General Advice on Immunisation

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Contraindications and Special Considerations

All vaccines are contraindicated in those who have had a confirmed anaphylactic reaction to:

a previous dose of a vaccine containing the same antigens, or
another component contained in the relevant vaccine, e.g. neomycin, streptomycin or polymyxin B (which may be present in trace amounts in some vaccines).

Live vaccines may be temporarily contraindicated in individuals who are:

immunosuppressed
pregnant

Some vaccines are contraindicated in specific groups:

Egg allergy: As of 2017, it
As of 2017, it has been recommended that egg allergic individuals may be safely vaccinated with the measles mumps rubella (MMR), the measles mumps rubella varicella (MMR-V)vaccine (which contains no egg protein) and the infuenza vaccine (which may contain minute traces of egg protein).
Special precautions such as split dosing, prior allergy testing with the vaccines, allergy specialist review before vaccination or prolonged waiting times after administration are not required.
The yellow fever and Q fever vaccines potentially contain higher amounts of egg protein and an allergy specialist evaluation is recommended before vaccination.

Severe latex allergy: While it is theoretically possible that latex protein in the tip cap and/or rubber plunger or vial stoppers may cause allergic reactions, there is little evidence that such a risk exists and any such risk would be extremely small (around 1 per 1 million vaccine doses). Even so, as a precaution, vaccines supplied in vials or syringes that contain latex should not be administered, unless the benefit of vaccination outweighs the risk of an allergic reaction to the vaccine.

For latex allergies other than anaphylactic allergies (e.g. a history of contact allergy to latex gloves), vaccines supplied in vials or syringes that contain latex can be administered.

Pregnancy: There is no evidence that any live vaccine (including rubella and MMR) causes direct foetal injury or birth defects. However, since the theoretical possibility of foetal infection still exists, live vaccines should generally be delayed until after delivery. Women should avoid conception for 4 weeks after vaccination with live vaccines. Termination of pregnancy following inadvertent immunisation is not recommended.

Even though inactivated vaccines cannot replicate and cause infection in either the mother or the foetus, they should be administered to pregnant women only if protection is required without delay.

Immunosuppression: Live vaccines can, in some situations, cause severe or fatal infections in immunosuppressed individuals (including the HIV-infected) due to extensive replication of the vaccine strain. For this reason, severely immunosuppressed individuals (see section on Immunocompromised Patients) should not be given live vaccines.

Killed or recombinant vaccines and toxoids may be administered to immunosuppressed individuals since they cannot replicate. Since they may elicit a lower immune response than in immunocompetent individuals, a double dose may be required.

Other Considerations:

Adults on stable long term low dose corticosteroid therapy (up to 20mg prednisolone per day for more than 14 days) either alone, or in combination with other low dose immunosuppressive drugs or low dose non-biological oral immune-modulating drugs (e.g. methotrexate, azathioprine, 6-mercapto (purine), are not considered sufficiently immunosuppressed. These patients can therefore receive live vaccines.

Non-systemic corticosteroids, such as aerosols or topical or intra- articular preparations, do not cause systemic immunosuppression. Neither does replacement schedule of corticosteroids for people with adrenal insufficiency. Therefore, administration of live vaccines is not contraindicated.

Live vaccines should not be given to the following:

Patients receiving immunosuppressive treatment including radiotherapy or systemic high-dose steroids.
Patients with evidence of primary or secondary immunodeficiency.

Contact with an individual with immunodeficiency, on current/recent immunosuppressive therapy:

Historically, smallpox and oral polio were contraindicated in healthy household contacts of immunocompromised patients.

For most of the current live vaccines in use, transmission through contacts does not occur or can be minimised by simple precautions (e.g. MMR, varicella. See vaccine specific advice).

In addition, vaccination of close contacts of vulnerable people has a major benefit by reducing the risk of exposure to wild-type infection. Thus, some vaccines should be actively encouraged in family and household contacts of those at risk.

