Vaccination of persons with immunodeficiencies

For all people with immunodeficiency, only live vaccines that can cause disease are dangerous. The diagnosis of immunodeficiency is clinical, although it requires laboratory confirmation.

According to the WHO classification, the following types of immunodeficiencies are distinguished:

• primary (hereditary);
• immunodeficiency associated with severe diseases (mainly lymphoproliferative and oncological);
• drug and radiation immunosuppression;
• acquired immunodeficiency disease (AIDS).

Immunodeficiency should be suspected in patients with severe recurrent bacterial, fungal or opportunistic infections. In children without such manifestations - only on the basis of frequent acute respiratory infections, general asthenia, etc., the diagnosis of immunodeficiency is unfounded, such children are vaccinated as usual. The terms "secondary immunodeficiency", "reduced reactivity", etc., which have become widespread in Russia and usually imply conditions after an infection, cannot be considered equivalent to an immunodeficiency state; such a "diagnosis" cannot serve as a reason for exemption from vaccination.

Laboratory confirmation of the diagnosis of "immunodeficiency" is based on the identification of immunological parameters outside the normal range (which is quite wide). In a child who does not have the corresponding clinical picture, deviations in "immune status parameters" are usually detected that do not reach the levels characteristic of a specific immunodeficiency state. Such changes cannot in themselves serve as a reason for refusing vaccination. Fluctuations in immunoglobulin levels and the number of T-cells, changes in the ratio of lymphocyte subpopulations, phagocytosis activity, etc. naturally occur in various diseases and conditions, without reaching threshold levels and without clinical manifestations. Their pathological significance is questionable; they most often reflect cyclical fluctuations in very dynamic immunological parameters during illness. Enormous expenditures on the production of immunograms in children without clinical manifestations of immunodeficiency are not justified, and "profound" conclusions based on them are akin to astrologers' horoscopes.

General rules for vaccination of persons with immunodeficiency

In patients with immunodeficiency, inactivated vaccines are completely safe. Live vaccines are contraindicated in principle, although they are administered to HIV-infected patients.

Primary immunodeficiency states

An increased risk of complications for these patients has been proven with live vaccines. This is vaccine-associated poliomyelitis (VAP) when using OPV and encephalitis in response to the measles vaccine in individuals with a- and hypogammaglobulinemia, generalized BCG-itis and BCG-osteitis in children with combined forms of immunodeficiency, with chronic granulomatous disease and defects in the interferon-y and interleukin 12 systems. Clinical manifestations of immunodeficiency are absent in newborns when BCG is administered, and most often at the age of 3 months, when OPV was administered (this is due to compensation of the insufficiency of maternal immunoglobulins by maternal IgG); for this reason, a universal examination of children in the first months for the presence of immunodeficiency is not informative, and practically unrealistic.

Immunization with live vaccines of immunocompromised individuals

Type of immunodeficiency	Timing of administration of live vaccines
Primary immunodeficiencies	Live vaccines are not administered, OPV is replaced by IPV
Immune-suppressing diseases (tumors, leukemia)	Live vaccines are administered in remission at individual times
Immunosuppression, radiation therapy	Not earlier than 3 months after the end of therapy
Corticosteroids (doses are given for prednisolone)
Orally >2 mg/kg/day (>20 mg/day for weight over 10 kg) for more than 14 days	1 month after completion of the course
The same dose for less than 14 days or a dose less than 2 mg/kg/day (<20 mg/day)	Immediately after completion of treatment
Supportive care	Against the background of the treatment being carried out
Local therapy (eye drops, nose drops, inhalations, sprays and ointments, in the joint)	Against the background of the treatment being carried out
HIV infection
Asymptomatic - in the absence of laboratory signs of immunodeficiency	Measles, mumps, rubella - with antibody monitoring after 6 months and repeated vaccination in case of low levels
With signs of immunodeficiency	Protection is provided by immunoglobulin

Conditions that raise the possibility of primary immunodeficiency (in the person to be vaccinated or in a family member) are:

• severe, especially recurrent purulent disease;
• paraproctitis, anorectal fistula;
• the presence of persistent candidiasis of the oral cavity (thrush), other mucous membranes and skin;
• pneumocystis pneumonia;
• persistent eczema, including seborrheic;
• thrombocytopenia;
• the presence of a patient with immunodeficiency in the family.

In children with such conditions, it is necessary to determine the content of 3 classes of immunoglobulins; immunodeficiency is probable when the levels of immunoglobulins of at least one class are below the lower limit of the norm. A decrease in the proportion of y-globulins below 10% in the protein fractions of the blood allows one to suspect humoral immunodeficiency. Skin tests with tuberculin (in those vaccinated with BCG) and candidin are used to assess the state of T-cell deficiency; the loss of negative tests requires further examination. The diagnosis of chronic granulomatous disease is confirmed by a test with tetrazolium blue or similar.

BCG is not administered to newborns in families where there are children with any signs of immunodeficiency, or children who died from an undiagnosed pathology.

To protect children with primary immunodeficiency from measles in case of contact with sick people, human immunoglobulin is used (these children usually receive replacement therapy with immunoglobulin, which protects them from infection).

