CHAPTER -1 – OVERVIEW OF IMMUNIZATION

Immunizing agents are used for conferring immunity in susceptible hosts. These are used for inducing artificially active or passive immunity to susceptible hosts. This process of conferring immunity in susceptible hosts is known as immunization. The immunizing agents may be classified as vaccines, immunoglobulins & antisera (1).

As evidenced, immunizing agents are being used to prevent development of diseases in susceptible hosts from centuries. Edward Jenner in 1796, introduced scientifically immunization against smallpox. He was the first successful scientist to induce successful immunization. Before that many attempts were made across the world for immunization, but no body succeeded. After a century, Louis Pasteur laid the foundation of immunology by developing vaccines against Anthrax in sheep in 1881, followed by vaccine against rabies in man. Salk & Sabin introduced Polio Vaccine which later in this century led to eradication of Polio from many countries including India. Later on gradually many vaccines were developed for protection of humans against specific diseases (table 1).

The credit of introducing Passive Immunization goes to Emil Von Behring who used antitoxin serum against diphtheria and tetanus. Treatment of diphtheria with antitoxin was introduced by the Behring & Wernicke in 1891.

At present immunization is a leading measure of prevention and control of communicable diseases in man. Global Eradication of Smallpox became possible only because of immunization or vaccination strategy. Many diseases like Polio, Measles, Pertussis, and Tetanus & Diphtheria have been eliminated or eradicated from many developed and developing countries by using the weapon of immunization. Many more communicable diseases can be eradicated in the near future from the world by the practice of immunization.

In India officially BCG was the first vaccine used in the National TB Control Program. In years to come first Expanded Program on Immunization (EPI) & later Universal Immunization Program were launched. Later many vaccines were added into vaccination program in the country which are mentioned below –

Immunization Milestones (India)

(Govt. of India; Immunization Handbook for Medical Officers; MOHFW, GOI, 2017)

TYPES OF IMMUNIZATION –

Broadly speaking, Immunization is of three types –

• Active Immunization
• Passive Immunization
• Passive- active Immunization

ACTIVE IMMUNIZATION –

It is a process of conferring immunity by administration of live or dead immunizing agents, their products or derivatives. Immunity appears after an interval of 2-3 weeks after immunization and last for long period. Indications –

• Routine Immunization of susceptible population
• Selective immunization of population at risk

PASSIVE IMMUNIZATION –

Passive immunization is a process of inducing immunity by administration of ready- made antibodies of human or animal origin. Immunity appears immediately after passive immunization and lasts for smaller period.

Indications –

• Selective protection of high risk individuals
• Treatment of certain infectious diseases e.g. measles, mumps etc.

PASSIVE – ACTIVE IMMUNIZATION –

It is a process in which immunity is conferred by simultaneous administration of agents for inducing active and passive immunity. Immunity appears immediately and lasts for a longer period. Rapid onset passive immunity is sustained by slow onset active immunity.

Indications –

• Post exposure management of rabies and tetanus pro wounds.

In passive active immunization, it is important that the two immunizing agents be administered at two different sites of the body e.g. in two different arms.

IMMUNIZING AGENTS –

Immunizing agents are used for inducing artificially active or passive immunity to susceptible hosts. The immunogenic preparations used for inducing active immunity are vaccines and antibody preparations administered for conferring passive immunity are immune sera and immunoglobulins. The immunizing agents may be classified as VACCINES, IMMUNOGLOBULINS and ANTISERA.

VACCINES –

Vaccine is an immune-biological substance designed to produce specific protection against a given disease. It stimulates the production of protective antibody and other immune mechanisms. Vaccines may be prepared from live modified or attenuated organisms, inactivated or killed organisms, extracted cellular fractions, toxoids or combination of these. Recently arrived vaccines are sub-unit vaccines and recombinant vaccines. The use of vaccines is now extended to immunize against tumors/cancers (Human Papilloma Virus Vaccine for protection against cervical cancer) or to block fertilization (Contraceptive Vaccine). Even though no vaccine is entirely safe or completely effective, their use is strongly supported by their benefit to risk ratio.

Properties of ideal vaccine –

• Provide long lasting immunity
• Should induce both humoral and cellular immunity
• Should not induce auto immunity or hypersensitivity
• Should not be expensive to produce
• Should be easy to administer and store
• Vaccines must also be perceived to be safe

The vaccine vial may contain relevant antigens, adjuvants, preservatives and/ or traces of protein derived from the cells in which the vaccine agent was cultured e.g. egg protein.

Vaccines may be classified as attenuated, inactivated, derived and refined.

ATTENUATED VACCINES –

Attenuated vaccines are also known as LIVE VACCINES and are prepared from live but attenuated organisms. These organisms after repeatedly passed in tissue culture or in the chick embryo in the laboratory, have lost their capability to induce the active disease but retain the immunogenicity. The attenuated organisms possess all the antigenic compounds and generate a complete response, humoral as well as cell mediated. They colonize the natural target cells and block the invasion of pathogen. These organisms also replicate in the tissues of the recipient host and therefore enhance the antigenic dose, which generate an augmented antibody response. Attenuated vaccines have a long lasting immune response.

ADVANTAGES –

• As attenuated organisms can multiply in the host, fewer quantities administered may induce full protection.
• Provides long lasting immunity even on single administration. Multiple booster doses may not be required.
• Induces both cellular as well as humoral immune responses.
• Some attenuated organisms can be given orally; such vaccines induce mucosal immunity and IgA synthesis, which give more protection at the normal site of entry.
• Oral attenuated vaccines are less expensive than injectable vaccines.
• These vaccines can lead to elimination of wild type of viruses from the community.
• Attenuated organisms spread to contacts of vaccine recipients thus protecting them also in some cases.

DISADVANTAGES –

• Attenuated vaccines very rarely can cause clinical illnesses.
• These vaccines cannot be given safely to immunosuppressed individuals as may cause serious illness or death in them.
• Proper storage of vaccine is must & Critical.

INACTIVATED VACCINES –

Inactivated vaccines are also known as killed vaccines and prepared from intact organisms killed by heat, U-V radiation, or by treatment with chemicals such as phenol, alcohol, formalin or beta – propiolactone.

The inactivated are incapable of replicating in target organs of the recipient host, and so unable to generate a sustained and elevated immune response, or prevent colonization by natural infectious organisms.

Inactivated vaccines produce little or no cell mediated immunity, the immunity induced is also short lived. Inactivated Vaccines usually require a primary series of 2 or 3 doses of vaccine to produce an adequate antibody response and in most of the cases booster injections are required. Killed or inactivated vaccines are usually administered by subcutaneously or by intramuscular route. The only absolute contraindication of these vaccines is a severe local or general reaction to a previous dose.

ADVANTAGES –

• Safe to use and can be given to immune-defecient and pregnant individuals.
• Vaccine is cheaper than attenuated vaccines.
• It’s storage is not so critical as attenuated vaccines.

DISADVANTAGES –

• Since organisms are inactivated and cannot multiply, a large number/quantity are required to stimulate immunity.
• Periodic boosters are required to maintain the immunity.
• Only humoral immunity can be induced.
• Most killed vaccines have to be injected.
• Inactivation, such as by formaldehyde in the case of the salk vaccine, may alter antigenicity.
• Presence of some un-inactivated organisms can lead to vaccine –associated disease.

DERIVED VACCINE –

These vaccines are derived from bacterial toxins, bacterial capsules and viral envelopes. The toxins produced by certain bacteria e.g. diphtheria and tetanus bacilli are detoxicated and used in the preparation of vaccines. The toxoids retain their immunogenicity but lose their toxicity. These vaccines induce the production of antitoxic antibodies.

Certain vaccines in this category are derived from extracted cellular fractions e.g. meningococcal vaccines from the polysaccharide antigen of the cell wall, pneumococcal vaccine from the polysaccharide contained in the capsule of the organism and Hepatitis B poly – peptide vaccines.

The Surface antigen vaccine against influenza is also an example of derived vaccine which is prepared from the haemagglutinin and neuraminidase surface antigens obtained from the causative viral agent.

Another example of derived vaccine is pertussis acellular vaccine which consists of pertussis toxin and haemagglutinin derived from the causative bacterial antigen.

Derived vaccines generates only antibody mediated immune response. This vaccine can be used for immunization against tetanus, diphtheria, meningococcal meningitis, pertussis, influenza and hepatitis B etc.

RECOMBINANT VACCINE –

Recombinant vaccines consists of pure disease agents developed through genetic engineering technology. The gene encoding the antigen of a disease agent is identified, the segment of the genome encoding the gene is isolated and removed. A living but attenuated virus particle is selected to serve as a carrier. A segment of genome of the carrier virus excluding the one encoding the property of replication is excised and replaced by the segment obtained from the donar virus encoding the antigen protein. The carrier virus is propagated to obtain adequate stock of vaccine material. When administered, the attenuated carrier virus replicate in the tissues of the recipient host, releasing large quantities of pure antigens and generating massive immune response. Under the recombinant vaccine technology, more than one gene can be cloned in a carrier virus, empowering it with multiple immunogenic potential. Thus single shot recombinant vaccine can be developed for simultaneous immunization against a group of communicable diseases.

Advantages –

Recombinant Vaccines simulate natural infection, stimulate humoral as well as cell mediated immune response, posses no reactogenic material and satisfy economic as well as operational feasibility criteria.

Disadvantages –

There is possibility of carrier virus regaining pathogenicity, emergence of antibodies against carrier virus itself, the existence of previous immunity against carrier virus and the complications associated with carrier virus infection e.g. against vaccine virus.

Recombinant vaccines and synthetic vaccines are the examples of refined vaccines.

COMBINED VACCINES –

Combined Vaccine contains more than one type of immunizing agents in a single vaccine. It is also known as Mixed Vaccine. The aim of combined vaccine is to simplify administration, reduce costs and minimize the no. of contacts of the user with the health system. Established examples of combined Vaccines are as follows –

• DPT (Diphtheria, Pertussis & Tetanus)
• Pentavalent Vaccine( Diphtheria, pertussis, tetanus, Hib, Hepatitis B)
• DT (Diphtheria, Tetanus)
• MMR(Measles, Mumps, Rubella)
• DPTP (DPT plus inactivated polio) and many others.
• MR (Measles, Rubella)

The term Polyvalent Vaccine means vaccine which are prepared from 2 or more strains of the same species of infectious agent e.g. Polio and Influenza Vaccine.

The term Autogenous Vaccine means that the organism present in the vaccine is derived from the same individual.

