Vaccines in children

What they are How they work

N. Iagru Associate Professor of Pediatrics

A short history (What Do Cows to Do with Vaccines?)

The word vaccine comes from Latin vaccinus which means pertaining to cows Edward Jenner (more than 200yrs ago), a country physician, noticed that milkmaids rarely suffer from smallpox. Jenner took a few drops of fluid from a skin sore of a woman who had cowpox ( a related but far less serious disease), and injected the fluid into the arm of a healthy young boy who never had cowpox or smallpox.

Six weeks later, Jenner injected the boy with fluid from a smallpox sore, but the boy remained free of smallpox

Dr. Eduard Jenner

The modern vaccine

A preparation of proteins, polysaccharides, or nucleic acids of pathogens that are delivered to the immune system as single entities, as part of complex particles, or by liveattenuated agents or vectors, to induce specific responses that inactivate, destroy, or suppress the pathogen

Public Health
Vaccines are crucial to maitaining public health: Vaccines are safe, cost-effective, and efficient way to prevent sickness and death from infectious diseases Vaccines has lead to some of the greatest public health triumphs ever, including the eradication of naturally occurring smalpox from the globe and the near eradication of polio

Variola virus
Which causes smallpox, was once the scourge of the world This virus passes from person to person trough the air : fever, severe aches and pains, scarring sores that cover the body, blindness, and, often,death In the 18th century, variola killed every 7th child born in Rusia and every 10th in Sweden and France

Naturally acquired immunity

Before vaccines, the only way to become immune to a disease was to actually get it, and, with luck, survive it (naturally acquired immunity) This means to suffer the symptoms of the disease and also the risk of complications, which can be quite serious or even deadly On the other side, the patient may by contagious and pass the disease to family members, to friends and to colleagues

Vaccination against variola

WHO:1950/50million killed people 1967/10-15 million killed people 1977: the last case of naturally occurring smallpox was in Somalia

Diphteria
1900, USA: diphteria killed more than cancer did Corynebacterium diphteriae : upper airway infection with a grayish, thick membrane that grows in the throat and obstructs breathing, fever, hoarseness, and coughing Deaths not only by blocked airways but from the paralyzing toxin secreted by the bacterium, which can cause heart or other organs to fail

Infectious poliovirus
USA, till 1954: polio crippled 13,000 to 20,000 people every year 1954, before the first polio vaccine: 18,000 cases of paralizing polio in USA Just 3 year later: 2,500/yr 2006, WHO: 2,000 cases worldwide

Statistica in Romania
1957-1961 cazuri

1987-1991 cazuri 74 decese 2

Scadere (%) cazuri decese 99,3 99,9

decese 889

Poliomielita 1531

Difterie
Tetanos Pertussis Rujeola

3982
4224 448.882 513.547

319
1843 663 860

9
144 10.413 23.976

1
65 22 25

99,7
96,5 97,6 95,3

99,6
99,7 96,6 97,1

Active Immunisation Artificially acquired immunity

Vaccinations or immunizations (hard core of primary profilaxy) are, generally speaking, interchangeable terms ( active immunisation!)

Active immunization 2

Vaccination is administration of any vaccine (inactivated or killed whole organisms or a part from an organism), toxoid (inactivated toxin), or of a specific recombinant product in order to produce an immune response similarly to those from naturally infection.

To become immune

Once the immune system is trained to resist a disease, the person are said to be immune to it Is provided by vaccines and are an easier and less risky way to become immune

Herd immunity
Vaccines protect not only yourself but also others around you Similarly, when other people are vaccinated, they are less likely to give the disease to you So, vaccines protect not only individuals, but entire communities

Community immunity
If a critical number of people within a community are vaccinated against a particular ilness, the entire group becomes less likely to get the disease. This protection is called community immunity, or herd immunity

Community immunity: if enough people in a community are vaccinated against a particular ilness, the entire group becomes less likely to get the disease, even those who are not vaccinated

Efectul indirect / Herd protection: Populatia vaccinata partial

x x

Passive immunity

Immunity transferred from one person to another: - antibodies passed from mothers before birth or through breastfeeding protect the babies against some diseases - purified blood serum which contains the antibodies produced after someone suffered from an ilness in the past

Passive immunization II
Involves also the administration of preformed antibody in the form of intramuscular immunoglobulin, intravenous immunoglobulin, or concentrated monoclonal antibodies (Palivizumab for RSV) Indications: after high-risk exposure to individuals not immunized against the disease in question; high-risk of severe complications (children born to women who are chronic carriers of hepatitis B surface antigen); PID ( replacement IVIG)

