Theme 3

Theme 3.

ACTIVE IMMUNIZATION OF CHILDREN. THE VALUE OF VACCINATION FOR THE PREVENTION OF INFECTIOUS DISEASES. POST-VACCINATION COMPLICATIONS AND THEIR PREVENTION. PREVENTING THE MOST COMMON RESPIRATORY DISEASES AND TUBERCULOSIS. TUBERCULINDIAGNOSIS.

 

Protection from infectious diseases is referred to immunity. Thats why immune prophylaxis is the most potential method of infectious diseases prevention. World experience shows that potential risk of post immunization reactions and complications is very low. And risk of infectious diseases complications and mortality really overweight them. Ambulatory pediatrician plays the main role in immune prophylaxis program. Organization of immune prophylaxis is the main prophylactic work of the ambulatory medical staff.

 The immunoprophylaxis task is management by immunological answer to prevent the disease beside separate persons and groups of the population.

 The ways of the immunoprophylaxis:

Active - stimulation of own antibodies production,

Passive - introduction of ready antibodies.

 Vaccines preparations characteristic

1.     Vaccines, which include complete killed microorganisms (pertussis, typhoid, cholera) or inactivated viruses (influenza, poliomyelitis Salk vaccine)

2.     Anatoxins, which contains inactivated toxin of the bacteria (diphtheria, tetanus)

3.     The vaccines from alive attenuated viruses (measles, mumps and others.)

4.     Vaccines, which contains crossing alive microorganisms (BCG)

5.     Chemical vaccines from fraction of killed microorganisms (pneumococcal, meningococcal)

6.     Gene-engineering recombinant, chemical synthesized (hepatitis , influenza)

7.     Associated (in composition of which enters several vaccines)

 Composition of vaccines:

1. Active or immunizing antigens

2. Fluid base

3. Preservatives, stabilizers, antibiotics

4. Auxiliary facilities

 Ways of the vaccination

1. Intramuscular (DTP, DT, DT-M, antirhabic, meningococcal B)

2. Subcutaneous (measles, mumps, rubella, meningococcal A+C)

3. Intracutaneous (BCG)

4. On skin (plague, tularemia, brucellosis)

5. Peroral (poliomyelitis)

6. Intranasal (Influenza, inactivated)

Ukrainian Immunization Schedule

The Calendar of preventive vaccinations in Ukraine (hereinafter - Calendar) includes four sections: vaccination by the age, vaccination by the health, vaccination, conducted in endemic and enzootic areas and the epidemic evidences for recommended vaccinations.

 

Section 1. Vaccination by the Age

Age

Vaccination for prevention

 

Notes

1day

 

Hepatitis 2

 

 

 

 

 

3-7 days

Tuberculosis1

 

 

 

 

 

 

1 mo.

 

Hepatitis 2

 

 

 

 

 

3 mo.

 

 

Diphtheria, tetanus, pertussis3

Poliomyelitis4,
IPV

Hemophilus influenza infection5

 

By DTaP vaccine for children with a high risk of postvaccinal complications

4 mo.

 

 

Diphtheria, tetanus, pertussis3

Poliomyelitis4,
IPV

Hemophilus influenza infection5

 

By DTaP vaccine for children with a high risk of postvaccinal complications

5 mo.

 

 

Diphtheria, tetanus, pertussis3

Poliomyelitis4,
OPV

Hemophilus influenza infection5

 

By DTaP vaccine for children with a high risk of postvaccinal complications

6 mo.

 

Hepatitis 2

 

 

 

 

 

12mo.

 

 

 

 

 

Mumps, measles, rubella6

 

18 mo.

 

 

Diphtheria, tetanus, pertussis3 ,
By aDTP vaccine

Poliomyelitis4,
OPV

 

 

 

6 years

 

 

Diphtheria, tetanus3

Poliomyelitis4,
OPV

 

Mumps, measles, rubella6

 

7 years

Tuberculosis1

 

 

 

 

 

 

14 years

 

 

Diphtheria, tetanus3

Poliomyelitis4,
OPV

 

 

 

15 years

 

 

 

 

 

Rubella
(
girls),
Mumps
(
boys)6

 

18 years

 

 

Diphtheria, tetanus3

 

 

 

 

Adults

 

 

Diphtheria, tetanus3

 

 

 

 

 1 Vaccines are injected to all newborns, which has no contraindications. Immunization is done by a vaccine to prevent tuberculosis (hereinafter - the BCG). For vaccination of premature infants weighing ≥ 2000 g should be used TB vaccine with reduced antigen content (hereinafter - the BCG-M).

  http://intranet.tdmu.edu.ua/data/kafedra/internal/distance/classes_stud/English/2%20course/Community%20Health%20and%20Community%20Nursing/Lesson%2003.files/image002.jpg

 

http://intranet.tdmu.edu.ua/data/kafedra/internal/distance/classes_stud/English/2%20course/Community%20Health%20and%20Community%20Nursing/Lesson%2003.files/image004.jpg

 

Vaccination for tuberculosis prevention could not be done in the same day with other vaccines or other parenteral manipulations.

Children, who were not vaccinated in the maternity hospital for any reason, need to be vaccinated in children's ambulatory departments. For vaccination of children not immunized in the maternity hospital because of medical contraindications BCG-M or half-dose of BCG vaccine must be injected.

 

http://intranet.tdmu.edu.ua/data/kafedra/internal/distance/classes_stud/English/2%20course/Community%20Health%20and%20Community%20Nursing/Lesson%2003.files/image006.jpg

 

If the child is not vaccinated in the maternity hospital because of no medical contraindications, BCG vaccine is used. Children who are under 2 months dont need Mantoux test before vaccination against TB. Mantoux test before vaccination against TB should be done for babies elder than 2 months. A negative test result allows making vaccination.

Tuberculin is a glycerol extract of the tubercle bacillus. Purified protein derivative (PPD) tuberculin is a precipitate of non-species-specific molecules obtained from filtrates of sterilized, concentrated cultures. It was first described by Robert Koch in 1890. The test is named after Charles Mantoux, a French physician who built on the work of Koch and Clemens von Pirquet to create his test in 1907.

http://intranet.tdmu.edu.ua/data/kafedra/internal/distance/classes_stud/English/2%20course/Community%20Health%20and%20Community%20Nursing/Lesson%2003.files/image007.jpg

The tuberculosis skin test is a test used to determine if someone has developed an immune response to the bacterium that causes tuberculosis (TB). This response can occur if someone currently has TB, if they were exposed to it in the past, or if they received the BCG vaccine against TB (which is not performed in the U.S.). The World Health Organization estimates that 2 billion people worldwide have latent TB, while around 3 million people worldwide die of TB each year. The tuberculosis skin test is also known as the tuberculin test or PPD test.

