Tutorial

Infectious Disease & Immunity

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

1; Immune System

Immune system
Neonates have immature immune system(esp. adaptive system; lymphocytes, antibodies)Lymphocytes ↑ (thymus) & mature with antibody production relative to exposureFoetal/ Neonatal monocytes, slow to process foreign antigensInfants produce a/b against simple proteins (eg. Vaccines) not polysaccharides until 2 years

Foetal Lymphocytes from 9/40 in liverBone, liver, spleen 12/40 T-cells from 14/40 & In utero sterile environment (ideally)Therefore no anti-bodies producedMum’s IgG only crosses placenta

Neonatal antibodies

IgG; Transplacental ie maternal 60% of adult’s level at 1 year100% by 6-10 yearsIgM; v low at birth; 75% adult level at 1 yr *IgA, IgD, IgE; 10-40% at 1 yr

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


Immune system; ‘in balance’ Infection; viral/bacterial/opportunistic Hypersensitivity; Allergy, Atopy, Intolerance Autoimmune disorders Immunodeficencies Therapeutic; Vaccinations

2; Vaccinations

“Medicine’s greatest lifesaver”

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

Those born before July 2008

No Routine Hepatitis B or Pneumococcal vaccine PCV Catch-up programme (for <2 year olds)
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


Table : Vaccination Schedule for Infants and Children 2012 Age Type of vaccine 0-1 Week OPV0 dose , HepB1 , BCG 2 Months OPV1 , PENTA1,ROTA1 4 Months OPV2 , TETRA1,ROTA2 6 Months OPV3 , PENTA2,ROTA3 9 Months Measles + VIT A 15 Months MMR (Measles , Mumps , Rubella) 18 Months TETRA2, OPV First Booster dose + VIT A 4-6 Years DPT , OPV Second Booster dose + MMR2


Table : National Immunization Schedule for Infants and Children 2015 Age Type of vaccine 0-1 Week HepB1 , BCG + OPV0dose 2 Months HEXA 1,ROTA1 ,PREV13- 1+OPV1 4 Months HEXA2,ROTA2,PREV13-2 + OPV2 6 Months HEXA3,ROTA3,PREV13-3 + OPV3 9 Months Measles + VIT A 15 Months MMR(Measles , Mumps , Rubella) 18 Months PENTA (DTP+IPV+Hib ) OPV + VIT A 4-6 Years TETRA (DTaP +IVP ) + OPV + MMR

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 worldwideImmunisation now saves >3,000,000 lives each yearProtects millions more from illness and permanent disability

Other vaccines

Influenza Varicella Hepatitis A HPV Travel vaccines

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

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

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

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:
0 months
Birth
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.
12 months
15 months
MMR vaccine first given
First signs of autism

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 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.



Late Entrants To some European countries 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

Contraindications/ Precautions

……..NOT Contraindications Family history of adverse reactions to immunisationsMinor infections without fever or systemic upsetFamily hx of convulsionsHistory of measles, mumps, pertussis in the absence of proof of immunityChild’s mother is pregnant or Child being breast-fedImpending surgeryChild over the recommended ageCorticosteroid replacement therapy

Diphtheria

Corynebacterium diphtheriaeAffects upper respiratory tractIncubation – 2-5 daysSpread; droplet/close contactDisease characterised by an inflammatory exudate  obstructive membrane over the airwayOther manifestation:MyocarditisVocal cord paralysisGuillain 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

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

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



‘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


VaccineAcellular pertussis6 in 1 x 3Booster at 4-5 yrsNo upper age limit but considered unnecessary > 7 yrsEfficacy variable; 35 – 100% in studiesPrevious concern re; seizures induced by Cellular Vaccine (not used anymore)

Pertussis - special precautions

Advice from the child’s paediatrician may need to be sought prior to immunisation where there is:A personal history of convulsionsAn evolving neurological problemIf 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

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

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

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

Traditionally only vaccinated high risk groupsSex workersIndividuals who change sexual partner frequentlyIVDU’sPrisonersTattoo artistsHomeless peopleImmigrants from, or travellers to, areas with a high prevalence of HBV Security and emergency services personnelFamily contacts of HBV ptsCRF / HIV / chronic hepatitisHealthcare workers

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

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

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 caseHave shared living or sleeping accomodationHad mouth kissing contact with the patientNursery/creche /daycare contactsMedical personnel who have had ‘intimate’ contact with the patient ( mouth-to-mouth, intubation)Rifampicin is drug of choiceAlternative prophylaxis is Ceftriaxone 250 mg im for adults and 125mg for childrenFor 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

Pneumococcal Conjugate Vaccine

7 serotypes (75-80% invasive pneumococcus)↑ immunogenicity with mutant diphtheria toxin> 90% effective23-valent polysaccharide available for high risk children > 2years age eg. AspleniaEffective for 5 yearsNot in Primary Immunisation Schedule


Measles
Transmission; airborne/dropletIncubation; 10-14 days Clinical; Prodrome; high fever, harsh cough, coryza, conjunctivitis, Rash; ‘morbilliform’, maculo-papularBegins d3-6 from hairline, down face to trunkLasts up to 10/7Koplik’s spots

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

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

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 – difficult to diagnoseFever <38.5, LN + (esp Post Triangle)May have splenomegaly, palatal petechiaeMild self limited disease in children – 25 -50% subclinicalIncubation 2 – 3 weeksInfectious (droplets) for <1wk from rash onsetBuccal swab, urine, rising antibody titreRare complications:Polyarthralgia / Polyarthritis Thrombocytopenia Encephalitis (1 in 6000)

Congenital Rubella

LBW, growth retardationMicrocephaly, learning disability, psycheMicrophthalmia, catarract, glaucomaMicrognathiaSensori-neural deafnessHepato-Spleno-megaly (transient), diabetesThrombocytopenic purpura ‘blueberry muffin’PDA


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


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

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

Neonates & Infants immature immune systems Vaccines very effective protection Know schedule (old & new & catch-up) 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



Sensitivity of vaccines to freezing Vaccines damaged by freezing DPT DT Td TT Hepatitis B Vaccines unaffected by freezing BCG * OPV Measles * Mumps


IMPORTANT!• Measles, BCG and mumps vaccines must be reconstituted only with the diluent provided by the manufacturer of the vaccine in use.• Never use other diluent.• Diluent must be cold, between 0 and 8 degrees Celsius, before being mixed with the vaccine.• When reconstituted, the vaccine must be used within 6 hours, and any remainder discarded

IMPORTANT:• All vaccines lose potency gradually, even at correct.• Storage temperatures - observe expiry dates.• All vaccines suffer much faster loss of potency when exposed to temperatures above +8 degrees C.• Any loss of vaccine potency is irreversible.• Damage due to successive exposures to heat or light is cumulative.• Hepatitis B, DPT, DT, Td and TT are destroyed by freezing.• BCG and measles vaccines are damaged by exposure to strong light as well as heat.

SUMMARY POINTS!• In health facilities, keep vaccines for a maximum of one month. • Store all vaccines in the refrigerator at 0 to +8 o C.• Place OPV, measles and mumps vaccine closest to the evaporator.• Place DPT, DT, Td, BCG and hepatitis B on lower shelves, away from the evaporator;• Do not keep vaccines in the door shelves.• Keep sealed water bottles in the bottom of the refrigerator.• Keep diluent next to its vaccine or mark it clearly if it is placed on a different shelf

Thank you