Immunity
ACTIVE IMMUNITY
• Immunity through transmission of infections or vaccination.
PASSIVE IMMUNITY
• It is the immunity provided by the administration of antibodies (Ig) or antiserum. Passive immunity can be innate or acquired.
innate passive immunity
• It happens with antibodies passed from the mother through the placenta. It lasts for 4-6 months on average. There is no innate passive immunity in pertussis.
acquired passive immunity
• It is a short-term immunity provided by the application of various sera or antibodies (Ig) obtained from the sera. These antibodies can be of different types according to the content, ratio and the antigen with which they are active.
Standard Immunoglobulin
• It is especially used in immunocompromised patients. It can be used in contact with a patient with measles, in hepatitis A prophylaxis, in pregnant women who have contact with a person with rubella.
FDA-approved intravenous immunoglobulin (IVIG)
Indications
• Primary immunodeficiency
• Kawasaki disease
• Bacterial infection prophylaxis in HIV-infected children
• Severe bacterial infection prophylaxis in patients with hypogammaglobulinemia in chronic B-cell leukemia
• Immune thrombocytopenia
• Infection prophylaxis after bone marrow transplantation
• Toxic shock syndrome
• Guillain-Barré syndrome
• Parvovirus B19 mediated anemia
• In the prophylaxis of post-exposure varicella infection (when VZIG is not found)
Hyperimmunobulin
• It is obtained from the serum of people who have had a certain infection or have been vaccinated against it. It is considered non-allergenic. It is used to prevent Rh incompatibility, to create passive immunity against diseases such as rabies, hepatitis B, varicella zoster, tetanus.
monoclonal antibody
• Products produced from a single lymphocyte clone and containing antibodies against only one antigen (monoclonal RSV antibody-Palivizumab).
The immune response to vaccines, their types and methods of administration
• Vaccines are solutions containing live (attenuated) or inactivated microorganisms (bacteria or viruses) or fractions of these microorganisms, which are prepared to stimulate the immune system and prevent disease or its sequelae when administered.
• The immune response that develops after the first administration of the vaccine is called "primary", and the immune response that develops when the injections are repeated is called "secondary".
• In the primary immune response, IgM and IgA type antibodies appear first and then IgG type antibodies.
• In the secondary immune response, both specific and multiple antibodies appear rapidly and are all IgG .
3 consecutive periods occur after a vaccine is administered
1. Latent period: 24 hours-2 weeks
2. The period of reproduction. 4 days-4 weeks
3. Decreasing period After 4 weeks
VACCINE TYPES
Bacterial vaccines
• Live attenuated vaccines: BCG, tularemia, oral typhoid
• Dead vaccines: pertussis, typhoid, cholera
• Toxoids: diphtheria, tetanus.
• Polysaccharide vaccines: HiB, meningococcal A+C, pneumococcus
virus vaccines
• Attenuated live vaccines: OPV, MMR, yellow fever, chickenpox, rotavirus, nasal influenza (LAIV)
• Inactivated vaccines: Influenza, IPV, rabies, hepatitis A
• Recombinant vaccines: Hepatitis B and HPV vaccine
HOW THE VACCINES ARE GRANTED
Intradermal
• BCG; Subcutaneous injection is generally not recommended.
intramuscular
• DBT, DT, dT, DTaB, Hib, pneumococcal (conjugated), hepatitis A, hepatitis B, influenza (influenza), rabies (HDCV), polysaccharide typhoid vaccines are administered IM.
• Vaccines containing additives such as aluminum hydroxide and aluminum phosphate (DBT, Hepatitis A, Hepatitis B) and gammaglobulins (specific and nonspecific) may cause local irritation, inflammation, granulation and necrosis if administered subcutaneously. Hips with excessive subcutaneous fat should not be chosen as the injection site, but the thigh and upper arm should be preferred.
Subcutaneous
• Rubella, mumps, measles, varicella
Oral
• OPV (Sabin), rotavirus, live typhoid vaccine
Nasal
• Live cold-adapted attenuated influenza vaccine
Note: IPV (Salk) and 23-valent polysaccharide pneumococcal vaccine can be given SC or IM.
IMPORTANT INFORMATION ABOUT VACCINATION
• Mild to moderate diarrhea should not be considered a contraindication for oral poliomyelitis vaccine. However, it is appropriate to administer an extra dose of vaccine 4-8 weeks after the first 2 vaccines to children with diarrhea given TOPV.
• Live virus vaccines (measles) impair the tuberculin skin test.
• Hepatitis B vaccine is given to babies whose birth weight is over 2000 g, adequate antibody response is not formed under 2000 g.
• Since the antibody response is low during chemotherapy and radiotherapy, vaccination is not performed.
• In general, there is no harm in administering all vaccines, live or inactivated, on the same day. While there is no harm in sequential administration of different inactivated vaccines without taking into account the time between doses, different live vaccines (for example MMR and varicella) should be administered in different places on the same day; If it cannot be done together, at least 1 month should be left in between.
• Oral live vaccines do not interact with other live vaccines.
• BCG does not interact with other live vaccines.
• Diphtheria toxoid is reduced by 1:12 over 7 years of age (Td).
• Cold, prematurity, antibiotic use, breastfeeding, asthma and non-specific allergies, egg allergy, diarrhea, history of febrile convulsions, local steroid therapy do not constitute a contraindication for the vaccine.
• Contraindicated vaccines in patients with chronic kidney disease and diabetes mellitus are live typhoid vaccine and intranasal influenza vaccine.
• In cases where the vaccination program is delayed, it will continue from where it left off.
• More than one vaccine can be given on the same day. If multiple vaccines are to be given to the same extremity, there should be at least 2 cm between them.
• Oral polio and rotavirus vaccines should be administered at least 4 weeks apart, not on the same day.