The tuberculin skin test is based on the fact that infection with M. tuberculosis bacterium produces a delayed-type hypersensitivity skin reaction to certain components of the bacterium. The components of the organism are contained in extracts of culture filtrates and are the core elements of the classic tuberculin PPD (also known as purified protein derivative). This PPD material is used for skin testing for tuberculosis. Reaction in the skin to tuberculin PPD begins when specialized immune cells, called T cells, which have been sensitized by prior infection, are recruited by the immune system to the skin site where they release chemical messengers called lymphokines. These lymphokines induce induration (a hard, raised area with clearly defined margins at and around the injection site) through local vasodilation (expansion of the diameter of blood vessels) leading to fluid deposition known as edema, fibrin deposition, and recruitment of other types of inflammatory cells to the area.

 Children exposed to someone with tuberculosis will likely develop a positive tuberculin skin test about 2-12 weeks later. Some children, especially with immune system problems, can have a negative tuberculin skin test and still be infected with tuberculosis.

 Most children with tuberculosis do not have symptoms. They have a positive PPD, a normal chest x-ray and no signs or symptoms of tuberculosis and are said to have a tuberculosis infection or a latent tuberculosis infection. Even though they do not have symptoms, people with a positive PPD need treatment, which usually consists of 9 months of isoniazid (INH). If the infection is thought to be resistant to isonizid, then rifampin may be used for 6 months.

 Children with symptoms of tuberculosis, a positive tuberculin skin test and/or a positive chest x-ray are said to have tuberculosis disease. This is more serious than just have a tuberculosis infection. If untreated, children with a tuberculosis infection can develop tuberculosis disease (usually within six months to two years), with symptoms including a cough, fever, night sweats, swollen glands, descreased appetite and activity, weight loss and difficulty breathing.

 In addition to the tuberculin skin test, children with tuberculosis disease should have additional testing to try and culture the tuberculosis bacteria so that it can be determined what drugs the infection is sensitive to. Because tuberculosis is a slow growing bacteria, culture can take as long as ten weeks for a final result. To obtain a culture, unless the child has a productive cough and can produce a sputum sample, cultures may need to be obtained from a gastric aspirate in the early morning. Children with tuberculosis disease should also be tested for HIV.

 In the lungs, tuberculosis causes the formation of cavitary lesions, pleural effusions and enlarged lymph nodes. These can usually be seen on a chest x-ray. In addition to the pulmonary symptoms described above, tuberculosis disease can also cause meningitis and infections of the ear, kidney, bones and joints.

 Indications for Testing

1. Routine skin testing is not recommended for children in areas of low TB prevalence

2. Children in areas with high prevalence of TB but with no other risk factors should be tested between the ages of 4-6 and 11-16

3. Immediate testing should be performed

a. Contact with individuals suspected of having TB or has an infiltrate consistent with TB on chest radiograph

b. Radiograph suspicious of TB

c. Children who have come from endemic countries (Asia, the Middle East, Africa, and Latin America)

d. Travel recently to a country where TB is endemic

4. Annual Testing

a. Child is HIV + or an HIV + individual lives in the house

b. Incarcerated adolescent

5. Testing every 2-3 years

a. On-going exposure to HIV + individuals, migrant workers, incarcerated individuals, nursing home residents, IV drug users, and homeless individuals.

6. Testing at 4-6 and 11-16 years of age

a. Children whose parents emigrated with unknown TST status from endemic areas

b. Children who have continued exposure by ravel to endemic areas, or household contact with people from endemic areas.

 

http://www.veoh.com/watch/yapi-bR86G-itrTQ?autoDownload=true&h1=TB+Skin+Test+-+Mantoux+Method

 

http://intranet.tdmu.edu.ua/data/kafedra/internal/distance/classes_stud/English/2%20course/Community%20Health%20and%20Community%20Nursing/Lesson%2003.files/image009.jpg

"Lemon peel" after the injection of tuberculin

 Interpretation of PPD

1. The test must be interpreted between 48-72 hours by an individual trained in evaluating PPD's. Studies have shown that parental interpretation of PPD's have been inaccurate and almost 60% of PPD's placed are never read.

2. The interpretation is based on the size of induration, not redness.

3. A thorough history of the child, family members, other household members, and prevalence in the community is important in the interpretation of the test.

 

Positive Tests: only the induration should be measured without erythema.

 

 

Positive Mantoux test

 > 5 mm

1. Children in close contact with a known or suspected person with active TB.

2. Children suspected to have TB

a. + chest radiograph consistent with active disease or previously active disease

b. Clinically picture consistent with TB, i.e. meningitis, pleural effusion, TB pericarditis, lymphadenopathy/scrofula, Potts disease.

3, Immunocompromised individuals i.e. children on immunosuppresive drugs including high doses of steroids, HIV + patients, , or those with other immunosuppressed states

 > 10 mm

1. < 4 years old

2. Diabetics, chronic renal disease, malnourished individuals, lymphoma, and Hodgkin's disease

3. Child or their parents are born in endemic areas

4. Exposure to HIV+ individuals, incarcerated or institutionalized persons, IV drug users, nursing home residents, healthcare workers, and migrant workers.

5. Travel to endemic areas ( Africa, Southeast Asia, Western Pacific)

> 15 mm

1. > 4 years old without any risk factors

False Positives

1. Improper application of the test

2. Cross reactivity with non-tuberculosis mycobacterium

False Negatives

1. Within the incubation period of developing TB, 2-12 weeks

2. Incorrect interpretation

3. Disseminated disease

4. Viral illness- measles, chicken pox, influenza, HIV

5. T cell disease

6. Steroids

7. Malnutrition

8. Chronic illnesses

9. 5% of culture proven TB will have negative PPD. A negative PPD never excludes TB

  

Booster (revaccination) by BCG is given to children aged 7 years with negative Mantoux test.

 In the absence of vaccination (BCG) navel children with negative Mantoux test should have additional vaccine 2 years after vaccination.

Mantoux test is done with 2 tuberculin unites (TU). Due to the fact that preventive vaccination may affect the sensitivity to tuberculin, thats why Mantoux test needs to be planned before preventive vaccination. In the other case Mantoux test should be done no earlier than 1 month after vaccination.

