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Infectious Disease & Immunity

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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Infectious Disease & Immunity

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  1. Infectious Disease & Immunity Dr. D. Barry

  2. Part 1 1) Immune System 2) Vaccinations 3) Vaccine Preventable Diseases

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

  4. 1; Immune System

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Immune system; ‘in balance’ • Infection; viral/bacterial/opportunistic • Hypersensitivity; Allergy, Atopy, Intolerance • Autoimmune disorders • Immunodeficencies • Therapeutic; Vaccinations • Monoclonal antibodies • IVIG

  11. 2; Vaccinations “Medicine’s greatest lifesaver”

  12. 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

  13. Those born before July 2008 No Routine Hepatitis B or Pneumococcal vaccine PCV Catch-up programme (for <2 year olds)

  14. 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?

  15. Other vaccines Influenza Varicella Hepatitis A HPV Travel vaccines

  16. 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’

  17. 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

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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

  23. Contraindications/ Precautions

  24. ……..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

  25. 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

  26. 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

  27. 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)

  28. ‘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

  29. 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)

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

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

  38. 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.

  39. Capsular organism Gram + Diplococci Some asymptomatic carriers Diseases; Meningitis with effusions Pneumonia with effusions Bacteraemia/Sepsis Otitis Media Sinusitis Streptococcal Pneumoniae

  40. 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

  41. 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

  42. 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

  43. 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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