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Home , Attenuated vaccine

Prof RN Basu 181 • What is ? o A biological preparation that elicits immunity to a particular disease. o In addition to the antigen, it can contain multiple components, such as adjuvants, preservatives, stabilizers, each of which may have specific safety implications. 26 • Immunity27 o Immunity is the ability of the human body to tolerate the presence of material indigenous to the body (“self”), and  To eliminate foreign (“nonself”) material

182 • Active Immunity o Active immunity is protection that is produced by the person’s own immune system o This type of immunity usually lasts for many years, often during a lifetime • Passive immunity o It is protection by products produced by an animal or human and transferred to another human, usually by injection o Passive immunity often provides effective protection, but this protection wanes (disappears) with time, usually within a few weeks or months

183 o The immune system is a complex system of interacting cells  The primary purpose is to identify foreign (“nonself”) substances  These foreign substances are known as antigens o Antigens can be:  Live: . such as viruses and bacteria  Inactivated: o The immune system develops a defense against the antigen  The defense is known as the immune response

184  This involves production of proteins molecules by B lymphocytes . These protein molecules are called (or immunoglobulin)  Also specific cells are produced . These cells include T-lymphocytes  The cell production is known as cell-mediated immunity  The purpose of these specialised cells is elimination of foreign substances o The most effective immune responses are produced by a live antigen  The antigen need not always be alive as occurs with natural with a virus or bacterium, to produce an immune response

185 o Some proteins, such as hepatitis B surface antigen are easily recognised by the immune system o Other material, such as polysaccharide, are less effective antigens  Polysaccharides are the constituent material of cell wall of some bacteria o Polysaccharides may not produce as good response as in protein antigens • Passive Immunity o Immunity produced by another human or animal is transferred to another man or animal

186 o Passive immunity is temporary and provides protection only for sometime against some  Antibodies will degrade during a period of weeks to month and will no longer be available for protection o Most common form of immunity is what an infant receives from its mother  Mother’s immunity is transferred to the foetus through placenta during the last one or two months of pregnancy o A full term infant will have the same immunity as that of its mother and that will protect the infant for up to one year

187 • Sources of passive immunity o Many blood products contain  Specific Immune gamma globulin which is contained in plasma provides protection against that specific infection . Washed or reconstituted red blood cells contain very little antibody  Some other plasma products such as intravenous immune globulin contain large amount of antibody o In addition, there are three other major sources of antibody used for therapeutic purposes

188 o These are: 1. Homologous pooled human antibody 2. Homologous human hyperimmune globulin, and 3. Homologous hyperimmune serum o Homologous pooled human antibody is also known as immune globulin  It is produced by combining (pooling) the Immunoglobulin G (IgG) antibody from serum of many thousand adult donors . As it is pooled, it contains antibody from many different antigens  It is mainly used for postexposure prophylaxis for hepatitis A and measles and treatment of certain congenital immunoglobulin deficiencies

189 o Homologous (from same evolutionary origin) human hyperimmune globulin contains high titres (concentration) of specific antibody  This also contains other antibodies of lesser concentration  The hyperimmune globulins are used for postexposure prophylaxis for several diseases: . Such as, hepatitis B, , tetanus, and varicella o Heterologous (from animals, usually horses) hyperimmune serum is also known as antitoxin  These serum contains antibody against only one antigen

190 o Monoclonal antibody  Immune globulin from human sources is polyclonal . It contains different kinds of antibodies  Techniques are available to produce antibody from single clone of B cells . Monoclonal is one that appears to be a copy of an original form  Monoclonal antibody acts against only one kind of antigen or only a group of related antigen  Certain antibody products like immune globulin may interfere with live virus  Monoclonal antibodies have many uses . This includes, diagnosis of certain form of cancer, treatment of cancer, prevention of transplant rejection and treatment of autoimmune diseases

191 • Active Immunity o Body’s immune system is stimulated to produce specific humoral antibody and cellular antibody  Active immunity lasts for a long time for years or even for lifetime o Natural infection with an organism produces active immunity  The duration of protection may be lifelong . Exception: malaria o The persistence of protection after the infection for several years is known as immunologic memory

192  After the exposure of immune system B memory cells are produced . These B cells continue to circulate in blood and also reside in the bone marrow for many years . When another exposure to the antigen occurs, these memory cells begin to replicate and produce antibody quickly to protect the organism  Active immunity is also produced by . Vaccination produce immunity in the same way as natural infection . However, the individual does not suffer from the disease or the disease related complications . Many vaccines also produce immunologic memory like natural disease