 

  Immunization by monovalent hepatitis B vaccine is done to all newborns.

If mother of a newborn is HBsAg "-" (negative), which is documented, the child may begin vaccination during the first months of life, or combined with vaccination against pertussis, diphtheria, tetanus, polio. In the case of immunization with a combination of vaccination against pertussis, diphtheria, tetanus, polio recommended scheme: 3-4-5-18 months, or: 3-4-9 months.

        Newborns weighing <2000 g born by HBsAg negative mothers, vaccination is done when the childs weight will be 2000 g or at the age of 1 month.

        If the newborn child is in critical condition, the child immunization should be done when he will better before hospital discharge.

Vaccination against viral hepatitis B of newborns, whose mothers are carriers of HBsAg, is necessary to do by the accelerated scheme: 0-1-2 and 12 months (0 - date of first vaccination at birth, the minimum interval between the first, second and third vaccine 1 month, third and fourth vaccine - 10 months). The first dose is entered in the first 12 hours of a child's life regardless of body weight. If there is a specific immunoglobulin against hepatitis B with vaccine in other parts of the body is entered a specific immunoglobulin 40 IU / kg body weight, but not less than 100 IU, in this case vaccination may be used for pattern: 0-1-6 months. If the weight of a newborn child less than 2000 grams, vaccination is required, but this dose is not count as a dose of primary immunization; when the child reaches the age of 1 month a series of three doses of vaccine should be done 0-1-6 (0 - date of first vaccination, the minimum interval between the first and second vaccine - 1 month, second and third vaccine - 5 months).

 

 

If mothers HBsAg status is unknown, child requires vaccination in the first 12 hours of life, while the HbsAg status of mother is researched. If a result is positive a newborn baby is vaccinated as a newborn of HBsAg "+" mother.

For vaccination of children and adults against hepatitis B outside the vaccinations calendar a scheme 0, 1, 6 months is recommended.

Do not start the vaccination series, if the dose was omitted, no matter how much time has passed. You must enter a doze, for missing the schedule with the minimum spacing (see section 1.2 "Vaccination of children in violation of the calendar).

 3 Vaccinations for the prevention of diphtheria, tetanus and pertussis in the age 3, 4 and 5 months by diphtheria-tetanus-pertussis vaccine (hereinafter - DTP), or vaccine with acellular pertussis component (hereinafter - DTaP). The interval between the first and second, second and third vaccination is 30 days. The interval between the third and fourth vaccination should be not less than 12 months.

 

The first booster at 18 months is done by DTaP.

DTaP is used for further inoculations for children who have had previous complications after DTP vaccination, and immunization for all children with high risk of complications. For the prevention of diphtheria, tetanus, pertussis, polio, hepatitis B and infections caused by bacteria Haemophilus influenza type b (hereinafter - Hib), you can use the combined vaccine (with variations of antigens combinations) that are registered in Ukraine.

 

 

Vaccination of children less than 4 years off the calendar dates should be done with such calculation, that the child will be managed to get DTP or DTaP immunization fourfold up to 3 years 11 months and 29 days.

For children who received primary vaccinal complex (in 3, 4, 5 and 18 months) DTaP or have received three doses DTaP and one DTP, revaccination in 6 and 14 years by diphtheria-tetanus-pertussis acellular vaccine with reduced antigen content (hereinafter - DTaP-M).

For children who received for primary vaccinal complex DTP or received two doses DTP and two doses DTaP the first vaccination against diphtheria and tetanus (6 years) by a diphtheria-tetanus toxoid (hereinafter - DT), second (in 14 years) and third (at 18) - by a diphtheria-tetanus toxoid with reduced antigen content (hereinafter - DT-M ). For children, vaccinated against tetanus because the injury by tetanus toxoid (hereinafter - T) over the past two years, a regular vaccination against diphtheria only with a reduced content of diphtheria antigen in diphtheria toxoid (hereinafter - D-M) should be done.

Children under 5 years 11 months 29 days, which had pertussis, receive DT. Vaccination is triple, interval between the first and second inoculation 30 days between the second and third - 9-12 months.

The first routine adult vaccination by age and epidsituation that were previously vaccinated should be made by DT-M at interval of 5 years after the last vaccination. Further routine vaccinations for adults by DT-M with a minimum 10 years interval from the previous vaccination.

Teenagers and adults who have not previously been vaccinated or do not have data on immunization, vaccination is triple by DT-M (interval between the first and second inoculation should be 30-45 days between the second and third - 6-12 months). Revaccination of those teenagers (who are vaccinated outside the scheme) with a minimum interval of 3 years after the last diphtheria and tetanus vaccination.

For active immunization against tetanus person elder than 60 years, not vaccinated last 10 years, a shortened vaccination scheme is used (single inoculation T-toxoid in double dose - 20 oz / ml, with a booster dose at 12 months - 10 oz / ml) and further every 10 years with no age restrictions.

Do not start the vaccination series, if the dose was omitted, no matter how much time has passed. You must enter a doze, missing the schedule, with a minimum spacing.

Because of possible postvaccinal reactions (after DTP-input), such as increased body temperature, which may lead to convulsions, recommend paracethamol in age doses within 1 day after vaccination.

 

4 Inactivated vaccine to prevent polio (hereinafter - IPV) is used for the first two immunizations, while the oral polio vaccine (hereafter - OPV) contraindications - for all these immunizations on the calendar.

 

OPV vaccine is used for 3 - 6th vaccination (third vaccination and age revaccination) with no contraindications to OPV.

 

 

 

After the OPV is proposed to restrict injections, parenteral intervention, routine operations for 40 days, exclude contact with HIV-infected.

Do not start the vaccination series, if the dose was omitted, no matter how much time has passed. Enter dose, which lacks the schedule, with minimum spacing.

 

5Vaccination to prevent Hib-infection can be done by mono- and combined vaccines containing Hib- components. In the case of Hib-vaccine and DTP-vaccine are from various manufacturers they should be inserted in different parts of the body. It is advisable to use combined Hib-vaccines for primary vaccination.

6 Vaccination to prevent measles, mumps and rubella by the combined vaccine (hereafter - MMR) at the age of 12 months. The second vaccine to prevent measles, mumps and rubella - in 6 years.

 

 

Kids who were not vaccinated against measles, mumps or rubella by age 12 months and 6 years, vaccination can begin at any age before 18 years. In this case, the child should receive 2 doses in compliance with the minimum spacing between them.