• Tetanus vaccine should not be given frequently, since a hypersensitivity reaction may develop, it should be administered at least 10 years apart. Sometimes Arthus reaction (Type 3 hypersensitivity reactions) may develop even after a single dose of vaccination.
Conditions in which vaccination is contraindicated
- Having developed anaphylactic hypersensitivity to the vaccine before (if the vaccine is absolutely necessary, the vaccine can be administered in a controlled manner by applying desensitization.
- Moderate or severe acute illness (vaccination is delayed until the child recovers)
Note: An anaphylactic reaction to a vaccine component is an absolute contraindication for vaccines containing this substance.
Situations where live vaccines are contraindicated
- Congenital and acquired immunodeficiencies
- Patients with malignant disease and receiving chemotherapy
- Patients on steroid therapy - Patients receiving radiotherapy
- Skin infections
- Pregnant women (MMR, varicella, live attenuated influenza vaccine, zoster)
- If there is an immunocompromised patient at home, IPV (motive) is given to the child instead of OPV.
Non-live vaccines are not contraindicated in congenital and acquired immunodeficiency. However, when immunity is not sufficient, the vaccine may be ineffective, so its postponement may be considered.
False contraindications for vaccination
Vaccination should not be delayed in the following cases:
- Mild disease picture (with or without fever)
- Mild or moderate local reaction (swelling, redness, pain, etc.)
- Mild or moderate fever at previous vaccination
- Antimicrobial treatment
- Recovery period of the disease
- Prematurity (including rotavirus)
- Recent history of contact with an infectious disease
- Having a history of nonspecific allergy or having a history of allergy in relatives
- Non-anaphylactic allergic reaction to penicillin or other antibiotics other than anaphylactic reaction to neomycin or streptomycin
- The mother is pregnant or has domestic contact with other healthy people (including rotavirus)
- Breastfeeding (including OPV does not constitute a contraindication)
- Having unvaccinated household contacts
- Child of breastfeeding mother
- Having a family history of convulsions (for DBT, DTaB)
- mild diarrhea
- PPD positivity
DaPT-IPA-Hib: Diphtheria, acellular pertussis, tetanus, inactivated polio, Haemophilus influenzae type B vaccine (combined vaccine of 5)
PCV: Conjugated pneumococcal vaccine
MMR: Measles, rubella, mumps vaccine
DaPT-IPA: Diphtheria, acellular pertussis, tetanus, inactivated polio (4-in-1 mixed vaccine)
OPA: Oral polio vaccine
Td: Adult type diphtheria tetanus vaccine
R: Rapel (reinforcement)
The childhood vaccination schedule will be continued with school vaccinations.
1. Children over 59 months should be administered DaBT - IPA. A single dose of Hib is sufficient for children aged 15 to 59 months.
2. Children aged 12 to 23 months should be given two doses, 8 weeks apart. For children older than 24 months, a single dose is sufficient.
3. - The first dose of DaBT-IPA-Hib vaccine should be administered to children at 12-14 months of age, and the second dose should be administered as DaBT-IPA-Hib.
NOTE : The second dose of Hib is only required if the first dose was given between 12 and 14 months. For children aged 15 to 59 months, a single dose of Hib is sufficient. The Hib vaccine is not required for children over 59 months of age. Hepatitis A Vaccine is administered to children in two doses at least 6 months apart. Chickenpox Vaccine is administered to children as a single dose.
BCG VACCINE
• It is a live bacteria vaccine with reduced virulence.
• It is prepared from M. bovis strain.
• The vaccine reduces the development of serious infections such as miliary tuberculosis or tuberculous meningitis, not microbacterial infection.
• BCG vaccine is administered intradermally to the left shoulder, there is no harm in administering it together with other vaccines.
• Within 2-6 weeks after vaccination, the papule ulcerates in 6-8 weeks and heals by scarring in the 3rd month. After the 5th year, its protection decreases.
• Babies under three months are vaccinated directly. If a baby older than 3 months is to be vaccinated for the first time, PPD is performed first, if PPD is (-) it is vaccinated, if (+) it is not vaccinated.
• In cases where the PPD test falls below 5 mm, vaccination is repeated.
• The most common complication after vaccination is lymphadenitis, which is seen at a rate of 1%, develops 2-3 months after vaccination, and is often observed unilaterally and under the armpit. If the adenopathy heals spontaneously in 6-9 months, but if it is large, tends to fistula or ulcerate, INH at a dose of 10 mg/kg can be given for 3 months.
• The most important complication is post-vaccine dissemination (seen in those with IF gamma and IL-12 receptor defects).
DIPHTHERIA-Pertussis-TETANUS (DBT/DTAB) VACCINES
• Diphtheria and tetanus contain formaldehyde-treated toxins (toxoid), Pertussis is an inactivated suspension of Bordatella pertussis.
• The disease picture in pertussis infection is caused by pertussis toxin (PT), filamentous hemagglutinin (FHA), agglutinogens, adenylate cyclase, endotoxin antigens.
• Whole cell pertussis vaccine (B); It contains all toxic substances, including endotoxin.
• Acellular pertussis vaccine (aB); Contains PT, FHA, pertactin, fimbria type 2,3.
• Td containing adult type diphtheria vaccine is administered to those older than 7 years of age and repeated every 10 years.
Exceptions
• Even if the mother is immune to pertussis, pertussis can be seen from the newborn period. Because the antibodies formed are in IgM structure.
• If the mother is immune to tetanus and diphtheria, she protects babies for 4-6 months with the antibodies passed from the mother (congenital passive immunity).
• Since treated diphtheria and tetanus infections will not give immunity, people who have had this disease should be immunized again.
Absolute contraindications for DBT vaccine
• Presence of severe allergic reaction (anaphylaxis, etc.) at the previous dose or at the same dose (DBT and DTaB are contraindicated).
• DBT and DTaB are contraindicated, but TD or Td can be applied if there is any other unexplained encephalopathy (coma, confusion, and prolonged convulsions) that develops within the first 7 days after the previous dose.