FUTURE VACCINES –

Immunology and modern technologies in conjunction have led to the development of novel approaches for newer vaccines or future vaccines. The ultimate success of these vaccine will depend on the future and yet to be determined. But definitely the vaccine will become safer. Few examples are listed below –

• Recombinant DNA Vaccines
• Synthetic vaccines using synthetic peptides
• Purified Protein Vaccines
• Development of edible vaccines
• Use of naked DNA Vaccines
• Aerosol vaccines for respiratory disease viruses

Immunizing Agents for Passive Immunization

Three types of immunizing agents are available for Passive Immunization. These are 

• Antisera or antitoxins
• Normal Human Immunoglobulins and
• Specific(Hyper immune) human immunoglobulins

These are used in the prophylaxis of Viral & Bacterial infections, and in replacement of antibodies in immunodefecient patients.

Antisera or Antitoxins –

Antiserum are the immunological materials prepared in animals & humans. Initially administration of antisera or antitoxins prepared from the non-human sources such as horses were used for the passive immunization. Since there are limited immunoglobulins preparations at present, antitoxins prepared from non-human sources are still the mainstay of passive immunization in the tetanus, diphtheria, botulism, gas gangrene & snake bite.

Antisera administration sometimes cause serum sickness and anaphylactic shock due to abnormal sensitivity of the recipients. Where ever possible use of immunoglobulins should be encouraged.

Human antisera are antiviral or antibacterial, and are either obtained from volunteers who are subjected to repeated immunization to produce an adequate quantity of antibodies (Immune sera) or from recovering cases from an attack of a particular communicable disease (Convalescent sera).The limitations with the immune sera is the lack of human volunteers and that with the convalescent sera is the difficulty in obtaining adequate supply from recovering patients, usually being children.

Being prepared from humans, human antisera do not contain any foreign proteins, hence hypersensitivity reactions are uncommon. But its limitation is its higher cost which is not affordable to average patients in developing countries. Furthermore, it has been found to be associated with disappointing results. It is now being replaced by human immunoglobulins which produce satisfactory response.

                         (Table -2 -Passive Immunization procedures with antisera)

(Refer: K. Park, Park’s textbook of Preventive & Social Medicine; 26 edn, 2021)

Normal Human Immunoglobulins –

The normal human immunoglobulins are also called standard or polyvalent immunoglobulins and represent the normal pool of immunoglobulins possessed by healthy individuals. Normal human immunoglobulin preparation standards were laid down by WHO which includes –

• Preparation should contain at least 90% intact IgG.
• Should be free from IgG aggregates as much as possible.
• All subclasses of IgG should be present.
• There should be low IgA concentration and
• The level of antibody against at least 2 bacterial species and two viruses should be ascertained etc.

USES  –

• To prevent measles in highly susceptible individuals.
• To provide 12 weeks temporary protection against Hepatitis A infection for travelers to endemic areas.
• To Control institutional & household outbreak of Hepatitis A infection.

After an injection of normal human Immunoglobulin, Live vaccines should not be given for 12 weeks. If Live Vaccine has already been given, immunoglobulin injection should be avoided for 2 weeks.

Specific Human Immunoglobulins –

The Specific or hyper immune human Immunoglobulins should contain at least five times the antibody potential of the standard human immunoglobulins per unit volume. These immunoglobulins are prepared from the plasma of the patients who have recently recovered from an infection or are obtained from an individual who have been immunized against a specific infection. These preparations provide immediate protection.

USES – 

• Prophylaxis of chickenpox for highly susceptible individuals.
• Post exposure prophylaxis of hepatitis B & Rabies
• For tetanus prophylaxis in the wounded

Immunoglobulin preparations are available for both intramuscular and intravenous injections. Peak blood levels are reached within 2 days of I/M injection. The half-life of preparation is 20-35 days.

Advantages of Immunoglobulins –

• Freedom from Hepatitis B.
• Small volume of injection contains higher concentration of antibodies
• Its stability ensured if properly stored.

Adverse Effects –

• Local Reactions (e.g. pain, sterile abscesses etc.)
• Systemic Reactions – 2 types –
• Rapid Reactions – Anaphylactic Reaction
• Late Reactions – Urticaria, Arthralgia, Pyrexia or Diarrhoea

Systemic reactions are very rare i.e. one in 500-1000 injections. They are more common with intravenous injections. Systemic reactions can be prevented by giving Hydrocortisone before the injection.

*of limited availability at the present time.

(Table – 3; Human Immunoglobulins in the prevention & treatment of diseases)

(Refer: K. Park, Park’s textbook of Preventive & Social Medicine; 26 edn, 2021)

Other additives in immunizing agents

Immunological Adjuvants

An adjuvant, in immunology, is a component that potentiates the immune responses to an antigen and/or modulates it towards the desired immune responses.

An immunologic adjuvant is defined as any substance that acts to accelerate, prolong or enhance antigen specific immune responses when used in combination with specific vaccine antigens.

Advantages –

• Immunological response resulting in greater output of antibodies.
• Lesser quantity of vaccine and fewer number of doses of vaccines are required.
• Both primary & secondary immune responses are achieved by a single injection of a vaccine.
• Peak of antibodies generated is maintained over a long period.

Examples – Mineral Adjuvants – Aluminium Hydroxide & Aluminium phosphate.

• Emulsified Adjuvants – Water in Oil.
• Bacterial Adjuvants – BCG, B. Pertussis & Corynebacterium parvum.

Contraindication to Active Immunization

• ABSOLUTE CONTRAINDICATIONS –
• Allergy
• Immunodeficiency
• RELATIVE CONTRAINDICATIONS –
• Acute Febrile illness
• Pregnancy in case of live vaccines
• Chemotherapy
• Client on Immunosuppressive drugs
• Immunotherapy

Chapter 2 – Childhood Vaccines as per National Immunization Schedule (NIS)

Schedule of Immunization –

An immunization Schedule is a time frame that regulates immunization by ensuring appropriate timing, appropriate dosage, appropriate combinations, intervals and frequencies for administration of vaccines.

Immunization Schedule ensures –

• To protect all the susceptible population against the major communicable diseases.
• Dosage, intervals and combinations of the vaccine that generates adequate antibody response.
• Flexibility, simplicity, acceptability & convenience.
• Maximum benefits with minimum visits, without involving any associated risk.

National Immunization Schedule – (As on 2017-2022)

VACCINES, ITS DOSES, SITE & ROUTE OF ADMINISTRATION –

(Table 6 – National Immunization Schedule, India, 2017)

(Govt. of India; Immunization Handbook for Medical Officers; MOHFW, GOI, 2017)

National Immunization Schedule (2017) – Summary for childhood Immunization

1. BCG VACCINE-

INTRODUCTION

Vaccine is used for active immunization against tuberculosis. BCG Vaccine is derived from Bovine tuberculosis strain and was first developed in 1921. CALMETTE & GUERIN developed it after 231 repeated subcultures in 13 years, hence known as bacilli Calmette Guerin or BCG.

TYPE OF VACCINE

It is the one of commonly used live bacterial vaccine and is the only effective vaccine against tuberculosis. The two common strains in use are Copenhagen (Danish 1331) & Pasteur strains. Of these Danish 1331 strain of bacteria is used for vaccine production in India till recently.

Freeze- dried or lyophilized vaccine is more stable than liquid vaccine. Lyophilized (Freeze-dried) vaccine is supplied as a vacuum sealed, multi-dose, dark coloured ampoules or vials of 1ml or 2ml with normal saline as diluent. The vaccine must be saved from direct sunlight during storage & field otherwise deteriorates.

STORAGE

In lyophilized form, it can be stored at 2 – 8 degree C for up to 12 months without losing its potency.

RECONSTITUTION

Diluents should be used for reconstitution of the vaccine. Sterile Normal Saline may be used if diluent is not available. Distilled water is not used as it causes irritation. As the vaccine contains no preservative, bacterial contamination and consequent toxic shock syndromemay occur if kept for longer period after reconstitution. The reconstituted vaccine should be stored at 2-8 degree C, protected from light and discarded after 3 hours of reconstitution, if not used.

DOSE, SCHEDULE, ROUTE & SITE OF INJECTION

BCG vaccine contains 0.1- 0.4 million live viable bacilli per dose. For BCG vaccination, dose is 0.1 mg in 0.1 ml volume but for newborn less than 4 weeks, dose is 0.05 ml. In newborn, the skin is thin and an intradermal injection of 0.1 ml may break the skin or penetrate the deeper tissue and may cause local abscess and enlarged axillary lymph nodes. There is no need to give booster dose of BCG as most Indians develop immunity in the long term.

Vaccine is given intradermally by using a tuberculin syringe on the left upper arm. The convex aspect of the left shoulder at level of deltoid insertion is preferred for easy visualization of BCG scar and for optimum lymphatic drainage. BCG is given on the left upper arm to maintain uniformity and for helping surveyors in verifying the receipt of the vaccine.

No spirit or antiseptic should be applied over the injection site before BCG vaccination. One can wash the injection site with soap & water or by using normal saline.

Direct BCG Vaccination i.e., vaccination without a prior tuberculin test is the national policy in India.

BCG may be given with all vaccines on the same day or at an interval with the exception of Measles, MR or MMR vaccine where both the vaccines can be given simultaneously at different sites. It is generally given at birth along with zero dose of OPV and 1^st dose of Hepatitis B Vaccine (Newborn Vaccination). Otherwise BCG can be given till one year of age.

Immediately after the BCG vaccine there is formation of a small swelling at the injection site, which persists for 6-8 hours. After that swelling disappears and injection site looks normal. After 6-8 weeks a nodule develops which breaks and forms a ulcer. The ulcer heals by forming a scar. The whole process completes in 2-5 weeks. Sometimes process of ulceration reoccurs 2-3 times. Ultimately the typical puckered scar is formed which remains for life time. If ulcer forms within seven days of injection, it may be a sign of tuberculosis in the child. There is no need to revaccinate the child if no scar appears on left upper arm after BCG vaccination.

IMMUNITY

BCG induces cell mediated immunity, but protection varies. At its best BCG vaccine is 80% effective in preventing tuberculosis for a duration of 15 years, its protective effect appears to vary according to geography. Various studies indicate that the BCG reduces the risk of getting TB by about 50%.

COMPLICATIONS  

• Prolonged severe ulceration at the site of inoculation
• Suppurative lymphadenitis
•  
• Disseminated infection.
•  

CONTRAINDICATIONS

• Infective Dermatosis.
• Generalized eczema.
•  
• H/0 deficient immunity.
• Patient on Immunosuppressive therapy.
•  

NOTES

HIV positive infants can be given BCG only if they are asymptomatic & living in high endemic area for TB.

In Children, BCG Vaccination protects them from Tubercular meningitis & military tuberculosis.

2. MONOVALENT HEPATITIS B VACCINE

INTRODUCTION

Vaccine is used for active immunization against hepatitis B infection among newborns in India under UIP. Now a days Recombinant Hepatitis B vaccine which was introduced in 1986 is being used.

