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Background Coccidioidomycosis is a fungal infection that usually presents as a primary lung infection. The fungus is endemic to the Southwest United States of America, northern Mexico and parts of Central and South America the infection is rare outside these areas. However, some patients develop disseminated infection that can lie dormant for several years and can present itself in travelers. We report the first case of extra pulmonary Coccidioidomycosis in a non-immunocompromised individual in Denmark. Case presentation A 32 year old Danish woman presented at the Emergency department with abdominal pain. Computed tomography scan and ultrasound examination of the pelvis raised suspicion of salpingitis. A laparoscopy exposed a necrotic salpinx and several small white elements that resembled peritoneal carcinomatosis. Histological workup however determined that she suffered from disseminated coccidioidomycosis. The patient had lived 2 years in Las Vegas, in the United States of America, 7 years prior and had no memory of lung infection at the time. Conclusions Disseminated coccidioidomycosis is rare in non-immunocompromised individuals. The patient in this case underwent several rounds of in vitro fertilization treatment in the years before admittance. We suspect that the hormonal treatment in combination with low-dose prednisolone may have triggered reemergence of the disease and present literature that support this.

Background. In human immunodeficiency virus (HIV)–infected patients, fluconazole prophylaxis is associated with reductions in the rate of fungal infection. However, concerns exist with regard to the use of fluconazole prophylaxis and the risk of development of fluconazole treatment—refractory infections. Methods. We performed a randomized, open-label trial that compared oral fluconazole given continuously (200 mg 3 times weekly; the “continuous fluconazole arm”) with fluconazole that was provided only for episodes of orophayngeal candidiasis (OPC) or esophageal candidiasis (EC) (the “episodic fluconazole arm”) in HIV-infected persons with CD4+ T cell counts of <150 cells/mm3 and a history of OPC. The primary study end point was the time to development of fluconazole-refractory OPC or EC, which was defined as lack of response to 200 mg fluconazole given daily for 14 or 21 days, respectively. Results. A total of 413 subjects were randomized to receive continuous fluconazole, and 416 were randomized to receive episodic fluconazole. After 42 months, 17 subjects (4.1%) in the continuous fluconazole arm developed fluconazole-refractory OPC or EC infections, compared with 18 subjects (4.3%) in the episodic fluconazole arm, with no difference between treatment arms with regard to the time to development of a fluconazole-refractory infection within 24 months (P = .88, by log-rank test) or before the end of the study (P = .97, by the log-rank test). Continuous fluconazole therapy was associated with fewer cases of OPC or EC (0.29 vs. 1.08 episodes per patient-year; P < .0001) and fewer invasive fungal infections (15 vs. 28 episodes; P = .04, by χ2 test), but not with improved survival, compared with episodic fluconazole therapy. Conclusion. Continuous fluconazole therapy is not associated with significant risk of fluconazole-refractory OPC or EC, compared with episodic fluconazole therapy, in HIV-infected patients with access to active antiretroviral therapy.

An 11-year-old neutered male domestic longhair cat was diagnosed with histoplasmosis from fine-needle aspirates of an abdominal lymph node. Lymph node size initially decreased with fluconazole therapy (11.8 mg/kg PO q12h); however, after 13 months of continuous fluconazole therapy, lymphadenomegaly worsened and samples were collected for culture and antifungal susceptibility. The Histoplasma capsulatum isolate had a very high fluconazole minimum inhibitory concentration (MIC) of 64 µg/ml and an itraconazole MIC of 0.06 µg/ml. The owner declined a change to itraconazole and, ultimately, the cat developed neurologic signs and was euthanized. Owing to the initial response to fluconazole followed by treatment failure and high MIC value, acquired fluconazole resistance was suspected. Clinical breakpoints for fluconazole for the dimorphic fungi are not available to define true antifungal resistance. This is the first published report of reduced susceptibility to fluconazole in a cat being treated for histoplasmosis. Fluconazole failure and increases in MIC between pretreatment and long-term treatment isolates are known to occur in humans with histoplasmosis. Practitioners should be aware of this possibility when treating cats with fluconazole (particularly in cases with long-term [>1 year] fluconazole therapy or in cases with disease recrudescence).

