Transcript ID immunity-part1

Infectious Disease &
Immunity
Dr. D. Barry
Part 1
1) Immune System
2) Vaccinations
3) Vaccine Preventable Diseases
Part 2
1) Assessing the Febrile Child
2) Common Childhood Infections
3) Antibiotic choices
4) Immunodeficiencies
1; Immune System
Immune system
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Neonates have immature immune system
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(esp. adaptive system; lymphocytes, antibodies)
Lymphocytes ↑ (thymus) & mature with
antibody production relative to exposure
Foetal/ Neonatal monocytes, mØ slow to
process foreign antigens
Infants produce a/b against simple proteins
(eg. Vaccines) not polysaccharides until 2 years
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Foetal Lymphocytes from 9/40 in liver
Bone, liver, spleen 12/40
 T-cells from 14/40 &
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In utero sterile environment (ideally)
Therefore no anti-bodies produced
Mum’s IgG only crosses placenta
Neonatal antibodies
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IgG; Transplacental ie maternal
T1/2 21 days
 Nadir at 3-5months
 Infant’s own IgG takes over
 60% of adult’s level at 1 year
 100% by 6-10 years
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IgM; v low at birth; 75% adult level at 1 yr *
IgA, IgD, IgE; 10-40% at 1 yr
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Exposure; 7-8 viral infections/yr
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↑ with contacts (creche / school)
Vast array of childhood infections from benign
to critical; your job to find out which
Hygiene Hypothesis
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↑ allergic / immune-mediated disorders in
developed nations
? ‘too clean’ environment
Microbial exposure needed
Causes shift from predominance of Th1 to Th2
cells, causing over-production of IgE etc.
Hypersensitivity ensues
[J Hopkins & T Shirakawa Science 1997
Immune system; ‘in balance’
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Infection; viral/bacterial/opportunistic
Hypersensitivity; Allergy, Atopy, Intolerance
Autoimmune disorders
Immunodeficencies
Therapeutic; Vaccinations
Monoclonal antibodies
 IVIG
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2; Vaccinations
“Medicine’s greatest lifesaver”
Ireland;
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Mycobacterium
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Diphtheria
Tetanus
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Pertussis
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Polio
Haemophilus influenza b
Hepatitis B
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Meningococcal C
Pneumococcus
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Measles
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Mumps
Rubella
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}
12 vaccines
BCG* x 1
}
6in1
x3
Men C x 3
PCV x 3
MMR* x 2
Age
Vaccination
Birth
BCG
2 months
6in1 & PCV
4 months
6in1 & Men C
6 months
6in1 & Men C & PCV
12 months
MMR & PCV
13 months
Men C & Hib
4 – 5 years
4in1 & MMR
11-14 years
Td
Those born before July 2008
Age
Birth
2 months
4 months
6 months
12-15 months
4-5 years
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Vaccine
BCG
5in1, MenC
5in1, MenC
5in1, MenC
MMR, Hib
4in1, MMR
No Routine Hepatitis B or Pneumococcal vaccine
PCV Catch-up programme (for <2 year olds)
Why Immunise?
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In 1974, only 5% of the
worlds children had
access to vaccines.
A global effort in the
early ’80’s aimed to
provide six vaccines to
80% of children
worldwide
Immunisation now saves
>3,000,000 lives each
year
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Protects millions more
from illness and
permanent disability
Other vaccines
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Influenza
Varicella
Hepatitis A
HPV
Travel vaccines
What is immunisation?
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Immunisation is the process of inducing or providing
immunity artifically.
This may be done by the administration of a vaccine,
toxoid or externally produced antigen in order to
stimulate antibody production.
The aim; to reduce the incidence of, or to eliminate a
particular disease.
Immunisation has both a direct and an indirect effect.
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Direct effect; antibody protection in the individual
Indirect effect; reduction of the incidence of the disease in
others – so called ‘herd immunity’
Vaccine Considerations
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Pathogen factors; How common?
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Vaccine factors; vaccine immunogenicity
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efficacy, side-effects & risks?
Host factors; maturity immune system,
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How dangerous / complications?
When is infant most at risk of this disease?
Population factors; disease prevalence,
vaccine uptake & herd immunity,
 cost-benefit
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Live Attenuated
Measles
Mumps
Rubella
BCG
Killed Orgs
Polio (IPV)
Influenza
Subunits
Hib
Men C
Pneumo (PCV)
Hep B
Acellular Pertussis
Varicella
Cellular Pertussis
Cholera/typhoid/ Cholera/Typhoid Hep A
yellow fever
/Rabies
Oral Polio
MMR Vaccine: Is It Really A
Factor In Autism?