TYPE OF VACCINE

Presently used Hepatitis B Vaccine (rDNA) is a non-infectious recombinant DNA Hepatitis B vaccine. It contains purified surface antigen (HBsAg) of the virus obtained by culturing genetically engineered Hansenula polymorpha yeast cells having the surface antigen gene of the Hepatitis B Virus. It is formulated as a suspension of the surface antigen (HBsAg) adsorbed on Aluminium hydroxide and thiomersal is added as a preservative. The vaccine does not contain any material of human or animal origin.

STORAGE

Vaccine should be stored at 2- 8 degree C. Vaccine should not be allowed to be frozen as it dissociates antigen present in vaccine from the alum adjuvant. Discard the vaccine, if became frozen.

DOSE, SCHEDULE, ROUTE & SITE OF INJECTION

Hepatitis B vaccine is given to newborns (Birth dose) in a dose of 0.5 ml intramuscularly on antero-lateral aspects of mid-thigh within 24 hours of birth to prevent transmission of hepatitis B infection from mother at the time of birth.

The vaccine can be safely and effectively given simultaneously but at different injection sites with BCG to the newborns. Hepatitis B Vaccine should not be administered in the gluteal region or intradermally since this may result in a lower immune response.

ADVERSE EFFECTS

Adverse Effects include –

• Mild reaction at injection site
• Low grade fever, malaise, fatigue, headache, nausea rarely.

IMMUNITY

The duration of protection is lifelong (minimum 15 years).

Oral Polio Vaccine (OPV) –

INTRODUCTION

OPV was discovered by Sabin in 1957. Initially was used as trivalent vaccine containing type 1, 2 & 3 polio virus but now given as bivalent vaccine containing type 1 & 3 polio virus of Sabin strain. Vaccine is used to provide protection from wild polio virus.

TYPE OF VACCINE

Live attenuated vaccine. Attenuated live viruses are grown in primary monkey kidney or human diploid cell cultures.

STORAGE

Now a days supplied OPV (Heat stabilized by adding magnesium chloride) can be stored at 4 degree Celsius for a year without losing potency. Non-stabilized vaccines can be stored at -20 degree Celsius in a deep freezer until used.

DOSE, SCHEDULE, ROUTE & SITE OF INJECTION

Zero dose (OPV at birth) of OPV is recommended in institutional deliveries to the newborns. Zero dose of OPV can be given up to 15 days. Primary immunization constitutes three initial doses, starting at 6 weeks of age, orally, at an interval of 4 weeks; booster dose of OPV is recommended at 16-24 months. Those who are unimmunized can receive OPV up to 5 years of age.

Dose – 2 drops of vaccine orally.

ADVANTAGES

• Easy to administer, does not require trained professional
• Induces both humoral & intestinal immunity
• Quickly produced antibodies for protection against disease
• Immunizes the contacts by excreting the vaccine virus
• Inexpensive
• Useful in controlling epidemics

COMPLICATIONS

Rarely Vaccine associated paralytic polio because of mutant type 3 polio virus.

CONTRAINDICATIONS & SPECIAL PRECAUTIONS

Contraindications include immunodeficiency conditions.

Special Precautions should be taken during Diarrhoea & pregnancy.

IMMUNITY

The duration of immunity produced is probably life-long.

PENTAVALENT VACCINE

INTRODUCTION

Pentavalent Vaccine provides protection to a child against five life threatening diseases namely Diphtheria, Pertussis, Tetanus, Hepatitis B & Haemophilus influenzae type b. Pentavalent vaccine can prevent over a third of pneumonia cases & 90% of Hib meningitis cases.

ADVANTAGES

DPT & Hepatitis B are already part of routine immunization in India; Hib vaccine is a new addition. Together this combination is called Pentavalent. Hib vaccine can prevent serious diseases caused by Haemophilus influenzae type b like Pneumonia, meningitis, bacteremia, epiglottitis, septic arthritis etc.

Giving pentavalent vaccine not only reduces the number of pricks to a child but also provides protection against all five diseases. The Pentavalent vaccine will replace the current Hepatitis B & DPT primary vaccination schedule in the immunization programme. Additionally,

• Hepatitis B birth dose will continue as before, in institutional birth within 24 hours of the birth.
• DPT boosters at 16-24 months & 5-6 years will continue as before.

TYPE OF VACCINE

In UIP, pentavalent vaccine comes in a liquid form in a vial which contains 10 doses. Pentavalent vaccine is available in various forms of liquid & lyophilized. However under the UIP in India, the vaccine is available in liquid formulation only. The Government of India has opted the Open Vial Policy for Pentavalent Vaccine.

DOSE, SCHEDULE, ROUTE & SITE OF INJECTION

Vaccine is given to infant on 6, 10 & 14 weeks of life. Each dose is 0.5 ml to be given by intra muscular injection in anterolateral aspect of mid-thigh using AD syringes. Discard injection waste as per guideline for immunization waste management.

Generally all children aged up to 1 year of age (after 6 weeks & less than 1 year) should receive pentavalent vaccine as part of routine immunization.

STORAGE

Pentavalent vaccine is a freeze sensitive vaccine and should be stored and transported at +2 to +8 degree Celsius in ice lined refrigerators and vaccine carriers with conditioned ice packs. Discard if vaccine is frozen or VVM reaches discard point (the colour of the square matches or is darker than the Circle).

ADVERSE EFFECTS

Side effects – Pentavalent vaccine has not been associated with any serious side effects. However, redness, swelling & pain may occur at the injection site. These symptoms usually appear the next day of immunization and last for one to three days. Less commonly children may develop fever for a short period of time after immunization.

Cases of AEFI (Minor or Major) will be reported as per existing Government of India AEFI reporting guidelines.

CONTRAINDICATION

1) A child who has had a severe reaction to pentavalent vaccine earlier should not receive another dose.

2) Children with moderate or severe acute illness.

IMMUNITY

This vaccine is safe & efficacious and provide 85% to 95% protection after completion of the schedule. Vaccine generally provides protection for 15 years. A booster dose is not recommended in India.

FRACTIONAL DOSE INACTIVATED POLIO VACCINE (f IPV)

INTRODUCTION

FRACTIONAL IPV VACCINE

INTRODUCTION

A fractional dose of the IPV (f IPV) is equal to 1/5^th of a standard dose of IPV. Studies show that three doses of f IPV administered by intradermal route produce an even stronger immune response than a single full dose of the IPV (0.5 ml). It provides protection against poliomyelitis.

It is an inactivated vaccine. Intradermal administration of f IPV is safe, effective & immunogenic. Fractional IPV can benefit children previously vaccinated for polio & zero-dose receiving children. For children who have previously received OPV, f IPV will help to boost their immunity.

Fractional IPV can be given alone or at the same time as any OPV vaccine. Accelerated routine immunization with f IPV is recommended to enhance eradication of wild polio virus and reduce the risk of emergence of Vaccine Derived Polio Virus 2 (VDPV2). Fractional IPV can be used for VDPV2 outbreak or event response in settings where immunity is already high and recommended by global technical experts. IPV induces humoral antibodies but does not induce local or intestinal immunity. Circulating antibodies protect the individual from paralytic polio but does not prevent reinfection of gut by wild polio virus.

DOSE, SCHEDULE, ROUTE & SITE OF INJECTION

The dose of vaccine is 0.1 ml or 1/5^th of a full dose of IPV (0.5 ml). Vaccine is given intra-dermally using BCG syringe on the right upper arm at 6 week, 14 week & 9 months (third dose included from 1^st January 2023 in NIS) in left upper arm along with MR1 dose (right upper arm). Children who have already received their MR1 dose, may not be given additional dose of f IPV for operational easiness.

Angle of syringe should be close to flat on the skin (10 – 15 degree angle). Vaccine is administered slowly and formation of bleb (5-10 mm diameter) observed. Do not repeat the vaccination, even if no bleb is observed after injection. OPEN VIAL POLICY is applicable for f IPV (from opening of vial to 28^th day).

STORAGE, SUPPLIES & TRANSPORTATION

Several manufacturers supply IPV in both single & multiple dose vials. Cold chain is essential, always store at 2 to 8 degree Celsius. IPV is freeze sensitive & heal sensitive vaccine; discard any vial suspected to have undergone freezing. Do not keep the vaccine on icepacks at the session site. Do not use SHAKE TEST, as not effective for IPV.

Check the VVM before each use & discard vial if the color of square is same as or darker than the surrounding circle. Mark the vial with the time & date of opening. Vaccine can be used up to 28 days after opening vial, if stored appropriately and VVM has not expired.

ADVANTAGES

Being an inactivated polio vaccine, it is safe to administer –

• In persons with immune deficiency diseases
• In persons undergoing corticosteroids or radiation therapy
• In old age persons
• During pregnancy

In less dose fractional IPV generates more stable immune response.

CONTRAINDICATIONS

Serious reaction history with a previous dose of vaccine.

Rationale for 3^rd f IPV dose

• Seroconversion against polio virus 2 with the current schedule of f IPV at 6 and 14 weeks in the immunization schedule is 79%.
• Even two full doses at 6 & 14 weeks with IPV, it only reaches up to 89%.
• Addition of delayed 3^rd dose of f IPV or IPV, seroconversion reaches up to 100%.
• Therefore schedule of administration of f IPV administration at 6 weeks, 14 weeks & 9 months is recommended.

NOTE

• If at least one dose of f IPV has been given before one year of age, then remaining doses should be administered and the schedule must be completed at earliest.
• If the first dose is not administered before one year of age, then vaccine should not be administered to the child under UIP.

ROTAVIRUS VACCINE (RVV)

WHO recommends that Rotavirus vaccines to be included in National Immunization Programs as part of comprehensive approach to reduce the impact of diarrhoeal diseases due to rotavirus. The National Technical Advisory Group on Immunization (NTAGI) has recommended introduction of Rotavirus Vaccine (RVV) in the National Immunization Program of India.

Currently two Rotavirus Vaccines (Rotavac & Rotasil) are used in UIP in India. These vaccines have been shown to be safe and effective in large scale clinical trials.

INTRODUCTION

• ROTAVAC Vaccine

It is a live attenuated, oral liquid vaccine and is available in 5 dose vial & does not require reconstitution. Each dose is of 5 drops (0.5 ml). The vaccine is in a liquid or frozen form. In liquid form, the vaccine is generally pink in color.

The vaccine is generally supplied with a pink colored dropper. The vaccine should be administered only with the dropper supplied by the manufacturer. Rotavirus Vaccine vial can be used up to a maximum of 4 hours after opening. It is mandatory to write date and time of opening of a vial. RVV does not follow the OPEN VIAL POLICY.

• ROTASIL Vaccine

It is a live attenuated, heat stable, freeze dried vaccine & is available in 2 dose vial which must be reconstituted before use with the supplied diluents (Citrate bicarbonate) only. Each dose is of 2.5 ml. The carton pack for 2 dose vial contains 50 vials (100 doses). It is a lyophilized vaccine.