Background Antibody detection is the main method for diagnosis of coccidioidomycosis but has limitations including sensitivity and turnaround time. The MVISTA Coccidioides antigen enzyme immunoassay (EIA) is recommended for testing CSF in suspected Coccidioides meningitis. The early reports on urine and serum antigen testing evaluated small numbers of patients who were mostly immunocompromised with advanced disease. Methods A retrospective study, including all patients in whom Coccidioides antigen testing was performed between January 2013 and May 2017, was conducted at Maricopa Integrated Health System (MIHS). Sensitivity and specificity of antigen testing at MiraVista Diagnostics and antibody testing at MIHS or commercial laboratories were evaluated in 164 cases and 508 controls. Results The sensitivity of antigen testing was 51% and specificity was 99%. The sensitivity of antigen detection was highest if both urine and serum were tested (57%) than if only urine was tested (38%). The sensitivity of antibody testing was 84% and the specificity was 94% by immunodiffusion (ID). The sensitivity and specificity of antigen or ID antibody testing both were 94%. Sensitivity of antigen testing was 57% in proven and 58% in probable cases, ID antibody in 85% of proven and 75% of probable and antigen or ID antibody in 93% of proven and 95% of probable cases. Antigen was detected more often in disseminated (79%) than pulmonary cases (42%) as was ID antibody, 91% and 79%, respectively. Antigen testing was more sensitive in immunocompromised (76%) than non-immunocompromised patients (41%) while ID antibody was less sensitive in immunocompromised (74%) than in non-immunocompromised patients (93%). Combined antigen and ID antibody testing provided the highest sensitivity, 94% in all cases, 94% in immunocompromised and 95% in non-immunocompromised patients. Conclusion These findings support testing urine and serum for Coccidioides antigen and serum for ID antibodies for diagnosis of progressive pulmonary or disseminated coccidioidomycosis. Disclosures All authors: No reported disclosures.

The diagnosis of Histoplasma capsulatum infection by serologic testing for the presence of antibodies is limited by a high rate of false positive and false negative results and by the requirement that the patient have a normal immune response. We have developed a radioimmunoassay for the detection of H. capsulatum antigen in urine and serum specimens. Antigenuria was noted in 20 of 22 episodes of disseminated histoplasmosis that occurred in 16 patients, in 6 of 32 patients with self-limited infection, in 2 of 32 patients with cavitary histoplasmosis, and in 4 of 8 patients with a sarcoid-like illness caused by H. capsulatum . The detection of antigen in urine was reproducible in 38 of 41 (93 percent) retests of specimens. H. capsulatum antigen was also detected in the serum during 11 of the 22 episodes of disseminated histoplasmosis, in none of the 12 episodes of other types of histoplasmosis in patients with antigenuria, in 1 of the 33 patients with histoplasmosis who lacked the urinary antigen, and in none of the 50 controls. Antigenemia and antigenuria decreased after initiation of antifungal therapy and recurred in patients who had a relapse. We conclude that this radioimmunoassay for H. capsulatum antigen represents a useful new method for the rapid diagnosis of disseminated histoplasmosis. (N Engl J Med 1986; 314:83–8.) Serologic tests are used routinely for the diagnosis of histoplasmosis. However, the usefulness of these tests is hampered by the high frequency of false positive 1 and false negative reactions. 2 , 3 Furthermore, since the antibody levels may remain elevated for several years after self-limited infections, serologic test results may suggest incorrectly that patients with other diseases have active histoplasmosis. 2 , 4 Although more sensitive radioimmunoassays for IgM and IgG antibodies to H. capsulatum have proved to be helpful in identifying patients with early acute histoplasmosis who are found to be seronegative by complement-fixation and immunodiffusion tests, 4 their increased sensitivity is accompanied by decreased specificity. . . .

Of patients with staphylococcal infections, high levels of IgM antibodies to staphylococci measured by radioimmunoassay were present in 13 of 17 patients with endocarditis, nine of 23 with complicated bacteremia, one of 20 with uncomplicated bacteremia, and two of 21 with nonbacteremic infections. Of control subjects, high levels of IgM antibodies were present in seven of 26 individuals with gram-positive infections, two of 16 with gram-negative infections, two of 20 with rheumatoid arthritis, and two of 50 uninfected persons. Concomitant elevation of IgO and IgM antibody levels occurred in 20 of 40 patients with endocarditis or complicated bacteremia compared with two of 41 patients with other types of staphylococcal infections and three of 112 control subjects. IgM antibodies only were present early in the infection in six of 13 patients with staphylococcal endocarditis or complicated bacteremia. IgO or IgM antibody levels remained elevated at least four weeks after initiation of treatment.