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There has been a concern about a link between the MMR
(measles, mumps, rubella) vaccine and the development
of autism in children because:
– MMR vaccine is first given at age 12 to 15 months.
– The first signs of autism (e.g. poor social interaction and speech,
repetitive behaviors) often appear between 12 to 18 months of age.
MMR vaccine first given
Birth
0 months
First signs of autism
12 months
15 months
Independent Studies Have Found No Link
Between Autism and MMR.
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A United States study by Dr. Loring Dales showed
that the number of autism cases in young children
increased even when the number of MMR vaccines
decreased over the same time period!
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A British study by Dr. Brent Taylor showed that the
number of diagnosed autism cases did not increase
after the MMR vaccine was introduced in 1988.
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If a link existed between the MMR vaccine and
autism, then one would expect the number of autism
cases to increase or decrease over time as the number
of children immunised with MMR decreases or
increases over the same time. No study has shown
this trend.
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Additional studies conducted in the United States and
in Europe have found no association between the
MMR vaccination and autism.
WHO opinion on MMR
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"WHO has noted that other scientists have not been
able to reproduce the results claimed by Dr Wakefield
and his team regarding measles virus in the gut. His
published observations regarding the onset of autism
following administration of MMR vaccine do not meet
the scientific criteria required to suggest that the
vaccine is the cause. Other studies not cited by Dr
Wakefield find no link with autism or Crohn's disease."
WHO strongly endorses the use of MMR (measles,
mumps and rubella) vaccine on the grounds of its
convincing record of safety and efficacy.
IRISH Working Party Consensus
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The Joint Committee considers that:
there is no evidence of a proven link between MMR
and autism.
there is no evidence to show that the separate vaccines
are any safer than the combined MMR vaccine.
Babies are very susceptible to measles, mumps and
rubella, which are killer diseases, so they much be
protected as soon as possible and this can only be done
with the MMR vaccine.
Giving separate measles, mumps and rubella vaccines
would leave children unnecessarily exposed and
vulnerable.
Late Entrants To Irish Health
Care System
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MMR; Immunisation recommended
 2 doses recommended between 12-15 mo and 4-6 yrs at least
1 month apart
Men C; recommended under 22 years
Hib; Recommended under aged 4 years
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( 3 doses < 1 yr, 1 dose > 1yrs)
Polio; 4 doses recommended before the age of 4-6 yrs
DtaP; recommended under 12 years
 If it is likely 3 or more doses given,
 serological testing for IgG antibodies +/- booster
 If a child at presentation is > 10yrs Td is given
Contraindications/ Precautions
……..NOT Contraindications
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Family history of adverse reactions to immunisations
Minor infections without fever or systemic upset
Family hx of convulsions
History of measles, mumps, pertussis in the absence of
proof of immunity
Child’s mother is pregnant or Child being breast-fed
Impending surgery
Child over the recommended age
Corticosteroid replacement therapy
Diphtheria
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Corynebacterium diphtheriae
Affects upper respiratory
tract
Incubation – 2-5 days
Spread; droplet/close contact
Disease characterised by an
inflammatory exudate 
obstructive membrane over
the airway
Other manifestation:
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Myocarditis
Vocal cord paralysis
Guillain Barre type ascending
paralysis
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Since vaccination; virtually
eliminated in Ireland
Vaccine
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Toxoid
Component of 6 in 1
Booster at 4-5yrs and low dose
booster at 11-14 yrs
Adverse reactions
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Transient local reactionc occur
in > 50%
Malaise, headache and transient
fever occur occasionally
Tetanus
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Clostridium tetani
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Muscular rigidity with
superimposed
contractions
Organism is
ubiquitous
Nb; puncture wounds,
bites etc.
Incubation period: 4-21
days
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Vaccine
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Primary immunisation
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Toxoid
Poor immunogen
6 in 1, three doses
Booster dose at school
entry and at 11-14yrs
Immunised adults who
have received 5 doses do
not need further booster
doses
Pertussis (Whooping cough)
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Bordetella pertussis
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Highly infectious (90% of
nonimmune contacts
acquire it)
3 phases
Transmitted; droplets etc.
1-2 week incubation
Endemic with periodic
outbreaks
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Diagnosis; often clinical
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Peri-nasal swab; poor
yield
Lymhocytosis
Treatment;
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Isolate
Erythromycin reduces
infectivity
Supportive
Vaccination
‘100 day cough’
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Catarrhal phase; 1-2 weeks of low fever, URTI
 Highly infectious
 Transmission; Droplet/ close contact
Paroxysmal phase; Whoop (gasps for breath between
coughing fits) 3-5 weeks
 Often associated vomiting etc.
