During a 9-month study of patients being evaluated for coccidioidomycosis, 1 or more serum samples were obtained from 138 patients with an illness suggestive of recent infection. In this group, standard immunodiffusion tests of unconcentrated sera were positive for 25; 49 additional patients had at least 1 reactive test result by newer enzyme-linked serologic tests. At least 11 of these 49 patients had coccidioidomycosis as determined by culture or subsequent standard serologic tests. Patients with coccidioidomycosis identified only by newer tests had fewer or milder clinical abnormalities than did patients in whom the disease was detected by standard tests. For 31 other patients with illness of a chronic or undetermined duration, newer tests detected only 10 more than the 18 identified by standard tests, suggesting that later in the course of illness, standard testing gains in sensitivity for coccidioidal infection.
Arizona college students suspected of having recently acquired coccidioidomycosis were tested for anticoccidioidal antibodies and circulating fungal antigens using conventional antibody detection methods and new ELISA procedures. Of 233 patients with compatible symptoms, 26 had anticoccidioidal antibodies detected by conventional tests. ELISA detected antibodies in sera from 20 of these patients and also from another 25 patients. Patients with antibodies detected by either conventional or ELISA procedures were significantly more likely to have abnormal chest radiographs, elevated erythrocyte sedimentation rates, or absent upper respiratory symptoms than were other patients. Circulating antigen was found in sera from 35 patients, 33 of whom had no detectable anticoccidioidal antibodies at that time. Detectable antigen was noted frequently in sera obtained within the first month after the onset of symptoms and was infrequently detected later when more patients exhibited antibodies. These results indicate the feasibility of developing ELISA procedures using spherule-derived antigens for earlier detection of coccidioidal infections.
Since 1951, the tuberculin PPD-S1 has been used to standardize commercial PPD reagents and perform special tuberculin surveys. PPD-S1 is now in short supply and a new standard (PPD-S2) has been manufactured. To determine if PPD-S2 is equivalent and can replace PPD-S1, we conducted a double-blind clinical trial. Between May 14 and October 28, 1997, 69 subjects with a history of culture-proven tuberculosis (TB patients) and 1,189 subjects with a very low risk for TB infection were enrolled, received four skin tests (with PPD-S1, PPD-S2, and one each of the commercially available PPDs), and had reactions measured by two trained observers. Among the TB patients, we found statistically indistinguishable immunogenicity (mean reaction size +/- standard deviation): 15.6 +/- 6.6 mm for PPD-S1 and 14.8 +/- 5.6 mm for PPD-S2. Among low-risk subjects, the tests had equally high specificities (PPD-S1, 98.7% and PPD-S2, 98. 5%), using a 10-mm cutoff. The number of discordant (negative versus positive) interpretations for PPD-S2, assuming that low-risk subjects who had a >/= 10 mm reaction to PPD-S1 were truly infected, was low (0.5%) and indistinguishable from the rate of discordant interpretations of the same test when read by two different observers (0.8%). The study results indicate that PPD-S2 is qualified to be used as the new U.S. reference standard for PPD tuberculin.
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