Esteghamati MD, MPH

1.Live attenuated (oral polio, BCG, VZV)2. Killed vaccine (influenza, IPV, hepatitis A, pertussis) 3. Toxoid (tetanus, diphtheria)4. Purified (subunit) antigen (meningococcal vaccine, Haemophilus influenzae vaccine)5. Recombinant antigen (hepatitis B)6. DNA vaccines (in investigational phase)7. Synthetic peptides (in investigational phase)

Suspending agents e.g. water, salinePreservatives e.g. thiomerosalStabilisers e.g. sorbitol and hydrolyzed gelatin - MMR Adjuvants e.g. aluminium Salts

Other substances which may be presentResiduals in the growth mediumAntibiotics, e.g. neomycin, streptomycin - IPV, varicella vaccine consider these components as well when assessing causality!

Diphtheria-tetanus-pertussis (DPT) pertussis component has adjuvant effect for diphtheria and tetanus toxoids Different viruses in one vaccination e.g. OPV-type 1, 2, 3 polioviruses How will the use of combination vaccines influence investigation of adverse events?

allergy or asthma (with the exception of a known allergy to a specific component of the vaccine mentioned above);any minor illness, such as respiratory tract infections or diarrhoea with temperature below 38.5Cfamily history of adverse events following immunizationfamily history of convulsions, seizures, or faints;treatment with antibiotics;known or suspected HIV infection with no signs and symptoms of AIDS;signs and symptoms of AIDS, except as noted in Table 6.1;child being breast fed;chronic illnesses such as chronic diseases of the heart, lung, kidney, or liverstable neurological conditions, such as cerebral palsy or Downs Syndrome;premature or low-birthweight (vaccination should not be postponed);recent or imminent surgery;malnutrition; andhistory of jaundice at birth.

Recommendations for immunization of HIV-infected children and women of childbearing age

VaccineAsymptomatic HIV infectionSymptomatic HIV infectionBCGvaccinateDo not vaccinateDTPvaccinatevaccinateOPVvaccinatevaccinateMeaslesvaccinatevaccinateH. influenzae type bvaccinatevaccinateHepatitis BvaccinatevaccinateYellow fevervaccinateDo not vaccinate aTetanus toxoidvaccinatevaccinate

Diluent are not interchangeable, different vaccines have different diluents; mixing and administering the wrong diluent has led to serious adverse events including death. Always use diluent from the same manufacturer as the vaccine.

Diluents should be cooled before being mixed with the vaccine

Do not reconstitute vaccines until you are ready to immunize.

You must discard reconstituted vaccine after six hours or at the end of the immunization session, whichever comes first.

Name of vaccineBCGDTP or DTP-HepB, HepBMeasles/ Yellow FeverOPVWhere givenOuter upper left arm or shoulderOuter mid-thigh in infants/outer upper arm if olderOuter mid-thigh/upper arm depending on the ageOralHow givenIntradermal injectionIntramuscular injectionSubcutaneous injectionOral dropperDose0.05 ml 0.5 ml0.5 ml2 dropsNeedle size10mm, 26 gauge25mm, 23 gauge25mm, 23 gaugeTypePowder + DiluentReady-to-usePowder + DiluentVial with oral dropperAppearanceWhite, cloudy liquid with sediment that suspends when shaken (see shake test Module 3)White, cloudy liquid with sediment that suspends when shaken (see shake test Module 3)Clear, slightly yellow liquidClear, pink or orange liquid

Position the infant sideways on the mother's lap with the infants whole leg bare.

The parent should hold the infant's legs.

Gently stretch the skin flat between your thumb and forefinger. Insert the needle at a 90 angle.

Quickly push the entire needle straight down through the skin and into the muscle. Inject slowly to reduce pain.