Recovery phase; 2-3 weeks
Complications;
 Apnoea in neonates
 Bronchopneumonia
 Cerebral hypoxia; Seizures, Encephalopathy
 Death
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Vaccine
Acellular pertussis
 6 in 1 x 3
 Booster at 4-5 yrs
 No upper age limit but considered unnecessary > 7
yrs
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Efficacy variable; 35 – 100% in studies
Previous concern re; seizures induced by
Cellular Vaccine (not used anymore)
Pertussis - special precautions
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Advice from the child’s paediatrician may need
to be sought prior to immunisation where there
is:
A personal history of convulsions
 An evolving neurological problem
 If an event listed in precaution section has occurred
after a previous dose
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Poliomyelitis
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Caused by polio virus 1-3
Transmission;
faecal/oral, droplet
Incubation: 3- 21 days
Clinical disease
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Non-paralytic fever
Aseptic meningitis
Paralysis
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Pre-vaccine;
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20,000 cases/yr USA
1,900 deaths /yr
Ireland most recent case
1984
Endemic in developing
world
Vaccine
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Most infections
asymptomatic
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IPV since 2001
Part of 6 in 1
3 doses + 4th at 4- 5 yrs
OPV not recommended
Haemophilus influenzae type B
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Hib vaccine introduced 1992
80% of invasive haemophilus
infections caused by type B
After 12 months of age, Hib
disease declines
Clinical disease includes:
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Meningitis
Epiglottis
Septicaemia
Cellulitis
Osteomyelitis
Septic arthritis
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Vaccine
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Capsular poly or
oligosaccharide
Part of 6 in 1
3 doses + booster
If first dose given at > 1 yr
need only 1 dose
Children > 4 yrs do not need
immunisation with Hib
Persons with asplenia or
undergoing splenectomy
should be vaccinated
Hib Treatment
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Index case; tx with cefotaxime or ceftriaxone
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Household contacts / Play-group/ creche; chemoprophylaxis
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Immunise 1 month after disease if < 2 yrs
Except pregnant women
Non-immunised contacts < 4yrs need vaccine
All household contacts irrespective of age or immunisation history IF
there are any unvaccinated children< 4yrs
Chemoprophylaxis; Rifampicin
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Neonates and infants < 1 yr : 10mg/kg od for 4 days
Children > 1 yr: 20mg/kg od for 4 days ( max 600mg/day)
Adults : 600mg one daily x 4 days
Hepatitis B
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DNA virus
Highly contagious
30% transmission rate with puncture injury
 High risk contacts
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10% chronic infection, 1% fulminant hepatitis
Risk of Hepatocellular Ca
Hepatitis B vaccination
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Traditionally only vaccinated high risk groups
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Sex workers
Individuals who change sexual partner frequently
IVDU’s
Prisoners
Tattoo artists
Homeless people
Immigrants from, or travellers to, areas with a high
prevalence of HBV
Security and emergency services personnel
Family contacts of HBV pts
CRF / HIV / chronic hepatitis
Healthcare workers
Hepatitis B vaccine
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Vaccine; HBsAg in 6in1
Primary Immunisation Schedule (since July)
At 2, 4, 6/12
 At birth with HBIG if risk of vertical transmission
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+ follow-up testing
No Catch-up unless at risk
Meningococcus C
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Neisseria Meningitidis
Gram neg. cocci
Causes Meningitis, Septicaemia
Notifiable disease
Contact tracing & chemoprophylaxis required
Contact tracing/ prophylaxis
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Antibiotic prophylaxis for close contacts of confirmed or
suspected cases:
Close contacts defined as those who in the seven days prior to
the onset of illness in the index case
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Rifampicin is drug of choice
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Have shared living or sleeping accomodation
Had mouth kissing contact with the patient
Nursery/creche /daycare contacts
Medical personnel who have had ‘intimate’ contact with the patient (
mouth-to-mouth, intubation)
Alternative prophylaxis is Ceftriaxone 250 mg im for adults and 125mg
for children
For vaccine preventable strains (A, C, W-135) vaccination is
offered.
