Sex: U
Vaccine: PPV
Symptoms: Antibody test negative, Therapy non-responder
Clinical narrative: This literature market report has been received from authors of a Letter to the Editor referring to 23 children of unknown gender. They had two sets of pneumococcal titers to 23 serotypes drawn 4-12 weeks apart between January 2005 and December 2014. The patients' exclusion criteria included treatment with an immunosuppressive agent in the 3 months prior to the testing, history of solid organ or bone marrow transplants, and diagnosis of another immunodeficiency. Information of concomitant medication was not reported.The reporters thoroughly reviewed the patients' chart to ascertain that the specific or selective antibody deficiency (SAD) patients did not have clinical or laboratory features that may raise concerns for other immunodeficiencies that could potentially present with impaired response to vaccines. On unknown dates between January 2005 and December 2014, the patients were vaccinated with PNEUMOVAX 23 (one dose, strength, frequency, route, lot# and expiration date were unknown) for prophylaxis. A second set of antibody levels were obtained 4-8 weeks following the booster. To define an adequate response to PNEUMOVAX 23, the reporters utilized cutoffs recommended by a task force of the Academy: a post-immunization level is more than 1.3 microgram per milliliter (mcg/mL), or at least a 4-fold rise in a titer, compared to the pre-immunization level to greater than or equal to 50% of serotypes tested for 2-5 years of age, or greater than or equal to 70% of serotypes tested for children 6 years and older. On unknown dates, these 23 patients demonstrated inadequate responses to PNEUMOVAX 23 and were diagnosed with specific or selective antibody deficiency (SAD). The outcome of the event was unknown. The reporter considered the event was related to the PNEUMOVAX 23. These patients were diagnosed with SAD because they had an inadequate response to PNEUMOVAX 23, but demonstrated normal total immunoglobulin levels and had documented protective titers to tetanus toxoid and Haemophilus influenza type b. Multiple univariable analyses that evaluated the ability of a post-immunization antibody level of more than 1.3 mcg/ml to each serotype in predicting SAD revealed a wide range of predictive abilities for each individual serotype (area under the receiver operating characteristic (ROC) curve (AUCs) range from 0.57 (unit not provided) to 0.81 (unit not provided)). A multivariable stepwise regression revealed that the post-immunization levels of five specific serotypes: 4, 5, 11A, 18C, and 20 were negatively associated with the presence of SAD, P was less than 0.05 (unknown unit), and indicated that among children with post-immunization antibody level more than 1.3 mcg/mL to each of these serotypes, the predicted odds of a SAD diagnosis decreased by 88%- 99%. The estimated ROC, AUC, using the post-immunization levels to the combination of these five serotypes alone to predict whether or not the patient had SAD, was 0.96 (95% CI 0.92-1.0 (unknown unit)). Upon internal review, specific or selective antibody deficiency (SAD) was determined to be medically significant.