Diagram showing how to locate the site to give IM injection to infants

For vaccinating older children, adolescents and adults, the deltoid muscle of the upper arm may be used. In infants and young children under 15 months of age the deltoid muscle does not provide a safe intramuscular (IM) site due to the superficiality of the radial nerve and the deltoid muscle being insufficiently developed to absorb medication adequately

Diagram showing how to locate deltoid

Ask the woman to sit down.Tell her to drop her shoulder and place her left hand behind her back or resting on the hip. This relaxes the muscle in the arm and makes the injection nearly painless. Put your finger and thumb on the OUTER part of the upper arm. Use your left hand to squeeze up the muscle of the arm.Quickly push the needle straight down through the skin between your fingers. Go deep into the muscle.Press the plunger with your thumb to inject the vaccine.Pull out the needle quickly and smoothly and ask the woman to press the site gently with a cotton pad in case of bleeding

Should elicit immune response with minimal risk Deep IM preferable for vaccines with adjuvants (depot effect and less granuloma formation) SC/intradermal - better for live vaccines to lessen risk of neurovascular injury but still immunogenic (e.g. BCG)

A medical incident that takes place after an immunization, causes concern, and is believed to be caused by immunizationVaccine reaction - caused by vaccines inherent properties Programme error - caused by error in vaccine preparation, handling, or administrationCoincidental - happens after immunization but not caused by it (a chance association)Injection reaction - anxiety or pain of injection not vaccineUnknown - cause cannot be determined

Common, minor reactionsvaccine stimulates immune systemsettle on their ownwarn parents and advise how to manage

Rare, more serious reactionsanaphylaxis (serious allergic reaction)vaccine specific reactions

* Rate of local reactions likely to increase with booster doses, up to 50-85%** Symptoms include diarrhoea, headache, and/or muscle pains

VaccineLOCAL REACTIONFEVERSYSTEMIC REACTIONBCG90-95%--------------------Hib5-15%2-10%---------Hepatitis BAdult%15 Child 5%-----------1-6%MMR10%5-15%5% rashPOLIO--------

AbscessAtrophyCellulitesErythemaGranuloma/cyst /noduleHematoma/bleedingIndurationPain/tendernessPigmentationPruritusSwellingUlcerationWarmth

Color: The color of the lesion should be documented(e.g., skin color, brown, red, yellow, tan or blue).

Number: The approximate number of lesions should be recorded.

Size: The average size of lesions (with range) should be recorded in centimeters

Distribution: The anatomic distribution of the eruption should be documented on a standardized diagram of the human body.

Host factors (immune status, medications, etc.)

Biologic characteristics of the vaccine (e.g., live attenuated versus inactivated component vaccines)

Biologic characteristics of the vaccine-targeted disease

Biologic characteristics of the vaccine associated with a mucocutaneous change

incidence and pattern of mucocutaneous changes seen in previous trials.

Bulla : a fluid filled cavity or elevation >1 cm in diameter fluid can be clear, serous, hemorrhagic or pus Cyst : a closed cavity or sac containing fluid or semisolid materialMacule : a flat generally

Erosion: a localized loss of epidermal or mucosal epithelium Crusting : died exudates of plasmaScaling : whitish scale present on the skinAtrophy: thinning or absence of the dermis or subcutaneous fat Excoriation: oval or linear depression of the skin exposing a broad area of red dermis Fissure: linear or wedge shape crack in the epidermis Ulcer : a circumscribed loss of epidermis or mucosa extending to the dermis

we defined persistence as more than 3 h. It is recognized that this is an arbitrary, historical cut off.

Recognizing cultural differences and the subjectivity of qualitativedescriptions of crying (e.g., fierce and high-pitched)

We agreed to choose the term persistent crying for two reasons. First, the term implies the apparent discomfort of the child, a prolonged duration of the episode as well as various futile attempts to comfort the child. Second, it is the combination of these characteristics which concerns parents and thus affects their benefit to risk balance of the immunizationby fearing long term sequelae of the episode.