DBT and DTaB are contraindicated in the presence of progressive neurological disease (infantile spasm, uncontrolled epilepsy, progressive encephalopathy) until the disease is under control
Side effects of DBT vaccine
• Moderate or severe infection with or without fever
• Fever exceeding 40.5°C within 48 hours after previous DBT or DTaB
• Collapse/shock-like condition
• Hypotonic-hyporesponsive response
• Convulsion occurring within 3 days of previous DBT/DTaB
• Unstoppable crying lasting 3 hours or more within 48 hours after previous DBT/DTaB • In the above situations, DBT/DTaB vaccines are not contraindicated.
• In the case of Guillain-Barre syndrome, which occurs within 6 weeks after the previous administration of tetanus toxoid-containing vaccine, vaccines containing tetanus toxoid should be administered carefully and with a profit-loss calculation.
Tetanus prophylaxis
In cases where TIG cannot be found, IVIG can be given.
diphtheria prophylaxis
• A single dose of benzathine penicillin or erythromycin for 10 days is given to the person who has come into contact with a patient with diphtheria, whether vaccinated or not.
• An additional dose of vaccine is given in the following cases:
If <3 vaccines, 1 dose of vaccine is given
If there are 3 or more vaccines, 1 dose of vaccine is given if there is a missing vaccine.
DTaB ; < 7 years old uses
DTaB; Uses between 7-10 years old
dTab: The ideal age is 11-12 years old and uses in adult vaccination. Minimum time is 10 years old
whooping cough prophylaxis
• Neither getting a pertussis infection nor getting vaccinated creates a complete immunity against whooping cough.
For this reason, every child who has been in contact with whooping cough is given erythromycin for 14 days, azithromycin for 5 days, or clarithromycin for 7 days. or sulfamethoxazole and trimethoprim for if a macrolide cannot be given.
• An additional dose of vaccine is given in the following cases:
- >6 months after 3rd dose of vaccine
- If ≥ 3 years have passed since the 4th dose of the vaccine
- DTaB: Used at <7 years old.
- dTaB: Used between the ages of 7-10.
- dTab: It is used for ideal age 11-12 years and adult vaccination. The minimum deadline is 10 years.
Measles-Rubella-Mumps Vaccine MMR
• In our country, protection against measles, mumps and rubella diseases is mainly provided by the combined MMR vaccine.
• MMR vaccines are live attenuated virus vaccines. Contains gelatin and neomycin
• MMR is administered subcutaneously at a dose of 0.5 ml alone or on the same day as other vaccines.
• The first dose is administered at the age of 12-15 months, and the second dose is administered at the age of 4-6 years (in the first grade of primary education in our country).
• If the first dose was administered before 12 months of age, it should be given as 2 doses again after 12 months, since it is considered that there is not enough protection. The shortest interval between two doses should be 4 weeks.
• Measles vaccination within 72 hours of contact with measles is effective in protection. Those who pass this period are given 0.25 ml/kg of standard gammaglobulin 6 days after the contact.
• MMR vaccination should generally be given to women of childbearing age at least 1 month before pregnancy. If pregnancy occurs within 28 days of vaccination, the risk of teratogenicity is very high.
Side Effects of MMR Vaccine
General
Fever
Febrile convulsion
Rash (due to measles and rubella components)
allergic reaction
Transient thrombocytopenia
Suppression in cellular immunity
Arthralgia, arthritis (due to measles and rubella components)
Associated with measles com nent
• Encephalopathy occurring within the first 30 days
• Decrease in Vitamin A level
Attached to rubella component
• Polyneuropathy
• Carpal tunnel syndrome and Horner's syndrome
• LAP
Depends on the mumps component
• parotid
• Orchitis
• Aseptic meningitis
• Unilateral deafness
POLYOMYELITE VACCINES
Inactivated Poliomyelitis vaccine (IPV, Motivation vaccine)
• It is a dead virus vaccine. It is prepared by inactivating 3 poliovirus serotypes with formalin.
• Stimulates only humoral immunity. It is the only vaccine recommended for those who are immunocompromised or have immunodeficiency at home, those with malignant diseases, those who receive immunosuppressive, steroid, cytotoxic drugs and radiation therapy. Guillain-Barré syndrome or anaphylaxis may rarely occur after IPV.
Oral Poliomyelitis Vaccine (OPV, Sabin vaccine)
• It is a live virus vaccine. Trivalent vaccine (TOPV) contains all three polio serotypes.
• Stimulates local IgA production in the oropharynx and intestine. It stimulates both humoral and local immunity.
• It prevents the spread of the street virus that causes disease in the society by spreading the vaccine virus excreted with the feces to the unvaccinated people. However, it is known that paralytic poliomyelitis may develop at a rare rate, such as one in ten million, due to vaccines.
• For both OPV and IPV, there are no reported side effects on expectant mothers and fetuses, but it is still recommended not to be done during this period.
• IPV should be preferred because of the risk of vaccine-associated poliomyelitis Vaccine Associated Paralytic Polio (VAPP) in adults.
Situations where IPV should be applied instead of TOPV
• Primary immunodeficiency diseases
• Malignant diseases
• Those receiving immunosuppressive therapy
• Those who use corticosteroids
• Those receiving cytotoxic drugs or radiotherapy
• Siblings of children with immunodeficiency
• Adults without primary vaccination
POLYSACCARIDE VACCINES
• Polysaccharide vaccines provide antibody production by stimulating mature B cells independently of T cells, but they do not create immunological memory because they do not stimulate memory T cells. It has no booster dose effect and does not prevent carriage.
In addition, children <2 years of age do not respond adequately to polysaccharide antigens. Therefore, pure polysaccharide vaccines are used in children aged >2 years and in risky groups.