Children age 15 who received 1 or 2 vaccinations against measles, but not vaccinated against rubella and mumps and didnt ill with these infections, vaccinations against mumps (guys) or rubella (girls) is scheduled.

 

18 years or older who have not previously been vaccinated against these infections can be vaccinated with one dose of vaccine at age to 30 years.

Previous diseases as measles, mumps or rubella are not contraindications to vaccination by trivaccine. In a history of these two diseases, vaccination should be done by monovaccine against the infection, which the child was not ill before.

Women of childbearing age that were not sick and have not been vaccinated against rubella may receive vaccination at their own request in accordance with the instruction to vaccines.

 

1.2. Vaccination of children in violation of the calendar

In deciding on the vaccination of children in violation of the calendar, you should plan with the following minimum intervals.

 

For children from 4 months to 6 years 11 months 29 days

Vaccines

Minimal interval between doses

1st and 2nd doses

2nd and 3rd doses

 3rdand 4th doses

DTP, DTaP

1 month

1 month

12 months

DT

1 month

9 months

 

Polio vaccine

1 month

1 month

12 months

Hepatitis B vaccine

1 month

1 month

 

MMR

1 year

 

 

Hib - vaccine

4 weeks: if the first dose is introduced to 12 months.

8 weeks (as the last dose): if first dose is entered at the age of 12-14 months.

Do not put: if the first dose is entered in 15 months or later

4 weeks: if a second dose is introduced to 12 months.

8 weeks (as the last dose): if a child age 12 months or more and a second dose was put under 15 months.

Do not put: if the first dose is entered in 15 months or older

 

 

For children from 7 to 18 years

Minimal interval between doses

 

1st and 2nd doses

2nd and 3rd doses

 3rdand 4th doses

DT-

1 month

6-9 months

 

MMR

1 year

 

 

Hepatitis B vaccine

1 month

1 month

 

Polio vaccine

1 month

1 month

12 months

         When planning the application of certain vaccines or toxoids for prevention of various infectious diseases should observe the following features:

 

Combination of drugs for vaccination

Recommended intervals

>= 2 inactivated vaccines and / or toxoid

Vaccine could be introduced with time interval as in immunization Calendar

Living vaccines + inactivated vaccine or toxoids

>= 2 live vaccines for parenteral administration (except BCG)

Vaccines can be introduced simultaneously in different parts of the body or with an interval no less 1 month

BCG vaccine combination with other vaccines

BCG vaccine does not spend the same day with other vaccines.
Other preventive vaccination eligible taken at intervals not less than 2 months before or after vaccination with BCG vaccine (except hepatitis B vaccine)

 

If necessary, the doctor has the right to enter all vaccines, toxoids, which are shown on the plan (except BCG), per one visit, providing injections in different parts of the body. Otherwise, the doctor plans vaccination with the minimum intervals between vaccines, toxoids and their combination against various infectious diseases.

 

1.3. HIV / AIDS children Vaccination

Defining the situation

Vaccines

Holding vaccinations

 

A baby is born HIV-infected mother (Z20.6; R75) - child HIV status is not defined

OPV*, BCG, measles, mumps, rubella

Do not vaccine before HIV status

identifying

Inactivated vaccines, toxoids

By the calendar

 

Asymptomatic HIV carrier state (Z21) or with weakly expressed clinic (clinical stage I and II **) in the absence of immunosuppression (CD4 +> 25%) or with moderate immunosuppression (CD4 +> 15%)

OPV*, BCG,

Do not vaccine

Other vaccines, toxoids

By the calendar

 

Child AIDS (clinical stage III, stage II by WHO with severe immunosuppression (CD4 + <15%)

Do not vaccine

* OPV Vaccination is replaced with IPV throughout the calendar. OPV is not given to family members of HIV-positive person who cares for him.

** Classification of the World Health Organization (hereinafter - WHO)

 

1.     When vaccine vitamins that contain vitamin A should be administered.

2.     Vaccinations are carried out in outpatient or inpatient departments.

3.     A child patronage by medical workers on 3-4th and 10th-11th day of postvaccinal period should be done.

4.     Persons with HIV / AIDS passive immunization by immunoglobulin preparations because of epidemic is independent from previously held active immunization.

Persons with HIV / AIDS need to receive additional vaccinations as provided in Calendar section 2, "Vaccinations for health".

 

Section 2. Vaccinations for health

Vaccinations for health are required in the medical support of patients with high risk of infection and its possible severe course, against which vaccination by age is not provided in terms of vaccinations.

 

2.1. Vaccination scheme for children by health

Vaccination against

Vaccination scheme

Indications

Note

Flu

 

Annually. Permission for vaccination of children 6 - month old. The optimal time for vaccination is October-November.  

 

Children under the age of 9 years that had not received vaccination against influenza, vaccination is carried out with minimum 2 doses at intervals of 1 month.

HIV infection

See Calendar subsection 1.3

Immunization of HIV-infected Children and AIDS patients

 

Primary immunodeficiency (select IgA deficit , IgG subclasses deficiency, transient hypogammaglobulinemia, phagocytosis deficits, complement system deficits)

 

 

Chronic liver disease (including cirrhosis and fibrosis)

 

Bronchial asthma

 

Renal (chronic renal failure or nephrotic syndrome)

 

Chronic lung disease (birth abnormalities, acquired disease, cystic fibrosis)

 

Chronic lesions of the cardiovascular system (birth and acquired heart defects, cardiomyopathy)

 

Functional or Anatomic asplenia (including - sickle-cell anemia)

 

Transplantation of bone marrow

Vaccination is not earlier than 6 months after transplantation

 

Patients continued hold acetylsalicylic acid

 

Lymphoma

Multiple Myeloma

Leukemia

Vaccination is made not earlier than 3-4 weeks after

immunosuppressive therapy (chemotherapy) and the increase granulocytes and lymphocytes in peripheral blood > 1000 cells / mcl (> 1.0 *109 / l)

 

Staphylococcus pneumonia infection

Vaccination by unconjugated Polysaccharide vaccine patients 2 years or older, once (except for recipients of bone marrow) with the need to revaccination no earlier than 5 years

HIV infection

See Calendar subsection 1.3

"Immunization of HIV-infected Children and AIDS patients




Renal (chronic renal failure or nephrotic syndrome)

 

Primary immune deficiency - deficiency of complement system (early proteins - C1, C4, C2, C3), selective IgA deficiency

 

Bronchial asthma

Vaccine is carried out at PSV OFV1 or 80% of the required parameters, variability in performance or PSV OFV1 <20-30% with stable severe disease

