The Journal for Nurse Practitioners
Volume 6, Issue 7 , Pages 534-539, July 2010

Pneumococcal Vaccination and Specific Polysaccharide Antibody Deficiency Syndrome

  • Shannon Munro Cohen

      Affiliations

    • Shannon Munro Cohen, PhD, APRN, BC, FNP, is a nurse practitioner working in an asthma, allergy, and immunology practice.

Article Outline

Abstract 

Every year invasive pneumococcal disease kills 5,000 people in the United States and 2 million people worldwide. The pneumococcal vaccine is considered 60% to 70% effective in preventing pneumococcal disease. Reasons for incomplete protection include ineffective antibody response, compromised immunity, poor nutritional status, and switching of pneumococcal genes to nonvaccine serotypes. Patients with specific polysaccharide antibody deficiency syndrome present with a history of frequent infections requiring antibiotics, including sinusitis, pneumonia, and otitis media, which could be prevented with vaccination. Thus, it is imperative that nurse practitioners promote the use of pneumococcal vaccination and have an understanding of specific polysaccharide antibody deficiency.

Keywords:  pneumococcal vaccination , specific polysaccharide antibody deficiency

 

Every year, invasive pneumococcal disease kills 5,000 people in the United States and 2 million people worldwide.1, 2 More than half of all deaths from pneumococcal disease occur in people over 65 years old.3 Pneumococcal pneumonia leads to 175,000 hospitalizations, 34,500 cases of bacteremia, and 2,200 cases of meningitis annually.1 Pneumococcal disease in young children leads to otitis media, sinusitis, meningitis, and bacteremia and is particularly dangerous in children younger than 2 years old; 2.6 million children under the age of 5 die each year from pneumonia, worldwide.1, 4 Half of all children and 5% of all adults are nasopharyngeal carriers of pneumococci.5 Thus, it is imperative that nurse practitioners promote the use of pneumococcal vaccination to prevent these diseases and have an understanding of specific polysaccharide antibody deficiency (SPAD) syndrome.

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Pneumococcal Vaccination for Adults 

Pneumococcal vaccination is recommended for people over 65 years old; cigarette smokers; people with chronic medical conditions including chronic obstructive pulmonary disease, asthma, diabetes, chronic renal failure, alcoholism, cancer, human immunodeficiency virus, and sickle cell disease; and people without a spleen.1, 3, 6 Immunocompromised individuals are at highest risk, followed by cigarette smokers.7, 8 Adults receive one lifetime dose of the 23-valent pneumococcal vaccine, which may be repeated 5 years later for those at high risk, if there is a poor response to the initial vaccine or if the first dose was given before age 65.9 The 23-valent polysaccharide vaccine contains serotypes 1-5, 8-9, 12, 14, 17, 19-20, 22-23, 26, 34, 43, 51, 54, 56-57, 68, and 70.10

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Pneumococcal Vaccination for Children 

Children younger than 2 years old should receive four doses of the pneumococcal 7-valent conjugate (Prevnar) vaccine at 2, 4, and 6 months of age, and a booster vaccination at 12 to 15 months of age.1, 11 Prevnar vaccine contains the following seven serotypes: 4, 6, 9, 14, 18, 19, and 23.10 The 23-valent pneumococcal polysaccharide vaccine is not effective in children under the age of 2 as it does not elicit protective levels of antibodies, and this vaccine is generally reserved for adults, except in certain circumstances.12 Prevnar vaccine is conjugated and elicits a stronger protective response in infants than the pneumococcal polysaccharide vaccine, because infants and children under age 2 have a lower ability to make antibodies to the polysaccharide coatings of bacteria.12

Pneumococcal vaccination of children with either Prevnar or adult 23-valent polysaccharide vaccine, for those older than 2 years old, decreases the rate of hospitalizations by 65% and has the added benefits of decreasing nasopharyngeal colonization and transmission to others and providing protection in the community.4, 11, 13 Among children, day care center attendance increases the risk of invasive pneumococcal disease and otitis media by 2- to 3-fold among children under age 5.3

