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Vaccination. Immune system. Complex network of specialized organs and cells that protect bodies from destruction by foreign agents and microbial pathogens.
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Immune system • Complex network of specialized organs and cells that protect bodies from destruction by foreign agents and microbial pathogens. • It acts by degrading and removing damaged or dead cells, and exerts a surveillance function to prevent the development and growth of malignant cells. • The immune system is composed of immune cells and central and peripheral lymphoid structures. • The immune cells move throughout the body, searching for and destroying foreign substances but avoiding cells regarded as self.
Natural immunity: It is not produced by the immune response. This type of immunity is present at birth and appears to be present in all members of a species. Acquired immunity: It develops after birth as a result of exposure to an antigen, thereby activating the immune response. Acquired immunity can be either active or passive, depending on whether the immune response took place in the host or a donor. Types of immunity
Immune system of children compared to adults • Normally humans do not have a fully active immune system at birth because of immaturity. The infant relies instead on passively transferred antibodies from the mother. This maternal antibody slowly decreases in concentration. • The infant own production of antibody begins to be meaningful at 7 or 8 months of age when the total of maternal and infant antibody is low. This is the age when many of the infectious disease processes of infancy begin.
Passive Immunity • Transfer of antibody produced by one human or other animal to another • Temporary protection Sources of passive immunity: • Transplacental most important source in infancy • almost all blood or blood products • Human antibody (immune globulin)
Immunization • Immunization is the process whereby a person is made immune or resistant to an infectious disease, typically by the administration of a vaccine. Vaccines stimulate the body’s own immune system to protect the person against subsequent infection or disease. • Immunization is a proven tool for controlling and eliminating life-threatening infectious diseases and is estimated to avert between 2 and 3 million deaths each year. • It is one of the most cost-effective health investments, with proven strategies that make it accessible to even the most hard-to-reach and vulnerable populations. It has clearly defined target groups; it can be delivered effectively through outreach activities.
Immunization • Immunization averts an estimated 2 to 3 million deaths every year from diphtheria, tetanus, pertussis (whooping cough), and measles; • However, an additional 1.5 million deaths could be avoided if global vaccination coverage improves. • Global vaccination coverage – the proportion of the world’s children who receive recommended vaccines – has remained steady for the past few years. • During 2015, about 86% (116 million) of infants worldwide received 3 doses of diphtheria-tetanus-pertussis (DTP3) vaccine, protecting them against infectious diseases that can cause serious illness and disability or be fatal. • By 2015, 126 countries had reached at least 90% coverage of DTP3 vaccine.
Global immunization coverage 2015 • Haemophilus influenzaetype b (Hib) causes meningitis and pneumonia. Hib vaccine had been introduced in 191 countries by the end of 2015. Global coverage with 3 doses of Hib vaccine is estimated at 64%. There is great variation between regions. • Hepatitis Bis a viral infection that attacks the liver. Hepatitis B vaccine for infants had been introduced nationwide in 185 countries by the end of 2015. Global coverage with 3 doses of hepatitis B vaccine is estimated at 83%.
Global immunization coverage 2015 • Human papillomavirusis the most common viral infection of the reproductive tract, and can cause cervical cancer, other types of cancer, and genital warts in both men and women. Human papillomavirus vaccine was introduced in 66 countries by the end of 2015. • Measlesis a highly contagious disease caused by a virus, which usually results in a high fever and rash, and can lead to blindness, encephalitis or death. By the end of 2015, 85% of children had received 1 dose of measles vaccine by their second birthday, and 160 countries had included a second dose as part of routine immunization and 61% of children received 2 doses of measles vaccine according to national immunization schedule.
Global immunization coverage 2015 • Meningitis Ais an infection that can cause severe brain damage and is often deadly. By the end of 2015 – 5 years after its introduction – more than 235 million people in African countries affected by the disease had been vaccinated. • Mumpsis a highly contagious virus that causes painful swelling at the side of the face under the ears (the parotid glands), fever, headache and muscle aches. It can lead to viral meningitis. Mumps vaccine had been introduced nationwide in 121 countries by the end of 2015.
Global immunization coverage 2015 • Pneumococcal diseasesinclude pneumonia, meningitis and febrile bacteraemia, as well as otitis media, sinusitis and bronchitis. Pneumococcal vaccine had been introduced in 129 countries by the end of 2015, and global coverage was estimated at 37%. • Poliois a highly infectious viral disease that can cause irreversible paralysis. In 2015, 86% of infants around the world received 3 doses of polio vaccine. Targeted for global eradication, polio has been stopped in all countries except for 2: Afghanistan and Pakistan. Polio-free countries have been infected by imported virus, and all countries – especially those experiencing conflict and instability – remain at risk until polio is fully eradicated.