Passive Immunization Products

Rabies immune globulin Tetanus immune globulin Diphteria antitoxin(horse serum derived) Hepatitis B immune globulin Cytomegalovirus immune globulin I.V. Varicella-zoster immune globulin I.V.I.G.(PID) Botulism immune globulin I.V. Immune globulin for prevention of Hepatitis A in unimmunized individual after exposure

Types of vaccines Live, Attenuated Vaccines Inactivated Vaccines Subunit Vaccines Toxoid Vaccines Conjugate Vaccines DNA Vaccines

Recombinant

Vector Vaccines

Live, Attenuated Vaccines

Contain a version of the living microbe that have been weakened (attenuated) in the lab so it cant cause disease Because a live, attenuated vaccine is the closest thing to a natural infection, these vaccines are good teachers of the immune system: they elicit strong cellular and antibody responses, and often confer lifelong immunity with only one or two doses

I. Live, attenuated vaccines

This image shows the live microbes antigens, membrane, and genetic material

Downsides
The organisms used in live, attenuated vaccines can change or mutate ( is the nature of living things to change!), and could revert to a virulent forme and cause disease Persons with damaged or weakened immune systems (PID, HIV, chemotherapy) Need to be refrigerated to stay potent(the shipping overseas and stored by health care workers in developing countries that lack widespread refrigeration)

Live, attenuated
Are relatively easy to create for certain viruses (contain a small number of genes): -measles, rubella,polio (Sabin vaccine),mumps chickenpox,yellow fever Are more difficult to create for bacteria (have thousands of genes, much harder to control): vaccine against Vibrio cholerae

II. Inactivated Vaccines (killed vaccines)

By killing the disease-causing microbe with chemicals,heat, or radiation Are more stable and safer than live vaccines(the dead microbes cant mutate!) Dont require refrigeration ( can be easily stored and transported in a freeze-dried form) Stimulate a weaker immune system response than live vaccines (need booster shots, that could be a drawbackin developing areas !)

Exemples for inactivated vaccines

V. bacteriene inactivate : DTPa sau DTPw, HI tip b, meningococic (A,C,Y,W135), cholera, plague Vaccinuri virale inactivate: Flu, VPI(Salk vaccine), hepatita B, hepatita A, rabies,Japanese encephalitis.

Inactivated vaccines

Inactivated vaccines contain microbes that have been inactivated with chemicals, heat, or radiation. The microbes antigens, membrane, and genetic material are still present.

III. Subunit vaccines

Instead of entire microbe, subunit vaccines include only the antigens that best stimulate the immune system In some cases, Subunit Vaccines use epitopes (the very specific parts of the antigen) that antibodies or T cells recognize and bind to Because SUV contain only the essential antigens (1-20 or more antigens) and not other molecules that make up the microbe, the risks of adverse reactions to the vaccine are lower

Subunit vaccines

The imagine depicts antigens that have been separated from the rest of the microbe for use in a subunit vaccine

Subunit Vaccines

SUV are vaccines produced by recombinant technology They are called Recombinant Subunit Vaccines : - vaccine against hepatitis B virus Scientists inserted hepatitis B genes that code for important antigens into common bakers yeast The yeast then produced the antigens, they are collected and purified for use in the vaccine

Other vaccines: pertussis, pneumonia caused by S.pneumoniae

IV. Toxoid vaccines

They are used when a bacterial toxin is the main cause of illness Toxins are inactivate by treating them with formalin (a solution of formaldehyde and sterilized water) Detoxified toxins are called toxoids and they are safe for use in vaccines

Toxoid Vaccines

Harmless toxoid molecules (artists representation) are used in toxoid vaccines to immunize and protect people against harmful toxins secreted by some microbes

Toxoid Vaccines

The immune system produces antibodies that lock onto and block the toxin Exemples of toxoid vaccines: - Vaccine against diphteria - Vaccine against tetanus

V. Conjugate Vaccines
Are used against bacteria which possessed an outer coating of sugar called polysaccharides Polysaccharide coating disguise a bacteriums antigens so that the immature immune systems of infants and younger children cant recognize or respond to them Scientists link antigens or toxoid from a microbe that an infants immune system can recognize, to the polysaccharides. The linkage helps the immature immune system react to polysaccharide coating and defend against the disease-causing bacterium

Conjugate vaccines

Conjugate vaccines link antigens or toxoids to the polysaccharid or sugar molecule that certain bacteria use as a protective coating,thereby allowing the immune system to recognize and attack thes disguised bacteria. A conjugate vaccine contains the molecules shown in the foreground. The bacterium, part of which is shown in the upper left background, is not part of the vaccine. In fact, this kind of vaccine is a subunit vaccine

Exemples of Conjugate Vaccines

Vaccine against HI b Vaccine against Streptococcus pneumoniae: Prevenar 7 valent Prevenar 13 valent