193 • Principles of Vaccination o There are many factors that affects immunity development following vaccination o These are:  Presence of maternal antibody  Nature and dose of antigen  Route of administration  Presence of an adjuvant  factors: . Age, nutritional factors, genetics, and coexisting diseases

194 • Classification of vaccines o Two basic types: 1. Live attenuated 2. Inactivated o The characteristics of these two types are different  These characteristics determine how the vaccine is used o Live attenuated vaccines are produced by modifying the “wild” virus or bacterium in a laboratory  “Wild “means disease producing

195 o The altered organism retains the ability to multiply and produce immunity  This altered organism do not produce any disease o Inactivated vaccines can be made up of either the whole virus or bacterium, or fractions of any of these  Fractional vaccines are either protein based or polysaccharide based  Protein based vaccines include and subunit or subviron products  Polysaccharide vaccines are mostly composed of pure cell wall polysaccharide from bacteria  Conjugate polysaccharide vaccines contain chemically linked to a protein . This protein bonding makes the more potent

196 o General rule of a vaccine  The more similar a vaccine is to the disease producing form of the organism, the better the immune response to the vaccine • Live Attenuated Vaccines o These vaccines are made from “wild” or disease-causing viruses or bacteria  These viruses or bacteria are attenuated or weakened in a laboratory usually by repeated culturing  Example: . Measles virus was isolated from a child in 1954 . It took 10 years of in tissue culture media to transform into virus

197 o Immune response from a live attenuated virus requires that the virus must multiply in the recipient of vaccine o A small dose of live attenuated vaccine is administered  It replicates into enough number of organism to be able to produce immunity  If the live organism in the vaccine is damaged somehow like by heat or sunlight, or . Anything that interferes with replication of the organism in the body, the vaccine becomes ineffective

198 o Live attenuated vaccine do not produce disease as the ‘wild’ organism does  Even if it does, the disease is much milder than the natural disease . In this case, it is described as adverse reaction o The immune response from live attenuated vaccine is almost similar to natural infection by the wild form of the organism  The immune system does not differentiate between an infection with a weakened vaccine virus and an infection with a wild virus  Parenteral administration of live attenuated vaccine usually requires only a single dose to produce immunity in most recipients

199 o A small percentage of recipients may need two doses to produce immunity o Live attenuated virus may cause severe or fatal reactions  This is because of uncontrolled replication of the vaccine virus . This occurs in recipients who are immunodefficient, or being treated with certain drugs or are with HIV infection . Theoretically, a live attenuated virus may revert to its original pathogenic form . This is known to happen with live oral vaccine

200 o Active immunity from a live attenuated vaccine may not develop due to circulating antibody to the vaccine virus  The circulating antibody may come from many sources such as transplacental maternal antibody, or transfusion  The poor response from vaccination is referred to as vaccine failure o Live attenuated vaccines are delicate and should be handled and stored with care o Currently available live attenuated vaccines:  The viral vaccines are: Measles, , rubella, vaccinia, varicella, zoster, yellow fever, rotavirus, and influenza, polio  The bacterial vaccines are: BCG and oral

201 • Inactivated Vaccines o Virus or bacterium growing in culture media is inactivated by heat or by chemicals like formalin o For fractional vaccines, the organisms further purified to obtain components to be used in vaccine  E.g., The Polysaccharide capsule of Pneumococcus o Organism in are not alive and do not multiply  The entire dose of antigen is administered in the injection

202  These vaccine does not cause disease even in immunodefficient persons  These vaccines are less affected by circulating antibody than live antigens  Therefore, these vaccines can be administered when antibody is present . E.g., in infancy or following receipt of anti-body-containing blood products  Inactivated vaccines always require multiple doses  Usually, the first dose does not produce immunity . But the immune system is primed by the first dose  Immune response is developed after second or third dose  In inactivated vaccine the immunity developed is only humoral, whereas, immunity due to natural infection is also cellular

203  Antibody titre after immunisation by inactivated vaccine diminish over time . Therefore, periodic booster dose is required to maintain the immunity level o Currently, the inactivated vaccines include  Whole viral vaccines . Polio, hepatitis A, rabies, polio and rabies  Inactivated bacterial vaccines . Pertussis, typhoid,, cholera and plague  Fractional vaccines include: subunits: . Hepatitis B, influenza, acellular pertussis, human papilloma virus,  Toxoids: . Diphtheria, tetanus