Functional or anatomic asplenia (including sickle-cell anemia)

Vaccination 2 weeks before planned splenectomy. Otherwise the most earlier after it

Chronic liver disease (including cirrhosis and fibrosis)

 

Nasal liquorrea (chronic, remittent)

 

Diabetes type 1

 

Chronic lung disease (birth abnormalities, acquired disease, cystic fibrosis)

 

Tuberculosis (infected ILO)

 

Chronic lesions of the cardiovascular system (birth and acquired heart defects, cardiomyopathy)

 

Lymphoma

Multiple Myeloma

Leukemia

Hodgkin's disease

 


Vaccines are held 2 weeks prior to the immunosuppressive

therapy. Otherwise - 3 months after cessation of immunosuppressive therapy

Immunosuppressive hormone therapy (as defined. "List of Medical Contraindications to preventive vaccination" this order)

Vaccination is made 2 weeks before the beginning of immunosuppressive therapy or after its termination

Bone marrow transplantation

 

The optimal vaccination is at 12 and 24 months after transplant

Internal organs transplantation

Optimal vaccination 6 months after transplantation

Meningococcal infection

Persons older than 18 months are vaccinated only once

Functional or anatomic asplenia (including sickle-cell anemia)

 

Deficiency of complement system (early proteins - C1, C4, C2, C3, 5-9 ), properdyn, factor

 

Varicella zoster vaccine

Is made to persons over 12 months are vaccinated only once  

 

 

While vaccination persons older than 13 years - double with 4-weeks intervals

Chronic renal failure

 

 

HIV infection /AIDS

 

Vaccines are held at the level of CD4 + > 25% of the age range, CDC class N1 or A1, two doses with3 - month intervals

 

 

Transplantation of bone marrow

Vaccination is not earlier than 24 months and the absence of Immunosuppression (increased granulocytes and lymphocytes in peripheral blood > 1000 cells / mcl / > 1.0 *109 / l

 

Primary immunodeficiency without T-cell lesions

 

Hepatitis B

Vaccination of children not vaccinated before

Chronic liver damage (infectious and noninfectious genesis)

 

Transplantation

 

Children who are on hemodialysis

See subsection 2.2. Scheme vaccination hepatitis in children with malignant neoplasms, children are on hemodialysis and receiving long-term repeated blood transfusion

Children who receive long term repeated blood transfusion

 

Children who need a landmark surgery

 

Hepatitis

Is made to persons over 12 months of life double at intervals of 6 months

Chronic liver damage (infectious and noninfectious genesis)

 

Liver transplantation

Optimal to vaccinate before transplantation. Otherwise - best 6 months after transplantation

 

 

Influenza vaccine

 

 

Vaccine to prevent meningococcal infection

Varicella-Zoster vaccine

2.2. Hepatitis B vaccination scheme in children with malignant neoplasms, children that are on hemodialysis and receiving long-term repeated blood transfusion

Vaccination

Vaccination Term

Notes

The first

Begins at any age

Vaccination by a double dose of vaccine in an outpatient department

Or in a specialized department where the child receives the first course of treatment - if not vaccinated earlier.

Those HBsAg "+" (positive) are also subject to vaccination

 

The second

1 month after first vaccination

Third

1 month after the second vaccination

The fourth

6 months after the third vaccination

 

Section 3. Vaccines, held in endemic and enzootic areas and the epidemic evidences

 

Vaccines for the prevention

Vaccination Date

Revaccination Dates

Notes

Tularemia1

From 7 years

Every 5 years

Rroutine immunization for separate professional groups and those living in endemic regions

 

Brucellosis2

From 18 years of age

 

After 1 year

Anthrax3

From 14 to 60 years

After 1 year

Unscheduled Immunization is conducted by a territorial

authorities, local government and health service

Leptospirosis

From 7 years

After 1 year

Ku fever

From 14 years

According vaccine application instruction

Tick borne encephalitis

Since 4 years

Every year for three years

Plague

Since 2 years

According vaccine application instruction

Vaccination by the epidemiological evidences

Typhoid fever4

Since 7 years

Two years

Immunization is done in determining territory as unfavourable 2-3 months before epidemiological growth by a territoryChief Medical Officer

Influenza5

According vaccine application instruction

According vaccine application instruction

 

Yellow fever

Since 9 months

In 10 years

Immunization 10 days before traveling to countries endemic for this infection

Rabies6

When applying for medical assistance at the biting, scratches, salivation by animals ill or suspicious of rabies

According vaccine application instruction

Routine immunization of rabies risky individuals.

A course of vaccine and antirabic immunoglobulin

Diphtheria7

Vaccination by the epidemiological evidences

According vaccine application instruction

 

Tetanus

Vaccination by the epidemiological evidences

According vaccine application instruction

 

Hepatitis 8

Vaccination by the epidemiological evidences

According vaccine application instruction

 

Polio9

Vaccination by the epidemiological evidences

According vaccine application instruction

 

Measles10

Vaccination by the epidemiological evidences

According vaccine application instruction

 

Mumps10

Vaccination by the epidemiological evidences

According vaccine application instruction

 

Rubella10

Vaccination by the epidemiological evidences

According vaccine application instruction

 

Meningococcal infection11

Vaccination by the epidemiological evidences

According vaccine application instruction

 

Hepatitis 12

Vaccination by the epidemiological evidences

According vaccine application instruction

 

 

Vaccinations for:

1

        Personal of business items harvesting the industrial animal skin, their primary processing;

        Vegetable, grain, sugar mills, elevators workers;

        Hunters, forest guard, meliorators;

        Medical staff of the especially dangerous infections departments and laboratories, plague agencies that work with live tularemia cultures or infected material;

        Mills, feed mills, linen factories, enterprises processing agricultural products and raw materials of animal origin workers, who work with feed; shepherds, farmers, meliorators, geologists, builders who work in natural foci of tularemia;

        Others.

2

        Livestock farms workers, not prosperous for brucellosis, regardless of ownership;

        Meat workers, slaughter points and other enterprises on processing of raw materials and livestock products in the coming agricultural animals or raw materials originating from raising farms, not prosperous for brucellosis;

        Veterinary staff who work with live Brucella cultures or contaminated material, and serve economy not prosperous for brucellosis;

        Other categories of the population in case of trouble sustainable territories according to the decision of the territorial institutions of state sanitary-epidemiological service, emergency and preventive antiepizootic commissions.