After reconstitution the vaccine is pinkish in color. One vaccine vial is supplied with a diluent vial, an adopter for reconstitution and a two 6 ml syringes. Reconstituted RVV vial can be used up to a maximum of 4 hours after reconstitution. It is mandatory to write date & time of opening of vial. Reconstitution & administration of vaccine should be done only by using accessories supplied by the manufacturer. This RVV does not follow Open Vial Policy.

DOSE, SCHEDULE, ROUTE & SITE OF INJECTION

Dose of RVV is 5 drops for ROTAVAC & 2.5 ml for ROTASIL vaccine. Both are given orally at 6 weeks, 10 weeks & 14 weeks. For administration of Rotavac pink colored DROPPER is used while for Rotasil vaccine 6 ml syringe is used. The upper age limit for administering the 1^stdose of RVV is 1 year. Vaccine provides protection for 2 years.

STORAGE

• Rotavac Vaccine

This vaccine should be stored at state, regional & district level at – 15 to – 25 degree Celsius in the walk in the walk in freezers (WIFs) or deep freezer (DFs). It should be stored below district level at + 2 to + 8 degree Celsius, in ILRs. In the ILR, the vaccine should be stored at or above BCG level. It should be transported to session sites in vaccine carrier with 4 conditional ice packs.

The droppers for administration of vaccine are to be stored at room temperature as freezing can cause the droppers to crack. They are to be supplied to the immunization session site along with the other dry supplies outside the vaccine carrier. Cold chain storage volume occupied by each dose of RVV supplied in a 5 dose vial in 4.3 cubic cm. This RVV has a vaccine vial monitor – Type 2 (VVM-2).

• Rotasil Vaccine

This RVV should be stored at + 2 to + 8 degree Celsius at all levels. In the ILR, the vaccine should be stored at or above BCG level. At the last cold chain point from where the vaccines are supplied to the session site, diluent vials should be kept between + 2 to + 8 degree Celsius in ILR.

The pre cooled diluent vials should be carried to the session site at the same temperature as the vaccine in the vaccine carrier. 6 ml syringe and adopter used for administration of vaccine are to be stored at room temperature to avoid damage due to freezing. Storage volume is 10.5 cubic cm of cold chain per rotavirus each dose & 21.1 cubic cm for each dose of RVV with diluents. This new type of Rotavirus vaccine has a VVM type 30 (VVM-30).

CONTRAINDICATIONS

• Known or documented allergic reaction to vaccine
• History of documented intussusception or abdominal surgery or intestinal malformation.
• Known case of immunodeficiency.

Mild illnesses such as upper respiratory tract infection or mild diarrhoea is not a contraindication for RVV administration.

SPECIAL PRECAUTIONS

Administration of RVV should be postponed in infants suffering from moderate to severe diarrhoea or vomiting requiring rehydration therapy. In such case vaccine can be administered after recovery from illness.

ADVERSE EFFECTS

• Diarrhoea, vomiting & irritability in some children
• Intussusception (rarely)

NOTE

• All partially used vaccine vials should be sent back to cold chain point for disposal as per BMW management guidelines.
• Breastfeeding does not significantly impair the response to RVV. There are no restrictions on the infant’s feed, including breast milk, either before or after vaccination with RVV.
• During the initial introduction of Rotavirus vaccine, only infants coming for first dose of pentavalent vaccine and OPV will be started with Rotavirus vaccine schedule. Infants coming for the 2nd or 3rd doses of OPV and pentavalent vaccine will not be started with Rotavirus vaccine.
• The upper age limit for giving first dose of Rotavirus vaccine is one year. If the child has received first dose of Rotavirus vaccine by 12 months of age, subsequent two more doses of the vaccine should be given with an interval of 4 weeks to complete the course.

PNEUMOCOCCAL CONJUGATE VACCINE (PCV)

INTRODUCTION

PCV can protect children from streptococcus pneumoniae, the most common cause of severe bacterial pneumonia in children. PCV can prevent infections that can lead to pneumonia as a complication, such as influenza, measles and pertussis. This is also called as indirect protection.

Pneumococcal vaccines are derived from sugars (polysaccharides) from the capsule of the bacterium streptococcus pneumoniae. They may or may not be attached to carrier protein. Polysaccharide vaccines are not attached with carrier proteins while PCV are attached with carrier proteins. The carrier protein is selected to improve the immune response in the vaccinated.

Currently PCV 10 & PCV 13 vaccines are available. PCV 7, which was introduced in 2000, has been phased out. PCV 10 & PCV 13 are safe and effective and act against all serotypes prevalent in developing countries. NTAGI recommended PCV 13 (4 dose vial) as the preferred vaccine type for introduction in UIP. In case of shortage of PCV 13, the NTAGI recommended that other vaccine type e.g. PCV 10 may also be considered.

DOSE, ROUTE & SITE OF ADMINISTRATION

The vaccine in a dose of 0.5 ml is administered at 6 weeks, 14 weeks (primary doses) & 9 months (booster dose) of age intramuscularly in the antero-lateral aspect of right mid-thigh of infants using 0.5 ml auto-disable syringe.

If multiple injections must be given in the same thigh, distance between two injections should be at least 2.5 cm (1 inch). If the doses are delayed within the first year of life, delayed doses must be separated by a minimum interval of at least 8 weeks. In delayed cases beyond 1 year of age, due doses can be given to a child only if child has received at least one dose of PCV before his/her first birthday.

STORAGE

A freeze-dried vaccine, should be stored at temperature +2 to +8 degree Celsius in the basket of ILR. Do not freeze the vaccine. It is important to use conditioned ice packs to prevent freezing during transportation. The SHAKE TEST is applicable to PCV vaccine. Discard if frozen.

ADVERSE EFFECTS

Serious reaction is uncommon. Common adverse effects are Irritability, crying, swelling & tenderness at injection site & temperature more than 39 degree Celsius (102 degree F).

CONTRAINDICATIONS

Contraindications of PCV include –

• Severe allergic reaction to prior dose
• Severe illness

May be given in children with mild respiratory illness with or without low grade fever.

NOTE

Regardless of presence of underlying medical conditions (children with HIV infection, Sickle Cell Disease or immunocompromised state) the vaccine should be given as per schedule.

PCV vaccine cannot be mixed with other vaccines in the same syringe.

MEASLES-RUBELLA (MR) VACCINE

INTRODUCTION

Measles-Rubella (MR) vaccine is used for immunization of children against Measles & Rubella disease. It is a live attenuated vaccine and is safe & effective. Measles vaccine is available as monovalent (Measles vaccine), bivalent (MR), trivalent (MMR) & quadrivalent (MMRV) vaccine. When MR/MMR/MMRV vaccines are used, the protective immune response of each of the components remain unchanged.

MR vaccine contains Edmonston strain of measles virus & attenuated RA 27/3 strain of rubella virus propagated in human diploid cells. Vaccination results in high (>95%) seroconversion rates and protection is generally assumed to be lifelong, although rubella antibodies may fall below detectable level.

DOSE, ROUTE & SITE OF ADMINISTRATION

Dose of vaccine is 0.5 ml, given subcutaneously at 9-12 months as first dose & at 16-24 months as second dose on right upper arm.

Asymptomatic HIV infection is not a contraindication for MR vaccination, the vaccine should be offered as early as possible in the course of HIV infection. HIV infected infants should receive measles vaccine at 6 months of age, followed by an additional dose of MR vaccine at 9 months, in case they are not severely immune-compromised.

STORAGE

MR vaccine, a freeze dried vaccine, is a stable vaccine before reconstitution when stored between 2 to 8 degree Celsius. Following reconstitution, the vaccine must be stored at +2 to +8 degree Celsius & used within 4 hour. At the session site, the reconstituted vaccine should be kept inside the well of icepacks.

The open vial policy is not applicable to reconstituted MR vaccine. The MR vaccine is very sensitive to sunlight hence it comes in colored glass vial. Diluents, supplied by manufacturer, should be kept at +2 to +8 degree Celsius at least 24 hours before use and thus should be carried to session site at the same temperature as the vaccine inside the vaccine carrier.

MR vaccine can be safely frozen without loss of potency. Generally in UIP 10 dose vial is available. Storage space needed for vaccine dose & diluent dose in a ILR are 2.6 cubic cm each.

ADVERSE EFFECTS

Generally mild & transient. Slight pain and tenderness at the site of injection is observed within 24 hour, sometimes followed by fever.

Fever within 7- 12 days in 5% recipients.

Transient Rash is observed in 2% individuals.

Thrombocytopenic purpura (1:30,000) & Anaphylaxis (1 in 1 million) are rare.

Adverse effects, with the exception of anaphylactic reaction, are less likely to occur after receipt of second dose of MR vaccine.

CONTRAINDICATIONS

• High fever or serious illnesses
• Pregnancy
• Persons with history of anaphylactic reaction to neomycin, gelatin or other components of MR vaccine
• Immune-deficiency disorders

NOTE

• MR vaccine induces both humoral & cellular immune response, conferring long term immunity for the measles & rubella.
• There is no evidence of increased risk of encephalitis, permanent neurological sequel or Guillain-Barre syndrome following MR vaccination.
• There is no evidence to support reports that MR vaccination may be a high risk factor for inflammatory bowel disease or for autism. MR vaccine does not exacerbate tuberculosis.
• Following MR vaccination, administration of blood or blood products should be avoided for 2 weeks, if possible.
• Malnutrition & minor illnesses are not contraindications for MR vaccination.

JAPANESE ENCEPHALITIS (JE) VACCINE –

Vaccine is used for active immunization against JE. JE vaccination was introduced in UIP in 2006. It is provided only in JE endemic districts of India (336 districts across 22 states). Newly identified JE endemic districts by NVBDCP are taken up for JE vaccination campaign in children aged 1-15 years, followed by JE vaccination introduced in Routine Immunization as 2 doses provided at 9-12 months & 16-24 months of age.

Following JE vaccines are available under UIP –

• Live attenuated SA 14-14-2, Chengdu – China (LAJEV)
• Can be used in children & adults
• For use in RI & Campaign.
• Killed/Inactivated JenVac (M/S Bharat Biotech)
• Can be used in children & adults
• For use in RI & Campaign.
• Killed/Inactivated Jeev (M/S BE limited)

(Pediatric preparation 1-3 years, 3 micro gm)

• Can only be used in children
• For use in RI only
• Currently used in RI of Chhattisgarh, Odisha & West Bengal only.

LIVE ATTENUATED JE VACCINE

It is a live attenuated vaccine using SA 14-14-2 strain. It is a freeze dried vaccine. Five dose vial containing lyophilized vaccine is available. Needs to be reconstituted. Reconstituted vaccine should be used within 4 hours of reconstitution.