Children with primary immunodeficiency are vaccinated with all inactivated vaccines, including those given immunoglobulin replacement therapy. Since many of them produce a reduced immune response, it is advisable to determine antibody titers after the primary vaccination series and administer additional doses if necessary. The response to diphtheria and tetanus toxoids is completely absent in children with hyper-IgE syndrome and antibody deficiency syndromes.

Effect of immunosuppression on antibody levels

Infection	Preservation of antibodies
	Post-infectious	Post-vaccination
Tetanus		Saved
Diphtheria		Saved
Polio		Saved
Measles		Reduced
Pneumococcal		Preserved (lymphomas)
Chicken pox	Reduced
Hepatitis B	Reduced
Flu	Reduced

Transient hypogammaglobulinemia

This so-called "late immunological start" usually passes by 2-4 years, such children can be vaccinated with killed vaccines, and after the immunoglobulins are normalized, they can be vaccinated against measles, rubella and mumps. These children usually tolerate BCG.

Disease-associated immunodeficiency and immunosuppressive therapy

The immune response is suppressed in leukemia, lymphogranulomatosis and other lymphomas, and to a lesser extent in a number of solid tumors; this is a contraindication for the administration of live vaccines, especially since these children usually receive immunosuppressive therapy. Although the administration of killed vaccines to them in the acute period is not contraindicated, the immune response to a number of vaccines is often reduced:

• The response to diphtheria and tetanus toxoids is good (to the booster dose), worse to the primary series.
• Hib vaccine usually produces a good response.
• The response to Grippol does not decrease, but in preschool age 2 doses are required.
• Hepatitis B vaccine - the immune response is extremely weak.

For this reason, a number of vaccines are recommended to be administered no earlier than 4 weeks after the end of therapy (with a lymphocyte count of more than 1000 in 1 μl). Live vaccines are administered individually, at least 3 months after the end of immunosuppression.

In children with acute lymphoblastic leukemia, when exposed to chickenpox (or shingles, which often worsens in ward neighbors who have had chickenpox), it is necessary to interrupt the course of chemotherapy, prophylactically use acyclovir, and it is also possible to use intravenous human immunoglobulin. More reliable protection is achieved by vaccination, recommended by WHO and widely used in the world: it prevents the disease in 85% of patients, while in the rest the infection is mild. In those who have had the disease before, vaccination, acting as a booster, reduces the frequency of shingles exacerbations. Patients with leukemia are vaccinated after 1 year of remission against the background of maintenance therapy with a lymphocyte count of at least 700 in 1 μl and platelets over 100,000 in 1 μl. Vaccination is also effective in recipients of bone marrow and solid organ transplants.

Patients with leukemia have a high risk of hepatitis B due to repeated blood transfusions. Currently, these patients are protected from hepatitis B infection by administering specific immunoglobulin, usually in combination with active immunization at a later stage of treatment.

Patients with lymphogranulomatosis are vaccinated according to the above rules. Given their particular susceptibility to infections caused by capsular microorganisms, they are also recommended to be given Hib vaccine, and at the age of over 2 years - vaccines against pneumococcal and meningococcal A and C infections. Vaccination should be carried out 10-15 days before the start of the next course of therapy or 3 months or more after its completion. The same tactics are used in children with asplenia and neutropenia, who have an increased risk of bacteremic infection with capsular microorganisms.

Immunosuppression reduces antibody levels, so after remission, vaccination (or revaccination) is indicated against diphtheria and tetanus, measles (even after 1 or 2 vaccinations), rubella and mumps, influenza, hepatitis B, and chickenpox.

Children after bone marrow transplantation are vaccinated with killed vaccines no less than 6 months later, with live vaccines - twice after 2 years (interval 1 month).

Immune defects that cause increased susceptibility to infection by capsular pathogens (pneumococcus, H. influenzae type b, meningococcus). These include patients with asplenia (a defect in the formation of IgM antibodies) who have a high risk of pneumonia (incidence 226 per 100,000 patients, OR 20.5), which persists for decades after removal of the spleen. In sickle cell anemia (functional asplenia) in patients under 5 years of age, the incidence of pneumococcal infection (6.9 per 100 person-years) is 30-100 times higher than the incidence rates of the general population. In patients with diabetes, pneumococcal infection, although it occurs no more often than in healthy people, is severe, with a mortality rate of 17-42%.

Relapses of meningococcal infection are common in individuals with deficiency of properdin, C3 and a number of subsequent complement components; they are recommended to be vaccinated with a polysaccharide vaccine every 3 years.

Monitoring the results of vaccination of individuals with immunodeficiency and immunosuppression by determining the titers of the corresponding antibodies is mandatory.

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Corticosteroid therapy

Steroids cause significant immunosuppression only when high doses are used (prednisolone >2 mg/kg/day or >20 mg/day for a child >10 kg) for more than 14 days. Inactivated vaccines are administered to such children at the usual time after recovery, live vaccines are administered no earlier than 1 month after the end of treatment. Live and inactivated vaccines are administered in the usual manner to persons receiving steroid drugs in the form of:

• short-term courses (up to 1 week) in any doses;
• courses of up to 2 weeks in low or medium (up to 1 mg/kg/day of prednisolone) doses;
• long-term in maintenance doses (for example, 10 mg of prednisolone every other day);
• substitution therapy in low (physiological) doses;
• locally: on the skin, by inhalation, in the form of eye drops, inside the joint.

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