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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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Presentation Transcript
part 1
Part 1

1) Immune System

2) Vaccinations

3) Vaccine Preventable Diseases

part 2
Part 2

1) Assessing the Febrile Child

2) Common Childhood Infections

3) Antibiotic choices

4) Immunodeficiencies

immune system
Immune system
  • Neonates have immature immune system
    • (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

slide6
Foetal Lymphocytes from 9/40 in liver
    • Bone, liver, spleen 12/40
    • T-cells from 14/40 &
  • In utero sterile environment (ideally)
  • Therefore no anti-bodies produced
  • Mum’s IgG only crosses placenta
neonatal antibodies
Neonatal antibodies
  • 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
  • IgM; v low at birth; 75% adult level at 1 yr *
  • IgA, IgD, IgE; 10-40% at 1 yr
slide8
Exposure; 7-8 viral infections/yr
    • ↑ with contacts (creche / school)
  • Vast array of childhood infections from benign to critical; your job to find out which
hygiene hypothesis
Hygiene Hypothesis
  • ↑ 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
Immune system; ‘in balance’
  • Infection; viral/bacterial/opportunistic
  • Hypersensitivity; Allergy, Atopy, Intolerance
  • Autoimmune disorders
  • Immunodeficencies
  • Therapeutic; Vaccinations
    • Monoclonal antibodies
    • IVIG
2 vaccinations

2; Vaccinations

“Medicine’s greatest lifesaver”

ireland 12 vaccines
Ireland; 12 vaccines

}

}

Mycobacterium BCG* x 1

Diphtheria

Tetanus

Pertussis 6in1x 3

Polio

Haemophilus influenza b

Hepatitis B

Meningococcal C Men C x 3

Pneumococcus PCV x 3

Measles

Mumps MMR* x 2

Rubella

those born before july 2008
Those born before July 2008

No Routine Hepatitis B or Pneumococcal vaccine

PCV Catch-up programme (for <2 year olds)

why immunise
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

Protects millions more from illness and permanent disability

Why Immunise?
other vaccines
Other vaccines

Influenza

Varicella

Hepatitis A

HPV

Travel vaccines

what is immunisation
What is immunisation?
  • 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.
    • Direct effect; antibody protection in the individual
    • Indirect effect; reduction of the incidence of the disease in others – so called ‘herd immunity’
vaccine considerations
Vaccine Considerations
  • Pathogen factors;How common?
    • How dangerous / complications?
  • Vaccine factors;vaccine immunogenicity
    • efficacy, side-effects & risks?
  • Host factors;maturity immune system,
    • When is infant most at risk of this disease?
  • Population factors;disease prevalence,
    • vaccine uptake & herd immunity,
    • cost-benefit
mmr vaccine is it really a factor in autism

First signs of autism

MMR vaccine first given

Birth

0 months

12 months

15 months

MMR Vaccine: Is It Really A Factor In Autism?
  • 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.
independent studies have found no link between autism and mmr
Independent Studies Have Found No Link Between Autism and MMR.
  • 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!
  • 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.
  • 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.
  • Additional studies conducted in the United States and in Europe have found no association between the MMR vaccination and autism.
who opinion on mmr
WHO opinion on MMR
  • "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
IRISH Working Party Consensus
  • 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
Late Entrants To Irish Health Care System
  • 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
    • ( 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
not contraindications
……..NOT Contraindications

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
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:

Myocarditis

Vocal cord paralysis

Guillain Barre type ascending paralysis

Since vaccination; virtually eliminated in Ireland

Vaccine

Toxoid

Component of 6 in 1

Booster at 4-5yrs and low dose booster at 11-14 yrs

Adverse reactions

Transient local reactionc occur in > 50%

Malaise, headache and transient fever occur occasionally

Diphtheria
tetanus
Clostridium tetani

Muscular rigidity with superimposed contractions

Organism is ubiquitous

Nb; puncture wounds, bites etc.

Incubation period: 4-21 days

Vaccine

Toxoid

Poor immunogen

Primary immunisation

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

Tetanus
pertussis whooping cough
Bordetella pertussis

Highly infectious (90% of nonimmune contacts acquire it)

3 phases

Transmitted; droplets etc.

