Among the 44 culture-confirmed patients with a positive CF result, antibodies to both the yeast (Yst) and mycelial (Myc) antigens were detected in 30 (68.2%) cases, 29 of whom were also positive by the ID assay (Tables 2 and ?and3).3). (64.3%) and 15 (35.7%) cases, respectively. Among 18 serially tested patients, 12 remained ID and/or CF positive at the final time point (median, 154?days; range, 20 to 480?days). Serial CF testing showed that antibodies to the mycelial antigen serorevert to unfavorable more frequently (6/11) than antibodies to the yeast antigen (2/13). There was no statistically significant difference in antibody positivity relative JNJ 1661010 to patient immune status, degree of disease dissemination, or symptom JNJ 1661010 duration. Serologic testing remains a valuable asset to support the diagnosis of histoplasmosis, particularly when direct detection methods fail to identify an infection. KEYWORDS: is usually a dimorphic fungal pathogen endemic to the Ohio and Mississippi River Valleys of North JNJ 1661010 America, with a recently increasing incidence beyond these regions. Although exposure may lead to asymptomatic disease or limited, self-resolving symptoms in otherwise healthy individuals, morbidity and mortality are often more severe in older patients and those with impaired cellular immunity (1). As a JNJ 1661010 result, the rapid and accurate diagnosis of contamination with is necessary to guide appropriate antifungal treatment for the best possible patient outcomes. The recovery of in culture or tissue by histopathology remains the reference method for diagnosis. However, this method is usually associated with a number of limitations, including the need for invasive procedures to obtain optimal specimen types (which may be contraindicated in some patients), variable assay sensitivities depending on the extent of disease, and a long turnaround time for cultures depending on the inoculum and specimen type (2). In an effort to provide a timelier diagnosis, molecular methods have been developed, although these assays are also limited by the need for invasive specimen collection procedures and have been associated with variable sensitivities across studies (3,C5). Finally, assessment for circulating antigen in serum or urine offers a noninvasive means to directly detect contamination, with a significantly shorter turnaround time than culture. Key limitations associated with this method, however, include cross-reactivity with other dimorphic pathogens and variable sensitivity depending on the disease state (2, 6, 7). In addition to the above-mentioned methods, the detection of antibodies to in serum via different serologic methods is also frequently relied on to assist in making the diagnosis. Serologic testing is particularly useful in patients for whom invasive specimen collection is usually contraindicated and those presenting with subacute or chronic forms of histoplasmosis, for which antigen detection is less sensitive (2, 8,C10). Antibody detection, however, is associated with several Rabbit Polyclonal to ZNF280C limitations, including false positivity for some assays in patients infected with other dimorphic pathogens (i.e., cross-reactivity) and false-negative results in significantly immunocompromised patients and in those for whom sample collection occurs prior to the development of a detectable antibody response (i.e., seroconversion occurs between 4 and 6?weeks and as early as 2?weeks after contamination) (2, 11,C13). Available serologic methods for the detection of antibodies to include enzyme immunoassays (EIAs), complement fixation (CF) assays, and immunodiffusion (ID) assays; the latter two classic methods were originally developed in the 1950s and clinically JNJ 1661010 deployed in the 1970s and 1980s as part of outbreak investigations (14,C16). EIAs offer high-throughput and automated testing; however, given their qualitative results and lower specificity (depending on the assay), some laboratories have opted to confirm positive results via CF/ID testing. In contrast to EIAs, CF and ID methods are labor-intensive, technically complicated, and typically performed manually, with increasingly limited reagent availability and challenges associated with the interpretation of the results. Due to these complexities and the significant technologist expertise required to maintain these assays, CF and ID methods are available primarily through reference laboratories. Interestingly, although frequently ordered, the majority of studies evaluating the performance characteristics of CF/ID assays were conducted over 3 decades ago and used reagents developed in research laboratories or available through a single reference laboratory (2, 9, 17). Here, we present our institutional experience with CF and ID testing using commercially available reagents, to provide a current assessment of the clinical sensitivity of these assays in patients with culture-confirmed histoplasmosis. MATERIALS AND METHODS Study design. We performed a 10-year retrospective chart review of all adult patients with culture-confirmed histoplasmosis at Mayo Clinic (Rochester, MN) from January 2011 to December 2020. Using these criteria, 76 patients with culture-confirmed histoplasmosis were identified, among whom 67 had at least one serology order as part of the disease episode and were included in this analysis. serologic testing at Mayo Clinic.