Download Immunization infectious deseases in childhood

Immunization
Infectious diseases in
childhood
University of Pécs
Department of Paediatrics
Zoltán Nyul
Immunization

Passive immunization: Antibodies
– Natural immunity: Maternal antibodies 3-6 mo
– Passiv vaccination: Hepatitis, diphtheria-,
varicella-, measles hyperimmunglobuline etc
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Active immunization: Antigen
– Live, attenuated: BCG, MMR, Rotavirus, varicella
– Inactivated:
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Cellular: IPV, influenza
Antigen:
–
–
–
–
Toxoid: tetanus, diphtheria
Protein: HBV, Pertussis(acellular)
Polysaccharide (meningococcus, pneumococcus)
Conjugated polysaccharide: Haemophilus infl, Pneumococcus,
meningococcus
Vaccination schedule in Hungary
Age
Vaccine
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
Recommended Immunization Schedule for Persons Aged 0 Through 6 Years
United States • 2009
www.cdc.gov/vaccines
Factors determining
immunresponse
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Host:
– Genetic factors: MHC
– Age, gestation, nutrition
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Vaccine
– Dosis
– Route of vaccination

Oral, intracutaneous, subcutaneous,
intramuscular
– Adjuvants
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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.
Vaccine adverse events

Immunization reaction:
– Mild, not preventable
– Vaccine-related
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Complication, adverse event
– Severe, mostly not preventable
– Host-related or host-vaccine interaction (i.e.
immunodeficient host – BCG)

Vaccination accident
– Preventable
– Wrong administration, wild type vaccine
Morbilli, measles
(1th disease)
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Morbillivirus (paramyxoviridae)
Epidemiology:
– CI: 95%
– Airborne
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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)
Catarrhal symptoms:
Cough, conjunctivitis, rhinitis
Fever:
Koplik’s spot:
Rash:
exposition
Contagiosity
Incubation
10-11 days
Prodromum
3-4 days
Rash
5 days
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Laboratory: leukocytosis then leukopenia,

Complications:
eosinopenia
– Laryngitis
– Otitis media, mastoiditis
– Bronchopneumonia, pneumonitis (giant cell
pneumonitis)
– Encephalitis
– SSPE

Therapy: symptomatic
Scarlet fever
(2nd disease)

Pathogen: Streptococcus pyogenes (group A
Streptococcus) strains with erythrogen toxin

Epidemiology: winter, 2-8 yrs of age

Incubation period: 2-5 days
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Clinical manifestation:
– High-degree fever, headache, vomiting, sore
throat
– Throat:
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Exudative tonsillitis, pharyngitis, enanthems on the soft
palate
White-, then red „strawberry tongue”
Cervical lymphadenopathy
– Exanthems after 1-2 days:
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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
– Desquamation 2-3 weeks later
Circumoral pallor on the face
Strawberry tongue
Pastia’s sign
Desquamation
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Laboratory:
– Leukocytosis (neutrophils, „toxic”
granulocytes), eosinophilia,
urobilinogenuria
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Complications:
– Suppurative complications
– Glomerulonephritis, acute rheumatic fever

Diagnosis:
– Throat culture, rapid antigen test
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Dd: mononucleosis infectiosa, Kawasaki
disease, toxic shock syndrome
Therapy:
– Antibiotics: Penicillin
Rubella
(3rd disease)
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Rubella virus (rubivirus, RNS)
Infection via droplets, CI: 20-80%
Clinical picture:
– Incubation 18 days (12-23 days)
– Generally subclinical
– Prodromum:
occipital, cervical, retroauricular lymphadenopathy
(Theodor-Klatsch sign)
 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.

Rash:
Nuchal, retroauricular
lymphadenomegaly:
Prodromum: Mild or missing
catarrhal symptomes,
mild fever
Contagiosity
Incubation
14-21 days
Prodromum
1-2 days
Exanthema
3 days
rash
Nuchal lymphadenomegaly

Complication is rare
– Encephalitis, thrombocytopenia, arthritis

Congenital rubella syndrome (CRS):
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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)
Temporary symptoms:
HSM, tctpenia, anemia, osteopathy, pneumonitis,
exanthems
Late manifestation: Diabetes mellitus, hyper-,
hypothyreosis, SSPE
Erythema infectiosum
(megalerythema, fifth disease)

Parvovírus B19
(erythrovirus, DNA)
– Target: haemopoietic precursors
– immuncomplexes, often subclinical