204 o Polysaccharide Vaccines  Certain bacteria has a surface capsule of long chain sugar molecules . The polysaccharide vaccines are unique type of inactivated sub unit vaccine with this sugar molecule . Pure polysaccharide vaccines are available for three diseases: ◊ Pneumococcal diseases, meningococcal disease and for typhi  Immune response to a pure polysaccharide vaccine stimulate B cells without T helper cells . T-cell independent antigen, including polysaccharide vaccines, are not consistently immunogenic in children below 2 years of age . This may be because of immaturity of immune system

205  Booster doses of a polysaccharide vaccine do not increase antibody levels as happens in protein based vaccines . Antibody induced by polysaccharide vaccines has less functional antibody . The antibody response is mostly in the form of IgM, and little IgG is produced  This drawback of polysaccharide vaccines is overcome by a process of conjugation  Conjugated polysaccharides vaccines are available for pneumococcal diseases and meningococcal diseases o Recombinant Vaccines  Antigenic products can be produced by genetic engineering

206  These products are known as recombinant vaccines  Five genetically engineered vaccines are available . Hepatitis B, Human papilloma virus, Influenza are produced by inserting a segment of the respective viral gene into the gene of a yeast . The modified yeast cell or virus produces pure hepatitis B surface antigen, HPV capsid protein, or influenza haemagglutinin when it grows ◊ A capsid is the protein shell of a virus, enclosing its genetic material. . live typhoid vaccine is Salmonella typhi bacteria that have been genetically modified so that it does not cause disease . Live attenuated has been engineered to replicate effectively in the mucosa of the nasopharynx but not in the lungs

207 208 • The greatest impact on human health has been the use of vaccines o As far back as 496 B.C. , the Greek historian, Thucydides noted that those who survived small pox would never get reinfected  The history of vaccination has since confirmed the truth in this observation o Since 's experiment with cow pox in 1796, vaccination has played a major role in the battle of infectious diseases o There is a growing list of vaccine preventable diseases.29

209 o To be effective, immunogenic and to be able to achieve its purpose of prevention of infectious diseases, the vaccines must be properly handled and administered o Some of the aspects that need to be taken care of are: 1. The maintenance of . Maintenance of health facility cold chain equipment . Temperature Monitoring devices . Monitoring cold chain temperature . Arranging vaccines inside cold chain equipment . The shake test

210 WHO: https://mail.google.com/m ail/u/1/#inbox/FMfcgxwKk RDqKGLlGCgxjzTpjHPbQmX w

211 2. Using safe injection equipment and techniques  Preventing needle-stick injuries  Disposing of used syringes and needles 3. Unsafe practices 4. Preparing for the session 5. Communicating with caregivers 6. Assessing the recipient

212 o Giving o Closing the session o Recording data o Using the immunisation session checklist

213 o The Vaccine Cold Chain  The system used for storing vaccines in good condition is called the cold chain . It is sometimes referred to as vaccine supply chain  The cold chain consists of a series of links that are designed to keep the vaccine within a specified range of temperature  For the current National Immunization Programme in India, the temperature range is mentioned in the various National Health Mission guidelines . This is based on WHO recommendations

214 The Vaccine Cold Chain Source: https://www.path.org/artic les/vaccine-cold-chain-q/

215 • Health facility cold chain equipment o Different levels within the national cold chain system require different types of equipment for transporting and storing vaccines and diluents within the required temperature range  Primary Level (national) . Depending on the capacity required, the primary level generally uses: ◊ Cold or freezer room ◊ Freezers ◊ Refrigerators ◊ Cold boxes, and ◊ Refrigerated trucks for transportation

216 217 30-day electronic temperature loggers (30 DTR) These devices are placed with the vaccine load in a vaccine refrigerator. They record the refrigerator temperature at no more than 10- minute intervals and show the temperature history for any day in the last 30 days.

