BASIS OF VACCINE PROPHYLAXIS

Main Statements Vaccination is the most reliable measure of infectious diseases prophylaxis. Due to vaccination smallpox is eliminated in the world, morbidity and mortality

from such dangerous infections as poliomyelitis, measles, diphtheria, newborn tetanus, hepatitis B are considerably decreased.

All vaccines are divided into live, inactivated, recombinant and anatoxins. According to WHO terminology, all the diseases registered in vaccinated people are

divided into complicated course of postvaccination period and postvaccinal complications.

There are strict criteria which allow attribute unfavorable events after vaccination to postvaccination complications.

There is a strict schema of prophylaxis of postvaccination complications.

Vaccine prophylaxis is an artificial reproduction of specific immune

response with the goal of creation in human of nonsusceptibility to infectious

diseases by the method of vaccine application.

Currently about 40 diseases can be prevented with the usage of vaccines.

Medicine is capable to protect children from actually all the diseases against which

vaccines are developed. It became possible due to existence of national vaccination

schedule in almost every country. The schedule considers a lot of factors which

influence the scheme of vaccination in every separate country. Schedule of

prophylactic vaccines considers level of infectious morbidity, age particularities of

immunity formation in children, influence of maternal antibodies, side reactions,

complications and accessibility of vaccines.

Existence of unified standards in matters of immunization in some

particular countries allows provide considerable decrease of morbidity among

population with vaccine controlled infections. Such approach allowed defeat such a

wide-spread and dangerous disease of the past as smallpox. Currently vaccination

against smallpox is stopped, as circulation of causative agent is absent. In majority

of world countries, including Ukraine, poliomyelitis is eliminated. In majority of

American and European countries such severe diseases as measles, inborn rubella,

neonatal tetanus and diphtheria are not detected. Thanks to vaccination against

viral hepatitis B the frequency of hepatocellular carcinoma in children is

decreased.

Vaccination provides the possibility not only to prevent development of

infectious diseases, to decrease their severity and frequency of complications, to

minimize the risk of lethal outcome but it also has social and economical

significance. Thanks to vaccination the possibility of epidemics development is

excluded, stable tranquility of the whole society and parents of every concrete

child is established, the sureness of the doctors in the health of their patients is

provided. Besides, the number of hospitalizations, percentage of disabilities,

expenses on buying expensive drugs and causes of temporal incapacity to work are

decreased.

A very important issue in decreasing morbidity of infectious disease or

their elimination is the necessity to vaccinate maximal amount of children

population and every single child should follow the entire vaccination schedule.

Only in this case the appropriate level of population immunity is formed. If 95% of

the whole population is vaccinated, then the unvaccinated or partially vaccinated

people will also be protected from infections. It occurs due to formation of stable

population immunity. Vaccination of every individual person protects not only this

concrete person from infection but indirectly also protects all the members of

population.

If vaccination encompassing is not sufficient, the increased risk of the

infectious morbidity appears even in vaccinated people, as the vaccination does not

provide 100% resistance to the diseases. If the number of unvaccinated by different

reasons children will increase, there is a high probability of returning the

epidemics of infectious diseases. Due to vaccination in the world the morbidity and

mortality from many dangerous infections was considerably decreased, while such

fatal disease as smallpox was completely eradicated.

All the vaccines are divided into the following groups:

1. Live vaccines (against measles, rubella, mumps, varicella, poliomyelitis,

rotaviral infection, influenza, Q fever, tuberculosis, anthrax, tularemia, plague,

etc.).

2. Inactivated vaccines (against whooping cough, influenza, meningococcal

infection, pneumococcal infection, Haemophilus influenzae, viral hepatitis A,

poliomyelitis, rabies, typhoid fever, etc.).

3. Recombinant vaccines (against viral hepatitis B, papillomaviral infection).

4. Anatoxins (against diphtheria, tetanus).

There are monovaccines (against one infection) and combined vaccines

(against several infections). Combinant (combined) vaccines are two-component

(against diphtheria and tetanus, against hepatitis A and B), three-component

(against measles, rubella and mumps; against whooping cough, diphtheria and

tetanus), four-component (against measles, rubella, mumps and varicella; against

whooping cough, diphtheria, tetanus and hepatitis B), five-component (against

whooping cough, diphtheria, tetanus, poliomyelitis and haemophilic infection), six-

component (against whooping cough, diphtheria, tetanus, poliomyelitis,

haemophilic infection and hepatitis B).