In RI, given as 0.5 ml, subcutaneously in left upper arm in form of 2 doses; 1^st dose at 9-12 months & 2^nd dose at 16-24 months of age.

Open vial policy is not applicable with the reconstituted vaccine. VVM is available on the cap of vaccine vial (VVM 14).

Stored at +2 to +8 degree Celsius in the lower basket of ILR. Vaccine should be kept away from direct sunlight at the session site as sensitive to sunlight.

Side effects include transient fever, local irritation, rash & irritability.

INACTIVATED JE VACCINE (Jeev or JenVac)

These are inactivated JE vaccines using SA 14-14-2 strain. It is a five dose vial containing suspension of vaccine. There is no need for reconstitution – shake well before use.

Open vial policy is applicable. VVM of the vaccine vial is on the label (JenVac – VVM 7; Jeev – VVM 14)

Dose of the vaccine is 0.5 ml, given intramuscularly at antero-lateral aspect of mid-thigh in 2 doses; 1^st dose at 9-12 months & 2^nd dose at 16-24 months of age.

JEEV will not be used in campaign.

Stored at temperature +2 to +8 degree Celsius. Do not freeze this vaccine.

DIPHTHERIA-PERTUSSIS-TETANUS (DPT) VACCINE

INTRODUCTION

DPT vaccine is used for immunization of children against Diphtheria, Pertussis & Tetanus in UIP as booster doses at 16-24 months & 5-6 years of age of child. The pertussis component of DPT vaccine enhances the potency of the diphtheria toxoids. WHO recommends that only adjuvant DPT preparations should be used in UIP as adsorption increases the immunological effectiveness of the vaccine.

DOSE, ROUTE & SITE OF ADMINISTRATION

Dose is 0.5 ml, given intramuscularly, in left antero-lateral aspect of mid-thigh at 16-24 months as 1^st booster and in upper arm at 5-6 years as 2^nd booster. It is associated with high vaccine efficacy (around 95%).

STORAGE

DPT vaccine should not be allowed to freeze. They should be stored at a temperature of +2 to +8 degree Celsius. No diluent is required.

ADVERSE EFFECTS

Fever & mild local reactions following DPT immunization are common. Local reaction includes pain & swelling at the site of injection.

The most serious complications following DPT vaccination are neurological (encephalitis/encephalopathy, prolonged convulsions, infantile spasms and Reye’s syndrome) and are thought to be due primarily to pertussis component of the vaccine.

CONTRAINDICATIONS

• Shock
• Persistent screaming
• High fever
• Convulsions
• Other neurological reactions
• Anaphylaxis
• Previous reactions

NOTE

Minor illnesses such as cough, cold, mild fever are not considered contraindications to vaccination.

TETANUS & ADULT DIPHTHERIA (Td) VACCINE

INTRODUCTION

Since 1988, WHO has recommended that TT should be replaced by Td vaccine. NTAGI & MOHFW has also recommended the replacement of Tetanus toxoid (TT) vaccine with Tetanus & adult diphtheria (Td) vaccine in India’s immunization program for all age groups including pregnant women.

Tetanus & adult diphtheria vaccine protects recipients from the tetanus & diphtheria disease. Td vaccine is a combination of tetanus & diphtheria with lower concentration of diphtheria antigen (d) as recommended for older children & adults. It is a toxoid preparation.

STORAGE  

Td vaccine is a freeze and heat sensitive vaccine. VVM 30 is used as label on the vial. Never allow vaccine to freeze. Only VVM suitable vaccine should be used for administration of vaccine. VVM 30 is used for the vaccine vial. Open vial policy is applicable to vaccine. Vaccine should be stored at +2 to +8 degree Celsius. Thiomersal is the preservative contained in the vaccine.

DOSE, SITE & ROUTE OF ADMINISTRATION

FOR CHILDREN,

0.5 ml of Td vaccine is given in upper arm intramuscularly at the age of 10 years & 16 years.

FOR PREGNANT WOMEN,

0.5 ml of Td1 is given in early pregnancy on upper arm intramuscularly followed by same quantity 2^nd dose (Td2) 4 weeks after the Td1 on upper arm intramuscularly. Td booster dose (Td B), 0.5 ml in quantity, is given intramuscularly in upper arm, if pregnancy occurs within 3 years of last pregnancy in which 2 Td doses were received.

RATIONALE FOR Td VACCINE

• Majority of cases of diphtheria are occurring in age group 5 years & above, mostly in unvaccinated children (2/3^rd).
• Td vaccine in place of TT vaccine will help to decrease diphtheria outbreaks.
• The use of Td rather than TT is recommended in pregnancy to protect against maternal & neonatal tetanus & diphtheria during prenatal care.
• Vaccination during pregnancy will also increase the immunity & duration of protection in the pregnant women who have not received full course of recommended vaccine doses earlier in their life.

NOTE

• Available TT will be used first before starting use of Td.
• Td is a safe vaccine. Any minor, severe & serious AEFI event should be reported immediately.

CHAPTER 3 – CHILDHOOD VACCINES AS PER INDIAN ASSOCIATION OF PEDIATRICS (IAP)

Vaccination Schedule of IAP 2018-19 –

DPT (Diphtheria, Pertussis & Tetanus) Vaccine –

It is a trivalent vaccine used for primary immunization against Diphtheria, Pertussis & Tetanus. There are following vaccines available for protection against Diphtheria, Pertussis (whooping Cough) & Tetanus –

• DTwP –

INTRODUCTION

This vaccine is also known by name Triple Antigen. Vaccine is composed of Tetanus & Diphtheria toxoids as well as Killed whole cell pertussis bacilli adsorbed on insoluble Aluminium salts which act as adjuvants. The content of diphtheria toxoid varies from 20 to 30 Lf and that of tetanus toxoid varies from 5 to 25 Lf per dose. For years, immunization of infants with whole cell pertussis component in DPT vaccine has been very successful in reducing severe infections and deaths more than 95%.

STORAGE

The vaccine need to be stored at 2 to 8 degree C. These vaccines should never allowed to be frozen, and if frozen accidently, should be discarded.

IMMUNITY

The immunogenicity & effectiveness against diphtheria/tetanus of 3 doses of vaccine exceeds 95%. The disease can occur in vaccinated individuals but it is milder. The efficacy of the vaccine against pertussis is lower and ranges from 70-90%. Immunity against all 3 components wanes over the next 6-12 years and thus regular boosting is needed.

Pertussis component plays an important role in DPT Vaccine. It enhances the potency of the diphtheria toxoid.

IMMUNIZATION SCHEDULE

0.5 ml of DPT vaccine given intramuscularly in 3 doses along with OPV, 4 weeks apart, starting at 6 weeks of age. 1^st booster is recommended at the age of 1& ½ to 2 years. 2^nd booster (DT only) is given at the age of 5-6 years. Vaccine should be administered in lateral aspect of the mid-thigh.

CONTRAINDICATION

Contraindications include – 1) severe illness 2) H/O severe reaction with DPT

ADVERSE EFFECTS

Adverse effects include –

• Fever
• Mild local reactions
• Neurological Complications(Convulsions, Encephalitis, Infantile spasms ,Reye’s Syndrome)

Neurological complications following DPT administration are because of pertussis component of the vaccine.

• DTaP –

This vaccine contains same diphtheria & tetanus toxoids along with acellular Pertussis vaccine. Higher side effects seen with Pw component vaccines led to the development of this second type vaccine, called the acellular pertussis (aP) vaccine, composed of inactivated bacterial proteins. All Pa vaccines contain chemically inactivated pertussis toxin. Pa vaccines are easier to produce and better tolerated by infants. This vaccine is more costly and cause less side effects though not more efficacious than DTwP vaccines. The DTaP vaccines may be preferred in those children with H/O severe adverse effects following DTwP vaccines or children with neurological disorders, if affordable.

• Tdap Vaccine –

Recently, a low dose, adult formulated diphtheria, tetanus & acellular pertussis vaccine is recommended in several countries for use in adults & adolescents.

In individuals who have completed primary & booster vaccination with DTwP/DTaP, Tdap vaccine boosters every 10 years provide enough protection.

NOTE

• Thimerosal is a preservative sometimes used with certain DPT vaccines. WHO has concluded that there is no evidence of toxicity from thimerosal in vaccines.
• Preparation of choice for immunization of children> 12 years and adults against diphtheria is Td (Adult diphtheria – tetanus vaccine).
• Plain DPT vaccine can be used as booster.

Measles- Mumps- Rubella (MMR) Vaccine-

INTRODUCTION

It is a live attenuated viral vaccine developed by Mourice Hilleman.

STORAGE

MMR vaccine is a freeze dried vaccine and supplied in lyophilized form and should be frozen for long term storage. In the clinic/health facility, these vaccines can be stored at 2-8 degree C. The vaccines should be protected from light. Reconstituted vaccines should be stored at 2-8 degree C, protected from sunlight and used within 4-6 hours.

DOSE, SITE & ROUTE OF ADMINISTRATION

The dose is 0.5 ml given subcutaneously. The vaccine can be given along with all other childhood vaccines. Optimum age of vaccination is over one year of age, preferably between 12-15 months of age. MMR vaccine is given subcutaneously over the thigh or over the arm.

There is no need to give booster dose of MMR vaccine in India because the routine coverage of measles & MMR vaccine is poor. As a result naturally occurring measles, mumps & rubella are common which act as natural booster for the vaccine.

Booster dose of MMR vaccine is given in western countries at 5 or 15 years of age representing the time of school entry & school exit. This is because there is high routine coverage of MMR vaccine in western countries, as a result there is drastic reduction of natural infection of measles, mumps & rubella.

CONTRAINDICATION

• Pregnancy
• Acute Illness
• Patients on Immunosuppressive therapy
• Allergy to neomycin, Kanamycin or Polymyxin.
• Severe Immuno-deficiency

In case of mild egg allergy, measles & MMR vaccine can be given but with strict medical supervision.

IMMUNITY

Duration of immunity is not clear. Probably it is life long. The virus does not spread from vaccine to contacts.

MMR can protect non-immunized Measles contacts from the disease, provided given within three days of exposure.

It protects recipients of vaccines against Measles, Mumps & Rubella.

ADVERSE EFFECTS

• Malaise
• Fever
• Rash
• Febrile Convulsions
• Parotid Swellings
• Meningo-encephalitis(Rare)

NOTE

• There is now incontrovertible evidence that there is no causal relationship between MMR vaccine and autism, inflammatory bowel disease, GBS and many other neurological complications.
• MMR should not be given within three months of administration of immunoglobulins.
• Women who have received MMR should avoid pregnancy for at least one month.
• If a child comes late, MMR vaccine can be given up to the age of 5-15 years.
• The MMRV (Measles, Mumps, Rubella & Varicella) Vaccine has been proposed as a replacement for MMR vaccine to simplify administration of the vaccines in the western countries. Only drawback is high rate of fever induced seizures of 9 per 10,000 vaccinations with MMRV as opposed to 4 per 10,000 vaccinations for separate MMR & Varicella vaccines administration.