Local reactioncold cloth at injection siteparacetamol Fever >38Cgive extra fluidstepid sponging paracetamol Irritability malaise and systemic symptomsgive extra fluidsparacetamol

* Risk benefit assessment when administered to HIV positive individuals

* Risk benefit assessment when administered to HIV-positive individuals Adopted from Plotkin pg 66-67

WHO case definitions are used here Lack of standardized case definitions in the literaturee.g. feverThe Brighton collaborationdeveloping case definitions for AEFIpromoting global implementation of these definitionssecretariat@brightoncollaboration.org http://brightoncollaboration.org

Type 1 hypersensitivity reactionCirculatory failureBronchospasm +/- laryngospasm/laryngeal oedema respiratory distressMay include pruritis, flushing, angioedema, seizures, vomiting, abdominal cramps & incontinenceOccurs in previously sensitized individuals

Reported less from developing countriesLess sensitization?Less reporting?Anaphylaxis is rare (1/1 000 000 vaccinations)Fainting is commonUntrained staff may misdiagnose fainting/dizziness for anaphylaxis or vice versaAdministration of adrenaline in a faint may be dangerousPROMPT MANAGEMENT IS VITAL!

Disseminated BCGwidespread infection, 1-12 months after BCG usually in immunocompromised individualconfirm by isolation of Mycobacterium bovis BCG straintreat with antituberculous regimen including Rifampicin and Isoniazid

Osteitis/osteomyelitisinfection of the bone with M bovis BCG strainmanagement as above

Suppurative lymphadenitisoccurs within 2-6 months of BCG vaccinationcase definition 1 lymph node> 1.5 cm in size/draining sinus over a lymph nodeusually occurs in the axilla, on the same side as innoculationManagementheals spontaneously over monthsonly treat if sticking to skin or drainingsurgical drainage and local installation of antituberculous drugsystemic Rx is ineffective

World Health Organization

World Health Organization____________________________________________________________

World Health Organization

World Health Organization

Case definition: Abrupt onset of fever, vomiting and watery diarrhoea

Occurs within a few hours of immunization

Often leads to death within 24-48 hours

needs to be reported as possible indicator of programme error

Brachial neuritis Presents with pain in shoulder and upper armFollowed by weakness +/- wasting of arm and shoulder musclesSensory loss not prominentOccurs 2-28 days after vaccinationPossibly a manifestation of immune complex diseaseManagement is symptomatic

Particularly associated with measles and DTP vaccination (pertussis component)febrile seizures Temp >38afebrile seizures Temp normal

Febrile seizures more common with pertussisAn association with non-febrile seizures has not been proven

Possibly associated with measles & pertussis vaccine Case definition of encephalopathy2 out of 3 ofseizuresalteration of consciousness lasting for one day or moredistinct change in behavior for one day or more

Temporal relationshipwithin 48 hrs with DTPwithin 7-12 days after measles or MMR

An analysis of claims for encephalitis following measles vaccine in the USA found clustering of events 8-9 days after vaccination (Wetbel 1998, Duclos 1998)

This supports, but does not prove, the possibility that measles vaccine was causative

Risk is less than 1 case per million

Aseptic meningitis is commonly defined as a syndrome characterized by acute onset of signs and symptoms of meningeal inflammation, cerebrospinal fluid (CSF) pleocytosis and the absence of microorganisms on Gram stain and/or on routine culture Aseptic meningitis is frequently caused by viral agents, particularly by enteroviruses

In recent years, the use of polymerase chain reaction (PCR) for detection of viruses in CSF has become more common and the specific aetiology of aseptic meningitis can often be diagnosed in routine clinical practice

Measles and mumps viruses were important causative agents of aseptic meningitis before introduction of measles and mumps vaccines

Aseptic meningitis have been reported after oral polio,MMR, varicella, yellow fever and smallpox vaccines

The increased risk after MMR has been well documented

Immunization with MMR containing the Urabe, Leningrad-Zagreb and Hoshino mumps strains results in a 5.538-fold increased risk of aseptic meningitis approximately 27 weeks following immunization.