1-2 week incubation

Endemic with periodic outbreaks

Diagnosis; often clinical

Peri-nasal swab; poor yield

Lymhocytosis

Treatment;

Isolate

Erythromycin reduces infectivity

Supportive

Vaccination

Pertussis (Whooping cough)
100 day cough
‘100 day cough’
  • 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
slide33
Vaccine
    • Acellular pertussis
    • 6 in 1 x 3
    • Booster at 4-5 yrs
    • No upper age limit but considered unnecessary > 7 yrs
  • Efficacy variable; 35 – 100% in studies
  • Previous concern re; seizures induced by Cellular Vaccine (not used anymore)
pertussis special precautions
Pertussis - special precautions
  • 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
poliomyelitis
Caused by polio virus 1-3

Transmission;

faecal/oral, droplet

Incubation: 3- 21 days

Clinical disease

Non-paralytic fever

Aseptic meningitis

Paralysis

Most infections asymptomatic

Pre-vaccine;

20,000 cases/yr USA

1,900 deaths /yr

Ireland most recent case 1984

Endemic in developing world

Vaccine

IPV since 2001

Part of 6 in 1

3 doses + 4th at 4- 5 yrs

OPV not recommended

Poliomyelitis
haemophilus influenzae type b
Hib vaccine introduced 1992

80% of invasive haemophilus infections caused by type B

After 12 months of age, Hib disease declines

Clinical disease includes:

Meningitis

Epiglottis

Septicaemia

Cellulitis

Osteomyelitis

Septic arthritis

Vaccine

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

Haemophilus influenzae type B
hib treatment
Hib Treatment
  • Index case; tx with cefotaxime or ceftriaxone
    • Immunise 1 month after disease if < 2 yrs
  • Household contacts / Play-group/ creche; chemoprophylaxis
    • 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
    • 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
Hepatitis B
  • DNA virus
  • Highly contagious
    • 30% transmission rate with puncture injury
    • High risk contacts
  • 10% chronic infection, 1% fulminant hepatitis
  • Risk of Hepatocellular Ca
hepatitis b vaccination
Hepatitis B vaccination
  • Traditionally only vaccinated high risk groups
    • 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
Hepatitis B vaccine
  • Vaccine; HBsAg in 6in1
  • Primary Immunisation Schedule (since July)
    • At 2, 4, 6/12
    • At birth with HBIG if risk of vertical transmission
      • + follow-up testing
  • No Catch-up unless at risk
meningococcus c
Meningococcus C
  • Neisseria Meningitidis
  • Gram neg. cocci
  • Causes Meningitis, Septicaemia
  • Notifiable disease
  • Contact tracing & chemoprophylaxis required
contact tracing prophylaxis
Contact tracing/ prophylaxis
  • 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
    • 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)
  • Rifampicin is drug of choice
    • 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
Capsular organism

Gram + Diplococci

Some asymptomatic carriers

Diseases;

Meningitis with effusions

Pneumonia with effusions

Bacteraemia/Sepsis

Otitis Media

Sinusitis

Streptococcal Pneumoniae
pneumococcal conjugate vaccine
Pneumococcal Conjugate Vaccine
  • 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
Measles
  • Transmission; airborne/droplet
  • Incubation; 10-14 days

Clinical;

  • Prodrome; high fever, harsh cough, coryza, conjunctivitis,
  • Rash; ‘morbilliform’, maculo-papular
    • Begins d3-6 from hairline, down face to trunk
    • Lasts up to 10/7
  • Koplik’s spots
measles rubeola
Measles (Rubeola)

RNA Paramyxovirus

Clinical diagnosis

Salivary swab measles IgM

Treatment

Supportive

Ribavirin if patient Immunocompromised

?Contacts

Prevention: HNIG within 6/7 if imunocompromised contact

Complications;

Otitis, pneumonia, croup

Encephalitis 1/5000 within a week of rash

15% Mortality

20-40% Neuro sequelae

Late complication;

SSPE (subacute sclerosing panencephalitis) 1/100,000

measles1
Measles
  • 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
mumps
Mumps
  • 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
Rubella

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
Congenital Rubella
  • 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 rubella1
Congenital Rubella

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

slide55
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)
hiv and immunisation
HIV And Immunisation
  • Children With HIV infection whether symptomatic or asymptomatic should receive:
    • 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
Summary
  • Neonates & Infants immature immune systems
  • Vaccines very effective protection
  • Know schedule (old & new & catch-up)
  • Know diseases they prevent (MCQs)
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