Use of a sensitive microplate enzyme-linked immunosorbent assay in a retrospective serological analysis of a laboratory population at risk to infection with typhus group rickettsiae

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Abstract
A microplate enzyme-linked immunosorbent assay (ELISA), developed for the detection of antibodies to typhus group rickettsiae, was used to analyze human sera from individuals engaged directly or indirectly in rickettsial research. The earliest serum available from each of 112 individuals was tested for IgM and IgG antibodies against Rickettsia typhi and R. prowazekii by ELISA at a 1:500 dilution. In at least 1 assay, 9 sera had ELISA optical densities of > 0.2, which were above the mean optical densities plus 3 of the other 103 sera. Three of the positive sera were from individuals with known clinical cases of typhus infection. The other sera with predominantly IgG titers were from individuals with extended laboratory exposure to rickettsiae or histories of typhus vaccination, or both. During continued serological surveillance, 8 additional people with repeated occupational exposure to typhus rickettsiae had seroconversions in the ELISA to optical densities of > 0.02. No apparent clinical illness occurred in 2 individuals, whereas 6 clinical cases of infection occurred in others subsequent to accidental laboratory autoinoculation (1) or aerosol exposures (5). In the clinical infections, antibodies were first detected at 7 days, but in subsequent sera, rises and declines in titers were quite variable and were influenced by vaccination, relapse and time and extent of antibiotic therapy. In primary infections the sera of several individuals who received immediate antibiotic therapy had brief strong IgM responses without pronounced increases in IgG. In contrast, much higher IgG levels were attained in 3 cases in which relapse occurred, the individual was previously immunized or treatment was delayed. The microplate ELISA was a highly sensitive and reliable test for detection of the human serological response to typhus antigens.

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