Outbreaks of aseptic meningitis have been documented following mass vaccination campaigns using MMR with the Leningrad-Zagreb or Urabe mumps strains.

The Jeryl-Lynn mumps strain has not been shown to increase the risk of aseptic meningitis

incidence of aseptic meningitis associated with MMR vaccine ranged from a frequency of 1:2000 for the Urabe strain to 1 > 1,800,000 for Jeryl-Lynn

. There is a paucity of data on the Leningrad-3 mumps strain, a predecessor of the Leningrad-Zagreb strain

In one further study, the incidence of aseptic meningitis after mass immunization with measlesrubella vaccine without a mumps vaccine strain has been reported to be low with an incidence of1:867,000 doses .

Aseptic meningitis following immunizationusually is benign and resolves without sequelae

Mainly associated with DTPCase definition Event of sudden onset occurring within 48 (usually less than 12) hours of vaccination and lasting from one minute to several hoursIn a child < 10 years of ageALL of the following must be presentlimpness (hypotonic)reduced responsivenesspallor or cyanosis - or failure to observe/recallTransient, self-limiting, NOT a contraindication to further vaccination

HHE has been documented to occur after immunization with diphtheria, tetanus, Haemophilus influenzae type b, and hepatitis B vaccines.

Most reported episodes followed administration of pertussis component vaccines, (whole-cell vaccines more often than acellular)

HHE has also been observed most frequently during the primary immunization series, mainly after the first dose

Whether these features are related to characteristics of the vaccinee, an immunologic phenomenon, presence of toxic component(s) in the vaccine, combinations of the above, or some yet to be determined cause, remains unclear.

Sex attribution does not seem to be a factor of relevance

a slight majority (53%) of HHE among females was demonstrated in reports in the United States while male predominance was observed in the enhanced surveillance program in The Netherlands

Rates vary greatly even for the same vaccine, as has been noted in the reported incidence of HHE after receipt of DTPw

The median time to onset of signs after immunization is 34 h but ranges from immediately to 48 h postimmunization

Of 203 cases in children

Apart from the clinical triad of signs, there are no further investigations (e.g., laboratory examinations) helpful in confirming the diagnosis of HHE.

blood pressure is normal at the time of presentation Leukocytosis due to neutrophilia is observed in children with or without HHE following immunization There is no evidence of significant changes in insulin or glucose levels

Studies reporting on the follow-up of HHE relying on parental reporting and neurodevelopmental testing demonstrated HHE to be a self-limiting event without long-term sequelae

Vaccine associated paralytic poliomyelitisOccurs within 4-30 days of receipt of OPV or 4-75 days after contact with vaccine recipientCase Following a national immunization day in 1996, cases of paralysis were reported after receiving OPV. On laboratory analysis, the wild virus was found, showing that the children had been infected with wild poliovirus before immunization. The cases of poliovirus were coincidental, and not caused by the vaccine.

Influenza vaccine and Guillaine Barr SyndromeMMR and autism, Crohns diseasePolio and HIVHepatitis B and multiple sclerosis DTP and permanent brain damageDTP and increased risk of mortalityAluminium and macrophagic myofasciitisBovine spongiform encephalopathy (BSE)ThiomerosalMultiple vaccines given simultaneously

**Types of Antigens The various types of antigens used in the preparation of vaccines are:

1. Live Attenuated (oral polio, BCG, VZV)2. Killed vaccine (influenza, IPV, hepatitis A, pertussis) 3. Toxoid (tetanus, diphtheria)4. Purified (sub-unit) antigen (meningococcal vaccine, haemophilus influenzae vaccine)5. Recombinant antigen (hepatitis B)6. DNA vaccines (in investigational phase)7. Synthetic peptides (in investigational phase)

The characteristics of these various vaccine antigens will be discussed during this session.