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Vaccine Effectiveness 

More than 80% of healthy adults develop antibodies against the 23 serotypes contained in the pneumococcal polysaccharide vaccine within 2 to 3 weeks.3 The serotype-specific antibodies should remain at a protective level for 5 years or longer after vaccination and protect against the 23 strains that cause 88% of pneumococcal infections; these levels may trend downward earlier in people with chronic disease.3 The vaccine is considered 60% to 70% effective in preventing pneumococcal disease in adults, but its effectiveness has been called into question in a few studies.8, 14, 15 Reasons for incomplete protection include ineffective antibody response, which is considered an inheritable trait, compromised immunity, poor nutritional status, acute illness or use of prednisone at the time of vaccination, and switching of pneumococcal genes to nonvaccine serotypes.8, 16, 17 Emergence of antibiotic-resistant strains of serotype 19A also complicates the treatment of pneumococcal disease; this serotype is a frequent cause of sinusitis among children.18, 19

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Revaccination 

Revaccination has not been found to boost antibodies to significant levels in the majority of adults but is recommended if one is considered high risk, had a poor response to the initial vaccine, and/or 5 years have passed since the first vaccination.3 Only one revaccination with the pneumococcal polysaccharide vaccine is generally recommended, including for those at high risk, as this vaccine does not induce immunological memory.3, 10 Occasionally, adults are given a booster of Prevnar vaccine as well if antibody levels to the serotypes in this vaccine remain low, but this vaccination is not widely given. If there is no response to revaccination, immunoglobulin G (IgG) replacement is considered for patients with low IgG levels and severe recurrent infections.10 Management of patients with recurrent infections and partial responses to pneumococcal vaccine includes cultures and aggressive antibiotic treatment when warranted.10

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Specific Polysaccharide Antibody Deficiency (SPAD) Syndrome 

Routine assessment of pneumococcal antibody titers is not necessary for most patients and is not a beneficial diagnostic test for children under the age of 2, as their ability to develop antibodies is acquired slowly.12 Patients with SPAD syndrome present with a history of frequent infections requiring antibiotics (51 per year) including sinusitis, pneumonia, otitis media, and bronchitis.20 Meningitis, Epstein-Barr virus infection, shingles, hepatitis, atypical mycobacterium infection, and tuberculosis may also be seen frequently in patients with SPAD.20 SPAD is a disorder of the acquired immune system, specifically the humoral arm, which depends on lymphocytic B cells that mature in the bone marrow and are responsible for Ig and antibody formation.21 The family medical history of patients with this disorder may also include instances of cancer (except leukemia and lymphoma), thyroid disease, and autoimmune diseases such as rheumatoid arthritis.20 It is speculated that these patients and their families have reduced immune surveillance to malignancy as well as increased susceptibility to infections.20

SPAD is the preferred term but is also referred to in the literature as antigen-specific antibody deficiency, specific antibody deficiency, and selective antibody deficiency with normal immunoglobulins. The term polysaccharide nonresponse is also found in the literature but is a general term not typically used. SPAD is diagnosed by careful history and physical assessment, quantitative immunoglobulins, pneumococcal serotype-specific antibody levels, and IgG subclasses.20 Infection history should include onset, type, frequency, duration, and antibiotics used.21 Onset of frequent infections prior to 6 months of age warrants a workup for pediatric immunodeficiency.21

People with IgA and IgG deficiencies may also have lower pneumococcal antibody levels. IgA deficiency is associated with autoimmune disorders, gastrointestinal disease, and genetic neurological disease, and presents with frequent sinus and pulmonary infections, food allergy, atopic dermatitis, urticaria, and asthma. IgG deficiency is also associated with asthma and frequent sinus and pulmonary infections.21, 22

Immunologists' opinions vary regarding treatment and interpretation of tests for SPAD. When pneumococcal serotype-specific antibody levels are drawn, and if 9/14 serotype levels are low, vaccination is recommended with repeat titers 4 to 6 weeks later.20 Some health-care providers vaccinate if 5/14 serotypes are low. Additional tests that may be performed include flow cytometry to examine peripheral T and B lymphocyte surface markers, enzyme-linked immunosorbent assays to measure levels of tetanus and diphtheria serologies, and viral serologies.20 Children 2 to 5 years old should experience an improvement in 50% of the serotypes tested after vaccination, and children over the age of 6 are expected to have a 70% response.9 An impaired response in adults is defined as less than 64% improvement in titers after vaccination.20

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Barriers to Vaccination 

The goals of Healthy People 2010 include achievement of 90% vaccination rates among adults over the age of 65.3 However, only half of older adults have received the pneumococcal vaccine, and only 20% of adults with chronic disease have received it.1 Vaccination rates are lowest among African-American and Hispanic people over the age of 65.23 Barriers to receiving the vaccine include mistrust and misperceptions regarding vaccines, lack of health-care access, and provider bias which keeps them from offering the vaccine.18, 24, 25 A major barrier to receiving vaccines is the incorrect perception that vaccination will cause the disease .25