Organ transplant candidates should complete the recommended full vaccination schedule as early as possible because of the problem of reduced immune response to vaccines following transplantation as a result of immunosuppressive treatment.

Temporary Deferral of Immunisation

The following are situations where temporary deferral of immunisation is required:

Individuals with immunosuppression from malignant disease on chemotherapy should not receive live attenuated vaccines until at least 3 months after chemotherapy has finished.

Patients who received a hematopoietic stem cell transplant may be given inactivated vaccine or toxoid from 6 to 12 months after completing all immunosuppressive treatment, or longer if the patients developed graft versus-host disease.

For those on high dose systemic corticosteroids (for adults; daily doses in excess of 20mg for more than 2 weeks or 60mg of prednisolone), live attenuated vaccines should be postponed until at least 3 months after treatment has stopped.

Live virus vaccines, with the exception of yellow fever vaccine, generally should not be given during the 3 months following injection of immunoglobulin because the immune response may be inhibited. For MMRV vaccine, refer to Table 10.1.

The following are NOT contraindications to routine vaccinations (in some of these situations, additional precautions may be required – refer to the relevant chapter for further information):

Minor self-limiting illness without fever.
Asthma, eczema, or hay fever.
Treatment with antibiotics or locally-acting (e.g. topical or inhaled) steroids.
Contact with an infectious disease.
Family history of any adverse reactions following immunisation.
Previous history of the disease (with the exception of BCG for people who have evidence of past exposure to tuberculosis).
Someone in the household being pregnant.
Personal or family history of febrile convulsions or epilepsy.
Being a sibling or close contact of an immunosuppressed individual.
Recent or imminent elective surgery.
Imminent general anaesthesia.
Unknown or inadequately documented immunisation history.
Food intolerances.
Treatment with interferons & other non-immunosuppressing immunomodulatory.

Route and Site of Administration

By mouth:

Sugar lumps, if used, should be prepared with oral polio vaccine (OPV) immediately before administration. By allowing them to stand at room temperature for any length of time, may decrease the potency of the vaccine.

Cholera and typhoid vaccines are also to be given orally. Food and drink should be avoided for 1 hour before and 1 hour after vaccination. Oral administration of other medicinal products should be avoided within 1 hour before and after administration of the vaccine.

Intranasal (Currently no intranasal vaccines are available in Malaysia):

The live attenuated influenza vaccine (LAIV) is administered by the intranasal route (Fluenz®) and is supplied in an applicator that allows a divided dose to be administered in each nostril (total dose of 0.2ml, 0.1ml in each nostril). The device allows intranasal administration to be performed without the need for additional training.

Administration of either dose does not need to be repeated if the patients sneeze or blow their nose following administration. As heavy nasal congestion might impede delivery of the vaccine to the nasopharyngeal mucosa, defer administration of the vaccine until resolution of the nasal congestion has occurred. Alternatively, an appropriate intramuscularly administered influenza vaccine should be considered.

Subcutaneous (SC) and intramuscular (IM) injections:

Most vaccines are given by IM injections, rather than deep SC, as the former are less likely to cause local reactions. However, for individuals with a bleeding disorder, vaccines normally given by an IM route should be given by deep subcutaneous injection to reduce the risk of bleeding. Vaccines should never be given intravenously.

The preferred site for IM and SC immunisation is the deltoid area of the upper arm. The upper outer quadrant of the buttock (ventrogluteal) area is an alternative injection site.

IM injections should be given with the needle at a 90° angle to the skin and the skin should be stretched, not bunched. Deep SC injections should be given with the needle at a 45° angle to the skin and the skin should be bunched, not stretched. It is not necessary to aspirate the syringe after the needle is introduced into the muscle. (refer to Figure 1.1a & b).
Immunisations should not be given into the buttock, due to the risk of sciatic nerve damage and the possibility of injecting the vaccine into fat rather than muscle. Injection into fatty tissue of the buttock has been shown to reduce the immunogenicity of hepatitis B and rabies vaccines.