Global immunization coverage 2015 • Rotavirusesare the most common cause of severe diarrhoeal disease in young children throughout the world. Rotavirus vaccine was introduced in 84 countries by the end of 2015, and global coverage was estimated at 23%. • Rubellais a viral disease which is usually mild in children, but infection during early pregnancy may cause fetal death or congenital rubella syndrome, which can lead to defects of the brain, heart, eyes and ears. Rubella vaccine was introduced nationwide in 147 countries by the end of 2015 and global coverage was estimated at 46%.
Global immunization coverage 2015 • Tetanusis caused by a bacterium which grows in the absence of oxygen, for example in dirty wounds or in the umbilical cord if it is not kept clean. It produces a toxin which can cause serious complications or death. The vaccine to prevent maternal and neonatal tetanus had been introduced in 106 countries by the end of 2015. An estimated 83% of newborns were protected through immunization. Maternal and neonatal tetanus persist as public health problems in 19 countries, mainly in Africa and Asia. • Yellow feveris an acute viral haemorrhagic disease transmitted by infected mosquitoes. As of 2015, yellow fever vaccine had been introduced in routine infant immunization programmes in 35 of the 42 countries and territories at risk for yellow fever in Africa and the Americas.
Key challenges The WHO identified 5 factors to achieving results in immunization coverage: • quality and use of data • community involvement • better access to immunization services for marginalized and displaced populations • strong health systems • access to vaccines in all places at all times.
Key challenges • In 2015, an estimated 19.4 million infants worldwide were not reached with routine immunization services such as DTP3 vaccine. • Around 60% of these children live in 10 countries: Angola, the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Iraq, Nigeria, Pakistan, the Philippines, and Ukraine. • Monitoring data at subnational levels is critical to helping countries prioritize and tailor vaccination strategies and operational plans to address immunization gaps and reach every person with lifesaving vaccines.
Global Vaccine Action Plan (GVAP • The Global Vaccine Action Plan (GVAP) ― endorsed by the 194 Member States of the World Health Assembly in May 2012 ― is a framework to prevent millions of deaths by 2020 through more equitable access to existing vaccines for people in all communities.GVAP aims to strengthen routine immunization to meet vaccination coverage targets; accelerate control of vaccine-preventable diseases with polio eradication as the first milestone; introduce new and improved vaccines and spur research and development for the next generation of vaccines and
Global Vaccine Action Plan (GVAP • The GVAP recommends 3 key steps for closing the immunization gap: • integrating immunization with other health services, such as postnatal care for mothers and babies; • strengthening health systems so that vaccines continue to be given even in times of crisis; and • ensuring that everyone can access vaccines and afford to pay for them.
Vaccination • Administration of a substance to a person with the purpose of preventing a disease • Traditionally composed of a killed or weakened microorganism • Vaccination works by creating a type of immune response that enables the memory cells to later respond to a similar organism before it can cause disease
Era of Vaccination • English physician Edward Jenner • observed that milkmaids stricken with a viral disease called cowpox were rarely victims of a similar disease, smallpox • Jenner took a few drops of fluid from a pustule of a woman who had cowpox and injected the fluid into a healthy young boy who had never had cowpox or smallpox • Six weeks later, Jenner injected the boy with fluid from a smallpox pustule, but the boy remained free of the dreaded smallpox.
Era of Vaccination • In those days, a million people died from smallpox each year in Europe alone, most of them were children. • Those who survived were often left with blindness, deep scars, and deformities • In 1796, Jenner started on a course that would ease the suffering of people around the world for centuries to come. • By 1980, an updated version of Jenner vaccine lead to the total eradication of smallpox.
Since Jenner's time, vaccines have been developed against more than 20 infectious diseases • The date of introduction of first generation of vaccines for use in humans* • 1798 Smallpox • 1885 Rabies • 1897 Plague • 1923 Diphtheria • 1926 Pertussis • 1927 Tuberculosis (BCG) • 1927 Tetanus • 1935 Yellow Fever • After World War II • 1955 Injectable Polio Vaccine (IPV) • 1962 Oral Polio Vaccine (OPV) • 1964 Measles • 1967 Mumps • 1970 Rubella • 1981 Hepatitis B
Vaccination Today • Vaccines have been made for only 34 of the more than 400 known pathogens that are harmful to man.
Types of vaccines • The way in which the body responds to a vaccine depends on the type of vaccine being administered. There are several different types of vaccine available and with new technology there will be further additions.