218 Vaccine carriers Vaccine carriers are smaller than cold boxes and easier to carry (see Figure 2.7). Current prequalified vaccine carriers have a cold life with frozen ice packs of between 18 and 50 hours at +43 °C and a cool life with cool water packs of between three and 18 hours. Use of vaccine carriers • To transport vaccines and diluents to outreach sites and store them during health facility immunization sessions. • To store vaccines temporarily when the health facility refrigerator is out of order or is being defrosted. • To transport monthly vaccine supplies from the district store to small health facilities. 219  Intermediate level (State or District) . Depending on capacity required ◊ Cold and freezer rooms ◊ freezers ◊ Refrigerators ◊ Cold boxes ◊ In some cases refrigerated trucks for transportation . Peripheral level (health Centres) ◊ Refrigerators ◊ Cold boxes, and ◊ Vaccine carriers

220 C O V I D 1 9

V A C C I N A T I O N 221 Vaccine vial monitors A vaccine vial monitor (VVM) is a label that changes colour when the vaccine vial has been exposed to heat over a period of time. Before opening a vial, the status of the VVM must be checked to see whether the vaccine has been damaged by heat. Manufacturers attach VVMs to vials of most vaccines. The VVM is printed on the vial label or cap. It looks like a square inside a circle. As the vaccine vial is exposed to more heat, the square becomes darker. SOURCE: WHO Vaccine Safety Training. Available at: https://vaccine-safety- training.org/tl_files/vs/pdf/Module3_IIP.pdf

222 • Unsafe Immunisation practices o Some unsafe practices are:  Recapping the needle  Leaving the needle inside the vial  Touching the needle  Disposing of used needles in an open cardboard boxes  Overfilling the safety box

223 • General o Doctors and nurses providing immunisations are professionally accountable for this work, as defined by their professional bodies o All healthcare professionals advising on immunisation or administering vaccines must have received specific training in immunization  National Health Mission, Government of India has a number of publications for health workers including medical officers for imparting training to them on immunization.30,31  These guidelines are mostly for extended programme for immunization

224 • Royal College of Nursing has also a training manual on immunization for registered healthcare practitioners.32 o As per this document, the core areas of immunisation knowledge includes:  The aims of immunisation, national vaccine policy and schedules  The immune response to vaccines and how vaccines work  Vaccine preventable diseases  The different types of vaccines, their composition and the indications and contraindications  Current issues in immunisation

225  Communicating with patients, parents and carers about vaccines  Legal issues in immunisation  Storage and handling of vaccines  Correct administration of vaccines  Anaphylaxis and adverse reactions  Documentation, record keeping and reporting  Strategies for optimising immunisation uptake o All practitioners involved in immunisation should be able to demonstrate current, evidence-based and best practice-based knowledge and understanding of these areas

226 o Preparation of vaccine  Each vaccine should be reconstituted and drawn up when required in order to avoid errors and maintain vaccine efficacy and stability . Vaccines should not be drawn up in advance of an immunisation session  The vaccine must be checked to ensure that the right product and correct dose is used in the appropriate way for each individual . Vaccines must not be used after their expiry date  Different vaccines must not be mixed in the same syringe  Freeze-dried (lyophilised) vaccines must be reconstituted with the correct volume of diluent

227  Unless supplied in a pre-filled syringe, the diluent should be drawn up using an appropriately sized syringe and 21G needle and avoid slowly to the vaccine to avoid frothing  For injecting appropriate sized needle should be used o Vaccine administration  Individuals giving vaccination must have received training in management of anaphylaxis . Appropriate equipment and drugs should be available  Before any vaccine is given consent must be obtained  Suitability of administration must be established with the individual to be vaccinated

228 o Prior to administration vaccinators should ensure that:  There are no contraindications to the vaccine being given  The vaccine or carer is fully informed about the vaccine to be given and understands the vaccination procedure  The vaccine or carer is aware of possible adverse reactions (ADRs) and how to treat them o Route and site of administration  There are certain factors that affect immunogenicity and risk of local reactions  These factors are:

229 . Injection technique . Choice of needle length and gauge, and . Injection site o Route of injection  Most vaccines are given by intramuscular (IM) injection  Injections given by intramuscular, rather than deep subcutaneously, are less likely to cause local reactions  Vaccines should not be given intravenously

230  Some vaccines are not given intramuscularly. These are: . BCG given by intradermal injection . Green Cross Japanese encephalitis and are given by deep subcutaneous injection . is given by mouth  Some individuals may have bleeding disorders . They should be given vaccine by deep subcutaneous route o Suitable sites for vaccination  The site should be chosen so that the injection avoids major nerves and blood vessels