The regulation determining the age and sequence of prophylactic

vaccination performance is National schedule of prophylactic vaccines. In Ukraine,

according to National schedule of prophylactic vaccines, the obligatory vaccination

is performed against 10 infections: tuberculosis, viral hepatitis B, whooping cough,

diphtheria, tetanus, poliomyelitis, haemophilic infection, measles, rubella, mumps.

Besides obligatory vaccines the National schedule of prophylactic vaccines of

Ukraine also includes vaccines according to health conditions (against influenza,

pneumococcal infection, meningococcal infection, varicella, hepatitis A and

hepatitis B); according to epidemiological indications (against tularemia,

brucellosis, anthrax, leptospirosis, Q fever, tick-born encephalitis, plague, typhoid

fever, influenza, yellow fever, rabies, diphtheria, tetanus, hepatitis A,

poliomyelitis, measles, mumps, rubella, meningococcal infection and hepatitis B);

recommended vaccines (against varicella, hepatitis A, hepatitis B, influenza,

pneumococcal infection, meningococcal infection, rotaviral infection,

papillomaviral infection).

With considerable decrease of infectious morbidity and mortality reached

with modern programs of immunization, postvaccinal reactions and complications

acquire more and more significance. Besides antigens causing immune response,

vaccines contain a large amount of other substances, including solvents, stabilizers,

components of nutritive media, conservants, adjuvants, antibiotics. Any of these

components can provoke local or systemic side effect after vaccination injections.

According to WHO terminology (1991) all the diseases registered in

vaccinated are recommended to name as “unfavorable events” after vaccination.

They are divided into:

1. Complicated course of postvaccination period.

2. Postvaccinal complications.

Complicated course of postvaccinal period includes different diseases

simultaneous with vaccination but without cause-effect relation.

Postvaccinal complications (PVC) are conditions which develop as a

result of vaccination performance and have evident or proved connection to

vaccination and are not typical for usual course of vaccination process.

Postvaccinal complications are divided into:

- toxic (excessively strong);

- allergic (local and general);

- caused by infectious vaccination process (live vaccines).

Criteria according to which the “unfavorable events” can be attributed to

postvaccinal complications:

1. Proved relation in time with performance of vaccination.

2. Dose-dependent relation is detected.

3. Known tropism of live vaccines to certain tissues and organs.

4. Analysis of alternative causes is performed and degree of their non-

relation is proved.

5. After abandoning the usage of the vaccine, “unfavorable events” are not

registered any more.

6. Clinical presentation of the disease developed during postvaccinal

period is corresponding to clinical presentation typical for already known

postvaccination complications.

For postvaccination complications the following signs are typical:

• typical clinical signs of “standard case”;

• stereotypic terms of development.

Majority of specialists describe the following reasons of PVC appearance:

1. Vaccine reactogenicity.

• direct toxic effect of vaccine components;

• pharmacodynamic and immunologic activity of the vaccine;

• tropism of live vaccines to different tissues and organs;

• possible reversion of vaccine strain, acquisition of wild strain properties

(live poliomyelitis vaccine);

• contamination of vaccines by toxic substances.

2. Individual properties of macroorganism.

• pre-existing pathology which can be exacerbated in post-vaccination

period;

• sensitization, changes of immune reactions, perversion of endogenous

daily biorhythms in post-vaccination period;

• inborn or acquired defects of immunity, at which live vaccines can

cause a vaccine-associated disease;

• genetic predisposition of the child to given pathology (nervous system

disturbances, allergic, autoimmune diseases), which can develop in response to any

provoking factor. Vaccine, as a trigger, can be similar to any other outer influence,

e.g., acute viral infection.

3. Presence of program mistakes:

• violation of technique of immunization, when vaccines are injected

incorrectly. For example, vaccine against tuberculosis is injected subcutaneously

instead of intracutaneous injection. And the opposite, vaccines containing

aluminium hydroxide are injected intracutaneously (both these situations can cause

development of local pathological reactions);

• accidental usage of different medicinal drugs instead of solvents for

dried vaccines;

• violation of sterility requirements at vaccine injection which can lead to

development of abscess in place of vaccine injection;

• mistaken usage of some vaccines instead of others, in wrong dosage, to

children who should not be vaccinated with given vaccines according to age.

