Interpretive Handbook

Streptococcus pneumoniae causes infectious diseases in children and adults, including invasive infections (eg, bacteremia and meningitis) and infections of the respiratory tract (eg, pneumonia and otitis media).(1,2) Streptococcus pneumoniae is responsible for approximately 40,000 deaths and 500,000 cases of pneumonia annually in the United States. There are more than 90 serotypes of Streptococcus pneumoniae. The serotypes responsible for disease vary with age and geographic location. In children <6 years, 7 serotypes (4, 6B, 9V, 18C, 19F, and 23F) account for 80% of invasive disease and up to 100% of all isolates that are highly resistant to treatment with penicillin.(3,4)

In adults, risk factors for pneumococcal disease include chronic cardiovascular diseases, chronic pulmonary diseases, diabetes, alcoholism, asthma, and treatment with corticosteroids. The highest risk situations are associated with immunosuppression, including those that are disease associated (eg, multiple myeloma or iatrogenic, asplenia [sickle cell disease], neutropenia, and humoral immune deficiencies).

Bacterial polysaccharides elicit antibodies in children by a T-cell independent mechanism and immune responses to polysaccharide antigens such as Streptococcus pneumoniae are generally poor in children <2 years of age. Active immunization of children <2 years requires multiple injections of vaccine prepared from purified polysaccharides conjugated to an immunogenic carrier (Corynebacterium diptheria strain C7 protein). The recommended vaccine for children <2 years (Prevnar) contains the 7 serotypes mentioned above, and is administered in 4 doses. The vaccine is highly effective in preventing invasive disease in children with reported efficacy of 88% to 100%. Active immunization of adults and children >2 years is performed with unconjugated polysaccharide vaccines that contain additional serotypes (eg, PNEUMOVAX or Pnu-Imune 23). PNEUMOVAX and Pnu-Imune 23 contain 23 different purified polysaccharides from serotypes that account for 90% of the isolates from blood and 85% of isolates from normally sterile body fluids. Protective levels of antibodies develop in nonimmunocompromised adults and older children approximately 3 weeks following immunization and overall rates of efficacy range from 60% to 80% for protection against pneumonia and bacteremia. Serotype-specific antibodies persist for up to 10 years following immunization.

Assessing the response to active immunization with nonconjugated, 23-valent vaccines

Determining the ability of an individual to respond to polysaccharide antigen(s)

The minimum concentration of IgG antibody necessary to insure protection against invasive disease has not been determined for any serotype of Streptococcus pneumoniae.

It is not possible at this time to define a universal "normal value" for IgG antibodies to Streptococcus pneumoniae serotypes that is appropriate for all healthy adults and children >2 years of age, either prior to or following immunization with unconjugated vaccines. The normal value cutoffs were determined from measurements in healthy, nonimmunized adults in Rochester, MN, and are offered as guidelines for comparison with adult persons elsewhere.

As a general guideline, nonimmunocompromised adults respond to immunization with unconjugated vaccines by approximately 3 weeks following immunization, and the concentrations of IgG antibodies to Streptococcus pneumoniae serotypes often show at least a 2-fold increase (paired sera). The number of different serotypes to which healthy adults respond is variable. The minimum serologic response necessary to identify an individual as "normal" has not been defined, either for the number of serotypes or the magnitude of response in units of concentration.

Serotype-specific antibodies may persist for up to 10 years following immunization or infection.

The humoral immune response to Streptococcus pneumoniae is age dependent and the database of IgG antibody concentrations to different serotypes is incomplete. Protective levels of IgG antibodies to Streptococcus pneumoniae are not defined for any serotype.

Results are reported in mcg/mL. 

1. Schuchat A, Robinson K, Wenger JD, et al: Bacterial meningitis in the United States in 1995. Active surveillance team. N Engl J Med 1997 October;337(14):970-976

2. Zangwill KM, Vadheim CM, Vannier AM, et al: Epidemiology of invasive pneumococcal disease in southern California: implications for the design and conduct of a pneumococcal conjugate vaccine efficacy trial. J Infect Dis 1996 October;174(4):752-759

3. Butler JC, Breiman RF, Lipman HB, et al: Serotype distribution of Streptococcus pneumoniae infections among preschool children in the United States, 1978-1994: implications for development of a conjugate vaccine. J Infect Dis 1995 April;171(4):885-889

4. Butler JC, Hoffman J, Cetron MS, et al: The continued emergence of drug-resistant Streptococcus pneumoniae in the United States: an update from the Centers for Disease Control and Prevention's Pneumococcal Sentinel Surveillance System. J Infect Dis 1996 November;174(5):986-993

5. Jacob GL, Homburger HA: Simultaneous Quantitative Measurement of IgG Antibodies to Streptococcus Pneumoniae Serotypes by Microsphere Photometry. J Allergy Clin Immunol,2004;113(2) Suppl (Abstract 1049, pS288)

6. Plikaytis BD, Holder PF, Pais LB, et al: Determination of parallelism and nonparallelism in bioassay dilution curves. J Clin Microbiology 1994 October;32:2441-2447

7. Plikaytis BD, Goldblatt D, Frasch CE, et al: An analytical model applied to a multicenter pneumococcal enzyme-linked immunosorbent assay study. J Clin Microbiology 2000 June;38(6):2043-2050