VI. DNA Vaccines

Experimental stages ! (but several types already tested in humans) DNA vaccines take immunization to a new technological level Dispense with both the whole organism and its parts and get right down at the essentials: the microbes genetic material DNA vaccines use the genes that code for those all-important antigens

DNA Vaccines II
When the genes for a mirobes antigens are introduced into the body, some cells will take up that DNA The DNA then instructs those cells to make the antigen molecules The cells secrete the antigens and display them on their surfaces

DNA Vaccines

In other words, the bodys own cells become vaccine-making factories, creating the antigens necessary to stimulate the immune system DNA vaccines are relatively easy and inexpensive to design and produce

DNA Vaccines

DNA vaccines use a microbes genetic material, in particular, the genes that code for important antigens. The DNA in these vaccines is a circular form known as a plasmid

DNA Vaccines III

SO-called naked DNA vaccines consist of DNA that is administered directly into the body These vaccines can be administered with a needle and syringe or with a needle-less device that uses high-pressure gas to shoot microscopic gold particles coated with DNA directly into cells Tested in humans: influenza, herpes, HIV

VII. Recombinant Vector Vaccines

These experimental vaccines are similar to DNA vaccines, but they use an attenuated virus or bacterium to introduce microbial DNA to cells of the body Vectors refers to the virus or bacterium used as a carrier In nature, viruses latch on the cells and inject their genetic material into them

Recombinant Vector Vaccines II

In the lab, scientists have taken advantage of this process. They figured out how to take the roomy genomes of certain harmless or attenuated viruses and insert portions of the genetic material from other microbes into them The carrier viruses then ferry that microbial DNA to cells

Recombinant Vector Vaccines III

They closely mimic a natural infection and therefore do a good job of stimulating the immune system Attenuated bacteria as vectors : the inserted genetic material causes the bacteria to display the antigens of other microbes on its surfaace. In effect, the harmless bacterium mimics a harmful microbe provoking an immune response Researches: vaccines for HIV, rabies, and measles

Recombinant Vector Vaccines

Recombinant vector vaccines use the harmless shell of one microbe. The genetic material contains the code for marking vaccine antigen inside some of the bodys cells, using those cells as factories

Reportable events after vaccinations

Anaphylaxis or anaphylactic shock, brachial neuritis and their sequela(DTP, DTPHiB) Idem, Encephalopathy(or encephalitis):MMR; chronic arthritis (rubella in any combination); Thrombocytopenic purpura (measles in any combination); Paralytic polio (OPV); Intussusception (Rotavirus).

Romanian National Program for Immunization (Calendarul de vaccinare 2009)

Varsta recomandata Primele 24 ore 2-7 zile
2 luni 4 luni 6 luni

Vaccin Hep. B BCG

DTP, VPI, Hep. B DTP, VPI DTP, VPI, Hep. B

Comentarii In maternitate
Simultan Simultan Simultan

12 luni
4 ani 7 ani (cls.I) 9 ani (cls. a III-a) 14 ani (cls. a IV-a)

DTP, VPI, RRO(MMR)

DTaP* RRO (MMR) VPI dT

Simultan

Campanii scolare Campanii scolare Campanii scolare

U.S. Vaccine-Preventable Infectious Diseases

Anthrax, Bacterial meningitis, Chickenpox, Diphteria,Haemophilus influenzae type b,Hepatitis A, Hepatitis B, Cervical cancer(HPV),Influenza, Japanese encephalitis,Measles, Mumps, Pertussis, Pneumococcal pneumonia, Polio, Rotavirus diarrhea, Rabies, Rubella, Smallpox, Shingles, Tetanus, Tuberculosis, Typhoid,Yellow fever

Programul national de imunizare (PNI)

Absente notabile fata de PNI-urile din tarile dezvoltate din UE si din SUA :

Vaccinarea Vaccinarea Vaccinarea Vaccinarea Vaccinarea

anti-HI tip b antipneumococica anti-Rotavirus anti-varicela anti-meningococica

U.S.Routine Immunization Schedule

American Academy of Pediatrics American Academy of Family Phisicians Advisory Committee on Immunization Practices of the Centers for Diseases Control and Prevention (CDC) jointly prepare and updated immunization schedule every January, which is published in the Pediatrics, Morbidity and Mortality Weekly Report and in Family Physician

Contraindications
For children with intact immune system there are few absolute contraindications to receiving the first dose of any vaccine ! Inactivated or subcomponent vaccines pose no additional risk to patients with immune deficiency disorders, but some patients may not be protected from the target disease

Contraindications

Immediate Hypersensitivity Reactions ( Anaphylaxis or angioedema after a previous dose of vaccine is usually a contraindication for the subsequent doses of the same vaccine) -Vaccines produced in the chick embryo tissue cultures do not contain detectable amounts of egg proteins -Some of hypersensitivity reactions are caused by components added to vaccines( the gel stabilizer in measles vaccine) - The mild allergic reactions are not a contraindication to receive the subsequent doses, but may require special investigations and a consult with an allergist or vaccine safety specialist

