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Serologic Evidence for Reactivation of Cryptococcosis in Solid-Organ Transplant Recipients

D. C. Saha,^1, D. L. Goldman,^2, X. Shao,² A. Casadevall,² S. Husain,³ A. P. Limaye,⁴ M. Lyon,⁵ J. Somani,⁵ K. Pursell,⁶ T. L. Pruett,⁷ and N. Singh^3*

All India Institute of Medicine, New Delhi, India,¹ Albert Einstein College of Medicine, Bronx, New York,² University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania,³ University of Washington School of Medicine, Seattle, Washington,⁴ Emory University School of Medicine, Atlanta, Georgia,⁵ University of Chicago School of Medicine, Chicago, Illinois,⁶ University of Virginia, Charlottesville, Virginia⁷

Received 12 June 2007/ Returned for modification 19 September 2007/ Accepted 15 October 2007

Cryptococcosis is a significant infection with a high mortality in solid-organ transplant recipients. Nonetheless, the pathogenesis of this disease is poorly understood. It has been hypothesized that cryptococcosis may result from either primary infection or reactivation of a latent infection. Sera were obtained from transplant recipients prior to transplantation and at the time they developed cryptococcosis. Control sera were obtained before and after transplant from patients who did not develop cryptococcosis. Sera were tested for antibodies against Cryptococcus neoformans by using an immunoblot assay. Antibody responses were also compared with those observed in sera from rats with experimental pulmonary cryptococcosis. In all, 52% of the transplant recipients who developed cryptococcosis exhibited serologic evidence of cryptococcal infection before transplantation. These patients developed cryptococcosis significantly earlier after transplant than patients without preexisting reactivity did (5.6 ± 3.4 months compared to 40.6 ± 63.8 months, respectively [P = 0.0011]). The results from our study suggest that a substantial proportion of transplant-associated cryptococcosis cases result from the reactivation of a latent infection. These findings also highlight the potential utility of serologic studies in identifying patients at risk for the development of cryptococcosis after transplantation.

Published ahead of print on 24 October 2007.

Both authors contributed equally to the manuscript and should both be considered first authors.