• Conjugate vaccines contain a carrier protein (tetanus or diphtheria toxoid or meningococcal outer membrane protein) that is covalently attached to the polysaccharide structure. Thanks to this protein, the antigen becomes T cell dependent, stimulating immunological memory and a longer and greater immunity is formed. It has a booster dose effect and prevents carriage.
• Conjugated vaccines are used under <2 years of age.
Risk group and vaccine indications for encapsulated bacterial infection
PCV In some cases PPSV23
Immunocompetent child
Chronic heart disease (cyanotic congenital heart disease)
Chronic lung disease (including asthma requiring oral steroids)
type 1 diabetes
CSF leak
cochlear implant
Anatomical and functional asplenia
chronic liver disease
Immunocompromised conditions
HIV
Kronic renal Failure
Nephrotic syndrome
immunosuppressive or radiation therapy
Malignancies (leukemia, lymphoma)
Solid organ transplantation
Immunodeficiencies
MCV4
Anatomical and functional asplenia
Lack of complement
They will travel to Africa
meningococcal epidemic
HIV infection
Hib
Anatomical and functional asplenia
Immunocompromised conditions:
HIV
immunosuppressive therapy
Immunoglobulin deficiency
Early complement deficiency
stem cell recipients
MenB
Anatomical and functional asplenia
Lack of complement
Meningococcal serogroup B outbreak
PNEUMOCOCK VACCINE
• There are 90 serotypes according to the polysaccharide structure of pneumococci.
• Invasive pneumococcal infections in children are most commonly caused by serotypes 1, 4, 6, 7, 9,14, 18, 19, and 23.
• Especially under the age of 2 and over the age of 65, the risk of disease increases.
Pure polysaccharide vaccines
• It is used over 2 years of age, since T cell response is not sufficient before 2 years of age (PPSV-Pneumo-23).
- Vaccine antibodies decrease to their former level in 5-10 years. For this reason, booster vaccines are given to people with splenectomy or immunodeficiency after 5 years.
Conjugated pneumococcal vaccine
• It is produced by making the pneumococcal capsule polysaccharide (T' cell independent antigen) T cell dependent by covalently binding to a protein carrier. 13-valent pneumococcal conjugate vaccine used in our country (contains PCV-Prevenar 13-mutant diphtheria toxoid)
• Conjugate pneumococcal vaccine applications vary according to age: - According to the calendar adopted in 2019 in our country, pneumococcal vaccine is administered as a booster in the 2nd, 4th and 12th months. IM or SC 0.5 ml. It rarely causes anaphylaxis.
- between 12-24 months; 2 doses are given 2 months apart.
- after >24 months; A single dose is sufficient.
- Children in the risk group between the ages of 6-18 should have both PCV13 and PPSV23 vaccines. Whichever is done first, the other should be done at least 8 weeks later.
HAEMOPHILUS INFLUENZAE TYPE B VACCINE
• It is one of the most common causes of bacterial meningitis in non-vaccinated countries. The only known host is humans.
• Vaccines contain the capsule polysaccharide Polyribosyl-Ribizol-Phosphat (PRP).
• In vaccines used today, a protein that stimulates the T response (tetanus toxoid or meningococcal outer membrane protein) has been added as a carrier hapten (conjugated vaccine).
• Within the routine vaccination program in our country, 2-4-6-18. 4 doses are applied monthly.
• Children aged 6-12 months are given 2 doses at intervals of 4 weeks and a booster at 15 months of age.
• Children aged 12 to 4 months receive 1 dose of vaccine and at least 8 weeks later, a booster is given.
• It is applied as a single dose between the ages of 15 months and 5 years.
• It is not done after the age of five.
Meningococcal Vaccines
• N. meningitidis is a gram-negative, encapsulated, aerobic diplococcus and the meningococcal disease it causes is one of the most important causes of morbidity and mortality in children and young adults worldwide.
• The main transmission route of N.meningitidis is droplet route or close contact with respiratory secretions of the infected person. The frequency of invasive meningococcal disease increases in late components of the complement system and properdin deficiency, in functional or anatomical asplenia cases and in HIV-infected individuals.
• Meningococci are only infectious agents in humans and the 5 serogroups A, B, C, Y and W135 are the most common causes of meningococcal disease all over the world.
Polysaccharide meningococcal vaccines (MPSV)
• There are polysaccharide vaccines developed against serogroups A,C,Y and W-135 (MPSV). There are divalent polysaccharide vaccine named lmovax Meningo A+C and A/C/Y /W135 tetravalent polysaccharide vaccine named MenCvax in Turkey.
• These vaccines are weak immunogens in children under 2 years of age. In older children and adults, the effectiveness of the vaccine is between 85-100%.
• The vaccine is administered as a single dose, 0.5 ml, subcutaneously.
Meningococcal B vaccine
• Type-B is the most common epidemic and severe infection in children. Meningococcal B disease is especially common under the age of one.
• MenB-FHbp (Trumenba): Vaccine containing factor H binding protein. Between the ages of 16-23, 3 doses are given.
• 4CMenB (Bexsero): Contains outer membrane vesicles and 3 recombinant proteins (Factor H binding protein, Adheezin A and heparin binding protein).
Conjugated meningococcal A, C, Y, W 135 vaccine (MCV 4)
• It is a conjugate vaccine effective against 4 out of 5 serogroups (A, C, Y and W135) that cause meningococcal disease.
• Minimum age for those who will travel to high-risk groups (complement deficiency, asplenia, and endemic meningococcal infection);
- Men ACWY-CRM [Menveo]-Mutant Contains diphtheria toxoid: 2 months
- Hib-Men CY: Contains [MenHibrix]-Tetanus toxoid: 6 weeks
- Men ACWY-D [Menactra]-Contains diphtheria toxoid; 9 months
- Men ACWY-TT [Nimenrix] Contains Tetanus toxoid: 6 weeks
Rabies Vaccine
• Rabies is a deadly disease that is transmitted by being bitten by an infected animal such as a dog, cat, bat, or by contact with its infectious saliva. After the virus replicates in muscle cells adjacent to the wound site, it travels to peripheral nerves via acetylcholine receptors. After this period, it is not possible to stop the disease with vaccines and immunoglobulins.