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Contraindications to Vaccination and Adverse Reactions 

Contraindications to vaccination include severe allergy to the vaccine, acute illness, and pregnancy.3 Women who are at high risk for pneumococcal disease are advised to receive the vaccine prior to pregnancy, and those who are ill should wait until their condition improves.3 Adverse reactions to vaccination/revaccination are generally mild and include pain, swelling, and redness at the injection site, which resolve in less than 48 hours.26 Fever and myalgia occur in less than 1% of cases, and more severe reactions are rare.3 Systemic and local reactions are slightly higher among those revaccinated than those receiving their first vaccine: 4% to 8% systemic and 40% to 60% local reactions in adults, and 1% systemic and 50% local reactions in children.27, 28

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Vaccination Strategies 

Strategies to improve vaccination rates include reminders and recall systems, standing orders, prompts and improved vaccination records, and performance improvement measures.23, 25 Combining influenza and pneumonia vaccines on the same day is one strategy recommended to improve guideline adherence for adults.25 If, however, there is a concern about possible vaccine reactions, the vaccines should be administered on separate days. A case study follows that highlights the management of a young patient with SPAD syndrome with a slightly low IgG level.

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Case Study 

A 3-year-old Caucasian female presented for evaluation. Her mother reported that her child was seen in the local emergency room multiple times over the past year for various respiratory tract and sinus infections because the office hours were not convenient for her family. The child had not been exposed to second-hand smoke and attended day care. Her father had asthma. Her mother had no known health problems. The child had completed a 10-day course of cefdinir (Omnicef) 3 months previously for sinusitis. As she did not improve, 1 month later, she was prescribed clarithromycin (Biaxin) for 20 days. Her mother reported she was consistently administering her daughter's medications.

Her mother reported her daughter had a history of frequent upper-respiratory infections with nonproductive cough, increased nasal congestion, purulent nasal drainage, and fever. Two months previously, the child had a prolonged episode of wheezing that required nebulized albuterol treatment five times in a 36-hour period. Although the child had been evaluated in the emergency room, she had never been hospitalized.

Her medical history included nonallergic rhinitis, probable asthma, and chronic sinusitis. A computed tomography scan of her sinus revealed extensive pansinusitis, with the frontal sinuses not yet fully developed. She had undergone placement of two sets of pressure equalization tubes and an adenoidectomy as outpatient procedures in the past. She had received 10 courses of antibiotics over the past year. Her vaccinations were up to date, and she had received Prevnar vaccine. Her mother received prenatal care, and the child's first 6 months of life were uneventful, except for a few ear infections, which resolved with antibiotics.

Current Medications 

The child's current medications included mometasone furoate (Nasonex) nasal spray, 50 mcg, 1 spray per nostril daily; nasal saline spray, twice per day as needed; budesonide (Pulmicort), 0.25 mg, twice per day via nebulizer during respiratory illness; and albuterol via nebulizer as needed.

Physical Examination 

The patient's physical examination showed a temperature of 37°C (98.8°F); pulse, 90 beats per min; respirations, 20 breaths per min; weight, 33.6 lbs; and height, 37 inches. Her general appearance was that of a well-nourished child in no acute distress. Head, eyes, ears, nose, and throat (HEENT) examinations revealed her eyes were clear to mildly injected; pressure equalization tubes in her ears appeared patent and functional, nasal mucosa was erythematous and injected. Turbinates were normal. Oropharynx was clear and moist. Posterior pharynx was clear, and no postnasal drainage was noted. Sinuses showed no tenderness to pressure or palpation; her neck appeared normal; cervical lymph nodes were not enlarged; the chest wall had no intercostal retractions; respiration was normal, with unlabored respiratory effort; lung fields were clear to auscultation, and excursions were normal; and skin had no rashes, a normal turgor, and no clubbing of nails, and no cyanosis. Although she was very young, the child was able to undergo spirometry testing, which was normal. She had a forced vital capacity (FVC) of 261%, a forced expiratory volume per 1 sec (FEV1) of 189%, and a FEV1/FVC ratio of 0.91.

Laboratory Studies 

Prior to receiving her last antibiotic, the child had a nasal smear that showed 90% neutrophils, 2% lymphocytes, 1% eosinophils, and 7% epithelial cells.