*Inactive Ingredients Suspending agents: Such as water/saline. Incorrect admin or use of suspending agent could be a cause of AEFI..Antibiotics: Used during the manufacturing phase to suppress the growth of any extraneous contaminants that may be introduced during various processing steps. Antibiotics such as kanamycin and neomycin are commonly recommended by FDA for plasmid DNA vaccines. Preservatives: Added to vaccines when there is a risk of contamination (e.g. multidose vials.) Combination vaccines - preservative/stablilser of 1 vaccine may affect potency of other. Thiomerosal adversely affected potency of IPV combination with DTP vaccine. Whether or not preservative is used, manufacturer still needs to evaluate vaccine potency and reversion to toxicity.Stablilizers - Stability is essential especially where we cannot guarantee cold chain. Instability can cause loss of antigenicity and decreased infectivity of live vaccine. Factors affecting stability - temperature and pH. Bacterial vaccines can become unstable due to hydrolysis and aggregation of protein and carbohydrate molecules.Stabilizers include: MgCl2 (OPV) , MgSO4 (for RSV, measles), lactose-sorbitol and sorbitol-gelatin. Because of concern about BSE - use non-animal products where possible. Residuals in Growth Medium:Speculation about the connection between HIV virus and polio vaccination- this postulated connection has been disproven*

Combination vaccine: A combination vaccine consists of 2 or more antigens which are in the same preparation. This approach is used in many of our vaccines including - MMR, DTP etc. It is very important, however, that these combination vaccines are carefully tested and tried out before introduced. For instance -adjuvants in a combination could reduce the activity of one vaccine and excessively increase the reactivity of the other vaccine. Also, there could be interactions with the buffers, stabilizers etc. E.g, Thiomersal in DTP and Hib vaccines can inactivate the IPV. Live vaccines can interfere with each other as well. The immune response to one vaccine can inhibit the replication of another virus.

************Route of Administration The ideal route of administration should elicit an immune response with minimal risk of adverse effects during injection. Deep IM injection preferable for vaccines containing adjuvants (this provides a depot effect and granuloma formation is less likely)The SC/ intradermal route is preferable for live vaccines to lessen risk of neurovascular injury but still immunogenic (e.g. BCG)

*What is an adverse event following immunization (AEFI)? Although the vaccines in general use in national immunization programmes are extremely safe and effective, adverse events can occur following vaccine administration and no vaccine is perfectly safe. In addition to the vaccines themselves, the process of immunization is a potential source of adverse events.An adverse event following immunization (AEFI) is any adverse event that follows immunization that is believed to be caused by the immunization. Using this terminology allows description and analysis of the event without pre-judging causality. Immunization will naturally be blamed for any event that happens after immunization.Reported adverse events can either be true adverse events, i.e. really a result of the vaccine or immunization process, or coincidental events that are not due to the vaccine or immunization process but are temporally associated with immunization. For the purpose of these guidelines AEFIs are classified into five categories. Immunization can cause adverse events from the inherent properties of the vaccine (vaccine reaction), or some error in the immunization process (programme error). The event may be unrelated to the immunization, but have a temporal association (coincidental event). Anxiety-related reactions can arise from the pain of the injection rather than the vaccine. In some cases the cause of the AEFI remains unknown.*Vaccine reactions Vaccine reactions result from the intrinsic properties of the vaccine. The purpose of a vaccine is to induce immunity by causing the recipient's immune system to react to the vaccine. Local reaction, fever and systemic symptoms can result as part of the immune response. In addition, some of the vaccines components (eg, aluminum adjuvant, stabilisers or preservatives) can lead to reactions. A successful vaccine reduces these reactions to a minimum while producing the best possible immunity.