3

        Employees of the especially dangerous infections laboratory departments of sanitary-epidemiological and veterinary laboratory workers who work with live anthrax cultures or infected material.

4

        Waterway and sewage networks employees;

        Others.

5

        Groups of medical risk (high chance of influenza clinical complications):

o       persons with chronic diseases (respiratory and cardiovascular system, kidneys, metabolism);

o       persons aged over 60 years;

o       persons who are in special groups (orphanages, homes for the elderly, children's homes, etc.).

        Epidemic risk groups (high possibility of influenza infection):

o       children of preschool age, children, adolescents, students of secondary and tertiary institutions;

o       healthcare personnel;

o       preschool staff, secondary and other schools, orphanages, childrens homes and homes for the elderly, etc.;

o       service sector workers, trade, transport, military, and persons who are in contact with many people;

o       personnel of enterprises, institutions and organizations (to prevent outbreaks).

6

        Employees of veterinary laboratories and clinics, hunters, veterinarians, dogs catchers, slaughter-houses workers;

        Person applying for medical help because the bites, scratches, salivation by ill or rabies suspected animals.

7

In case of diphtheria focus:

        Vaccination (after quarantine in this focus) persons not vaccinated against diphtheria (vaccination and the first booster vaccination according the age);

        Booster immunization according the calendar to individuals who are subject to re-vaccination in the current year;

        Supplementary immunization to persons vaccinated without scheme violating by one-dose D or D-M toxoid vaccination according the age, if the last vaccination for diphtheria has been more than a year.

8

With the epidemic rise:

        Children from 2 to 10 years living in endemic areas (average incidence of hepatitis A in the last 5 years higher than average incidence in Ukraine more than 2 times);

        In case of focus development contacts need to be vaccinated during the first week;

        Staff of the water treatment facilities, water mains, sewerage service and sewage treatment facilities;

        Persons involved in peacekeeping activities, humanitarian assistance, etc.;

        Travelers to regions with high hepatitis A.

9

        In case of importation of "wild" poliovirus to Ukraine.

10

        In case of measles, mumps or rubella focus vaccination in the first three days from the date of contact children over 1 year who were not ill these infections and were not vaccinated. Adults (before 30 years) if they were not ill these infections and were not vaccinated and revaccinated against them.

11

When epidemic rise of morbidity with generalized forms vaccination of:

        Persons living in endemic areas;

        In infection focus caused by appropriate serogroup of meningococcus.

12

        Medical staff, students of secondary and higher educational institutions that have professional contact with blood, its preparations and carry parenteral manipulations;

        Persons who have contact with hepatitis B patients;

        Recipients of donor blood and blood products;

        Children in the orphanages and child homes;

        Family members who have hepatitis B patients and hepatitis B virus carriers;

        Patients with chronic liver disease;

        Patients who are planned to the surgical intervention.

 

Section 4. Recommended vaccinations

 

Vaccines for the prevention

A high risk groups

Varicella zoster

- Healthy children who have reached 15 months of age and wasnt ill by chicken pox before;

- Children enrolling schools that have not been sick for varicella (according to documentation);

- Employees of health and education, with high risk of infection and not sick of chicken pox before

Hepatitis A

- Medical staff;

- Nurseries staff;

- The catering and food industry staff , which is involved in the preparation of (production), transportation and sales of food;

- Military personnel, firefighters, special services personnel (operational service);

- Personnel of water treatment facilities, water mains, sewerage service and sewage treatment facilities;

- Staff and patients of private institutions (psychiatric institutions, detention facilities for mentally retarded persons, etc.);

- Personnel and persons who are in penitentiary institutions;

- Students of medical schools;

- Persons who participate in peacekeeping activities, humanitarian assistance, etc.;

- Persons who use intravenous drugs, HIV-positive, individuals with venereal diseases;

- Persons living in endemic areas for hepatitis A;

- Persons traveling to regions with high hepatitis A level;

- Persons who have communicated with hepatitis A patients

Hepatitis B

- Soldiers, police, firefighters, social services personnel (operational service);

- Staff and patients of private institutions (psychiatric institutions, detention facilities for mentally retarded persons, etc.);

- Personnel and persons who are in penitentiary institutions;

- Staff of the service sector that may have contact with human biological fluids (hairdressers, the staff of beauty salons, masseurs, etc.) as well as those studying in these fields;

- Athletes;

- Persons who use intravenous drugs, HIV-positive, individuals with venereal diseases;

- Persons who frequently change sexual partners, prostitute, homosexual;

- Young people aged 20-40 years, especially women;

- Patients with chronic diseases and cancer, with chronic liver failure;

- Persons traveling to regions with high hepatitis B morbidity

Flu

- Soldiers, builders, workers of the State Automobile Inspection, etc.;

- People who care for flu patients at home;

- Pre-school children and students;

- Collectives of enterprises, institutions and organizations;

- Women who will likely be in the 2nd or 3 rd trimester of pregnancy during flu epidemic

Pneumococcal

infection

- Children older than 2 years;

- Adults with impaired immune status and the elderly, especially those living in boarding

 

Passive immunization is indicated

        To children with insufficient antibodies syntheses as a result of congenital or acquired cellular defects of -lymphocytes.

        At absence of vaccines against infection, when single way of protection is introduction of ready antibodies.

        If required immediate preventive maintenance of the disease for epidemiological causes (the contact with sick on measles, preventive maintenance of rabies, tetanus).

        For neutralization of the antigen-toxin by specific antitoxic antibodies.

        With medical purpose at the beginning of the diseases (at diphtheria, botulism, tetanus).

 

Vacinal process - is a change of homeostasis, which appears in organism in response to introduction of vaccinal preparation and include the complex of reactions to which belongs: formation of antibodies, adaptation and postvaccinal reactions, postvaccinal complications.

 

Vaccinal reactions appear in response to entering the vaccines, are characterized by appearance of clinical manifestations typical to this type of vaccine, which have a round-robin duration, are short, do not cause serious changes of vital activity in the organism.

 

List of the preventive vaccinations medical contraindications

 

Vaccine

Contraindications

All vaccines and toxoids

Severe complications from the previous dose in the form of anaphylactic shock.

Allergy to any vaccine component.

Progressive diseases of the nervous system, hydrocephalus in decompensation stage, epilepsy, epileptic syndrome with convulsions 2 times a month and more often.

