Infectious Disease

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Infectious Disease Immunity

• Dr. D. Barry

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Part 1

• 1) Immune System
• 2) Vaccinations
• 3) Vaccine Preventable Diseases

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Part 2

• 1) Assessing the Febrile Child
• 2) Common Childhood Infections
• 3) Antibiotic choices
• 4) Immunodeficiencies

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1 Immune System
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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

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• 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
• Mums IgG only crosses placenta

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Neonatal antibodies

• IgG Transplacental ie maternal
• T1/2 21 days
• Nadir at 3-5months
• Infants own IgG takes over
• 60 of adults 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

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• 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

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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

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Immune system in balance

• Infection viral/bacterial/opportunistic
• Hypersensitivity Allergy, Atopy, Intolerance
• Autoimmune disorders
• Immunodeficencies
• Therapeutic Vaccinations
• Monoclonal antibodies
• IVIG

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2 Vaccinations

• Medicines greatest lifesaver

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Ireland 12 vaccines

• Mycobacterium BCG x 1
• Diphtheria
• Tetanus
• Pertussis 6in1 x 3
• Polio
• Haemophilus influenza b
• Hepatitis B
• Meningococcal C Men C x 3
• Pneumococcus PCV x 3
• Measles
• Mumps MMR x 2
• Rubella

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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
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Those born before July 2008
Age Vaccine
Birth BCG
2 months 5in1, MenC
4 months 5in1, MenC
6 months 5in1, MenC
12-15 months MMR, Hib
4-5 years 4in1, MMR

• No Routine Hepatitis B or Pneumococcal vaccine
• PCV Catch-up programme (for lt2 year olds)

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Why Immunise?

• In 1974, only 5 of the worlds children had
  access to vaccines.
• A global effort in the early 80s aimed to
  provide six vaccines to 80 of children worldwide
• Immunisation now saves gt3,000,000 lives each year
• Protects millions more from illness and permanent
  disability

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Other vaccines

• Influenza
• Varicella
• Hepatitis A
• HPV
• Travel vaccines

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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

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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

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Live Attenuated Killed Orgs Subunits
Measles Polio (IPV) Hib
Mumps Men C
Rubella Pneumo (PCV)
BCG Influenza Hep B
Acellular Pertussis
Varicella Cellular Pertussis
Cholera/typhoid/ yellow fever Cholera/Typhoid/Rabies Hep A
Oral Polio
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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.

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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.

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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.

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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.

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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 lt 1 yr, 1 dose gt 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 gt 10yrs Td is given

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Contraindications/ Precautions
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..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
• Childs mother is pregnant or Child being
  breast-fed
• Impending surgery
• Child over the recommended age
• Corticosteroid replacement therapy

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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 gt 50
• Malaise, headache and transient fever occur
  occasionally

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Tetanus

• 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

• Clostridium tetani
• Muscular rigidity with superimposed contractions
• Organism is ubiquitous
• Nb puncture wounds, bites etc.
• Incubation period 4-21 days

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Pertussis (Whooping cough)

• Diagnosis often clinical
• Peri-nasal swab poor yield
• Lymhocytosis
• Treatment
• Isolate
• Erythromycin reduces infectivity
• Supportive
• Vaccination

• Bordetella pertussis
• 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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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

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• Vaccine
• Acellular pertussis
• 6 in 1 x 3
• Booster at 4-5 yrs
• No upper age limit but considered unnecessary gt 7
  yrs
• Efficacy variable 35 100 in studies
• Previous concern re seizures induced by Cellular
  Vaccine (not used anymore)

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Pertussis - special precautions

• Advice from the childs 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

• 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

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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 gt 1 yr need only 1 dose
• Children gt 4 yrs do not need immunisation with
  Hib
• Persons with asplenia or undergoing splenectomy
  should be vaccinated

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Hib Treatment

• Index case tx with cefotaxime or ceftriaxone
• Immunise 1 month after disease if lt 2 yrs
• Household contacts / Play-group/ creche
  chemoprophylaxis
• Except pregnant women
• Non-immunised contacts lt 4yrs need vaccine
• All household contacts irrespective of age or
  immunisation history IF there are any
  unvaccinated childrenlt 4yrs
• Chemoprophylaxis Rifampicin
• Neonates and infants lt 1 yr 10mg/kg od for 4
  days
• Children gt 1 yr 20mg/kg od for 4 days ( max
  600mg/day)
• Adults 600mg one daily x 4 days

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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

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Hepatitis B vaccination

• Traditionally only vaccinated high risk groups
• Sex workers
• Individuals who change sexual partner frequently
• IVDUs
• 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

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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

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Meningococcus C

• Neisseria Meningitidis
• Gram neg. cocci
• Causes Meningitis, Septicaemia
• Notifiable disease
• Contact tracing chemoprophylaxis required

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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.

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Streptococcal Pneumoniae

• Capsular organism
• Gram Diplococci
• Some asymptomatic carriers
• Diseases
• Meningitis with effusions
• Pneumonia with effusions
• Bacteraemia/Sepsis
• Otitis Media
• Sinusitis

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Pneumococcal Conjugate Vaccine

• 7 serotypes (75-80 invasive pneumococcus)
• ? immunogenicity with mutant diphtheria toxin
• gt 90 effective
• 23-valent polysaccharide available
• for high risk children gt 2years age
• eg. Asplenia
• Effective for 5 years
• Not in Primary Immunisation Schedule

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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
• Kopliks spots

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Measles (Rubeola)

• 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

• RNA Paramyxovirus
• Clinical diagnosis
• Salivary swab measles IgM
• Treatment
• Supportive
• Ribavirin if patient Immunocompromised
• ?Contacts
• Prevention HNIG within 6/7 if imunocompromised
  contact

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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

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Mumps

• Acute viral illness
• Swelling of one or more salivary glands usually
  the parotids
• CNS involvement is frequent
• Symptomatic meningitis occurs in lt10
• 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

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Rubella

• Rubella difficult to diagnose
• Fever lt38.5, 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 lt1wk from rash onset
• Buccal swab, urine, rising antibody titre
• Rare complications
• Polyarthralgia / Polyarthritis
• Thrombocytopenia
• Encephalitis (1 in 6000)

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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

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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
• gt80 women infected in 1st trimester affected
  infants
• Infants with congenital rubella may shed virus
  for over a year

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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

• 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

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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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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