Clinical manifestations of post-vaccination complications. Toxic. Toxic

reactions are most commonly seen after immunization with killed vaccines,

particularly DPT, much more seldom after anatoxin injections, usage of

polysaccharide and recombinant vaccines. At vaccination with live vaccines toxic

reactions are most often registered after injection of measles vaccine. Terms of

development of toxic reactions correspond to those of usual reactions. After

injection of inactivated vaccines (DPT, polysaccharide, recombinant, anatoxins)

toxic reactions develop during the first three days after vaccination and most often

(95% of cases) during the first day. They are characterized by development of

prominent disturbance of general condition, intoxication: fatigue or restlessness,

decreased appetite, sleep disturbances, possible vomiting. The most common

symptom is fever till 39.50С and higher. Clinical signs remain during 1-3 days. At

injection of vaccine against hepatitis B and influenza split-vaccines the toxic

reactions can be accompanied by myalgia.

Toxic reactions after injection of measles, mumps and rubella vaccines can

include intoxication signs, fever, as well as catarrhal symptoms from upper

respiratory tract and other typical for these vaccines signs of postvaccination

process. Sometime nasal bleedings can develop. The terms of reaction appearance

are from 4-6th days till 12-14th days, that is, their development corresponds to

height of vaccination process. Symptoms of toxic reaction are preserved during

several days and disappear by the end of height vaccination period.

Allergic. Local allergic reactions. Local allergic reactions are most

commonly registered after injection of inactivated vaccines containing hydroxide

aluminium as a sorbent: DPT, anatoxins and others. At usage of live vaccines local

allergic reactions are seen more seldom and are also caused by additional

substances of the vaccine.

Local allergic reactions are characterized by appearance of hyperemia and

swelling more than 8 cm in diameter in the place of vaccine injection. According to

WHO classification, local reaction is considered to be edema and hyperemia

spreading beyond borders of nearest joint or covering more than half of body part

in the place of vaccination, as well as tenderness, hyperemia and edema (regardless

of size), which is present longer than 3 days. In rare cases after usage of vaccines

containing hydroxide aluminium, formation of aseptic abscess is possible.

Terms of appearance of local allergic reactions are within the first 1-3 days

after immunization with both killed and live vaccines.

General allergic reactions. Extremely rare general allergic reactions

include anaphylactic shock and anaphylactoid reaction.

Anaphylactic shock (IgE mediated acute reaction of immediate type

hypersensitivity). Typical, generalized form of shock has the periods of precursors,

height and recovery after shock. The shock usually develops during 3-30 min and

till 2 hours; at fulminant course it develops immediately (or several minutes later)

after injection of any vaccine.

At the precursor period the child develops inner discomfort, restlessness,

chills, weakness, dizziness, tinnitus, decreased vision, extremities and tongue

numbness, sometimes angioneurotic edema or urticaria. At fulminant form of

shock this period is absent.

The height period is characterized by:

• circulation insufficiency (decrease of arterial blood pressure lower than

90/60 mm Hg at mild form and till absence of blood pressure, weakness and

absence of pulse on periphery vessels, cold extremities, pale skin, increased

sweating, decreased urination till 20 ml/min and less);

• respiratory insufficiency (bronchospasm and/or laryngospasm, edema

of larynx);

• decreased consciousness (at mild form during several minutes, at severe

from during an hour and longer); possible development of seizures.

Period of shock recovery sometimes continues till 3-4 weeks. During this

time acute myocardial infarction, allergic myocarditis, glomerulonephritis,

hepatitis, serum sickness, disturbances of brain circulation and damage of nervous

system can develop.

Anaphylactoid reaction (acute reaction of hypersensitivity). It develops

acutely but its appearance is more prolonged in time than anaphylactic shock,

during the first two hours after vaccination. It presents with acute decompensation

of blood circulation, acute respiratory distress as a result of respiratory tract

obstruction. Additional clinical signs of anaphylactoid reaction are skin

involvement (spread urticaria, Quincke’s edema or generalized angioneurotic

edema) and gastrointestinal involvement (colic, vomiting, diarrhea).

The most common presentation of generalized allergic reactions is rash on

the skin: urticaria and Quincke’s edema, which appears within the first 1-3 days

after vaccination with killed vaccines and since 4 – 5th till 14th days after

vaccination with live vaccines (in height period of vaccination). It develops most

often by IgE-dependent type.

Urticaria is edema of epidermis and papillary layer of dermis, widening of

capillaries and arterioles; Quincke’s edema (giant urticaria, angioneurotic edema)

is the edema of deeper layers of dermis and subcutaneous tissue. Approximately in

half of patients urticaria is accompanied by Quincke’s edema. Quincke’s edema

can be localized on face and in oral cavity, or it can affect respiratory system,

which present with coarse voice, barking cough, attacks of cough, suffocation,

until asphyxia. In 30% of cases edema of gastro-intestinal tract is possible, which

presents clinically with nausea, vomiting, flatulence, intestinal obstruction. At

involvement of nervous system headache, dizziness, nausea, vomiting and

meningeal signs are possible.