Parents should be advised about the common, minor reactions and how to manage them.Local reactions: Cold cloth at injection site; ParacetamolFever: Give extra fluids; Wear cool clothing; Tepid sponge or bath; ParacetamolIrritability, malaise, & systemic systems: Give extra fluids; ParacetamolParacetamol dose: up to 15mg/kg; maximum of 4 doses in 24 hours (more can damage liver)

******************Rare, more serious reactions Most of the rare and more serious vaccine reactions (e.g., seizures, thrombocytopaenia, hypotonic-hyporesponsive episodes, persistent inconsolable screaming) do not lead to long term problems. Anaphylaxis, while potentially fatal, is treatable without leaving any long term effects. Although encephalopathy is included as a rare reaction to measles or DTP vaccine, it is not certain that this is in fact caused by these vaccines.Seizures are mostly febrile and risk depends on age, with much lower risk in infants under the age of 4 months or over the age of six years.Reactions to measles/MMR (except allergic and anaphylaxis) do not occur if already immune (~90% of those receiving a second dose).*Rare, more serious reactions Most of the rare and more serious vaccine reactions (e.g., seizures, thrombocytopaenia, hypotonic-hyporesponsive episodes, persistent inconsolable screaming) do not lead to long term problems. Anaphylaxis, while potentially fatal, is treatable without leaving any long term effects. Although encephalopathy is included as a rare reaction to measles or DTP vaccine, it is not certain that this is in fact caused by these vaccines.Seizures are mostly febrile and risk depends on age, with much lower risk in infants under the age of 4 months or over the age of six years.Reactions to measles/MMR (except allergic and anaphylaxis) do not occur if already immune (~90% of those receiving a second dose).*Rare, more serious reactions Most of the rare and more serious vaccine reactions (e.g., seizures, thrombocytopaenia, hypotonic-hyporesponsive episodes, persistent inconsolable screaming) do not lead to long term problems. Anaphylaxis, while potentially fatal, is treatable without leaving any long term effects. Although encephalopathy is included as a rare reaction to measles or DTP vaccine, it is not certain that this is in fact caused by these vaccines.Seizures are mostly febrile and risk depends on age, with much lower risk in infants under the age of 4 months or over the age of six years.Reactions to measles/MMR (except allergic and anaphylaxis) do not occur if already immune (~90% of those receiving a second dose).*Contraindications Certain contraindications apply to all vaccines. An anaphylactic reaction to a vaccine contraindicates further doses of that vaccine. If an individual has had an anaphylactic reaction to a vaccine constituent, any vaccine containing that constituent is contraindicated. Moderate or severe illness with or without fever is a contraindication to vaccination.

However, mild intercurrent illnesss with low grade pyrexia is not a contraindication to vaccination. Nor are previous mild to moderate local reactions, or fever after previous doses. Concurrent antimicrobial therapy and recent exposure to infectious disease are not contraindications. A history of penicillin or other allergies either in the recipient or their family is also not a contraindication to vaccination.

OPV and MMR vaccine are contraindicated in immunocompromised patients. In HIV infected individuals their use is advocated despite the risk of pathogenicity in symptomatic patients, because of the benefits in protection against the vaccine-preventable disease.

*Contraindications See previous page*****Adverse reaction to BCG vaccinationDisseminated BCG:Widespread infection.with Mycobacterium bovis may develop 1-12 months after BCG . This usually occurs in immunocompromised individuals. It may be confirmed microbiologically by isolation of Mycobacterium bovis BCG strain.Patients with disseminated BCG should be treated with an antituberculous regimen including Rifampicin and Isoniazid.Osteitis/Osteomyelitis:Infection of the bone with M bovis BCG strain may occur. Patients developing this complication are managed in the same manner as those with disseminated BCG. Described particularly in Scandinavia and Eastern Europe. Association particularly with the Goteberg strain.Treatment: BCG strain is resistant to PZA - therefore need to consider addition of ethambutol. *Suppurative lymphadenitis: This occurs within 2- 6 months of BCG vaccination.Case Definition: 1 lymph node> 1.5 cm in size OR draining sinus over a lymph nodeSuppurative lymphadenitis usually occurs in the axilla, on the same side as innoculation.Management:The lesion will heal spontaneously over monthsOne only needs to manage actively if the involved nodes stick to skin or form draining sinuses. Management in such cases would involve surgical drainage and local installation of antituberculous drug.Note:Systemic Rx is with antituberculous drugs is ineffective in such cases.******Tetanus vaccine