Inadvertent SC injection of IM vaccines:

If a vaccine that is registered for IM administration is inadvertently given subcutaneously, check the vaccine product information and the relevant disease-specific chapters for more details.

This can increase the risk of significant local adverse events, particularly with aluminium-adjuvanted vaccines (e.g. HBV, DTPa, DTPa combination or DT vaccines).

Hepatitis B vaccines should usually be repeated if they are inadvertently given subcutaneously.

Some IM vaccines may still be immunogenic when given by the SC route. These vaccine doses do not need to be repeated.

Intradermal injections:

BCG vaccine is ALWAYS given intradermally. The preferred site of injection is over the insertion of the left deltoid muscle; the tip of the shoulder must be avoided because of the increased risk of keloid formation at this site. For the tuberculin test, the middle flexor surface of the forearm is the recommended site.

The BCG technique is specialised and the person giving the BCG vaccine requires specific training and assessment. The skin should be stretched between the thumb and forefinger of 1 hand and the needle inserted with the bevel upwards for about 2mm into the superficial layers of the dermis, almost parallel with the surface. The needle should be visible beneath the surface of the skin.

Whilst the IM route is preferred for rabies pre-exposure prophylaxis, suitably qualified and experienced healthcare professionals may give the vaccine via the intradermal route. The preferred site of administration is behind the posterior border of distal portion of deltoid muscle.

During an intradermal injection, considerable resistance is felt and a raised, blanched bleb showing the tips of the hair follicles is a sign that the injection has been correctly administered. A bleb of 7mm in diameter is approximately equivalent to 0.1ml and is a useful indication of the volume that has been injected. If no resistance is felt, the needle should be removed and reinserted before more vaccine is given (refer to Figure 1.1c).

Figure 1.1 Techniques of Administration

Table 1.1 Injection Routes for Common Vaccines

Note: Always refer to the package insert included with each biologic for complete vaccine administration information.

Table 1.2 Injection Sites and Needle Sizes Appropriate for Each Age Group

* A 5/8 in needle may be used only if the skin is stretched tight, subcutaneous tissue is not bunched, and injection is made at a 90° angle.

Suitable sites for immunoglobulin administration:

This should be administered deep into a large muscle mass. If the volume is more than 5ml when given to older children and adults, the immunoglobulin should be divided into smaller amounts and given into different sites. The preferred site of injection is the upper outer quadrant (that is, ventrogluteal site) of the buttock.

Rabies immunoglobulin should be infiltrated into the site of the wound.

Interruption to vaccination:

If the process of administering a vaccine intramuscularly or subcutaneously is interrupted (such as by syringe–needle disconnection) and most of the dose has not been given, repeat the whole dose as soon as practicable.

Post Vaccination

Recipients of vaccine should remain in the vicinity for at least 15 minutes until they have been seen to recover from the procedure. The area should be close enough so that the vaccinated person can be observed and medical treatment can be provided rapidly if needed.

Paracetamol is not routinely used before, or at the time of, vaccination, but may be recommended as required for fever or pain occurring following immunisation.

The most serious immediate adverse effect following vaccination is anaphylaxis. However, in adults and older children, the most common immediate adverse event is a vasovagal episode (fainting), either immediately or soon after vaccination. Because this can lead to serious consequences, anyone who complains of giddiness or light-headedness before or after vaccination should be advised to lie down until free of symptoms.

Anaphylaxis

Symptoms of anaphylaxis include:

Pallor, limpness, and apnoea.
Upper airway obstruction: hoarseness and stridor as a result of angioedema.
Lower airway obstruction: subjective feelings of retrosternal tightness and dyspnoea with audible expiratory wheeze from bronchospasm.
Cardiovascular: sinus tachycardia, profound hypotension in association with tachycardia; severe bradycardia.
Skin: rapid development of urticarial lesions – circumscribed, intensely itchy wheals with erythematous raised edges and pale blanched centres.