Acute illness or chronic disease exacerbation

All live vaccines

Congenital combined immunodeficiency, primary hypogammaglobulinemia (entering the vaccine is not contraindicated in selective Ig A and Ig M immunodeficiency), transitional hypogammaglobulinemia and malignant tumors, pregnancy, AIDS, immune suppression therapy

BCG

baby weight less than 2000 g:

1500 - 1999 g vaccinations are not done up to 1 month.

1000 - 1499 g - up to 2 months.

Complicated reactions to previous vaccine (adenitis, cold abscess, skin ulcers over 10 mm in diameter, kelloid scar, osteomyelitis, generalized BCG infection).

Tubinfection.

Defects of phagocytosis

OPV

Children whom live vaccine is contraindicated, as well as to members of their families is recommended vaccination by polio inactivated vaccine (IPV)

DTP

A history of convulsions (instead DTP vaccine - DTaP vaccine or DT toxoid is injected)

MMR

Allergic reactions to aminoglycosides.

Anaphylactic reaction to egg protein.

Introduction of blood preparations

 

Notes:

1.     Routine vaccination is delayed until the acute manifestations of the disease and exacerbation of chronic diseases will disappear and carried out immediately after recovery or during remission. Acute respiratory disease, that has a mild course and no increase in body temperature, is not a contraindication for the routine vaccinations. Contact with infectious patients, quarantine is not a contraindication for the routine vaccinations. Features of vaccination against tuberculosis see paragraph 3 of these notes.

2.     Immunosuppressive therapy is a therapy carried out by cytotoxic drugs, including cyclosporine A monotherapy, and others, immunosuppressive doses of corticosteroids and radiotherapy. Immunosuppressive therapy with corticosteroids is recognized, if the prednisolone dose is more than 1mg/kg/day and it lasts longer than 14 days, as systemic use. Routine vaccinations with inactivated vaccines and toxoids are conducted after the end of therapy, vaccination with live vaccines - at least 1 month after cessation of therapy. If the duration of corticosteroid therapy is less than 14 days regardless of dose or more than 14 days and a dose of prednisolone is less than 1mg/kg/dayi, or it is used as replacement therapy, or locally, such therapy is not immunosuppressive and is not a contraindication for the routine vaccination.

3.     It is unacceptable to unite in a same day immunization against tuberculosis with other vaccines, and parenteral manipulations. BCG and Mantoux test should be done within 4 weeks after infection, which was accompanied by fever or quarantine.

4.     After OPV vaccination is proposed to restrict parental interventions during the 40 days.

5.     Vaccinations against measles, mumps and rubella after the introduction of blood products (whole blood, plasma, immunoglobulin preparations, packed red blood cells), except for washed red blood cells, is possible within the time specified in the instructions to the drug, but not earlier than 3 months. After the emergency prevention of neonatal tetanus by tetanus human immune globulin BCG vaccination is carried out according to the standard scheme. If the interval between vaccination against measles, mumps, rubella and the introduction of blood products with therapeutic and prophylactic purposes less than 14 days, vaccination against these infections should be repeated.

 

Recommended intervals between the administration of blood products containing specific antibodies, and vaccination against measles, mumps, rubella and varicella

 

Drug / indication for use

The recommended interval (months)

Tetanus emergency immunoprophylaxis by the tetanus immunoglobulin

3

Hepatitis A passive immunoprophylaxis by the normal human

immunoglobulin

3

Hepatitis B passive immunoprophylaxis by the specific immunoglobulin

against hepatitis B

3

Measles passive immunoprophylaxis by the normal human

immunoglobulin

- Standard contact (without immunodeficiency)

- Immunocompromised

 

 

5
6

Blood Transfusion

- The washed erythrocytes

- Red blood cells with the addition of preservative (adenine saline)

- Whole blood (Ht 65%)

- Whole blood (Ht 35-50%)

- Plasma / Platelets

 

 

-
6

6
6
7

CMV Immunoglobulin IV

6

IV immunoglobulin

- Sepsis

- Thrombocytopenic purpura

- Kawasaki disease

 

8
10
11

 

Postvaccinal complications - all pathological phenomena, which appear after vaccination and are not inherent to the usual vaccinal process, but obvious, their relationship with performed vaccination:

1. Postvaccinal unusual reactions and complications, caused strictly by vaccine ("true").

2. Joining of intercurrent infections in postvaccinal period.

3. Exacerbation of chronic diseases and primary manifestations of latent diseases.

 

Postvaccinal reactions and complications

Postvaccinal reactions:

1.     Increased temperature to 39˚ C.

2.     Increased temperature over 39˚ C (severe total reaction).

3.     Temperature, which is not registered in medical documentation.

4.     Pain, soft tissue swelling > 50 mm, hyperemia in the place of injection > 80 mm, infiltration > 20 mm (severe local reaction).

5.     Lymphadenopathy.

6.     Headache.

7.     Irritability, sleep disturbance.

8.     Non allergic rash.

9.     Anorexia, nausea, abdominal pain, indigestion and diarrhea.

10.                       Catarrhal phenomena.

11.                       Myalgia, arthralgia.

Postvaccinal complications:

1.     Abscesses.

2.     Anaphylactic shock and anaphylactic reactions.

3.     Allergic reaction (Quinckes edema, urticaria rash, Stevens-Johnsons, Lyells syndrome).

 

Quinckes edema

 

urticaria rash

 

Stevens-Johnsons syndrome

 

Lyells syndrome

 

4.     Hyporesponsive-hypotensive syndrome (acute circulatory failure, hypotension, decrease muscle tone, short-term breach or loss of consciousness, vascular abnormalities in anamnesis).

5.     Arthritis.

6.     Continuous scream (duration of 3 hours or more).

7.     Febrile seizures.

8.     Afebrile seizures.

9.     Meningitis / encephalitis.

10.                       Anesthesia / paresthesia.

11.                       Acute flaccid paralysis.

12.                       Vaccinassociated paralytic polio.

13.                       Guillain-Barre syndrome (poliradiculoneuritis).

14.                       Subacute sclerotizing panencephalitis.

15.                       Mumps, orchitis.

16.                       Thrombocytopenia.

17.                       Subcutaneous cold abscess.

18.                       Superficial ulcers over 10 mm.

19.                       Regional lymphadenitis.

20.                       Kelloid scar.

21.                       Generalized BCG infection, osteomyelitis, osteitis.

 

 

Postvaccinal reactions

Postvaccinal complications

DTP-vaccination

1.      Temperature 37.5-39 º, anxiety, poor sleeping, rarely - vomiting.

2.      Local reaction (more often on revaccination) - in the manner of hyperemia, infiltration.

3.      Reinforcement of the allergic manifestations (in children with exudative-catarrhal diathesis)

1.      Quinckes edema.

2.      Anaphylactic shock, collapse.

3.      Continuous scream (duration of 3 hours or more)

4.      Febrile seizures (on background of the quick ascent of the temperature).

5.      Afebrile seizures, absances.

6.      Encephalitis

OPV-vaccination

Does not call any reactions

1.      Reinforcement of the allergic manifestations (in children with exudative-catharrhal diathesis)

2.      Quinckes edema, urticaria.

3.      Vaccine associated poliomyelitis in immunized and in contact persons (on background of immunodeficiency) - 1:1,500,000.