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

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
Roseola infantum
(exanthem subitum, sixth disease)
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HHV-6B (herpesviridae)
Infects almost all humans by age 2
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
Varicella (chickenpox)
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Varicella zoster virus
(herpesviridae, double-stranded DNS)
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Epidemiology:
– CI: 99-100%
– Mortality: 2/100 000
– airborne, winter, early spring
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Incubation: 2-3 wks
– 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
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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
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Treatment
– acyclovir
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(4x20mg/kg/die p.o., 3x500mg/m2 i.v.)
Atypical varicella
Complications
Immunocompromized patients
– Symptomatic, hygiene, antihistamines
– Bacterial superinfection: antibiotics
– Congenital varicella,
immunocompromized patients: VZIG
Pertussis (whooping cough)
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Pathogen: Bordetella pertussis,
parapertussis
Incubation period: 2 wks (1-3)
No transplacentar immunity
High contagiosity
– Transmission via droplets
– Infectivity: from the beginning of the
symptoms 6-8 wks long
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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
Conjunctival haemorrhage
Ulceration of the frenulum linguae
Pneumonia
„Görgényi-Götche”
triangle
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Diagnosis
– Laboratory:
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Leukocytosis
lymphocytosis (60-80%) (lymphocyta promoting
factor/pertussis toxin)
PCR
Complications:
– Bronchopneumonia, Encephalopathy
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Treatment:
– Supportive care
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Monitoring vital signs, hydration, oxygen
– Specific therapy: erythromycin, other macrolids,
TMP/SMX early
Diphtheria
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Corynebacterium diphtheriae
– Gram positive bacillus
– Toxin: cardiotoxic, nephrotoxic
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Incubation: 1-3 days
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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”)
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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
„collum proconsulare”
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Complications
– Cardiac toxicity 10-25%
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First-degree heart block – AV dissociation
Congestive myocarditis
– Nephrosis sy.
– Neurologic toxicity
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Local paralysis of soft palate, cranial neuropathies,
peripheral neuritis (motor defects mainly of the lower
extremities)
Sow, total resolution after 1-2 wks
Treatment
– Antibiotics: penicillin, erythromycin
– Antitoxin
– Supportive care
Parotitis epidemica, mumps
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Mumps virus (paramyxoviridae, RNA)
Incubation: 18 days (2-3 wks)
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
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Laboratory: leukopenia, elevated se-amylase
Complications:
–
–
–
–
–
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Meningitis (1-10%)
Encephalitis (1/400)
After puberty: orchitis, rarely oophoritis
Pancreatitis
Mild renal function abnormalities
Treatment: symptomatic
Infectious mononucleosis
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EBV (herpesvirus 4, double stranded DNA)
Incubation: 2-8 wks
Transmission: „kissing disease”
Receptor: CD21
– Nasopharyngeal epithelium (lytic infection)
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Main source of viral load
– B-lymphocytes (latent infection)
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Activation, polyclonal proliferation, immortalization –
autoimmunity during infection
Viral DNA incorporation in the human genom – source
of reactivation, malignity
„Atypical monocytes” = activated (T) lymphocytes
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Symptoms:
– Fever 2-3 wks long, sore throat, exudativ
tonsillitis
– Lymphadenopathy
– Splenomegaly, hepatomegaly
– Antibiotic-related rash (ampicillin,
cefalexin) on 8-9. day
Antibiotic rash
Exudative tonsillitis

Laboratory:
– Lymphocytosis, atypical lymphocytes in
peripheral smear
– Moderate elevation of ALAT, ASAT
– Heterophile antibodies
– EBV associated antibodies:
Virus capsid antigen IgM, IgG
 EBNA
 (Anti EA)

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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)
Appendix
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
Parental decision making
on vaccination

A decisional scenario:
Vaccination
Disease
Own experience, fact
Distant
Possible adverse events
Dangerous but unknown, unlikely
Emotional engagement
Rational approach
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Factors promoting vaccination:
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–
–
–
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Severity of the preventable disease
Trust in health care professionals
Informative campaigns, leaflets, brochures
Social responsibility
The level of sanctions by mandatory immunizations
Appendix
Misconceptions about
vaccination
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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
Answers: see http://www.quackwatch.org/03HealthPromotion/immu/immu00.html
Appendix
Ethical considerations
Feudtner C, Marcuse EK. Pediatrics. 2001;107:1158-64