• Rabies vaccine obtained from human diploid cell cultures (HDCV) is preferred because its antigenicity is higher, it is administered at lesser doses, and it has fewer complications.
Postexposure prophylaxis
1. The wound should be washed with plenty of soapy water. It removes the virus from the wound area at a rate close to 90%.
2. Human rabies immunoglobulin (HRIG) should be administered within the first 24 hours, if not found, within 7 days. Half is done in and around the wound, and half is done on a different extremity than the injured extremity.
3. One IM dose of vaccine is given on days 0, 3, 7, and 14. The vaccine is given to a different extremity than the bitten extremity that was administered imminglobulin.
4. If necessary, tetanus vaccination is given according to the tetanus vaccination scheme applied in case of suspected injury.
5. Antibiotic treatment: Antibiotics are started in the following cases (primarily Amoxicil in-Clovulonate)
• All human bites
• Face and hand bites
• Genital area bites
• Bites with bone and joint penetration
• Bites near the prosthetic bone
• Immunocompromised patient
If the person has been vaccinated in full dose before or if there is sufficient antibody in his serum, 2 doses of vaccine are given only on the 0th and 3rd days, regardless of the time elapsed. HRIG is not done.
If the dog or cat is healthy and can be followed for 10 days, follow-up is sufficient. When rabies symptoms are seen in the follow-up, vaccine + immunoglobulin is administered.
• Vaccination is unnecessary in contact with blood and can be vaccinated during pregnancy.
• Immune complex reactions such as generalized urticaria, angioedema, arthritis or arthralgia may occur 2-21 days after vaccination in booster-dose HDCV recipients. This complication is less common after PCECV (vaccine prepared from chick embryo) and RVA (adsorbed rabies vaccine).
• In cases with severe allergic reaction after HDCV vaccine, PCEC vaccine should be administered with the same dose schedule.
Pre-exposure prophylaxis
• For this purpose, 3 doses are administered on the 0th, 7th, and 21st or 28th days (veterinarians and people at high risk of contact with rabid animals). Booster is recommended 2 years after vaccination.
VARCELLA VACCINE
• Varicella zoster virus (VZV) is the causative agent of herpes zoster, also known as chickenpox and shingles. The vaccine contains OKA strain, neomycin and gelatin.
• Varicella vaccine is a live vaccine. 0.5 ml is administered subcutaneously or intramuscularly to the deltoid region.
• A total of 2 doses are recommended as 1st dose at 12 months of age and booster between 4-6 years of age.
• 2 doses are applied at intervals of 4-8 weeks over the age of 12.
Post-contact precautions
• Vaccination of children 12 months and older and susceptible adults within the first 3-5 days after encountering a sick individual may prevent the development of the disease.
Varicella-zoster immunoglobulin (VZIG), which is obtained from plasma and contains at least 10 times more antibodies to the virus than normal immunoglobulin, can prevent chickenpox if administered within the first 96 hours after exposure. It is the first choice for under 1 year old and immunocompromised contacts.
• In cases where VZIG cannot be found, standard intravenous immunoglobulin can be administered.
• Although there are no side effects reported with the use of salicylate after varicella vaccination, it is recommended not to use salicylate for 6 weeks after vaccination, since there is a relationship between aspirin use after varicella and Reye's syndrome.
Complications
• Anaphylaxis
• Ataxia
• Stevens-Johnson syndrome
• Thrombocytopenia
• Neuropathy
• Encephalitis
• Erythema-multiforme
• pneumonia
• Convulsion
INFLUENZA VACCINE
• Influenza is a disease characterized by sudden fever, chills, headache, weakness, widespread myalgia and dry cough. In the following days, sore throat, nasal congestion and cough become evident. The most important finding is myositis, which causes leg pain and difficulty in walking, especially after throat infection.
• Influenza viruses are RNA viruses that are in the group of orthomyxoviruses and are divided into four different antigenic types called A, B, C, D according to the antigenic properties of their internal proteins.
Structures that are important in typing the virus are the glycoproteins hemagglutinin (HA or H) and neuraminidase (NA and N). As a result of these different HA and NA structures coming together, different combinations of virus types emerge.
Inactivated influenza vaccine:
Inactivated influenza vaccines
• Triple (Trivalan) (IIV3)
• It is available as a quartet (Tet ravalan) (IIV4).
In triple influenza vaccines
1. A/Michigan/45/2015 (HlNl) pdm09-like virus,
2. Virus like A/Singapore/INFIMH-16-0019/2016 (H3N2)
3. Virus like B/Colorado/06/2017 (Victoria strain) is found.
Quadruple influenza vaccines contain, in addition to these three virus strains, an influenza Head virus, Phuket/3073/2013-like virus (Yamagata strain).
The optimal time to give the vaccine is between October and November. Children under the age of 9 who will be vaccinated for the first time are recommended a second dose 1 month later.
Children aged 6-35 months are given a half dose of vaccine to the anterolateral region of the thigh, and a full dose from 36 months of age. In the second and fourth months after vaccination, antibodies reach their highest level and then decrease in a short time.
Live cold-adapted attenuated influenza vaccine:
Live attenuated influenza vaccine is administered between the ages of 2 and 49. It is a large particulate aerosol and is administered intranasally. Unlike the inactivated vaccine, protective immunoglobulin A is formed. The goal of the vaccine is to generate high levels of secretory and local antibodies. Since it is a live attenuated vaccine, it may produce mild influenza-like symptoms after vaccination.
HEPATITIS B VACCINE
• Today, the vaccine produced with the recombinant ONA technique is used.
• In the vaccination calendar applied in our country, 0, 1, 6 months are applied.
