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The analytical shift from ng antibody nitrogen-based results to weight-based units has played a role in the difficulties in establishing defined cutoffs with modern assays, particularly in adult populations. Many of the original studies which established “protective” cutoffs for antibody levels (defined using infection rates in epidemiologic studies) or “adequate response” cutoffs for vaccine studies were performed using assays which reported in antibody nitrogen units. Little published data are available to establish the conversion factor between the two methods of measurement. The most commonly cited example for a conversion factor comes from recommendations published in 2007 which utilized data derived from a personal communication ( 10 ). This factor propagated through later publications and is the source of the commonly utilized cut points of 1.0 μg/ml and 1.3 μg/ml described in the clinical section which follows.

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Initial clinical application of serotype-specific PnAb measurement was largely limited to academic studies and vaccine development trials, in part because of the effort and expense required to run the multiple individual ELISAs needed to generate a comprehensive serologic response profile. This changed in the early 2000s with the commercial emergence of multiplex immunoassay platforms in clinical laboratories. One of the earliest described multiplex assays for PnAb measurement was developed using a bead-based flow cytometric methodology (Luminex) that measured quantitative levels of PnAb against 14 serotypes from a single assay ( 11 ). This test was subsequently validated using clinical specimens ( 12 ) and was eventually approved by the FDA and marketed as an in vitro diagnostic (IVD) assay in the United States for a period of time. Multiplex pneumococcal assays, including electrochemiluminescent assays and chemiluminescent microarrays, were also developed on other platforms ( Castaer Woman Calf Hair Slipon Sneakers Black Size 40 Castaner Gi8VAB
, 14 ). The increased availability of this testing at multiple reference laboratories and the associated reduction in costs and sample requirements greatly expanded clinical utilization of multiplex serologic PnAb measurements in routine practice.

This widespread application of multiplex PnAb assays, however, brought several additional challenges with interpretation. Quantitative comparisons of PnAb levels measured by multiplex assays were not always consistent with results from WHO-based ELISA methods ( 15 ), and the performance characteristics of these assays often did not meet the criteria set in the original WHO document developed for ELISA testing. Intralaboratory comparisons of assays from different laboratories showed substantial variation in quantitative results even when the same basic technology was being utilized ( front pleat cropped trousers Nude amp; Neutrals Fabiana Filippi qFkigi
), although clinical classifications of patients were relatively unaffected by these quantitative variations using published algorithms ( 17 , 18 ). As a result, interpretation of multiserotype test results could be a challenge for clinicians trying to apply pneumococcal serotype analysis to their practice in different clinical scenarios.


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