Meningococcal Vaccine –

INTRODUCTION

Meningococcal Vaccine protects against meningococcal disease caused by Neisseria meningitides. Meningococcal disease include meningitis and a life threatening blood infection. Disease can cause limb loss through amputation, hearing loss, problems of nervous system, mental retardation, seizures & strokes. Rarely disease can cause carditis, septic arthritis or pneumonia.

Two types of meningococcal vaccines are available –

• MPSV4 – Meningococcal Polysaccharide Vaccine licensed for those 2 year of age & older.
• MCV4 – Meningococcal Conjugate vaccine licensed for 9 months old to 55 years old.

Meningococcal Polysaccharide Vaccine (MPSV4) –

INTRODUCTION

The first MPSV4 vaccine was approved in 1978. Only one type of MPSV4 vaccine is available. It is a polysaccharide vaccine (derived from polysaccharide antigen of the Cell Wall).

IMMUNITY

About 10-14 days are required to develop immunity after vaccination. Immunity lasts for 3 years and therefore booster doses at 3 years intervals are required. High risk group should be identified & vaccinated. Vaccine should not be administered in infants and children less than 2 years because of possible poor immune response.

CONTRAINDICATION

Contraindications include –

• Febrile Illness
• A severe previous reaction.
•  

INDICATION

Meningococcal Vaccine is indicated in –

• Close contacts of Meningococcal C Meningitis
• Control of local outburst in close communities
• For travelers

ADVERSE EFFECTS

Adverse effects include- 1) Mild local reaction 2) Pain at injection site.

DOSE & ROUTE OF ADMINISTRATION

Vaccine is given 0.5 ml subcutaneously or intramuscularly.

Meningococcal Conjugate Vaccine (MCV4) –

INTRODUCTION

The newer vaccine MCV4 was licensed in 2005. It uses antigens derived from Polysaccharide capsule & then bound to a separate protein that targets body’s immune cells. This makes it easier for the body’s immune system to see & recognize the antigens. Two types of MCV4 vaccines are available, one can used in 2 years to 55 years aged individuals while other can be used in individuals 9 months to 55 years aged.

MCV4 has not been available long enough to compare the long term effectiveness with MPSV4. But most experts think that MCV4 provides better, long lasting protection.

IMMUNITY

MCV4 has enhanced duration of protection (around 5 years), increased immunity with booster vaccinations & help in building effective HERD IMMUNITY.

IMMUNIZATION SCHEDULE

Booster dose can be given at 16 years of age if primary immunization was done early with MCV4 vaccine. Adolescents who receive their first dose of MCV4 at or after age 16 years do not need a booster dose.

CONTRAINDICATIONS

Contraindications of MCV4 include –

• Life threatening allergic reaction to a previous dose of vaccine.
• H/O allergy to any vaccine component.
• Moderate to severe illness.

ADVERSE EFFECTS

Adverse effects of Vaccine Include –

• Local reaction – redness or pain at injection site.
• Fever – Not common.
• Allergic reaction – Rare.

NOTE

• Both MPSV4 & MCV4 vaccines protect against 4 types of Meningococcal disease (A, C, W-135 & Y types).
• Both MPSV4 & MCV4 are about 90% effective in preventing meningococcal disease.
• Meningococcal Vaccine may be given to pregnant women as both vaccines do not contain Live Bacteria. Safety of MPSV4 in pregnant women is much more established in comparison to MCV4 vaccine which is comparatively a newer vaccine.
• Except for children with Sickle Cell Disease or without a working spleen, meningococcal vaccine may be given at the same time as other vaccines.
• MCV4 is the preferred vaccine in IAP immunization schedule.

HiB Vaccine (Haemophilus Influenzae Type B Vaccine)

INTRODUCTION

Haemophilus Influenzae type B Vaccine is a conjugate vaccine developed for the prevention of invasive disease caused by H. Influenzae type B Bacteria. The vaccine not only prevents meningitis but also protects against certain Epiglottitis, Pneumonia, Bone & joint infection. HiB vaccine is one of the recommended childhood immunizations.

The first vaccine was licensed for use in 1985 was a polysaccharide vaccine but it wass not found effective in children aged 18 months and younger. Vaccine was withdrawn from the market in 1988. Shortcomings of polysaccharide HiB vaccine led the development of improved HiB vaccine, a conjugate vaccine, which was licensed for use in 1987.

The HiB conjugate vaccine is an inactivated vaccine, made by chemically bonding a polysaccharide (Sugar) to a protein. This long chain of sugar molecules make up the surface capsule of the bacterium.

IMMUNIZATION SCHEDULE

HIB vaccine is given in 3 primary doses at 6,10 & 14 weeks of age followed by a booster 12 -15 months age. Vaccine is given intramuscularly into the anterolateral thigh in infants & toddlers or in deltoid muscle of older children. Vaccine is generally painless. Combination with DTwP vaccine will be painful.

The HIB vaccine does not work well in children younger than 6 weeks old. Children over 5 years old and adults do not need to receive the vaccine for HIB unless they have certain medical conditions including HIV, Sickle Cell Disease etc.

CONTRAINDICATIONS

Delay or do not give the vaccine if –

• Child is less than 6 weeks old
• Child has a serious illness
• H/o Severe allergic reaction or anaphylaxis to previous vaccine dose.

ADVERSE EFFECTS

Adverse events following receipt of HIB conjugate vaccine are uncommon. The most common reactions are local reactions at the injection site e.g. redness & swelling in 5- 30% of recipients. Up to one out of 20 children may develop a fever more than 101 degree F.

IMMUNITY

All the vaccines are highly effective in producing immunity to invasive HIB disease. More than 95% of infants will be protected after two or three doses.

NOTE

Vaccine itself cannot cause HIB disease as HIB vaccine is a fractional vaccine containing only part of the HIB bacteria.

VARICELLA VACCINE –

INTRODUCTION

The Varicella Vaccine is used for active immunization against chickenpox. It is a live attenuated vaccine.

IMMUNIZATION SCHEDULE

Recommended for children up to 12 years & those above 12 years who never experienced chickenpox. Given in fatty tissues (over triceps) in two doses of 0.5 ml each subcutaneously. First dose is given at 12-15 months & second dose at the age of 4-6 years. For children more than 12 years of age, two doses are given 4 to 8 weeks apart.

CONTRAINDICATIONS

Contraindications include –

• Pregnant women
• Serious reaction with Varicella vaccine in the past
• Those allergic to neomycin & gelatin
• People with immunodeficiency
• Those received blood products or transfusions during the past 5 months.

ADVERSE EFFECTS

Adverse effects include –

• Fever, rash & local reaction at injection site.
• Seizures, pneumonia & Anaphylaxis rarely.
• Risk of developing Herpes Zoster following vaccination.

EFFICACY

Efficacy – 70- 90% in preventing varicella & more than 95% in preventing severe disease.

NOTE

• Can be combined with MMR vaccine – MMRV vaccine. MMRV is not approved for use in persons more than 12 years of age.
• Serological testing is not required prior to vaccination.
• Vaccine is recommended for outbreak control.
• Some Vaccinated Children (about 2%) may develop milder form of disease. The vaccine almost always prevents against severe form of disease.
• Vaccine when given to contacts within 72 hours of exposure, is 70 – 100% effective in protecting against the disease.
• The risk of Herpes Zoster following vaccination appears to be less than that following infection with varicella virus. The majority of cases of herpes zoster following vaccine have been mild and have not been associated with serious complications.
• The vaccine is contraindicated in Pregnancy as Chickenpox durinpregnancy may cause birth defects so there may be a risk that the chickenpox vaccine containing live attenuated virus could cause the same birth defects.

INFLUENZA VACCINE –

INTRODUCTION

Vaccine is used for active immunization against influenza virus infection. Bivalent vaccines containing Influenza A & B virus types or their components are being used. No cross immunity is seen. Influenza virus type C is less pathogenic.

There are two types of Influenza vaccine. The most common influenza vaccine is made from inactivated/killed viruses. In 2003, a live virus influenza vaccine was licensed. It contains live attenuated viruses. Every year researchers develop a vaccine that contains virus strains circulating in upcoming influenza season. Influenza vaccine typically contains both type A & Type B Viruses.

The virus selected for vaccine are grown in Chicken eggs. For the inactivated/injectable vaccine, the viruses are killed by formaldehyde and purified. It is given intramuscularly. Live virus vaccine is packaged in a special nasal sprayer. The live vaccine is sprayed into the nose.

IMMUNIZATION SCHEDULE

Inactivated Vaccine should be administered to all people aged 6 months and older who do not have a contraindication to the vaccine. Live vaccine should be given to 2 years to 49 years of aged people.

Vaccine is given in two doses first time 4 weeks apart and then yearly dose (the third dose) till 5 years of age. Children above 3 years are given adult dose of 0.5 ml of vaccine.

It is preferred that the inactivated vaccine be used for household contacts and caregivers of people with severe immunosuppression. Inactivated Influenza vaccine is recommended for pregnant women as they are at increased risk for serious medical complications from influenza. While the live intranasal vaccine is not recommended for use in pregnant women.

ADVERSE EFFECTS

Influenza vaccine is very safe. The most common adverse effects of the inactivated vaccine include Soreness, redness or swelling at the injection site. These reactions are temporary and occur in 15-20% of recipients. Less than 1% of vaccine recipients develop symptoms such as fever, chills & muscle ache for 1 to 2 days following vaccination.

Adverse effects of live influenza vaccine include cough, running nose, sore throat and fever.

Serious reactions to either vaccines are rare. Such reactions are most likely the result of an allergy to eggs or to a vaccine component.

CONTRAINDICATIONS

Contraindications of Live Influenza vaccine –

• Less than 2 years and more than 50 years age.
• Allergy to vaccine component
• H/O recurrent wheezing or have h/o wheezing episode within the past 12 months.
• Children on long term aspirin therapy.

NOTES

• Protection from vaccine varies by the similarity of the vaccine strains to the circulating strains, and the age & health of the recipients.
• Neither the inactivated vaccine nor the live attenuated vaccine can cause influenza.
• Protective immunity develops 1 to 2 weeks after vaccination.

HUMAN PAPILLOMA VIRUS VACCINE

INTRODUCTION

Human Papilloma virus (HPV) is a common virus that spreads through sexual contact. The Human papilloma virus vaccine works by preventing the most common types of HPV that cause cervical cancer & genital warts.

Two HPV Vaccines are currently on the market –

• Gardasil (Protects against four HPV types – 6,11,16 & 18)— Launched in 2006. Given also to males also of 9-26 years.
• Cervarix (Protects against 2 types of HPV Viruses – 16 & 18)— Launched in 2009. Given to females only of 9 to 45 years of age.