General Rule • The more similar a vaccine is to the natural disease, the better the immune response to the vaccine.
Classification of vaccines • There are two basic types of vaccines: live attenuated and inactivated. The characteristics of live and inactivated vaccines are different, and these characteristics determine how the vaccine is used. • Live attenuated vaccines are produced by modifying a disease-producing (“wild”) virus or bacteria in a laboratory. The resulting vaccine organism retains the ability to replicate (grow) and produce immunity, but usually does not cause illness. Live attenuated vaccines include live viruses and live bacteria.
Live attenuated vaccines • Live vaccines are derived from “wild,” or disease-causing, virus or bacteria. These wild viruses or bacteria are attenuated, or weakened, in a laboratory, usually by repeated culturing. For example, the measles vaccine used today was isolated from a child with measles disease in 1954. Almost 10 years of serial passage on tissue culture media was required to transform the wild virus into vaccine virus. • In order to produce an immune response, live attenuated vaccines must replicate (grow) in the vaccinated person.
Live attenuated vaccines • A relatively small dose of virus or bacteria is given, which replicates in the body and creates enough virus/bacteria to stimulate an immune response. • Anything that either damages the live organism in the vial (e.g., heat, light), or interferes with replication of the organism in the body (circulating antibody) can cause the vaccine to be ineffective. • Although live attenuated vaccines replicate, they usually do not cause disease, such as may occur with the natural (“wild”) organism. When a live attenuated vaccine does cause “disease,” it is usually much milder than the natural disease, and is referred to as an adverse reaction.
Live attenuated vaccines • The immune response to a live attenuated vaccine is virtually identical to that produced by a natural infection. The immune system does not differentiate between an infection with a weakened vaccine virus and an infection with a wild virus. • Live attenuated vaccines are generally effective with one dose, except those administered orally. Live attenuated vaccines may cause severe or fatal reactions as a result of uncontrolled replication (growth) of the vaccine virus. This only occurs in persons with immunodeficiency (e.g., from leukemia, treatment with certain drugs, or HIV infection). • A live attenuated vaccine virus could theoretically revert back to its original pathogenic (disease-causing) form. This is known to happen only with live (oral) polio vaccine.
Live attenuated vaccines • Active immunity from a live attenuated vaccine may not develop due to interference from circulating antibody to the vaccine virus. Antibody from any source (e.g., transplacental, transfusion) can interfere with growth of the vaccine organism and lead to a poor response or no response to the vaccine (also known as vaccine failure). Measles vaccine virus seems to be most sensitive to circulating antibody. Polio and rotavirus vaccine viruses are least affected. • Live attenuated vaccines can be damaged or destroyed by heat and light. They must be handled and stored carefully.Currently available live attenuated viral vaccines include measles, mumps, rubella, varicella, yellow fever, influenza (intranasal) and Oral polio vaccine. Live attenuated bacterial vaccines include BCG and oral typhoid vaccine.
Live attenuated vaccines • Characteristics • Able to replicate in the host • Attenuated (weakened) so they do not cause disease • Advantages • Induce a broad immune response (cellular and humoral) • Low doses of vaccine are normally sufficient • Long-lasting protection are often induced • Disadvantages • May cause adverse reactions • May be transmitted from person to person
Inactivated vaccines • Inactivated vaccines can be composed of either whole viruses or bacteria, or fractions of either: • Fractional vaccines are either protein-based or polysaccharide-based. • Protein-based vaccines include toxoids (inactivated bacterial toxin), and subunit or subvirion products. • Most polysaccharide-based vaccines are composed of pure cell-wall polysaccharide from bacteria. • Conjugate polysaccharide vaccines are those in which the polysaccharide is chemically linked to a protein. This linkage makes the polysaccharide a more potent vaccine.
Inactivated vaccines • These vaccines are produced by growing the bacteria or virus in culture media, then inactivating it with heat and/or chemicals (usually formalin). In the case of fractional vaccines, the organism is further treated to purify only those components to be included in the vaccine (e.g., the polysaccharide capsule of pneumococcus). • Inactivated vaccines are not alive and cannot replicate. These vaccines cannot cause disease from infection, even in an immunodeficient person. • Inactivated vaccines always require multiple doses.