Vaccination against measles

1. Specific vaccinal reaction from 4 to 14 days:

- temperature 37,5-38 º,

- catarrhal manifestations, conjunctivitis,

- pale-rose rash in a small amount,

- duration - 2-3 days,

- is not contagious

2. Lymphadenopathy.

1.        In children with exudative-catarrhal diathesis: Quinckes edema, urtica

2.        Hemorrhagic vasculitis.

3.        Hyperthermia 39-40 º with febrile seizures

Vaccination against mumps

1.      In some cases from 4 to 12 days - fever, catarrhal manifestations.

2.      Rare - a slight enlargement of parotid glands for a short time.

3.      Hyperthermia.

1.      Febrile seizures.

2.      Abdominal syndrome.

3.      Allergic rash.

4.      Very rare - serous meningitis.

BCG-Vaccination

1.      Local reaction: papule, vesicle, rib; lymphadenitis

1.      Subcutaneous cool abscess (BCG-tis).

2.      Superficial ulcers over 10 mm.

3.      Purulent lymphadenitis.

4.      Kelloid scars.

5.      Lymph nodes calcification.

6.      Generalized BCG-infection on background of immune deficiency (4: 1000000).

7.      Osteitis, osteomyelitis with dominating damage of long bones.

 


References:

Main:

1.     Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia: WB Saunders; 2000.

2.     Current therapy in pediatric infectious diseases 2 edited by John D. Nelson, M. D. B.C. Decker inc. Toronto, Philadelphia, 1988.

3.     Dershewitz RA, Macknin ML: Ambulatory Pediatric Care, 3rd ed. Lippincot Raven, 1999.

4.     Feigin RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases. Vol 2. 4th ed. WB Saunders Co; 1998.

5.     Krugman, Saul, et al. Infectious Diseases of Children. St. Louis: Mosby Year Book, 1992.

6.     Oski's Pediatrics: Principles and Practice. 3rd ed. Lippincott Williams and Wilkins; 1999.

7.     Principles and Practice of Pediatric Infectious Diseases. / Edited by Saran S. Long, Larry K. Pickering, Charles G. Prober, Philadelphia, Pa: Churchill Livingstone; 1997. 1921 p.

 

Additional:

1.    2000 Red Book: Report of the Committee on Infectious Diseases. American Academy of Pediatricians. 2000: 243-7.

2.    Bella J, Rossmann MG: Review: rhinoviruses and their ICAM receptors. J Struct

3.    Bellet, Paul S. The Diagnostic Approach to Common Symptoms and Signs in Infants, Children, and Adolescents. New York: Lea and Febiger, 1989.

4.    Bialecki C, Feder HM Jr, Grant-Kels JM: The six classic childhood exanthems: a review and update. J Am Acad Dermatol 1989 Nov; 21(5 Pt 1): 891-903

5.    Chameides L, Hazinski MF, eds. Textbook of pediatric life support. Dallas: American Heart Association, 1994:5-55-6.

6.    Collins PL, McIntosh K, Chanock RM: Respiratory Syncytial Virus. In: Fields' Virology. 3rd ed. 1996: 1313-1351.

7.    Committee on Infectious Diseases; American Academy of Pediatrics: Respiratory Syncytial Virus. In: Pickering LK, ed. 2000 Red Book: Report of the Committee on Infectious Diseases. 2000: 483-487.

8.    Dudas RA, Karron RA: Respiratory syncytial virus vaccines. Clin Microbiol Rev 1998 Jul; 11(3): 430-9

9.    Emmerson AM, Hawkey PM, Gillespie SH: Principles and Practice of Clinical Bacteriology. John Wiley & Sons; 1997: 373-88.

10.                       Fleisher, GR, Ludwig, SL: Gastrointestinal infections. In: Textbook of Pediatric Emergency Medicine. 4th ed. Baltimore, Md: Williams & Wilkins; 2000:757-762.

11.                       Garwood, John, and Amanda Bennett. Your Child's Symptoms. New York: Berkeley Books, 1995.

12.                       Griffin, DE: Billeter M, ed. Measles Virus. New York, NY: Springer-Verlag; 1995: 117-34.

13.                       Hostetter MK: Epidemiology of travel-related morbidity and mortality in children. Pediatr

14.                       Ledwith CA: Fluids and electrolytes. In: Handbook of Pediatrics. 17th ed. 1994:94-99.

15.                       Levin M, Nadel S: Bacterial meningitis: pathophysiology and causes and therapeutic approach. In: Oxford Textbook of Critical Care. Oxford University Press; 1999.

16.                       Nadel S, Levin M, Habibi P: Treatment of meningococcal disease in childhood. In: Meningococcal Disease. John Wiley & Sons; 1995:207-43.

17.                       Nelson, WE, Behrman, RE: Infections due to Salmonellae. In: Textbook of Pediatrics. 14th ed. 1992:729-734.

18.                       Ng VL, Balistrera WF: Hepatitis B-clinical perspectives in pediatrics. Clin Liver Dis 1999; 3 (2): 267-90.

19.                       Northrup RS, Flanigan TP. Gastroenteritis. Pediatr Rev 1994;15:461-72.

20.                       Pediatrics ( 2nd edition, editor Paul H.Dworkin, M.D.) 1992. 550 pp.

21.                       Smith MB: Acute rhinitis and pharyngitis. In: Evidence-Based Pediatrics. 2000: 83-90.

22.                       Textbook of Pediatric Nursing. Dorothy R. Marlow; R. N., Ed. D. London, 1989.-661p.

23.                       Viral Infections of Humans. Epidemiology and Control. 4th edition. New York, NY: Plenum Medical Book Company, 1997.

24.                       Ward DG: Acute infectious diarrhea disease and dehydration. In: Rosen P, Barkin RM. Emergency Medicine: Concepts and Clinical Practice. 4th ed. Mosby; 1998:1200-1212.