• The vaccine is administered intramuscularly to the anterolateral region of the thigh in infants, and to the deltoid region in older children and adults.
• There is no need to do a pre-vaccine screening test for children and young people in our country. Studies have shown that even if the antibody titer decreases over time, the immune memory formed by the vaccine administered as 3 doses is effective for at least 15 years in protection from acute and chronic HBV infection. When HBV is encountered again, immunological memory can provide protection with anamnestic antibody response.
• Depending on genetic factors and T helper cell dysfunction, 5-10% of healthy individuals may not have an antibody response after primary vaccination. Obesity, chronic diseases, immunosuppression, male gender, smoking, old age, errors in vaccine storage and administration, and unresponsiveness to the vaccine may be related. An additional 3-dose schedule should be re-administered to those who do not develop an antibody response to the vaccine.
• After the second 3 doses of vaccination, antibodies are formed in 30-50% of them. If there is no response after the second series, they may not respond to another dose of vaccine, and in case of encountering hepatitis, these people should be protected with hepatitis B immunoglobulin.
• Anti-HBs >10 mIU/mL is the protective titer.
• If there is a delay in the applied scheme, no additional dose is required.
• Hepatitis B vaccine can be administered together with other vaccines.
• Pregnant and nursing mothers can be vaccinated.
• If the mother is negative for HBsAg, vaccination should be started when the chronological age of babies is 1 month and under 2000 g or above 2000 g.
When the baby is 1 month old, the 1st dose should be given even if it is <2000 grams.
• Premature and low birth weight patients who are in good health and weigh more than 2000 g can be vaccinated upon discharge from the hospital.
Perinatal transition
• All infants born to HBsAg positive mothers should be administered HBIG with hepatitis B vaccine within 12-24 hours after birth, and then the vaccine series doses should be completed.
If the baby of the antigen positive mother weighs less than 2000 g at birth, the first vaccine administered should not be taken into account, and 3 doses should be completed with a new vaccine administered when the baby is over 2000 grams or 1 month old, whichever is earlier.
• If the hepatitis B serology in the mother cannot be learned within 12 hours after birth, the vaccine and HBIG should be administered to preterm babies under 2000 g. Babies over 2000 g should be vaccinated within 12 hours, but serology results can be expected up to 7 days for HBIG administration.
• Between 9-18 months, hepatitis B serology is checked.
parenteral transmission
• In the first 24 hours, HBIG should be given at the same time as the vaccine or within 24 hours.
Infection of skin and mucous membranes
• Vaccine and hepatitis B immunoglobulin should be administered within the first 48 hours.
transmitted by sexual contact
• Vaccine and hepatitis B immunoglobulin should be administered within 14 days.
HEPATITIS A VACCINE
• Hepatitis A is transmitted from person to person mainly by fecal-oral route and domestic transmission. It can also be transmitted through sexual contact and through food and food-touching hands.
• Most infants born to anti-HAV positive mothers can retain their passively acquired antibodies for up to 12-15 months, but after this age the antibodies passed from the mother disappear.
• The vaccine is a formaldehyde inactivated vaccine passaged in human diploid cells.
• Hepatitis A vaccine is recommended for all children from 12 months of age in the US routine immunization schedule today.
• In our country, the vaccine is in the routine vaccination schedule and is administered as 2 doses in the 18th and 24th months.
• Since there is no live vaccine, it can be used in pregnant women.
• It is not contraindicated in HIV positive and immunocompromised persons, but these individuals have a lower response to the vaccine.
• Pre-vaccination serological testing is not recommended in children.
Groups recommended to be vaccinated against hepatitis A
• Chronic liver disease
• Those awaiting liver transplantation
• Health personnel
• homosexuals
• Those who have parenteral drug habits
• Those staying and working in nursing homes
• Patients with coagulation disorders (hemophilia patients)
• Those who have close contact with acute hepatitis A patients • Those who work in the food industry
• Travelers to regions with high rates of HAV infection (Africa, Central/South America, Asia, Middle East, Russia)
Post-infection prevention
• Within 2 weeks of encountering the infection;
- 1-40 years old:
• HA vaccine to healthy individuals
• Those with immunodeficiency or chronic liver disease: HA vaccine + HAig should be administered.
- If <1 year and >40 years old: 0.02-0.12 ml/kg IM HAig is performed.
ROTAVIRUS VACCINES
• Rotavirus is the most common cause of gastroenteritis among children worldwide. Rotavirus infections are more severe especially in children aged 3-24 months and may cause mortality. Rotavirus does not infect blood and other organs other than the small intestine.
• There is no specific drug treatment for rotavirus infections. Treatment and supportive treatment of complications secondary to gastroenteritis are important. Immunity to rotavirus natural infection is incomplete. There may be reinfections. The protection provided by IgA and IgG type antibodies formed in the intestinal mucosa after rotavirus, natural and vaccine-related infections may continue for a while, and as an anamnestic response during reinfection, a rapid antibody increase occurs, resulting in a milder or subclinical course of the newly developed infection.
• Rotavirus vaccines are live attenuated human virus vaccines. As with natural infection, it may not prevent reinfections in vaccinated individuals; but it makes it easier to pass and it is protective from severe rotavirus acute gastroenteritis. The first rotavirus vaccine was withdrawn from use in 1999 because it caused cases of intussusception. It is recommended that the first dose be administered before 3 months in the new rotavirus vaccine schemes currently used, since 80% of the patients who developed intussusception in this vaccine received the first dose after 3 months.
Rotavirus oral vaccine administration
• Rotavirus vaccines are given as 1-2 ml orally and in 2 or 3 doses at 1-2 months (4-8 weeks) intervals.
• If possible, the first dose of vaccine should be started before 3 months (12 weeks) (can be done at the latest 14 weeks and 6 days old) and vaccination should be completed before 8 months (32 weeks).
