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Histoplasmosis Relapse in Patients with AIDS: Detection Using Histoplasma capsulatum variety capsulatum Antigen Levels

L. Joseph Wheat, MD; Patricia Connolly-Stringfield, BS; Robinette Blair, BS; Kathleen Connolly, BS; Todd Garringer, BS; and Barry P. Katz, PhD
[+] Article, Author, and Disclosure Information

Grant Support: In part by the Department of Veterans Affairs and the AIDS program of the National Institutes of Allergy and Infectious Diseases.

Requests for Reprints: L. Joseph Wheat, MD, OPW430, Wishard Memorial Hospital, 1001 West Tenth Street, Indianapolis, IN 46202-2879.

Current Author Addresses: Drs. Wheat and Katz, Ms. Connolly-Stringfield, Ms. Blair, Ms. Connolly, and Mr. Garringer: Department of Internal Medicine, Indiana University, 1100 West Michigan Street, Indianapolis, IN 46202.

Ann Intern Med. 1991;115(12):936-941. doi:10.7326/0003-4819-115-12-936
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Objective: To assess the accuracy of Histoplasma capsulatum variety capsulatum polysaccharide antigen testing for the identification of histoplasmosis relapse in patients with the acquired immunodeficiency syndrome (AIDS).

Design: A retrospective study using stored specimens.

Setting: A referral center and several private hospitals.

Patients: Twenty episodes of histoplasmosis relapse were evaluated in 17 patients with AIDS from November 1987 to August 1990. Controls included 30 patients with AIDS and histoplasmosis who did not have a relapse during maintenance therapy and who were initially tested during the same week as the patients with relapse. A second control group included seven patients with AIDS and histoplasmosis who were evaluated for relapse on 23 occasions; relapse, however, was excluded on each occasion.

Measurements: To avoid interassay variability, specimens were tested for H.c. var. capsulatum polysaccharide antigen with the same radioimmunoassay.

Main Outcome Measure: The change in the H.c. var. capsulatum polysaccharide antigen level during successful as opposed to unsuccessful maintenance therapy for the prevention of histoplasmosis relapse.

Main Results: For the 20 episodes of relapse (17 patients), H.c. var. capsulatum antigen levels increased by at least 2 radioimmunoassay units in 12 of 14 serum specimens tested (85.7%; 95% Cl, 57.2% to 98.2%) and in 17 of 18 urine specimens tested (94.4%; Cl, 72.7% to 99.9%). Antigen levels increased in the urine or serum in 1 of 83 specimens (1.2%; Cl, 0.03% to 6.6%) obtained on 56 occasions (1.8%; Cl, 0.04% to 9.6%) from controls (specificity, 98.2%; Cl, 90.4% to 99.96%). In three cases of relapse, antigen levels increased before clinical relapse was suspected. Complement fixation titers increased by at least 2 dilutions in 4 of 11 cases (36.4%; Cl, 10.9% to 69.2%) but in 0 of 9 control patients (Cl, 0% to 28.3%).

Conclusion: An increase in H.c. var. capsulatum polysaccharide antigen levels of 2 units or more strongly suggests histoplasmosis relapse. The presence of increasing titers of anti-H.c. var. capsulatum antibodies by complement fixation is less accurate for the diagnosis of relapse.





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