Streptococcus pneumoniae (SP) is the most common cause of community-acquired pneumonia. SP Diagnosis currently relies on isolation of the bacterium from clinical specimen, a process vulnerable to false-negative results and difficult to distinguish invasive infection from carriage. We evaluated a novel diagnostic method that measures circulating, SP-specific antibody secreting cells (ASC), which can be detected in the peripheral blood transiently during acute infection. As a proof of concept, patients with confirmed SP bacteremia were recruited and SP-specific ASCs were measured by ELISpot assay.
A total of 168 subjects were enrolled in this study. This includes 91 healthy individuals, 47 patients with blood culture-confirmed SP bacteremia and 30 patients with bacteremia of non-SP origin. Serum and peripheral blood were collected within 4 days of culture-confirmation which was within 5-11 days of symptom onset. Peripheral blood mononuclear cells were isolated and the frequencies of ASCs specific for four SP antigens were measured. Culture negative specimens were tested for lytA gene with lytA PCR assay.
Patients with SP and non-SP bacteremia were similar in age, comorbidities and disease severity. The average frequency of SP-specific IgG secreting cells per mL of blood measured in SP patients was higher than the frequency in non-SP patients. Among the SP antigens, ASC frequency for one particular SP-antigen was high in patients with SP bacteremia. In a Receiver Operating Characteristic curve, this SP-antigen was highly discriminating with area-under-the-curve (AUC) of 0.89 compared to other 3 antigens (AUC less than 0.75). A sum function of all SP-antigens yielded an AUC of 0.92. SP-specific ASCs were not detected in the two SP colonized adults nor in eleven of the non-SP colonized healthy controls.
SP-ASC frequencies within 5-11 days of symptom onset predicted SP bacteremic infections. The sensitivity and specificity of the SP-specific antibodies secreted from circulating ASCs demonstrate the utility of this novel diagnostic for acute SP infection, and the feasibility for acute respiratory SP infections.
S. Y. Kyu,
Y. F. Wang, None
A. R. Falsey, ADMA Biologics: Research Contractor , Fee for service laboratory work
E. Walsh, None
J. L. Daiss, MicroB-plex, Inc.: Employee , Salary
G. Rajam, None
V. Srinivasan, None
S. Ros, None
E. Ades, None
F. E. H. Lee, MicroB-plex, Inc.: Founder and Shareholder , Consulting fee
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