Management of anaphylaxis:

Lie the patient in a left lateral position. If unconscious, insert airway.
Give1:1000(1-in-1,000) adrenaline by deep intramuscular injection unless there is a strong central pulse and the patient’s condition is good.
Adrenaline is not required for generalised non-anaphylactic reactions (such as skin rash or angioedema). If in doubt, IM adrenaline should be given. No serious or permanent harm is likely to occur from mistakenly administering adrenaline to an individual who is not experiencing anaphylaxis.
For adults, the dosage is 0.5-1.0-mL repeated as necessary up to a maximum of 3 doses. The lower dose should be used for the elderly or those of slight build.
If oxygen is available, give it by face mask.
Never leave the patient alone.
If appropriate, begin cardio-pulmonary resuscitation (CPR).
Chlorpheniramine maleate 2.5-5.0mg may be given intravenously. Hydrocortisone 100mg may also be given intravenously to prevent further deterioration in severely affected cases.
If there is no improvement in the patient’s condition in 5 minutes, repeat the dose of adrenaline every 5 minutes up to a maximum of 3 doses or until improvement occurs.
All cases should be admitted to hospital for further observation and treatment.

Storage and Disposal of Vaccines

On receipt, vaccines are immediately placed under the required storage conditions. Vaccines should be stored in the original packaging, retaining batch numbers and expiry dates. Vaccines should be stored according to the manufacturer’s summary of product characteristics (SPC) – usually at 2-8°c and protected from light. Generally vaccines should not be kept frozen but there are some exceptions, e.g. Varicella containing vaccines. This causes deterioration or loss of vaccines and may give rise to a loss of potency and an increase in reactogenicity.

A maximum/minimum thermometer (Minimax), should be used in refrigerators where vaccines are stored, irrespective of whether the refrigerator incorporates a temperature indicator dial. Opening of the refrigerator door should be kept to a minimum in order to maintain a constant temperature. The fridge temperature gauge should be clearly visible to read without needing to open the fridge door. The temperature of the fridge should be measured at least twice a day even during the weekend or a public holiday. The door and drawers of fridges should be filled with bottles of water to maintain steady temperatures.

Within the refrigerator, sufficient space around the vaccine packages should be left for air to circulate. Vaccines should be kept away from the side and back walls of the refrigerator; otherwise the vaccines may freeze rendering them inactive and unusable (refer to Figure 1.2 showing appropriate vaccine storage in a designated refrigerator).

Special care should be taken when bringing the vaccine to room temperature to ensure that the temperature of the vaccine does not exceed the specified range. An insulated container with an appropriate number of ice packs should be used to keep the temperature between 2-8°C.

Figure 1.2 Appropriate Vaccine Refrigeration and Storage

Note: It is important to keep the temperature inside the refrigerator stable despite frequent opening and closing of the doors. Place containers of water (coloured, salted or plain), labeled “Do NOT Drink” in the shelves situated on the door. Extra ice packs or cold packs can also be stored in the freezer and lower compartment. Do not store food and drinks inside the refrigerator. Top loading fridge is preferred to domestic refrigerator as it can preserve temperature for at least 72 hours.

Reconstituted vaccine must be used within the recommended period, varying from 1-4 hours, according to the manufacturer’s instructions. Single dose containers are preferable. Once opened, multi-dose vials must not be kept after the end of the session and any unopened vaccine left unused must be discarded unless the temperature is at 2-8°C at all times. The reason is that opened vaccines, especially live vaccines, may have reduced potency and there is also the risk of possible contamination. Thus, it is recommended that multi-dose vials be used for mass vaccination campaigns.

Immunoglobulins should be stored in the original packaging at 2-8°c and protected from light. Although these products have a tolerance of ambient temperatures (up to 25°c) for up to one week, they should be refrigerated immediately on receipt.

Unused vaccine, spent or partly spent vials, should be disposed of safely, preferably by heat inactivation or incineration. Contaminated waste and spillage should be dealt with appropriately with heat sterilisation, incineration or chemical disinfection.