Inactivated vaccines • produce protective immunity, but only “primes” the immune system. A protective immune response develops after the second or third dose. In contrast to live vaccines, in which the immune response closely resembles natural infection, the immune response to an inactivated vaccine is mostly humoral, little or no cellular immunity results. • Antibody titers against inactivated antigens diminish with time. As a result, some inactivated vaccines may require periodic supplemental doses to increase, or “boost,” antibody titers. • Currently available inactivated vaccines are limited to inactivated whole viral vaccines (influenza, polio, rabies, and hepatitis A). • Whole inactivated bacterial vaccines include pertussis, typhoid, cholera, and plague. “Fractional” vaccines include subunits (hepatitis B, influenza, acellular pertussis), and toxoids (diphtheria, tetanus).
Polysaccharide vaccines • Polysaccharide vaccines are a unique type of inactivated subunit vaccine composed of long chains of sugar molecules that make up the surface capsule of certain bacteria. Pure polysaccharide vaccines available include: pneumococcal, meningococcal, andSalmonella typhi. • The immune response to a pure polysaccharide vaccine is typically T-cell independent, which means that these vaccines are able to stimulate B-cells without the assistance of T-helper cells.
Polysaccharide vaccines • T-cell independent antigens, including polysaccharide vaccines, are not consistently immunogenic in children <2 years of age. Young children do not respond consistently to polysaccharide antigens, probably because of immaturity of the immune system. • Repeated doses of most inactivated protein vaccines cause the antibody titer to go progressively higher, or “boost.” • Repeat doses of polysaccharide vaccines do not cause a booster response. • This is not seen with polysaccharide antigens. Antibody induced with polysaccharide vaccines has less functional activity than that induced by protein antigens. This is because the predominant antibody produced in response to most polysaccharide vaccines is IgM, and little IgG is produced.
Conjugate vaccines • In the late 1980s, it was discovered that the problems with polysaccharide vaccines could be overcome through a process called conjugation. Conjugation changes the immune response from T-cell independent to T-cell dependent, leading to increased immunogenicity in infants and antibody booster response to multiple doses of vaccine. The first conjugated polysaccharide vaccine was for Haemophilus influenzae type b (Hib). • Also now available are conjugate vaccines for pneumococcal disease and meningococcal disease.
Recombinant vaccines • Vaccine antigens may also be produced by genetic engineering technology. These products are sometimes referred to as recombinant vaccines. There are four genetically-engineered vaccines are currently available: • Hepatitis B vaccines are produced by insertion of a segment of the hepatitis B virus gene into the gene of a yeast cell. The modified yeast cell produces pure hepatitis B surface antigen when it grows. • Human papillomavirus vaccines are produced by inserting genes for a viral coat protein into either yeast (as the hepatitis B vaccines) or into insect cell lines. Viral-like particles are produced and these induce a protective immune response. • Live typhoid vaccine (Ty21a) is Salmonella typhi bacteria that has been genetically modified to not cause illness. • Live attenuated influenza vaccine (LAIV) has been engineered to replicate effectively in the mucosa of the nasopharynx but not in the lungs.
General Principles of the action of vaccines • Most vaccines are injected directly into muscle tissue. Briefly the following occurs*: • Vaccine antigen disassociates from adjuvant (i.e. aluminium hydroxide). • Cells of the non-specific immune system (i.e. macrophages and dendritic cells) recognise the antigen as foreign and engulf it. These cells then chop the antigen into smaller fragments and display these on their cell surfaces. • The dendritic cells move through the lymphatic system to a local lymph node where specific T cells and B cells which recognise the fragments of antigen generate a specific immune response.
General Principles of the action of vaccines • Other components in the vaccine such as the adjuvant and preservative, if present, are absorbed into the blood where they circulate and are excreted in the stools and urine. • *Live viral vaccines multiply several times in the relevant tissues as per natural infection, however these viruses are attenuated so they cannot multiply as much as a the normal infectious virus. • Different vaccines stimulate the immune system in different ways. Some provide a broader response than others. Vaccines influence the context of the immune response by the nature of the antigens, the amount of antigens, route of administration as well as adjuvants present.
Live attenuated Vaccine OPV Measles Rubella Mumps BCG Varicella Vaccine Inactivated organism or their products Diphtheria Tetanus Pertussis( whole cell/acellular) Hepatits Avaccine Hepatitis B Pneumococcal Polysaccharide vaccine Influenza IPV Hib Type of Vaccination
Allergy Fever HIV infection Immunodeficiency Neurological disorder Prematurity Reactions to Previous vaccine Simultaneous administration of Vaccines Thrombocytopenia Who should not be vaccinated?
Allergy Allergic Reactions to Egg-related antigens • Yellow fever and influenza vaccines do contain egg proteins and rarely induce immediate allergic reactions. Skin testing is recommended before administration with an history of allergic to egg • MMR- Even those with severe hypersensitivity are at low risk of anaphylaxis.