Brachial Neuritis This presents with pain in shoulder and upper arm. This is followed by weakness with or without wasting of arm and shoulder muscles. Sensory loss not prominent. Dysfunction is limited to the nerve plexus of the arm, without involvement of other peripheral or central nervous system structures.Brachial neuritis occurs 2-28 days after vaccination. The pathogenesis is not clearly understood. It is possibly a manifestation of immune complex disease. Usually associated with the administration of multiple doses.Management is symptomatic.

*SeizuresSeizures have been particularly associated with measles and the pertussis component of DTP vaccination Febrile seizures: a seizure occuring in association with pyrexia (temperature>38 degrees celsius)Afebrile seizures: a seizure occuring in an apyrexial patient.

Febrile seizures more common with Pertussis vaccination than with other vaccines. Any vaccine which provokes febrile response may potentially precipitate febrile seizures in a child. Such seizure are not associated with long term sequelae and do not predispose children to the development of epilepsy in later life.*Encephalopathy and encephalitis The development of encephalopathy and encephalitis are possibly associated with Measles and Pertussis vaccineIt is NOT certain that these vaccines are causative.Case definition of encephalopathy:2 out of 3 of:1. Seizures2. Alteration of consciousness lasting for one day or more3. Distinct change in behaviour for one day or moreA temporal relationship with the administration of the vaccine must also existWithin 48hrs with DTPWithin 7-12 days after measles or MMR

* Encephalitis and measles vaccinationAn analysis of claims for encephalitis following measles vaccine in the USA found clustering of events 8-9 days after vaccination (Wetbel 1998, Duclos 1998)This supports, but does not prove, the possibility that measles vaccine was causative.Risk is less than 1 case per million******Hypotonic hypotensive episode (HHE or shock-collapse) Mainly associated with DTPCase definition: An event of sudden onset occurring within 48 (usually less than 12) hours of vaccination and lasting from one minute to several hours.In a child < 10 years of age

3. ALL of the following must be present-Limpness (hypotonic)-Reduced responsiveness-Pallor or cyanosis- or failure to observe/ recallHHE is a transient, self limiting reaction of unknown pathogenesis.It is NOT a contraindication to further vaccination.

*********Influenza vaccine and GBS: The 1976 swine influenza virus was associated with an increase of Guillain- Barre Syndrome (GBS). The rate, that exceeded the background rate, was slightly less than 10 per million. CDC 1998.The risk from subsequent vaccines, prepared from different virus strains, is less clear. A recent study found an overall elevated risk of GBS of 1.7 in the 6 weeks following vaccination in the 1992-1993 and 193-194 seasons. This represented n excess of 1 or 2 cases per million vaccine recipients (Lasky et al, 1998)

MMR and Autism: There is at present no conclusive evidence to suggest an association between MMR and autism. The alleged association is based on studies with methodological problems, and has been refuted. (Duclos and Ward, 1998)

Polio and HIV:The postulated link between polio vaccine and the origins of the HIV epidemic have been disproved.

Hepatitis B and Multiple Sclerosis: At present available data, though limited, does not demonstrate a causal association. In France where the concern was raised, the background rate of demyelinating disease was 1-3 cases per 100 000. Notification rate of demyelinating disease in temporal association with Hep B vaccination was 0.6 per 100 000.

DTP and permanent brain damage: The USA Safety Committee agreed in 1994 that there was insufficient evidence to conclude that pertussis vaccine could cause permanent brain damage. (Edwards et al, 1999)

Aluminium and macrophagic myofasciitis- more research needed. Based on available evidence at present, there is no health risk from the administration of alumnium containig vaccines.

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