231  The preferred sites for IM and SC immunisation are the anterolateral aspect of thigh (Children) or the deltoid area of the upper arm (adult) . The anterolateral aspect of thigh is the preferred site for infants under one year old, because it provides a large muscle mass into which vaccines can be safely injected . For BCG, 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 Preferred site for intramuscular and formation at this site deep subcutaneous injections in older children and adults 232 Preferred site for intramuscular and Preferred site for BCG injections in deep subcutaneous injections in babies and adults infants under one year of age 233  Administering more than one injection at the same time . In this circumstances, they should be given at separate sites, preferably in different limbs ◊ If the same limb is chosen, at least the injections should be 2.5 cm apart ◊ Which injection is given at which site should be recorded in immunisation record  Immunisation should not be given into the buttock, due to the possibility of sciatic nerve injury . Also because of thick fatty layer in this area, there is a possibility of injecting into the fat ◊ It is shown that immunogenicity of hepatitis B is lower when the injection is in fatty tissue

234 o Suitable sites for immunoglobulin administration  For injecting a large volume, it should be given deep into a large muscle mass  The injection should be divided into smaller amounts and given into different sites, . For young children and infants, if the volume is more than 3 ml, or . For older children and adults, if the volume is more than 5 ml  the upper outer quadrant of the buttock can be used for immunoglobulin injection o Rabies immunoglobulin should be infiltrated into the site of the wound

235 o Cleaning the skin  If the skin is clean, no further cleaning is necessary  Visibly dirty skin needs to be washed with soap and water  It is not necessary to disinfect the skin . It does not make any difference of bacterial complications of injections o Choice of needle size  For IM injection, a 25mm long needle of 23 or 25 gauze needle is suitable for most vaccines for children and adults . This size needle reduces local vaccine

236  Only in pre-term or very small infants, a 16 mm needle is suitable for IM injections  In larger adults, a longer length (38mm) may be required . Individual assessment should be made for needle sizes for adults o Injection technique  IM injections should be given with the needle at a 900 angle to the skin and the skin should be stretched, not bunched  Deep SC injections should be given with the needle at a 450 angle to the skin and the skin should be bunched, not stretched

237 Intradermal injection

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.

238 National Health Mission:: Immunization Handbook for Medical Officers https://nhm.gov.in/Ne w_Updates_2018/NHM _Components/Immuniz ation/Guildelines_for_i mmunization/Immuniza tion_Handbook_for_M edical_Officers%202017 .pdf

239 o Use of multi-dose vials  Some vaccines are specifically provided in multi-dose vials  From this vial multiple individuals are vaccinated  These vaccines are are clearly labelled as multi-dose vial  Duration for which these vials can be used is specified in Summary of Product Characteristics (SPC) and should be followed  Appropriate infection control and aseptic techniques should be followed  Disposal of used syringes, needles and other items such as alcohol wipes should be disposed of as per BMW Management guidelines

240 • COVID vaccines are being supplied in 10 dose vials. • There is no VVM attached • There is no expiry date either • Therefore, the Open Vial Policy is not applicable • The vaccine has to be used up within 4 hours after opening the vial

241 • Implementation of Open Vial Policy (OVP) allows reuse of partially used multi-dose vials of applicable vaccines under the UIP o The partially can be used in subsequent sessions  up to 4 weeks (28 days) subject to meeting certain conditions. o This policy contributes to the reduction of . • Open Vial Policy is only applicable to: o DPT, TT, Hep B, OPV, PCV, Hib containing (Penta) and injectable inactivated vaccine (IPV).

242 • Conditions that must be fulfilled for the use of open vial policy o Any vial of the applicable vaccines opened/used in a session can be used at more than one immunization session up to 4 weeks (28 days) provided that:  The expiry date has not passed;  The vaccines are stored under appropriate cold-chain conditions both during transportation and storage in cold-chain storage point;  The vaccine vial septum has not been submerged in water or contaminated in any way;  Aseptic technique has been used to withdraw vaccine doses, i.e. needle/septum has not been contaminated in anyway;  The VVM has not reached/crossed the discard point;  Date and time is written on vial.