Streptococcal Pneumoniae
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Capsular organism
Gram + Diplococci
Some asymptomatic carriers
Diseases;
 Meningitis with effusions
 Pneumonia with effusions
 Bacteraemia/Sepsis
 Otitis Media
 Sinusitis
Pneumococcal Conjugate Vaccine
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7 serotypes (75-80% invasive pneumococcus)
↑ immunogenicity with mutant diphtheria toxin
> 90% effective
23-valent polysaccharide available
 for high risk children > 2years age
 eg. Asplenia
 Effective for 5 years
 Not in Primary Immunisation Schedule
Measles
Transmission; airborne/droplet
 Incubation; 10-14 days
Clinical;
 Prodrome; high fever, harsh
cough, coryza, conjunctivitis,
 Rash; ‘morbilliform’, maculopapular
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Begins d3-6 from hairline, down
face to trunk
Lasts up to 10/7
Koplik’s spots
Measles (Rubeola)
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Complications;
RNA Paramyxovirus
 Otitis, pneumonia, croup
Clinical diagnosis
Salivary swab measles IgM  Encephalitis 1/5000
within a week of rash
Treatment
 15% Mortality
 Supportive
 20-40% Neuro
 Ribavirin if patient
sequelae
Immunocompromised
 Late complication;
 ?Contacts
Prevention: HNIG within SSPE (subacute sclerosing
panencephalitis)
6/7 if imunocompromised
1/100,000
contact
Measles
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Vaccine; MMR
12-15 months of age, 2nd dose at 4-5 yrs
 Can be given to those with history of measles, mumps or rubella
infection
Mini-measles can occur 6 -10 days after immunisation
 Mild pyrexia and erythematous rash
Measles outbreak
 Immunise all susceptible individuals within 72 hrs
Contraindications;
 Pregnancy is a contraindication and should be avoided for 2 months after
vaccination
 Untreated malignancy and immunodeficiency states (except HIV)
 Immunosuppressive therapy
 History of anaphylaxis to a previous dose
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Mumps
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Acute viral illness
Swelling of one or more salivary glands usually the parotids
CNS involvement is frequent
 Symptomatic meningitis occurs in <10%
 Rarely transverse myelitis, cerebellar ataxia or encephalitis can
occur
Orchitis occurs in 20% of post-pubertal males
 Sterility rare
Other manifestations
 Arthritis, carditis, nephritis, pancreatitis, thyroiditis, hearing
impairment
Transmission is by droplet
Incubation period: 12 -25 days
Vaccine; live MMR
Rubella
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Rubella – difficult to diagnose
 Fever <38.5, LN + (esp Post Triangle)
 May have splenomegaly, palatal petechiae
Mild self limited disease in children – 25 -50%
subclinical
Incubation 2 – 3 weeks
Infectious (droplets) for <1wk from rash onset
Buccal swab, urine, rising antibody titre
Rare complications:
 Polyarthralgia / Polyarthritis
 Thrombocytopenia
 Encephalitis (1 in 6000)
Congenital Rubella
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LBW, growth retardation
Microcephaly, learning disability, psyche
Microphthalmia, catarract, glaucoma
Micrognathia
Sensori-neural deafness
Hepato-Spleno-megaly (transient), diabetes
Thrombocytopenic purpura ‘blueberry muffin’
PDA
Congenital Rubella
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1964-1965 USA; Rubella epidemic;
 12.5mil cases
 with 20,000 cases congenital rubella
2001; 19 cases Rubella in USA
Serology checked on antenatal booking bloods
>80% women infected in 1st trimester; affected infants
Infants with congenital rubella may shed virus for over
a year
MMR
Prevention: Active vaccination
 Rubella component of MMR vaccine
occasionally produces mild arthralgia
especially in post pubertal girls (25%)
 Pregnancy remains a contraindication
 (no evidence of congenital rubella related
to vaccine)
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HIV And Immunisation
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Children With HIV infection whether symptomatic or
asymptomatic should receive:
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DtaP, IPV, Hib, Men C as per primary schedule
Yearly influenza vaccine beginning at 6 months
Pneumococcal (conjugate) vaccine at 2,4 and 6 months
MMR at 14 months ( unless severely immunocompromised),
2nd dose 1-2 months later
BCG if infant has 2 negative HIV PCR tests in the first 6
weeks of life
Hepatitis A
Hepatitis B
Summary
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Neonates & Infants immature immune systems
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Vaccines very effective protection
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Know schedule (old & new & catch-up)
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Know diseases they prevent (MCQs)
Age
Vaccination
Birth
BCG
2 months
6in1 & PCV
4 months
6in1 & Men C
6 months
6in1 & Men C & PCV
12 months
MMR & PCV
13 months
Men C & Hib
4 – 5 years
4in1 & MMR
11-14 years
Td