Results of a complete blood count (CBC) with differential was normal, with a white blood cell (WBC) count of 12.7 k/uL, an Hgb level of 12.6 g/dL, and a platelet count of 361 k/uL.

Ig levels were as follows: IgE, <1.5 IU/mL (range 0.4–351.6); IgG, 313 mg/dL (range, 341–1960; assessed as low); IgA, 26 mg/dL (range, 22–220); and IgM, 58 mg/dL (range, 43–163).

IgG subclass levels were as follows: IgG subclass 1, 257 mg/dL (low) [reference range, 315–945]); IgG subclass 2, 47 mg/dL (normal [reference range, 38–225]); IgG subclass 3, 29 mg/dL (normal [reference range, 17–68]); IgG subclass 4, 0.3 mg/dL (low [reference range, 1.0–54.0]). IgG subclasses 1 and 4 were low, accounting for her low total IgG. Subclasses 2 and 3 were normal.

Pneumococcal type-specific antibody levels of approximately 2.0 mcg/mL are protective against invasive pneumococcal disease. Twelve of 14 pneumococcal serotype-specific antibody levels were low. Six weeks after vaccination with the 23-valent pneumococcal polysaccharide vaccine 13/14 pneumococcal serotype-specific antibody levels were at protective levels.

In the 6 months since she received the 23-valent pneumococcal polysaccharide vaccine, the patient had not required any antibiotics, and her mother reported one viral illness, which resolved without incident. All of the pneumococcal serotype-specific antibody levels except one are now at protective levels (Table 1). Twelve of 14 serotypes were low before the vaccine. Because of the slightly low IgG subclass levels, titers may be rechecked in the future if the frequency of infections requiring antibiotics again increases. The child will continue to be monitored closely for recurrence of frequent infections and development of asthma, and her nonallergic rhinitis and chronic sinusitis are being treated with gentle nasal saline cleansing and nasal steroid therapy.

Table 1. Effect of 23 valent pneumococcal vaccine on serotype specific antibody levels
Antibody level (mcg/mL)
SerotypePre-pneumococcal serotype specific antibody levelsPost-pneumococcal serotype specific antibody levels
1 (1)<0.31.4
3 (3)<0.32.2
4 (4)<0.313.7
5 (5)<0.34.6
8 (8)<0.343.9
9 (9N)<0.38.8
12 (12F)<0.32
14 (14)0.815.9
19 (19F)15.97.4
23 (23F)0.416.6
26 (6B)4.9159
51 (7F)<0.33
56 (18C)0.311.2
68 (9V)0.67.6

*Pneumococcal type-specific vaccine antibody levels of approximately 2.0 mcg/mL are protective against invasive pneumococcal disease; 12/14 pneumococcal serotype-specific antibody levels are low. Six weeks after vaccination with the 23-valent pneumococcal polysaccharide vaccine, 13/14 pneumococcal serotype-specific antibody levels are at protective levels.

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Treatment of Patients with SPAD 

Patients with this disorder require observation for frequent infections, assessment for atopic diseases and asthma, and monitoring for disorders associated with low pneumococcal serotype-specific antibody levels and immunoglobulin deficiencies.22 As allergic disease is frequently found in patients with B-cell disorders, a referral to an allergist who also specializes in immunology is warranted.22 Referral to an ear, nose, and throat specialist may be needed for the patient with severe chronic sinusitis, as well. Laboratory studies may need to be repeated if the number of infections requiring antibiotics increases, and repeat vaccination with 23-valent polysaccharide vaccine may be warranted.

Prevention of pneumococcal disease has the potential to significantly reduce health-care costs, morbidity, and mortality. Nurse practitioners have the opportunity to significantly impact the incidence of pneumococcal disease in their communities through vaccination, which also reduces nasopharyngeal carriers of the disease and protects the unvaccinated.

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References 

  1. National Foundation for Infectious Diseases  . Facts about pneumococcal disease . Available at: http://www.nfid.org/pneumococcal/consumers_factsheet.html Accessed 10/20/09.
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 In compliance with national ethical guidelines, the author reports no relationships with business or industry that would pose a conflict of interest.

PII: S1555-4155(10)00036-X

doi:10.1016/j.nurpra.2010.01.015

The Journal for Nurse Practitioners
Volume 6, Issue 7 , Pages 534-539, July 2010

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