Encephalopathy or Encephalitis
Both of them, within a few days after DTP vaccine administration is a contraindication to receipt of the subsequent doses A febrile seizure after any vaccine is not a contraindication to receipt a subsequent doses of vaccine were other vaccines that might induce fever Children who have had encephalitis or encephalopathy of unknown cause unrelated to immunization can safely receive all recommended vaccines if neurologic condition is stable Children with progressive neurologic disorders should defer the DTaP vaccine until the condition is stable

Immune Deficiency Disorders

Live vaccines can cause serious adverse events in patients with immune deficiency disorders (i.e risk of vaccine-associated paralysis after OPV is increased at least 1,000-fold in persons with agammaglobulinemia) Patients with HIV infection can receive live MMR or varicella vaccine if their CD4 count is greater than 15% Other patients with primary or acquired deficiency of T cells generally should not receive live viral vaccines

Immune deficiency Disorders II

Some patients can safely receive live vaccines: - Patients successfully treated for cancer can be usually be immunized with both live and inactivated vaccines after completion of chemotherapy, but specific waiting times are recommended - Mild immune deficiency disorders, such a subclass IgG deficiency disorders, are not associated with adverse events following vaccination - Patients with disorders of white blood cell functions (CGD), can receive all inactivated varicella and live viral vaccines

Other contraindications
Severe ilnesses ( infectious diseases, TBC evolutiva, chronic nephropaty, chronic liver diseases, severe cardiovascular diseases) Cachexy

Pregnancy,live vaccines are prohibited in the first 3 months because they may be teratogenic.

Noncontraindications and Misconception

Children with mild upper respiratory infections or gastroenteritis can receive routine immunizations as there is no evidence of any increased risk from vaccinationof children with these infections

Low-grade fever-less than 39C-is not a contraindication to immunization ! ( Although, is more prudent to wait for a few days to be immunized if uncertainty exists regarding the cause of the concurent ilness) ---------------------------------------------------------
Neal A.Halsey. Immunization. Oskis Pediatrics Principle &Practice, 2006:118-134

Some specific immunizing agents

Meningococcal Vaccine : 1. A plain polysaccharide vaccine against Neisseria meningitides types A,C, Y, and W135 in children 2 or more years of age, recommended for children at increased risk of disease including those with asplenia or complement deficiency. It is not administered routinely to children because the risk of disease is relatively low 2. A polysaccharide-protein conjugate vaccine containing types A, C, Y, and W135 (2005) for all children 11-12 years of age, for previously unvaccinated 15-16 yr old, college freshman living in dorms, and others at high risk of disease

Vaccine strategies
Some vaccines come in combinations: DTP, MMR Combination vaccines reduce visit to the doctor, saving time and money and sparing children extra needlestick

Vaccine Concerns, Myths, and Safety Issues on the Web

Rumors and misinformation about vaccine safety abound Now that vaccines have virtually eliminated many once-feared diseases, the possibility of vaccine side effects or adverse reactions loom larger in some peoples minds than the diseases that vaccines prevent Most parents today have never seen a case of diphteria or measles, and some wonder why their children must receive so many shots

Safety Issues

Many parents are concerned that multiple vaccines may weaken or overwhelm an infants immune system or that certain vaccines may cause autism, multiple sclerosis, or diabet

Combination vaccines

May they overwhelm or weaken childs immune system ? The immune system contains billion of circulating B and T cells capable of responding to millions of different antigens at once Because the body constantly replenishes these cells, a healthy immune system cannot be used up or weakened by a vaccine According to one published estimation, infants could easily handle 10,000 vaccines at once !

Further reading
http://www.cdc.gov/vaccines/schedules/ http://www.cdc.gov/vaccines/vpdvac/vpd-vac-basics.htm http://www.cdc.gov/vaccines//vpdvac/vaccines-list.htm

List of Vaccine-Preventable Diseases [1]

Anthrax Cervical Cancer (Human Papillomavirus) Diphtheria Hepatitis A Hepatitis B

type b (Hib) Human Papillomavirus (HPV) Influenza (Flu) Japanese encephalitis (JE)

Haemophilus influenzae

Lyme disease Lyme disease vaccine no longer available in the United States. Measles Meningococcal Monkeypox There is NO monkeypox vaccine. The smallpox vaccine is used for this disease. Mumps Pertussis

List of Vaccine-Preventable Diseases [2]

Pneumococcal Polio Rabies Rotavirus Rubella Shingles (Herpes Zoster) Smallpox

Tetanus Typhoid Tuberculosis (TB) Varicella (Chickenpox) Yellow Fever