Rare but severe variant of general allergic reactions is toxic-allergic

dermatitis (syndromes of Stevens-Johnson, Lyell). Term of their appearance

coincide with height of vaccination process.

Involvement of nervous system. Seizure syndrome. The most frequent post-

vaccination complications from nervous system are seizure (encephalic) reactions

such as febrile seizures (at T >38.00С) or afebrile seizures (at Т <38.00С).

Seizure syndrome with hyperthermia (febrile seizures). These seizures

present as generalized tonic, tonic-clonic and clonic attacks, single or repeated,

usually of short duration. Febrile seizures can develop after all vaccines. The most

commonly they are provoked by DPT, on the second place by frequency is vaccine

against measles as monovaccine or in combination with other vaccines. Terms of

development are within 1st day, rarer 2-3rd days after vaccination with inactivated

vaccines. After live vaccines these seizures can develop on the 5-12 th days after

vaccination, at the height of vaccination reaction. Currently some authors do not

consider febrile seizures to be post-vaccination complication, as children of the

first three years are prone to seizure conditions at fever caused by different

reasons. These investigators consider febrile seizures after vaccination as reaction

of these children for fever. Older children develop hallucination syndrome as an

equivalent of seizure reaction during high fever.

Seizure syndrome with normal or subfebrile temperature with disturbances

of consciousness and behavior. Afebrile seizures are notable by polymorphic

features, from generalized seizures till small attacks (“absences”, “nods”, “pecks”,

“freezings”, fibrillations of separate muscle groups). Small attacks are usually

repeated, serial; they more often appear at falling asleep and wakening of the child.

Afebrile seizures are mostly seen after injection of pertussis vaccine and, unlike

febrile ones, they can appear later after vaccination, in 1-2 weeks. After measles

vaccination afebrile seizures are seen extremely seldom. Development of afebrile

seizures justifies pre-existing organic damage of nervous system in the child which

was not timely diagnosed before vaccination, and the vaccination in these cases is

a provoking factor (trigger) of already existent latent CNS disease.

Differential diagnosis of seizure syndrome (encephalic reaction):

• febrile seizures in post-vaccination period should be differentiated with

seizure attack at intercurrent infectious disease developed in the vaccinated child;

• afebrile seizures are differentiated with debut of epilepsy, other organic

diseases of nervous system with seizure syndrome (West syndrome, infantile

spasms, etc.); somatic diseases which can be accompanied by seizures

(spasmophilia, diabetes, etc.).

Differential diagnosis is based on:

•term of seizures development, at the height of vaccination process or

outside this time;

•presence or absence of intercurrent disease symptoms;

•data about presence of seizures in the patient earlier, as well as in

his/her relatives;

Laboratory investigations for exclusion of the etiology of seizures

(hypocalcemia, hypoglycemia, etc.).

Vaccine-associated diseases. The most severe ones from the group of

pathological process with involvement of nervous system are vaccine-associated

poliomyelitis, encephalitis and meningitis. This group of postvaccination

complications is observed rather rarely and only after usage of live vaccines.

Vaccine-associated poliomyelitis (VAP) or acute flaccid paralysis caused

by vaccine virus.

The disease is caused by damage of anterior horns of spinal cord. It

presents as a rule with damage of one extremity with typical neurological

disorders: decreased muscle tone, reflexes, trophies (atonia, areflexia, atrophy) but

with preservation of sensitivity. It lasts not less than 2 months, leaving afterwards

prominent residuals. It develops in vaccinated children on the 4-30th days after

immunization with live vaccine and in contacts with vaccinated people within 60

days. It mainly develops after first application of vaccine, in the mean frequency 1

per 2.5 million vaccine doses. Risk of the disease in immunodeficient people is

many times higher than in healthy ones.

Differential diagnosis of VAP is performed with acute flaccid paresis

(AFP):

• infectious AFP caused by viruses of “wild” strain of poliomyelitis,

enteroviruses of ECHO or Coxsackie groups;

• not infectious AFP caused by neuromyalgic syndrome, organic

neurological, bones, joint or vessel pathology, revealed or decompensated during

post-vaccination period.