Vaccine Combinations

This is becoming more common since it will reduce the number of injections and thus increase compliance. Examples of licensed combination vaccines are highlighted in the separate sections on the individual vaccines.

Problems of combination:

Side effects may be more frequent and worse.
Reduced antibody response due to interference.

Multiple Vaccinations

Simultaneous administration on same day:

No contraindications to simultaneous administration of live attenuated vaccines with inactivated or toxoid vaccines.
The vaccines should never be mixed in the same syringe unless approved for mixing by the manufacturer.
Separate sites should be used for different vaccines. If more than 1 vaccine must be administered in the same limb, the injection sites should be separated by 2.5-5.0cm so that any local reactions can be differentiated.
The location of each injection should be documented in the patient’s health record.

Interval between vaccines not administered simultaneously:

There is no minimum interval between administration of inactivated or toxoid vaccines, or between inactivated and live attenuated vaccines.
However, 2 or more live vaccines should either be given concurrently or separated by a minimum interval of 4 weeks.

Vaccines and Immunoglobulin preparations:

If a vaccine and an immunoglobulin preparation are administered simultaneously, a separate anatomic site should be used for each injection.
If the vaccine and the immunoglobulin preparation are not administered simultaneously, the vaccine and the immunoglobulin should be separated by a minimum interval (refer to Table 1.3)

Table 1.3. Intervals Between Vaccines and Immunoglobulin Preparations Not Administered Simultaneously

With the recent availability of 2 live vaccines not given by a parenteral route (live attenuated nasal influenza vaccine and oral rotavirus vaccine), the guidance to either administer the vaccines on the same day or at 4 week interval period should not be generalised to all live vaccines. Intervals between vaccines should be based only upon specific evidence for any interference of those vaccines.

Table 1.4 Recommendations for Giving More Than One Live Attenuated Vaccine

Spacing of Multiple Doses of the Same Antigen:

Administration of doses of a multidose vaccine using intervals that are shorter than recommended might be necessary in certain circumstances, such as
> impending international travel,
> when a person is behind schedule on vaccinations but needs rapid protection.

Administering a dose a few days earlier than the minimum interval is unlikely to have a substantially negative effect on the immune response.
Vaccine doses administered ≤4 days (grace period) before the minimum interval are considered valid. Because of the unique schedule for rabies vaccine, the 4-day guideline does not apply to this vaccine.
Doses of any vaccine administered ≥5 days earlier than the minimum interval should not be counted as valid doses and should be repeated. The repeat dose should be spaced after the invalid dose by the recommended minimum interval.
For example, if the first and second doses of hepatitis A vaccine were administered less than 6 months apart, the second dose is invalid and should be repeated 6 months after the invalid second dose. However, if this repeat dose (the third dose) is administered anytime 6 months or more after the first dose, the series can be considered complete.
Regarding lapsed vaccination schedule, intervals between doses that are longer than recommended typically do not reduce final antibody concentrations, although protection might not be attained until the recommended number of doses has been administered. With some exceptions (e.g. oral typhoid vaccine) an interruption in the vaccination schedule does not require restarting the entire series of a vaccine or toxoid or addition of extra doses.

Interchangeability of Formulations:

A combination vaccine may be used interchangeably with monovalent formulations and other combination products with similar component antigens produced by the same manufacturer to continue the vaccination series.
For example, DTaP, DTaP-IPV/Hib, and DTaP-HepB-IPV vaccines that contain similar acellular pertussis antigens from the same manufacturer may be used interchangeably.

Interchangeability of Combination Vaccines from different manufacturers:

It is preferable that doses of vaccine in a series come from the same manufacturer.
If this is not possible or if the manufacturer of doses given previously is unknown, providers should administer the vaccine that they have available.

Adverse Event Following Immunisation (AEFI)

An adverse event following immunisation (AEFI) is any untoward medical occurrence which follows immunisation and which does not necessarily have a causal relationship with the usage of the vaccine. The adverse event may be any unfavourable or unintended sign, abnormal laboratory finding, symptoms or disease. Reported adverse events can either be true adverse events, ie, really a result of the vaccine or immunisation process, or coincidental events that are not due to the vaccine or immunisation process but are temporally associated with immunisation.