243 • Good Practice Guidance: the immuniser to ensure that: o The expiry date has not passed o Vaccines are stored under appropriate cold chain conditions before and in between use o The bung (vial septum) is visibly clean  Where there is visible contamination then the bung can be cleaned with an alcohol swab.  However, the bung should be left to dry before using as it is the drying process that kills contaminating organisms and residual alcohol could contaminate/inactivate vaccine

244 o A sterile syringe and needle are used each time vaccine is withdrawn from the vial o The needle is not in the vial for multiple redraws o The vial should be clearly marked with:  The date and time of reconstitution or first use  The initials of persons who reconstituted or first used the vial  The period that the vaccine can be used for (as defined in the SPC) o Disposal of equipment  All equipment used in vaccination should be properly disposed of as per BMW Management Rules, 2016

245 o Recording - The following information should be recorded:  Vaccine name, product name, batch number and expiry date  Dose administered  Site(s) used – including, clear description of which injection was administered in each site, especially where two injections were administered in the same limb  Date immunisation(s) were given  Name and signature of vaccinator

246 247 • Classification of Adverse Events35 o AEFIs are grouped into five categories  Vaccine product-related reaction  Vaccine quality defect related reaction  Immunisation error related reaction  Immunisation anxiety related reaction  Coincidental event

248 249 • Key Points36 o There is no such thing as a "perfect" vaccine which protects everyone who receives it, AND  No vaccine is entirely safe for everyone. o An Effective vaccines induces protective immunity  The effective vaccines may produce some undesirable side effects  These side effects are mostly mild and clear up quickly. o The majority of events thought to be related to the administration of a vaccine are actually not due to the vaccine itself

250 • Known Vaccine-Associated Adverse Events37 o Most vaccine-caused AEFIs are mild and transient such as fever or local reactions to injectable vaccines.  On very rare occasions, vaccines can cause more severe AEFIs, such as Guillain– Barré Syndrome (GBS) or anaphylaxis. o Vaccine benefit far outweighs the risks in terms of overall public health  And in most instances, the individual vaccine recipient is also benefited immensely o Vaccines have been highly successful in developed countries, and  Much of the public has forgotten the morbidity/mortality from vaccine- preventable diseases when they were endemic.

251 o The result is that segments of the public are more afraid of AEFIs caused by vaccines, or rumoured to be caused by vaccines o It is important to put the AEFI in their proper perspective so that the parents and public at large are properly informed o Common AEFIs are:  Fever . It is a normal part of the immune response to invading organisms and sometimes foreign material  Rash . Rashes after vaccination are often non-specific, occurring within 72 hours . Urticaria can occur and suggests an allergic or hypersensitivity reaction

252  Crying . Some crying is expected with any child receiving an injection . May also accompany post-immunization fever or myalgia  Febrile Seizure . It is a brief seizure associated with fever, lasting less than 15 minutes . Usually seen in a previously neurologically normal infant or young child without central nervous system infection . Febrile seizure is triggered by environmental and genetic factors  Syncope . It is loss of consciousness from decreased blood flow to the brain . Its pathogenesis varies with the precipitating event

253 o Uncommon or Serious Adverse Events Following Immunization  Individual practitioners have limited experience with uncommon and or serious AEFIs  It is important to assess as correctly as possible whether a serious AEFI is causally related to the vaccine  The fact that a rare AEFI, whether serious or not, temporarily follows vaccination does not prove vaccination was the cause. Some rare AEFIs are:  Pyogenic and Sterile Abscesses . This is often caused by Staphylococcus aureus . This is usually a complication of residual puncture . May be due to contaminated material

254  Extremity swelling . Mild local swelling is seen sometimes with conjugate polysaccharide vaccines, e.g., PCV7 or PCV13 and other DPT containing vaccine ◊ (PCV = Pneumococcal Conjugate Vaccine) . It is less common but reported during the primary series with diphtheria, tetanus or acellular compared to DTwP (Diphtheria, Tetanus, Whole cell Pertussis) . Since introduction of aP (acellular Pertussis) vaccines, however, there has been an increase in local reaction after the fourth and fifth doses, some involving the entire upper arm ◊ This is thought to be due to high antigen-antibody titre

255  Deltoid Bursitis . It is an inflammatory process of the deltoid bursa . This causes shoulder pain, stiffness and/or restricted range of motion . It may be idiopathic or secondary to injury  Complex Regional Pain Syndrome (CRPS) . CRPS seems similar to SIRVA (Shoulder Injury Related to Vaccination) but the points of differences are: ◊ In addition to pain, swelling, and decreased range of motion there is also autonomic dysfunction that affects one o/r more extremities ◊ It is caused by nerve trauma and not synovial trauma as in SIRVA . It is not related to any specific antigen but is due to injection procedure related

