Abstract
In a detailed study of 25 healthy laboratory workers, complement-fixation titers were increased from negative (<1:8) to as high as 1:256 in 7 of the 12 positive reactors following a single histoplasmin skin test. Agar gel diffusion tests converted from negative to positive in 9 of the 12. These results were obtained with histoplasmin but not with the whole yeast phase antigen, which was used only in the complement fixation test. The increased levels of circulating antibody occurred between 5 and 10 days after the single stimulus in some persons but not until after the 20th day in others; they persisted, with one exception, throughout an observation period of 81 days. Serum collected from 13 negative histoplasmin skin-test reactors were negative in both tests throughout the course of the study. There is good evidence that the skin-test stimulatory factor is present in all lots of histoplasmin, although possibly in varying degrees, and also possibly in certain lots of the whole yeast phase antigen. Failure to recognize this factor in earlier studies has probably contributed to error in estimating the number of active cases of histoplasmosis in serologic surveys of populations and in the diagnosis of individual cases. There is danger that these errors will be further compounded with the increasing use of agar gel diffusion tests because, unlike the more complex complement-fixation test, this simple procedure can be performed in any laboratory with histoplasmin that is commercially available. To obviate continuation of this error, it is recommended that the histoplasmin skin test be used with greater discrimination in persons in whom serologic tests are to be done, that skin and serologic tests be used together as seldom as possible, and that the concentration of the skin-test stimulatory factor be predetermined for each lot of antigen before its use in serologic tests, as part of the standardization procedure.

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