at a time increases the risk of harmful side effects and can overload the immune system Vaccines cause autism Children get too many immunizations Appendix Answers: see http://www.quackwatch.org/03HealthPromotion/immu/immu00.html

59. Ethical considerations Appendix Feudtner C, Marcuse EK. Pediatrics. 2001;107:1158-64