The diagnosis of VAP can be confirmed by:

• data about performed vaccination with live poliomyelitis vaccine or

contact with vaccinated people;

• typical terms of disease onset from the moment of vaccination;

• typical clinical presentation of acute flaccid paralysis;

• damage of anterior horns of spinal cord, proved by electromyogram

(EMG);

• data about immune deficient state of the patient;

• isolation of vaccine strain of poliomyelitis from the patients (confirmed

by genetic typing).

Vaccine-associated encephalitis are encephalitis caused by live viruses

tropic to nervous tissue (measles vaccine, rubella vaccine). In majority of cases it is

possible to prove intercurrent character of nervous system disease, which is only

connected to vaccination in time. Rare exclusions are immunocompromised people

when the virus of live vaccine can disseminate into all the organs, including the

brain.

Possibility of the development of vaccine-associated meningitis after

vaccination against mumps in some cases is proved by isolation of vaccination

strain from CSF.

However it is clear that not all the encephalitis and meningitis developed

during postvaccination period is vaccine-associated. It can be caused by other

causative agents not related to vaccines. That’s why every case of postvaccination

encephalitis or meningitis must be carefully examined.

Encephalitis after measles vaccine. Postvaccination encephalitis is a very

rare complication of measles vaccine. Its frequency is 1:1000000 vaccinated,

whereas after measles encephalitis develops in 1 per 1000 patients. Possible term

of disease onset is since 5 till 30 days after vaccination.

Clinical presentation is not specific and cannot be distinguished from the

one at viral encephalitis of other etiology. Morphological picture in case of fatal

outcome is described to be similar to one at other encephalitis.

Besides encephalitis, single cases of encephalomyelitis are described,

which is characterized by acute decrease of consciousness and multiple focal

neurological deficits developed several days after vaccination. On histological

examination the foci of periventricular inflammation and demyelination are seen,

more prominent in white matter of brain and spinal cord. The diagnosis is usually

made at pathomorphological examination.

However, none of the described in literature cases with fatal outcome

allowed isolation of measles vaccination strain from brain, which makes the

diagnosis of vaccine-associated encephalitis controversial.

Subacute sclerosing panencephalitis (SSPE). Cases of development of

SSPE after measles vaccine are well known. The disease is characterized by slow

progression. The process begins with disturbances of behavior and school

performance of the child, absence of appetite and weight loss. Later myoclonic

paroxisms appear at preserved consciousness. Further extrapyramidal dyskinesia

develop: athetosis, chorea, torsion dystonia. Gradually due to developing

chorioretinitis or atrophy of optical nerve vision is worsened.

Terminal stage is characterized by decortication and vegetative stage.

Length of SSPE development is from several weeks till several years with possible

periods of remission.

However, due to Advisory Committee on Immunization Practices (ACIP,

USA, 1997), in none of the cases direct interrelation of SSPE and vaccine strain of

measles is proved. Just the opposite, experts present the data that the frequency of

SSPE in vaccinated against measles children is much lower than after an episode

of measles. It is considered that SSPE develops in children vaccinated previously

against measles with non-efficacy of immunization, when they further develop

episode of measles.

Vaccine associated serous meningitis caused by mumps vaccine virus.

According to literature data, frequency of serous meningitis after mumps

monovaccines or combined vaccines containing mumps component depends on

used vaccine strain of the virus. So, for strain Uraba the frequency of

postvaccination meningitis is between 1:2000-1:20000; for strain Jeryl-Lynn it is

1:150000-800000. Due to obtained data the strain of Uraba was substituted with

Jeryl-Lynn strain in many countries. After this substitute the notifications about

vaccine associated meningitis became considerably rarer.

Guillain-Barre syndrome. It is an acute rapidly progressing ascending

symmetrical flaccid paralysis with loss of sensitivity, as a rule, without fever at the

disease onset. Case relation is not only proved after implementation of live

poliomyelitis vaccine; the syndrome is also described after usage of anatoxins,

vaccine against Haemophilus influenzae type B and influenza vaccines.

Development of Guillain-Barre syndrome after other vaccines is most possibly due

to previous disease before the vaccination.

Other post-vaccination complications.

Hypotensive-hyporesponsive syndrome. It is a rare complication

characterized by transitory acute cardiovascular insufficiency with arterial

hypotension, decreased muscle tone, shot-term loss or decrease of consciousness,

skin paleness.

Differential diagnosis of hypotensive-hyporesponsive syndrome is

performed with anaphylactoid post-vaccination reactions, syncopes caused by

other reasons (disturbances of cardiac rhythm, epileptic syndrome, hypoglycemia,

orthostatic reactions). The diagnosis can be confirmed with history data: presence

of syncopes before, orthostatic reactions, emotional instability in older age

children.