256 o Neurologic Adverse Events  These are very rare, and always cannot be distinguished with otherwise background prevalence of the disease  Expert consultation is necessary to arrive at a diagnosis o Acute Disseminated Encephalomyelitis (ADEM)  ADEMs are acute inflammatory demyelinating disease of the central nervous system  May result from autoimmune response following an infectious disease or vaccination  It has been reported following several vaccines, such as influenza, meningococcal, HPV, rabies, and DT, TT, or aP containing vaccines  However, an Institute of Medicine report says that there is insufficient evidence to establish causality with most of the vaccines39

257 o Transverse Myelitis  It is a rare spinal cord disease  It is thought to be due to autoimmune response triggered from infection or vaccination  It has been reported following many childhood vaccines and rabies, typhoid, oral polio, and recently H1N1 vaccine  As per the IOM report, the available evidence is insufficient to establish causality

258 o Optic Neuritis  It is a demyelinating disease of the optic nerve  The causality evidence to vaccination is insufficient o Bell’s Palsy (Seventh Cranial Nerve Neuropathy)  This an acute and usually idiopathic paralysis of the facial muscles  Usually due to injury/inflammation/compression of the 7th cranial nerve  Anecdotal reports have it following trivalent inactivated influenza and hepatitis B virus vaccines  No association could be found

259 o Guillain-Barre Syndrome  It is a rare paralytic neurologic disease with progressive ascending paralysis of voluntary muscles  A review of literatures from 1950 to 2010 concluded that with rare exceptions, associations between vaccines and GBS have been only temporal.40 o Hypersensitivity  Allergic reactions from vaccine may manifest in the form of mild local swelling to severe life threatening shock.  It is an immune mediated response to an allergen  The reactions can be immediate or delayed  Incidences range from 1 per 50o,000 to 1 per million doses for most vaccines

260 o Anaphylaxis  It is rare but frightening  Incidences are 0.65 cases/million  It is a most severe Type I IgE-mediated hypersensitivity reaction  An IOM report evidence convincingly supports a causal relation of anaphylaxis to MMR, , diphtheria or tetanus toxoids as well as varicella, influenza and meningococcal vaccines o Delayed Type Reactions  Classically present 3 to 8 hours post exposure, but may be delayed up to weeks after initial exposure to vaccine

261 o Many are simply coincidental events, others (particularly in developing countries) are due to human, or programme, error. • It is not possible to predict every individual who might have a mild or serious reaction to a vaccine, o There are a few contraindications to some vaccines. o By following contraindications the risk of serious adverse effects can be minimized.

262 • Introduction o Covid-19 is a new disease o In less than one year many vaccines against SARS CoV-2 virus have been developed, and  Many are still in the pipeline o Regulators in many countries including India have authorised some of the vaccines only for emergency use o For obvious reasons, the safety data for these vaccines are limited

263 • An adverse event following immunization (AEFI) 38 o Definition  An adverse event following immunization is any untoward medical occurrence which follows immunization . This event may not necessarily be causally related with vaccination . The adverse event may be any unfavourable or unintended disease, symptom, sign or abnormal laboratory finding o Reported adverse events can either be true adverse events or coincidental events  These coincidental events are not due to vaccine but are temporarily associated with immunization

264 265 • Prevention of AEFIs o The COVID-19 pandemic has created disturbance and destruction world over with a large number of lives lost  Under such situation use of a vaccine against the disease which has produced little serious adverse events may not be unjustified o These vaccines may have different modalities of administration o Appropriate measures need to be taken to avoid possibilities of anxiety reactions in individuals and groups o Beneficiaries should be observed at the session site for at least 30 minutes post-vaccination to detect, manage and treat immediate adverse reactions

266 o  It refers to delay in acceptance or refusal of vaccines despite availability of vaccine services  Vaccine hesitancy is complex and context specific  This varies across time, place and vaccine  It includes factors such as complacency, convenience and confidence  All these factors need to be addressed to overcome vaccine hesitancy

267 WHO41

268 • A systematic review by WHO and SAGE identified strategies to intervene with the largest positive results.42 • These are summarized as under: 1. directly target unvaccinated or under-vaccinated populations; 2. aim to increase knowledge and awareness surrounding vaccination; 3. improve convenience and access to vaccination; 4. target specific populations such as the local community and HCW; 5. mandate vaccinations or impose some type of sanction for non-vaccination; 6. employ reminder and follow-up; and 7. engage religious or other influential leaders to promote vaccination in the community.