Rotarix (monovalent)
• The vaccine can be administered after 6 weeks. A total of 2 doses are given.
RotaTeq (pentavalent)
• The vaccine is administered in three doses.
• Since it is a live vaccine, all contraindications of live vaccines also apply to rotavirus vaccines.
• Mild infection, non-immunosuppressive drug intake, convalescence period, breastfeeding do not constitute a contraindication to the vaccine.
• It is appropriate to vaccinate babies with acute gastroenteritis, but if there is severe diarrhea, the vaccine may be delayed. • Babies with immunodeficiency or immunosuppressive therapy at home or who are pregnant can be vaccinated. In such cases, it is helpful to apply rigorous hand washing precautions for up to a week after vaccination.
• Clinically stable premature infants exceeding 6 weeks can be vaccinated at or after discharge from the hospital.
• The vaccine is not administered to adults and it is not recommended to be administered to pregnant women.
• The vaccine does not interact with food and can be administered simultaneously with other routine vaccines without causing a problem.
• The vaccine is generally accepted as safe and has side effects such as restlessness, loss of appetite, fever, vomiting and diarrhea up to 20%.
HUMAN PAPILLOMAVIRUS VACCINE
• Cervical cancers are the second most common cancer in women in the world.
• HPV-16 genotype is responsible for 60% of all cases and HPV-18 for 10%.
• HPV 6 and HPV 11 genotypes are low-risk, and more than 90% of genital warts are caused by these types.
• It should be routinely applied in cases of HIV infection and other immunodeficiency, and those with a history of sexual abuse.
Human Papillomavirus Vaccines
• It is an inactivated vaccine prepared from non-infectious capsid proteins. Each HPV vaccine contains at least 2 capsid proteins: L1 and L2. L1 protein contains virus like proteins (VLP). VLPs form the basic structure of the vaccine.
• Nine vaccines are recommended for girls and quadruple vaccines are recommended for boys.
Quadruple vaccine
• In addition to HPV-16 and HPV-18, it also provides protection against non-oncogenic HPV-6 and 11 types that cause condyloma. It is used as three doses, 0, 2, and 6 months.
• HPV vaccines are most effective when given to adolescent or preadolescent girls who have not started sexual activity.
• 12 years is the appropriate age for vaccination. 3 doses are required within 6 months. Vaccination of a sexually active woman is also effective if the individual has not been exposed to the virus before.
• Quadrivalent vaccine licensed for ages 9-26.
Nine vaccine
• Nine vaccines, in which five carcinogenic serotypes are added to the quadruple vaccine, have been put into use.
• 2 doses (0, 6 months) between the ages of 9-14, 3 doses (0, 2, 6 months) for those over 15 years of age or those with immunodeficiency.
VACCINATION IN SPECIAL SITUATIONS
Vaccination of premature and low birth weight infants
• Vaccination in premature babies should be done by considering the chronological age, like term babies. The only vaccine that needs to be changed in the vaccination calendar is the hepatitis B vaccine, it is recommended to be given in the 1st month or over 2000 g.
• Children with very low weight or born before 29 weeks of age should be administered by reducing or dividing the doses of vaccines, although there are no side effects, and vaccines should be administered in accordance with the normal vaccination schedule.
• While in the hospital, the oral polio vaccine should not be given until discharge to prevent transmission to other infants, even if the child is eligible.
Immunization of adolescents
• The vaccination history of children at this age should be reviewed starting from the primary school period, and missing vaccinations should be completed.
• If the chickenpox vaccine is administered for the first time after the age of 12, it should be known that it will be administered twice with an interval of 1 month.
• Influenza vaccine is given once for the first time to those over 8 years old.
• Tetanus vaccine should be repeated every 10 years, especially girls should be vaccinated against measles-rubella-mumps (MMR) twice. Adult-type diphtheriatanosis (dT) vaccine should be administered to adolescents.
• Adolescent pregnant women 27-36 of each pregnancy. A single dose of Tdap should be administered between weeks.
IMMUNIZATION OF CHILDREN WHO HAVE A BLOOD PRODUCT AND IMMUNGLOBULIN
• The response in inactivated vaccines is not affected by antibodies in the blood. Therefore, vaccine and immunoglobulin (Ig) can be administered simultaneously in hepatitis B, rabies and tetanus prophylaxis.
• Immunoglobulins can reduce the effectiveness of measles and varicella vaccines. Therefore, Igs should be administered at least 2 weeks after measles vaccination.
• If immunoglobulin therapy was administered within 14 days of the live vaccine, the last vaccine dose should be repeated.
• If Ig has been administered, but MMR vaccination is due or planned, MMR vaccination should be delayed for 3-11 months (average 9 months) depending on the amount of Ig administered.
• Immunoglobulin does not affect the immune response to rotavirus and live influenza vaccines.
Time to delay measles vaccination after immunoglobulin administration (months)
Tetanus lg (TIG) --------------------------------------------- -------------------3
Hepatitis A and B lg (HAIG-HBIG) -------------------------------------- 3
Rabies LG (RIG) --------------------------------------------- ------------- 4
Varicella lg (VZIG) --------------------------------------------- ------ 5
RSV lg (Palivisumab) --------------------------------------------- 0
CMV lg ---------------------------------------------------------- 6
Washed erythrocyte suspension --------------------------- 0
Erythrocyte suspension ---------------------------- 3-5
Whole blood -------- ----------------------- 6
Plasma or platelet ------------------------- 7
IYIG therapy (300-400 mg/kg) --------- 8
IYIG > 1600 mg/kg ------------------- 11
Immunization after malignancy treatment and bone marrow transplant
• Live vaccines can be administered at least 3 months after the end of treatment in children receiving leukemia-lymphoma treatment.
• Live vaccines can be administered at least 2 years after transplantation in children with bone marrow/stem cell/organ transplants.