Both Vaccines protect against the two HPV types (HPV- 16 & 18) that cause 70% of cervical cancers, 80% of anal cancers, 60% of vaginal cancers & 40% of vulval Cancer. These HPV types also cause the most HPV induced oral cancers and some other rare genital cancers. These HPV also cause 90% of genital warts.

IMMUNIZATION SCHEDULE

HPV Vaccine is an inactivated vaccine. Vaccine is given in two doses at 6 months interval at 9-14 years of age. Vaccine is given intramuscularly in 3 doses (0,1-2 & 6 months) in 15 years and older & in immunocompromised. The second dose should be given one to two months after the first dose and third dose should be given six months after the first dose. The HPV Vaccine can be administered with other vaccines also.

It is best if the vaccine is given before onset of sexual activity though people who are sexually active also may benefit from vaccination. HPV vaccine can be given to females who have had as abnormal pap test or genital warts. However, the vaccine will not have any beneficial effect on existing pap test abnormalities, HPV infection or genital warts.

EFFICACY

Both vaccines are nearly 100% effective in preventing cervical cancer (caused by targeted HPVs) up to four years after vaccination among women who are not infected at the time of vaccination.

The length of protection by vaccine is usually not known when a vaccine is introduced initially. However, studies have shown people to still be protected after five years.

ADVERSE EFFECTS

Adverse effects include pain at the site of injection, local redness or swelling, mild to moderate fever, itching & fainting in adolescents. It is better for the patients to sit during vaccination and then wait for 15-20 minutes at the clinic itself. Like other vaccines, monitoring is going on for serious side effects of HPV Vaccine.

NOTE

HPV vaccine is an inactivated vaccine so they can not cause disease like symptoms or HPV disease itself. 

HEPATITIS A VACCINE

INTRODUCTION

Hepatitis A vaccine was discovered by Maurice Hillman at Merck. Vaccine is used for active immunization against Hepatitis A viral infection. Two types of Hepatitis A Vaccines are available in India – Live but attenuated Vaccine & Inactivated Vaccine.

INDICATIONS

 Vaccine is recommended for –

• Children > 1 year age.
• People at risk because of sexual activity.
• Occupational exposure e.g. people dealing with virus.
• People with chronic liver disease.
• For outbreak response in the community.
• Treatment with clotting factor concentrates.
• Travelers to endemic areas/ countries.

IMMUNIZATION SCHEDULE

Vaccine is given intramuscularly in the muscles of upper arm for adults and older children and in thigh muscles of toddlers. Two doses are recommended with minimum gap of six months (Hep.A1 at 12 months & Hep.A2 at 16-28 months). Live vaccine is given subcutaneously in a single dose. Boosters may not be required.

EFFICACY

Hepatitis A Vaccine is very effective. It appears that all adults, adolescents and children become immune to HAV infection after getting two doses of vaccine. After one dose, at least 94% become immune for short term. Highly immunogenic Vaccine.

Estimates for long term protection for fully vaccinated people (i.e. full two dose of vaccine) suggest that it protects adults for at least 25 years and children at least 15-20 years from the Hepatitis A virus infection. Protection occurs against Hepatitis A within 2- 4 weeks of initial vaccination.

ADVERSE EFFECTS

Hepatitis A vaccine is very safe. No serious adverse effects have been reported till now generally except a generalized allergic reaction which is very rare. If this happens, it typically occurs within a few minutes to a few hours following the injection of the vaccine. Adverse reactions includes –

• Mild local reaction
• Headache, malaise & fatigue
• Fever, nausea
• Loss of appetite

CONTRAINDICATIONS

Contraindication includes hypersensitivity to vaccine component and severe febrile illness.

Special precautions should be taken in –

• Children< 1 year of age
• Thrombocytopenia/ Bleeding disorders
• Pregnancy

NOTE

• A combination Vaccine of Hepatitis A with recombinant Hepatitis B is available for children aged one year or more and is given in 3 doses series i.e. at 0, 1, & 6 months.
• Hepatitis A can be given after exposure to HAV. Those exposed recently with no history of past Hepatitis A Vaccination should be given a single dose of vaccine or Immunoglobulin as soon as possible.
• Immunoglobulin are preferred for adults > 40 years, Children < 1 year of age, immune-compromised people, people with chronic liver disease and in those in which vaccine is contra indicated.

TYPHOID CONJUGATE VACCINE (TYPBAR – TCV)

INTRODUCTION

Vaccine is recommended for the prevention of Typhoid fever. Vaccine TYPBAR TCV was first licensed in India in 2013 for intramuscular administration of a single dose (0.5 ml) in children aged 6 months and older and in adults up to 45 years of age. It is available in single dose vial or prefilled syringes & five dose vials.

Each vaccine dose comprises 25 microgram (per 0.5 ml) of purified Vi-PS conjugated to TT. In the multi-dose formulations, each dose also contain 5 mg of 2- phenoxyethanol as preservative.

STORAGE

The vaccine should be stored at a temperature of +2 to +8 degree Celsius. The vaccine is labelled with Vaccine Vial Monitor 30 (VVM 30). Protect the vaccine from light. Do not allow vaccine to freeze, discard if frozen. Shake well vaccine before use.

IMMUNIZATION SCHEDULE

Vaccine is given at 6 months of age in a single dose of 0.5 ml intramuscularly in the deltoid region or anterolateral aspect of mid-thigh. Vaccine may be co-administered with the other vaccines. A booster dose may be given after 3 years.

ADVERSE EFFECTS

Most common adverse effect following TCV is pain at the injection site & fever. No serious adverse reaction have been reported. Other adverse effects include feeling of discomfort, nausea, diarrhea & Headache.

CONTRAINDICATIONS

Contraindications include –

• Hypersensitivity to any constituent of the vaccine
• Pregnant & lactating women
• In the event of fever or serious infection.

CHOLERA VACCINE

INTRODUCTION

The parenteral killed vaccine which had a three month efficacy of 45% is no longer recommended. The killed whole cells of V. cholerae 01 & recombinant cholera toxin B subunit (WC-rBS) available internationally as DUKORAL oral vaccine and widely used in travelers is a vaccine comprising of killed V. cholerae 01 with recombinant B subunits of cholera toxin. Because of similarity in structure and functions of the cholera toxin B, this vaccine provides cross protection against enterotoxigenic E. Coli. However this vaccine is no longer marketed in India.

Apart from DUCKORAL, two other WHO pre-qualified oral cholera vaccines (OCV) SHANCHOL & EUVICHOL are available.

IMMUNIZATION SCHEDULE

All three vaccines require two doses for full protection at an interval of 1-6 weeks. Children aged 2-5 years require a third dose. DUCKORAL vaccine is mainly used in travelers with age more than two years. DUCKORAL Vaccine is administered with a buffer solution that requires 150 ml of clean water for adults.

SHANCHOL & EUVICHOL vaccines do not require a buffer solution for administration. These vaccines are given to all the individuals over the age of one year. There must be a gap of two weeks between the two doses.

IMMUNITY

Immunity provided after primary immunization with DUCKORAL vaccine is two years while for SHANCHOL & EUVICHOL, it is of three years.

NOTES

• SHANCHOL & EUVICHOL vaccines are used for mass vaccination campaign and is quite safe and effective.
• Cholera vaccination is indicated for individuals living in high endemic areas where risk of transmission is high.
• No serious adverse effects are observed after cholera vaccination.

INACTIVATED POLIO VACCINE (IPV)

INTRODUCTION

Inactivated polio vaccine (IPV) was developed by Dr. Jonas Salk in the year 1955. It is called as Salk vaccine. IPV consists of inactivated poliovirus strains of all three poliovirus types. As IPV is not a live vaccine, it carries no risk to vaccine associated paralytic polio. IPV triggers an excellent protective immune response in most people.

IMMUNIZATION SCHEDULE

IPV is given as primary immunization in IAP Schedule at 6 weeks, 10 weeks & 14 weeks intramuscularly 0.5 ml at anterolateral aspect of mid-thigh. Booster dose is recommended at 16-18 weeks.

IMMUNITY

IPV produces antibodies in the blood to all three types of poliovirus. In the event of infection, these antibodies prevent the spread of the virus to CNS and protects against paralysis. IPV is highly effective in preventing paralytic disease caused by all three types of polio virus.

ADVERSE EFFECTS

IPV is one of the safest vaccine in use. No serious systemic adverse reactions have been shown to follow its vaccination.

DISADVANTAGES

IPV induces very low level of immunity in the intestine. As a result, when a person immunized with IPV is infected with wild poliovirus, the virus can still multiply inside the intestines and be shed in the feces, risking continued circulation.

IPV is over 5 times more expensive than OPV. Administering the vaccine requires trained health workers, as well as sterile injection equipment and procedures.

NOTE

As IPV does not stop the transmission of the virus, OPV is used whenever a polio outbreak needs to be contained.

CHAPTER 4 – OTHER VACCINES

1. TETANUS TOXOID VACCINE

INTRODUCTION

Vaccine is used for active immunization against Tetanus. This vaccine is immunogenic but not pathogenic. The first inactive tetanus toxoid was discovered and produced in 1924. This vaccine was successful when used to prevent tetanus in the military during World War II.

The vaccine is made by growing the bacteria in a liquid medium and purifying & activating the toxin. Because it is a live vaccine, a person’s immunity tends to decline with time, that’s why booster doses are recommended. Each dose of TT of 0.5ml (human dose) contains Tetanus toxoid more than or equal to 5 Lf, adsorbed on aluminum phosphate equal to or more than 1.5 mg & thimerosal 0.01% as preservative. Purified tetanus toxoid (adsorbed) has replaced plain toxoid because it provides long lasting immunity.

IMMUNIZATION SCHEDULE

Immunization schedule includes two doses of vaccine, 0.5 ml each, given by intramuscular route at an interval of 4 – 6 weeks. Longer the gap between two doses, the better will be the immune response. The first booster is given after one year of 2 doses. 2^nd booster is given 5 years after the third dose. Frequent booster doses should not be given.

In pregnancy, two doses of vaccine was given in women between 16-36 weeks of pregnancy, with an interval of 4 – 6 weeks in between two doses. In subsequent pregnancies, one booster dose was sufficient. It has been replaced by Adult diphtheria-Tetanus toxoid (Td) vaccine in pregnant female.

ADVERSE EFFECTS

Adverse effects include mild local reaction at the injection site.

CONTRAINDICATIONS

Contraindications are-

• Outbreak of polio(in children)
• Acute illness
• Adverse reaction to a previous dose.
• High Fever

STORAGE

Vaccine should be stored between 4 to 8 degree C. should not be allowed to freeze. Product which has been exposed to freezing should not be used.