Thrombocytopenic purpura. It is an extremely rare post-vaccination

complication which present with acute decrease of platelets number in blood and

acute hemorrhagic syndrome. The cause-effect relation of thrombocytopenic

purpura and measles-containing vaccines is proved. The terms of development are

since 5th till 15th days after vaccination. The pathogenesis is based on infectious-

allergic and immune inflammatory mechanisms. Clinical presentations, disease

course, treatment and prognosis do not differ from those at thrombocytopenic

purpura of other etiology.

High-pitch cry. It is a persistent monotonous cry in children of the first six

months of age which develops several hours after vaccination and continues from 3

till 5 hours. It is registered mostly after vaccines containing whole-cell pertussis

vaccine. It is considered that development of high-pitch cry is due to possible

action of pertussis vaccine on changes in brain microcirculation. This leads to

increased intracranial pressure and appearance of headache.

Complications after BCG vaccine. Complications after BCG vaccine are

seen with frequency of 0.02%-0.004% from number of vaccinated newborns; after

revaccination they are even rarer and develop in 0.001%-0.0001% of revaccinated

children and adolescents.

Vast majority of complications present with local processes. They are

caused as a rule by violation of the technique of vaccination: the vaccine is injected

subcutaneously instead of intracutaneous; accidental use of higher dosage in

comparison to the one indicated in instructions; not sufficient sterile conditions of

vaccination. Presence of some (cellular or combined) forms of primary immune

deficiencies promotes development of certain local complications such as BCG-

lymphadenitis. According to WHO classification, suggested in 1984y.,

complications after anti-tuberculosis vaccine are divided into 4 categories:

• local complications, the most commonly seen;

• persistent and disseminated BCG infection without fatal outcome;

• disseminated BCG infection, generalized damage with lethal outcome

(2nd and 3rd variants are seen at inborn immune deficiencies);

• so called BCG syndrome. This disease develops soon after vaccination

or more often after revaccination and is characterized by allergic pathology:

nodular erythema, different allergic rashes. This category also includes formation

of colloid scar at the place of vaccine injection.

Local complications. Lymphadenitis, most commonly axillary and rarer

cervical. They develop 2-3 months later after vaccination. Lymphadenitis can be

closed or with fistula. They start to develop without symptoms. Lymph node

slowly begins to increase in size, is painless at palpation, intoxication can be

absent. In some cases purulent inflammation of the fistula develops with discharge

of pus. In these cases intoxication is prominent as a rule.

The pus is usually sterile, but sometimes vaccine strains of BCG can be

isolated. Reverse development of lymphadenitis is long-term and occurs within 1-2

years. At cytomorphological examination of lymph nodes caseous necrosis,

epithelioid cells and giant cells are seen. Similar morphological picture is seen at

tuberculosis lymphadenitis.

Lymphadenitis can progress to formation of calcifications in lymph node

more than 10 mm in diameter.

More rarely at the place of injection superficial or deep ulcer is formed.

Ulcers appear 2-4 weeks after vaccination and much rarer after revaccination.

Ulcer borders are elevated, granulation is poor.

Cold abscess develops 1-1.5 months after vaccination or revaccination. At

first hard subcutaneous infiltrate is formed, which is connected to nearest tissue

and is painless at palpation. Signs of inflammation are not seen: hyperemia, tissue

edema, pain at palpation. Intoxication, fever are also absent. Gradually the

infiltrate is softened, fluctuation appears, and fistula develops with discharge of

liquid sterile pus. Sometimes at the place of abscess deep ulcer appears. The course

is long-term. With the treatment the duration is 6-7 months long, without treatment

it can be prolonged till 1.5 years. Healing occurs with formation of star-like scar.

Majority of authors consider formation of the abscess to be a technical defect at

vaccination, subcutaneous injection of the vaccine.

At revaccination of female adolescents seldom formation of colloid scar is

observed. By the appearance this scar is not different from colloid scar of any other

origin – round or elliptical, hard, smooth, painless. If form of the scar is changed

and itching appears, this justifies its growth. Reasons of colloid scars formation are

not clear.

Sometimes local reaction is complicated by joining of secondary infection.

In these cases fistula is formed with discharge of pus. Usually common coccal

flora can be isolated from the pus.

Generalized complications. They are seen very seldom. Newborns with

primary immune deficiency can develop generalization of the infection with severe

damage of different organs and systems, including nervous system, with clinics of

serous meningitis.

