Serologic reactions in coccidioidomycosis

Abstract

Coccidioidal serologie tests consist of a qualitative precipitin test and a quantitative complement fixation (C.F.) test. The antigens for each of these tests are appropriately standardized “Coccidioidins” comparable to that used for skin testing. The tests are relatively specific, though there is some irregular crossreaction in the other deep mycoses of histoplasmosis and probably blastomycosis. The tests detect better than 99 per cent of all coccidioidal infections which have undergone dissemination. Repeated tests can diagnose 90 per cent of symptomatic primary infections. However, even in symptomatic primary infections, failure to detect these diagnostic humoral antibodies does not rule out a coccidioidal diagnosis. They are frequently negative in patients with coccidioidal pulmonary residuals with and without cavitation. Unless a patient's disease is undergoing dissemination, dermal sensitivity will be established during primary infection before the humoral antibodies have developed. Precipitins develop before complement-fixing antibodies and vanish sooner. Their presence connotes that the infection was acquired in the previous few months, although they may persist longer in patients with disseminated infections. Precipitins are of little diagnostic use in patients with asymptomatic pulmonary residuals or pulmonary cavities because of this time relationship. The titer of precipitins does not have prognostic significance. However, the quantitative determination of complement-fixing antibodies is very important prognostically. The more severe the infection, the higher the C.F. titer. Thus, in at least one-third of patients with primary infections which can be diagnosed serologically, only the precipitins will be positive. In those whose serum fixes complement, nearly half do so only in a 1:2 serum dilution and only 1 in 20 will fix it at a titer greater than 1:16 with the technique we use. However, over three-fifths of all those with disseminated disease exceed this titer as do ninetenths of those with extensive dissemination. With our technique this 1:16 serum dilution has proved to be a “critical” level. A rising titer is ominous, while a declining titer is reassuring. Complete fixation of complement by spinal fluid is diagnostic of coccidioidal meningitis and occurs in three-fourths of those with this dread complication. Because variations in C.F. techniques affect the titer, a positive serum control adjusted to the “critical” titer is needed as an index of comparison. Every effort is being made to develop such a material for the commercial distribution which should enable any competent clinical laboratory to perform the coccidioidal serologie tests.