VACCINATION OF INJURED PERSONS

For those persons who have evidence of complete primary immunization or receiving a booster dose in previous 5 years, no additional dose of TT is recommended.

If in case of injury, more than 5 years have passed, 0.5 ml of adsorbed TT should be given immediately.

Where immunization history is inadequate, 1500 IU Tetanus antiserum/ 250 units of Human tetanus immunoglobulin and 0.5ml of TT should be injected with separate syringes to different body sites. A second 0.5 ml dose of TT is recommended after 2 weeks followed by third dose after a further one month.

2. YELLOW FEVER VACCINE

INTRODUCTION

Yellow fever vaccine is used for vaccination against yellow fever. Approved Vaccine is 17- D Vaccine. It is a live attenuated vaccine, available in Freeze Dried preparation.

In 1937, Max Theiler developed a safe & highly efficacious Vaccine for Yellow Fever for which he received Nobel Prize in Medicine in 1951. The 17 D Vaccine has been used commercially since the 1950s. In 2013, The World Health Organization concluded that a single dose of vaccination is sufficient to confer life-long immunity against yellow fever disease.

IMMUNIZATION SCHEDULE

Given in single dose of 0.5 ml, subcutaneously at the insertion of deltoid. Immunity appears on 7^th day & is probably life-long (>35 years). WHO recommends revaccination every 10 years for international travel.

ADVERSE EFFECTS

• Mild flu like reactions i.e. Myalgia, headache & low grade fever
• Anaphylaxis (rare) because of allergy to eggs.
• Encephalitis in the very young
• Hepatic failure
• Rare reports of death from massive organ failure.

Mild problem as adverse effect of yellow fever vaccination occur in 1 person out of 4. They mostly begin soon after vaccination and can last up to a week.

SPECIAL PRECAUTIONS

Special Precautions include –

• Pregnancy
• Children less than 6 months of age.

STORAGE & RECONSTITUTION

Vaccine should be stored preferably below 0 degree C. Reconstituted with saline. Should be used within ½ hour of reconstitution, Kept on ice, away from sunlight. If not used within ½ an hour vaccine should be discarded.

CONTRAINDICATIONS

Contraindications include –

• Immune deficient persons
• Anaphylactic reaction to egg.
• Symptomatic HIV infection
• Hypersensitivity to previous dose

NOTES

1. Vaccine is recommended for –

• Laboratory workers in contact with infectious materials.
• International travel.
• Children>9 months & persons living in endemic areas or travelling to endemic areas.

2. People who get vaccinated with Yellow Fever vaccine should be given an international certificate of vaccination. Also note that the vaccine is to be given 10 days before travel to an endemic area.
3. Two available types of Yellow Fever Vaccine (17D-204 & 17 DD Strains) differ in their safety profiles.
4. One should not donate blood for 14 days following the vaccination because there is a risk of transmitting the vaccine virus through blood products during that period.
5. Vaccination is not mandatory in India as disease does not occur in the country.

3. PLAGUE VACCINE

INTRODUCTION

Vaccine is used for active immunization against Plague. Plague vaccine have been used since the late 19^th Century. Vaccine is effective in preventing Plague if given at least one week before an anticipated epidemic. Vaccine was developed by HAFFKINE in 1897. Plague vaccine is a formaldehyde inactivated vaccine and preserved in 0.5% phenol.

IMMUNIZATION SCHEDULE

Primary immunization consists of 3 doses of vaccine given intramuscularly. First dose in adults and children more than 11 years consists of 0.1 ml, followed by the second dose 0.2 ml, 4 weeks later. The third dose 0.2 ml is administered 6 months after the first dose.

If an accelerated schedule is essential, 3 doses of 0.5 ml each, administered at least one week apart, may be given. The efficacy of this schedule has not been determined.

In children less than or equal to 10 years old, the primary series is also of 3 doses of vaccine, but the doses are smaller. The intervals between injections are the same as for adults. 

Booster doses when needed because of continued exposure, 3 booster doses should be given at approximately 6 months interval. There after, antibody levels decline slowly and booster doses at 1-2 years interval should provide good protection.

INDICATIONS

Vaccine is recommended for –

• All laboratory & field personnel who are working with Plague organisms.
• Persons engaged in field operations with enzootic plague where prevention is not possible.
• Persons travelling to plague endemic areas.

ADVERSE EFFECTS

Adverse effects include –

• General malaise
• Fever
• Mild lymphadenopathy
• Erythema & induration at injection site.
• Sensitivity reactions

CONTRAINDICATIONS

Contraindications to vaccine includes known hypersensitivity to vaccine & its components.

NOTES

1. The Safety or efficacy of plague vaccination during pregnancy has not been determined, and therefore it should not be used unless there is substantial risk of infection.
2. A subunit vaccine based on the F1 and V antigens is highly effective against both Bubonic & Pneumonic Plague, when tested in animal models of disease.

4. RABIES VACCINE

Vaccine is used for active immunization against rabies in humans. Three types of rabies vaccines are available –

• Nervous tissue vaccines(NTV)
• Sheep Brain Vaccine
• Suckling mouse Brain vaccine
• Duck Embryo Vaccine (DEV)/ Chick Embryo vaccine(CEV).
• Cell – culture Vaccines
• Human Diploid Cell Vaccine(HDCV)
• 2^nd generation tissue culture vaccines

Nervous Tissue Vaccines –

Not in use in India since 2004.

Duck Embryo Vaccine (DEV)/ Chick Embryo Vaccine(CEV)-

Inactivated Duck Embryo Vaccine rarely have neuroparalytic hazards in comparison to nervous tissue vaccine. Prepared by injecting fixed virus in embryonated duck eggs. BPL inactivated lyophilized vaccine. Allergic reactions with vaccine are seen in persons sensitive to egg proteins.

A purified duck embryo Vaccine (PDEV) has been developed which is devoid of egg proteins. PDEV is now available in India.

Chick embryo vaccine once used in India is now no longer in use.

Cell Culture Vaccines –

Two types –

• Human Diploid Cell Vaccine(HDCV)
• Second generation tissue culture vaccines – Non human origin.

Human Diploid Cell Vaccine (HDCV) –

Contains propagated rabies fixed virus in human diploid fibroblast cells. Safe & highly effective. Used both for pre exposure & post exposure prophylaxis.

Second generation tissue culture Vaccines – 

Being preferred over HDCV because of low cost involved and high effectivity.

Derived from –

1. Primary cell subtracts (e.g. foetal bovine kidney, chick embryo fibroblasts etc.)
2. Non- tumorigenic continuous cell lines (e.g. Vero cells)

In India, HDCV, Second generation tissue culture vaccines & PDEV are available.

Cell Culture & purified duck embryo vaccine containing 2.5 IU per single dose given intramuscularly for post exposure prophylaxis on days 0, 3, 7, 14 & 28 days. Booster dose is given on 90^th day intramuscularly.

The vaccine may be given in reduced multisite intramuscular regimen (2-1-1) given on 0, 7 & 21 days. On 0 day, 1 dose each into both arms (deltoid) followed by 1 dose in deltoid region on day 7 and one dose on day 21.

Vaccines may be given intradermally (highly immunogenic) for post exposure prophylaxis in two schedules –

• 2 site intradermal schedule (2-2-2-0-1-1)
• 8 site intradermal schedule (8-0-4-0-1-1)

For pre exposure prophylaxis vaccines are given intramuscularly (1 ml) or intradermally (0.5 ml) on days 0,7, & 28.

Adverse effects of all cell culture vaccines include local redness, pain, headache & fever.

5. COVID 19 VACCINES

COVID 19 vaccines approved for public use are RNA vaccines, conventional inactivated vaccines and viral vector vaccines. In India, predominantly two vaccines COVISHIELD & COVAXIN has been approved for restricted use.

Persons who are not eligible for time being to get the vaccines are –

• Persons with active symptoms of COVID 19 infection.
• COVID 19 patients who have received monoclonal antibodies for SARS –CoV- 2 infection or convalescent plasma.
• Should be given with caution to persons with bleeding disorders or coagulation disorders or platelet disorders.
• Serious & hospitalized patients due to any illness.

Patients with a past history of COVID 19 infection, chronic disease with morbidities (Cardiac, neurological, kidney, pulmonary or metabolic) are eligible for COVID 19 vaccination. Person receiving vaccination should avoid alcohol and tobacco consumption. The vaccines cannot be interchanged.

1. COVISHIELD VACCINE

INTRODUCTION

Approved for emergency use for active immunization of individuals aged 18 years and older for the prevention of coronavirus disease 2019 (COVID 19). It was developed by ASTRAZENECA & Serum Institute of India. It is a recombinant vaccine.

STORAGE

It is stored at a temperature of 2 to 8 degree Celsius. Never allow vaccine to freeze.

IMMUNIZATION SCHEDULE

It is given 0.5 ml intramuscularly into the muscles of upper arm, in two doses, 12-16 weeks apart. Booster dose can be given at 9-12 months of last injection.

ADVERSE EFFECTS

Adverse effects include –

• Pain, swelling and redness at injection site
• Headache, nausea & vomiting
• Muscle & joint pain
• Fatigue & Malaise
• Fever, chills, flu like illness

Most of the adverse effects are mild and temporary that subside on their own within 2-3 days.

CONTRAINDICATIONS

Contraindications include –

• H/o allergy, bleeding disorders
• Immunocompromised state
• Fever
• Any other type of corona vaccine administration

1. COVAXIN

INTRODUCTION

It is India’s first indigenous COVID-19 vaccine developed by Bharat Biotech in collaboration with Indian Council of Medical Research (ICMR) and National Institute of Virology (NIV). It is approved for emergency use in India. The vaccine is developed using whole-virion inactivated vero cells derived platform strategy. Being an inactivated vaccine, do not replicate and cause infections in recipients and others.

IMMUNIZATION SCHEDULE

It is a two day vaccination regimen given 6-8 weeks apart. Each dose comprises of 0.5 ml given intramuscularly in upper arm. Booster dose is recommended 9-12 months later after the last injection.

STORAGE

It is a vaccine with no sub-zero storage. The vaccine does not require reconstitution and is supplied in ready to use liquid preparation. Vaccine is stable at 2-8 degree Celsius.

ADVERSE EFFECTS

Adverse effects include –

• Pain, swelling and redness at injection site
• Headache, nausea & vomiting
• Muscle & joint pain
• Fatigue & Malaise
• Fever, chills, flu like illness

Most of the adverse effects are mild and temporary that subside on their own within 2-3 days.

SUGGESTED FURTHER READINGS

• Park; Park’s textbook of Preventive & Social Medicine, 26th edition, 2021
• Immunization Handbook for medical officers by Ministry of Health and Family Welfare, Government of India, 2017
• IAP Guidebook on Immunization, by IAP Committee on immunization, 2009-2011
• IAP Guidebook on Immunization, by IAP Committee on immunization,

2018-2019