Similar generalized infection often has lethal outcome. From affected

organs BCG vaccine strain mycobacteria are isolated.

In later years there are reports about osteitis are a presentation of

generalized BCG vaccine infection in the literature. Osteitis develops 7-24 months

after vaccination. Clinically it presents as bone tuberculosis. Prognosis at timely

therapy is benign; the frequency of similar complication due to different sources is

from 0.1 till 30 per 100000 vaccinated.

As a very rare complication also related to disseminated vaccine strain of

mycobacteria tuberculosis, “lupus” is described which develops in the place of

vaccine injection or over regional lymph node. From affected skin mycobacteria of

BCG vaccine strain are isolated. Eye damage is also described which presents with

phlyctenular conjunctivitis, rarer iridocyclitis or scleritis.

Prophylaxis of postvaccination complications.

1. Usage of vaccines with complete cycle of pre-clinical and clinical trials

which are registered in Ukraine. Usage of modern types of vaccines (acellular

pertussis vaccine and inactivated poliomyelitis vaccine) plays an important part in

prophylaxis of postvaccination complications. So, implementation of inactivated

poliomyelitis vaccine in 2006 into National vaccination schedule of Ukraine

allowed exclude later such sever complication as vaccine-associated poliomyelitis.

2. To avoid post-vaccination complications, it is necessary to follow

strictly all the recommendations regarding storage, transport, doses, schema,

techniques of vaccine injection and contraindications to usage.

Besides contraindications described in regulations for every certain

vaccine, National vaccination schedule gives absolute contraindications for

vaccination usage and particularities of their usage at existence of temporal

contraindications.

The selection of children for vaccination is important in prophylaxis of

post-vaccination complications. With this goal, it is necessary to follow strictly

individual schedule of prophylactic vaccines for every child. Before vaccination

the child should be examined by a doctor, temperature must be measured as well as

history must be taken to exclude any disease which could be a contraindication for

vaccination. If the doctor has concerns about child’s health, specialist consultations

and laboratory investigations should be performed. Vaccination can only be

performed after exclusion of contraindications to vaccination. Children with

different chronic diseases with moderate and severe course in remission must be

vaccinated in hospital conditions with follow-up of corresponding specialists.

Important role belongs to obtaining allergy history. At the presence of

allergic reactions in the past for previous vaccine usage or components of vaccine,

the performance of given vaccination is contraindicated.

To exclude technical mistakes at vaccination, it is necessary to follow all

the rules of vaccine storage and transport. All the manipulations during

immunization must be done by specially trained personnel with strict adherence to

instructions of usage of every specific vaccine.

Correct technique of vaccination performance is important for prophylaxis

of post-vaccination pathology. During the first year of age, vaccines for

subcutaneous and intracutaneous injection are usually given to anterior-lateral

surface of thigh, whereas in older children and adults (if muscle layer is enough)

into deltoid muscle. Vaccines are not recommended to be injected into gluteus

muscle due to high risk of sciatic nerve damage and vaccine injection into fatty

tissue instead of muscles. In order not to inject accidentally the vaccine into blood

vessel, before vaccination the syringe plunger should be drown back to justify that

there is not blood in syringe.

In post-vaccination period medical personnel should perform active

follow-up to reveal timely all the disease cases in vaccinated children, to perform

monitoring and examination of every case suspected for postvaccination

complication.

Prophylaxis of vaccine-associated poliomyelitis

1. In close children groups (nurseries, boarding schools, etc.) it is necessary to

provide separate living of children who were vaccinated during the previous

3 weeks with live poliomyelitis vaccine and those who were not vaccinated.

2. During hospitalization of children to medical settings it is necessary to

collect carefully the vaccination history. Hospitalization of children and

unvaccinated children should be done into separate rooms.

3. Intramuscular injections (if not due to life-threatening situations) are

contraindicated during 2 weeks after vaccination with live poliomyelitis

vaccine.

4. Surgical procedures (including teeth extraction, tonsillectomy, adenectomy)

(if not due to life-threatening situations) are contraindicated during 2 weeks

after vaccination with live poliomyelitis vaccine.

5. Registration of contraindications of live poliomyelitis vaccine

administration.

Questions for self-control

1. Goals and tasks of immunoprophylaxis.2. National schedule of prophylactic vaccinations in Ukraine (vaccination according to age, health status, vaccinations on epidemiological indications, recommended vaccinations).3. Characteristics of vaccines for prophylaxis of diphtheria, pertussis and tetanus (DPT, DT, Tdap). Normal course of post-vaccination period and possible pathological reactions, their prophylaxis and treatment.