A serious event is defined by World Health Organization (WHO) as resulting in death, requires hospitalisation or prolongation of existing hospitalisation, persistent or significant disability, life-threatening or causing congenital abnormalities.

Malaysia has an established AEFI reporting system for vaccines by the National Pharmaceutical Regulatory Agency (NPRA), Ministry of Health Malaysia. All reports received will be assessed for causality and presented in the Malaysian Adverse Drug Reaction Advisory Committee (MADRAC), the advisory committee to the Drug Control Authority, for confirmation prior to submission to WHO. Malaysia, as a WHO Collaboration Centre, has been part of the International Drug Monitoring Programme since 1990.

Methods for reporting.

To report an adverse event following immunisation (AEFI), healthcare professionals can contact the National Centre for Adverse Drug Reaction Monitoring, National Pharmaceutical Regulatory Agency (NPRA):

PhIS version 1.7 & above* (for Ministry of Health only), OR
online web form via this link – https://quest3plus.bpfk.gov.my/front- end/adr_web_form_mid.php, OR
manual submission by mail/fax/e-mail by downloading the form via this link – https://www.npra.gov.my/images/Healthcare-professional/ reporting/ADR_Form_Healthcare_Prof_web.pdf

All manual forms to be submitted via the following mode:

By facsimile: 03-79567151
Through mail to:

NATIONAL CENTRE FOR ADVERSE DRUG REACTIONS MONITORING

National Pharmaceutical Regulatory Agency

Lot 36, Jalan Universiti,

46730 Petaling Jaya, Selangor, Malaysia

By email : fv@npra.gov.my

Repeated submission using multiple channels is NOT necessary.

*Note: If your facility is equipped with PhIS version 1.7 & above, your PhIS ADR report will be automatically pushed to NPRA. For any enquiries related to PhIS reporting, please contact PhIS Helpdesk.

The National Pharmaceutical Regulatory Agency has developed a Guideline for Pharmacovigilance of Vaccines in Malaysia available at the official website: http://npra.moh.gov.my Please refer to the guideline for further details.

References

Advisory Committee on Immunisation Practices. (2020) Recommended Immunisation Schedule for Adults Aged 19 Years or Older-United States, 2020 [Annual Report]. U.S. Centre for Disease Control. http://www.cdc.gov/vaccines/schedules/downloads/adult/adult- combined-schedule.pdf
Australian Immunisation Handbook (11th ed) 2018 (updated 27 May 2020). Retrieved 14 October 2020, from https: //www.immunisationhandbook.health.gov.au
Australian Society of Clinical Immunology and Allergy (2017) Guidelines on Vaccination of the egg-allergic individual. Retrieved 14 October 2020, from www.allergy.org.au
Dreskin SC, Halsey NA, Kelso JM, Wood RA, Hummell DS, Edwards KM, et al. (2016). International Consensus (ICON): allergic reactions to vaccines. World Allergy Organization Journal, 9:32. http://dx.doi 10.1186/s40413-0160120-5
Epidemiology and Prevention of Vaccine-Preventable Diseases (13th ed) 2015 (updated July 2020) Retrieved 14 October 2020, from http://www.cdc.gov/vaccines/pubs/pinkbook/ downloads
Ezeanolue E, Harriman K, Hunter P, Kroger A, Pellegrini C. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP) (2017) Retrieved 14 October 2020, from www.cdc.gov/vaccines/hcp/acip- recs/general-recs/downloads/general-recs.pdf
Immunisation Guidelines (2006). Dubai Health Authority, Dubai. Retrieved 14 October 2020, from www.dha.gov.ae
Mary Ramsay (Ed). Immunisation against Infectious Diseases (2017). Public Health England (latest update January 2020) Retrieved 14 October 2020, from www.gov.uk>collections

Guidelines for Adult Immunisation

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