269 • Threats to Global Health43 o WHO have identified ten threats to global health in 2019  Vaccine hesitancy is one of them . The benefits of vaccines rank them among the most successful interventions in the twentieth century . Vaccines have saved hundreds of thousands of lives worldwide . However, vaccine-induced protective immunity to the specific targeted can be accompanied by unwanted adverse event following immunization (AEFIs).  Health workers, especially those in communities, remain the most trusted advisor and influencer of vaccination decisions, and . They must be supported to provide trusted, credible information on vaccines.

270 26. WHO. Covid-19 Vaccine: Safety Surveillance Manual. Accessed from: https://www.who.int/vaccine_safety/committee/Module_AEFI.pdf?ua=1 27. Centers for Disease Control and Prevention. and Prevention of Vaccine- Preventable Diseases. Hamborsky J, Kroger A, Wolfe S, eds. 13th ed. Washington D.C. Public Health Foundation, 2015. 28. National Rural Health Mission, Government of India. Immunization handbook for Medical Officers (2015). Available at: https://nhm.gov.in/New_Updates_2018/NHM_Components/Immunization/Guildelines_for_im munization/Immunization_Handbook_for_Medical_Officers%202017.pdf 29. WHO. Immunization in Practice: A Practical guide for health staff. Available from: https://apps.who.int/iris/bitstream/handle/10665/193412/9789241549097_eng.pdf?sequence =1&isAllowed=y

271 30. National Health Mission, Govt. of India. Immunization Handbook for Medical Officers. Available from https://nhm.gov.in/New_Updates_2018/NHM_Components/Immunization/Guildelines_for_im munization/Immunization_Handbook_for_Medical_Officers%202017.pdf 31. National Health Mission, G of I. Immunization Handbook for Health Workers. Available from: https://www.nhm.tn.gov.in/sites/default/files/documents/ImmuHBforHW2018.pdf 32. Royal College of Nursing, Public Health England. National Minimum Standards and Core Curriculum for Immunisation for Registered Healthcare Practitioners. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_dat a/file/679824/Training_standards_and_core_curriculum_immunisation.pdf 33. Public Health England. Immunisation against infectious diseases: Green Book, Chapter 4: Immunization procedure (Updated on 27 November 2020). Available from: https://www.gov.uk/government/collections/immunisation-against-infectious-disease-the- green-book#the-green-book

272 34. M of H&FW, Govt. of India. COVID-10 Vaccines Operational Guidelines (Updated on 28 Dec 2020) 35. WHO. Vaccine Safety Basic, learning manual, Module 3: Adverse Events Following Immunisation. Available from: https://www.who.int/vaccine_safety/initiative/tech_support/Vaccine-safety-E- course-manual.pdf?ua=1 36. WHO. Global Vaccine Safety Adverse Events Following immunisation . Available from : https://www.who.int/vaccine_safety/initiative/detection/AEFI/en/ 37. Archana Chatterjee, Ed. Vaccinophobia and Vaccine Controversies of the 21st Century, Ch 3, Pahud BA, Harrison CJ. Known Vaccine-Associated Adverse Events. Springer 38. M of H&FW, Govt. of India. COVID-10 Vaccines Operational Guidelines (Updated on 28 Dec 2020), pp. 106 39. The National Academic Press, IOM. Adverse Events of Vaccines: Evidence and Causality (2012). Available from http://nap.edu/13164 40. Haber P, Sejvar et al. Vaccines and Guillain-Barre syndrome. Accessed from: https://pubmed.ncbi.nlm.nih.gov/19388722/

273 41. WHO. Vaccine Hesitancy: what it means and what we need to know in order to tackle it. Available from: https://www.who.int/immunization/research/forums_and_initiatives/1_RButler_VH_Threat_C hild_Health_gvirf16.pdf?ua=1 42. WHO SAGE working group dealing with vaccine hesitancy. Strategies for Addressing Vaccine Hesitancy – A Systematic Review. Available from: https://www.who.int/immunization/sage/meetings/2014/october/3_SAGE_WG_Strategies_ad dressing_vaccine_hesitancy_2014.pdf 43. WHO. Ten threats to global health in 2019. Available from: https://www.who.int/news- room/spotlight/ten-threats-to-global-health-in-2019

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