4. Characteristics of vaccines for prophylaxis of poliomyelitis: oral (live) and inactivated (killed).5. Normal course of post-vaccination period of vaccination against poliomyelitis. Possible pathological reactions, terms of their development and clinical presentations. What is vaccine-associated poliomyelitis?6. Characteristics of vaccines for prophylaxis of measles, mumps, rubella. Normal course of post-vaccination period of vaccination against measles, mumps, rubella. Possible pathological reactions, terms of their development and clinical presentations. 7. Clinics, diagnosis and emergency treatment of anaphylactic shock.8. Contraindications for prophylactic vaccinations.9. Prophylactic vaccinations by epidemiological indications in nidus of diphtheria, mumps, poliomyelitis, pertussis.

Tests for self-control

1. Vaccinations against which infectious diseases should be performed to children according to age, due to Schedule of vaccination:А. Poliomyelitis, tuberculosis, hepatitis A, diphtheria, measles, varicella, mumps, rubella, tetanus;В. Poliomyelitis, tuberculosis, hepatitis A, diphtheria, measles, pneumococcal infection, mumps, rubella, tetanus;С. Poliomyelitis, tuberculosis, hepatitis A, diphtheria, measles, haemophilus infection, mumps, rubella, tetanus, pertussis;D. Poliomyelitis, tuberculosis, diphtheria, measles, haemophilus infection, mumps, rubella, tetanus, meningococcal infection, pertussis;Е. Poliomyelitis, tuberculosis, hepatitis B, hepatitis A, measles, haemophilus infection, mumps, rubella, tetanus, meningococcal infection, pertussis, influenza.2. Which post-vaccination pathologic reaction in brain can develop after vaccination with DPT vaccine?А. Purulent meningitis;В. Serous meningitis;С. Subdural hemorrhage;D. Febrile or afebrile seizures;Е. All the answers are correct.3. What are the terms of local post-vaccination reactions development?А. Before 48 hour;В. Before 72 hours;С. During the first week after vaccination;D. Since 4th till 15th days after vaccination;Е. During 30 days after vaccination.4. At which age the child should be given the first vaccination against measles, mumps and rubella:А. 9 months;В. 12 months;С. 15 months;D. 18 months;Е. 6 months.5. Scheme of vaccination against poliomyelitis:А. 3 months, 4 months, 5 months, 18 months, 3 years, 6 years, 14 years;В. 3 months, 4 months, 5 months, 18 months, 7 years, 15 years;С. 3 months, 4 months, 5 months, 18 month, 6 years, 14 years;D. 3 months, 4 months, 5 months, 18 months, 3 years, 6 years, 15 years;

Е. 2 months, 3 months, 6 months, 18 months, 7 years, 15 years.6. At which age is the planned vaccination against diphtheria and tetanus with DT vaccine performed:А. 6 years;В. 18 months;С. 14 years;D. 18 years;Е. Every 10 years to adults vaccinated according to schedule.7. 4-years old child was not previously vaccinated against diphtheria, tetanus and pertussis. Which vaccine must this child be vaccinated with?А. Diphtheria tetanus anatoxin (DT);В. Adsorbed pertussis-diphtheria-tetanus vaccine (DPT);С. Adsorbed pertussis-diphtheria-tetanus vaccine with acellular pertussis component (DTaP);D. Diphtheria-tetanus anatoxin with decreased contain of antigens (Tdap);Е. Antidiphtherial serum (ADS) and tetanus anatoxin (T).8. Post-vaccination nervous system complications include everything except:А. Post-vaccination encephalitis;В. Meningoencephalitis;С. Encephalopathy;D. Brain abscess;Е. Afebrile seizures.9. The first revaccination of DPT is performed at the age:А. 2-3 years;В. 5 years;С. 6 years;D. 1-1.5 years after first vaccination;Е. Not performed.10. Vaccine-associated forms of poliomyelitis are characterized by all the listed signs except:А. Development of flaccid paralyses since 6 till 30 days after vaccination;В. Typical symptoms of the disease with development of persistent flaccid paralysis;С. Isolation of vaccine strain of poliomyelitis virus from the sick person;D. 4-fold increase of antibody titer to vaccine strain of the virus;Е. Development of sensitivity disturbances of affected skin dermatomes.

Test answers

1-С, 2- D, 3-А, 4-В, 5-С, 6-А, 7-А, 8- D, 9- D, 10-Е.