Vaccination of children with a history of allergies
• Gelatin is used as a stabilizer in single MMR and varicella vaccines. Studies have shown that anaphylaxis develops when the same type of vaccine is administered again in the presence of increased anti-gelatin IgE antibodies due to the previous vaccine.
• Since there is no penicillin in any vaccine, there is no problem in those with penicillin allergy; Since neomycin is found in MMR and varicella vaccines, this vaccine should not be given to those who have anaphylaxis to this drug.
• Those with egg allergy:
- MMR vaccine can be given.
- Influenza can be made (must be prepared for allergic reaction intervention conditions)
- Yellow fever vaccine is contraindicated (desensitization can be done)
Vaccination of children with hemophilia
• Due to the risk of hematoma during the vaccination of these children, intramuscular vaccines must be given subcutaneously or intradermally.
Vaccination of pregnant women
• The mother should be vaccinated in the 2nd or even 3rd trimester to minimize the possible teratogenic effect on the baby.
• Since influenza disease can cause problems during pregnancy, it can be done from the 14th week when the season comes.
• Pneumococcal vaccine is only recommended if there is a high risk.
• MMR and varicella vaccines are very risky shortly before conception and in the first 3 months of pregnancy. It has recently been reported that the interval between a mother's vaccination and conception should be at least 28 days.
• Pregnant women 27-36 of each pregnancy. A single dose of Tdap should be administered between weeks.
• There is no harm in administering inactivated or dead vaccines to pregnant women.
• Rabies vaccination can be given at any time due to the bite.
• Administration of immunoglobulin during pregnancy has no side effects for the baby and the pregnant woman, and it can be done easily.
• All other children of a pregnant or nursing mother can be vaccinated.
• Yellow fever vaccine is the only live vaccine that can be given to pregnant women.
Vaccination of immunocompromised children
• All inactivated and toxoid vaccines can be easily administered to children with such problems.
• Oral polio vaccine should not be given to healthy children living in the same house with children with congenital immunodeficiency due to the risk of transmission.
• All live vaccines except MMR and varicella are contraindicated in severe antibody deficiencies (Bruton or variable immunodeficiency).
• In mild antibody deficiencies (selective IgA deficiency and IgG subgroup deficiencies): OPV, BCG and yellow fever vaccines are contraindicated. Live influenza, live typhoid, MMR and varicella vaccines can be given.
• All live vaccines are contraindicated in T cell deficiencies.
• In cases of phagocyte dysfunction, all vaccines can be administered, except for BCG, Salmonella and other newly produced live bacterial vaccines.
• Live influenza vaccine is contraindicated in patients with chronic renal failure or asplenic patients.
• All vaccines, including live virus vaccines, can be administered in complement deficiencies.
Vaccination in HIV (+) Patients
Recommended
• DTaB • Hepatitis B
• Hib
• IPV
• MMR and Varicella (recommended in asymptomatic HIV (+) patients. Contraindicated if severely immunosuppressed and severely symptomatic)
• Pneumococcus, meningococcus
• HepatitisA
• Inactive Influenza
• Rotavirus
Contraindicated ones
• BCG (in countries where tuberculosis is common, vaccination is recommended if asymptomatic HIV (+))
• yellow fever
• OPV
• Live Influenza
• MMR and Varicella (moderate-severe symptomatic HIV (+)
• If the CD4+ T lymphocyte count is >15% in HIV (+) children, varicella and measles vaccines can be administered.
Vaccination of children receiving corticosteroid therapy
• If prednisone is low dose (<2 mg/kg/day or <20 mg/day in children > 10 kg), live vaccines can be given while on steroid therapy.
• If children are receiving prednisone >2 mg/kg/day or > 20 mg/day (children > 10 kg) and are receiving this treatment for more than 14 days, live vaccines can be given 1 month after steroid withdrawal.
• If he has taken this dose for less than 14 days, a live vaccine can be given as soon as the steroid treatment is finished.
Vaccine administration times and brief general information
Hepatitis B vaccine (minimum age; birth)
- If the mother is HBsAg (+), administer Hepatitis B vaccine and HBig within 12 hours after birth.
- If the mother's hepatitis B status is unknown, administer the hepatitis B vaccine within 12 hours. Check the mother's HBsAg and if HBsAg (+) apply HBig.
- Subsequently, the second dose should be administered in the 1st or 2nd month, and the 3rd dose in the 6th month. The third dose should not be given before the 24th week.
Rotavirus vaccine (minimum age; 6 weeks)
- First dose 6-14. apply per week (maximum age-14 weeks 6 days).
- Children older than 15 weeks should not be vaccinated.
- The last dose should be completed before 32 weeks.
DTaB vaccine (minimum age; 6 weeks)
- The 4th dose should be completed at least 6 months after the 3rd dose and before the 12th month.
Haemophilus influenzae Type B conjugate vaccine (minimum age; 6 weeks)
Pneumococcal vaccine (minimum age; 6 weeks for conjugate vaccine, 2 years for polysaccharide vaccine) Inactivated poliovirus vaccine (minimum age; 6 weeks)
- If 4 or more doses were administered before 4 years of age, an additional dose should be given at 4-6 years of age and there should be at least 6 months of the last dose.
Influenza vaccine (minimum age; 6 months for trivalent inactivated influenza vaccine, 2 years for live attenuated influenza vaccine)
- If children aged 6 months to 8 years are vaccinated for the first time, 2 doses should be administered 4 weeks apart.
Measles-Rubella-Mumps vaccine (minimum age; 12 months)
- It can be done from 6 months in cases of measles epidemic.
- The second dose should be administered at least 4 weeks after the last dose and before the age of 4 years.
Varicella vaccine (minimum age; 12 months)
- In children aged 12 months to 12 years, 2 doses should be administered and the interval between doses should be at least 3 months.
Hepatitis A vaccine (minimum age; 12 months)
- In our country, 2 doses should be administered at 6-month intervals at the 18th and 24th months.
