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Prevalence and Outcomes of Cryptococcal Antigenemia in HIV-Seropositive Patients Hospitalized for Suspected Tuberculosis in Uganda

Andama, Alfred O. MSc*,†,‡; den Boon, Saskia PhD*; Meya, David MBChB, MMed†,‡,††; Cattamanchi, Adithya MD§; Worodria, William MBChB, MMed, PhD*,†,‡; Davis, J. Lucian MD§; Walter, Nicholas D. MD; D. Yoo, Samuel MD; Kalema, Nelson MBChB*; Haller, Barbara MD, PhD#; Huang, Laurence MD§,**on behalf of the International HIV-Associated Opportunistic Pneumonias (IHOP) Study

JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1st, 2013 - Volume 63 - Issue 2 - p 189–194
doi: 10.1097/QAI.0b013e3182926f95
Clinical Science

Background: Cryptococcal infection occurs in HIV-seropositive patients and is associated with high mortality. However, limited information is available on the prevalence and outcomes of cryptococcal antigenemia among hospitalized HIV-seropositive patients in sub-Saharan Africa.

Objectives: To determine the prevalence of and risk factors for cryptococcal antigenemia among HIV-seropositive patients presenting to Mulago Hospital (Kampala, Uganda) with unexplained cough ≥2 weeks and suspected tuberculosis (TB) and also to determine if antigenemia is associated with an increased mortality.

Methods: Between September 2009 and September 2010, we enrolled consecutive HIV-seropositive adults hospitalized at Mulago Hospital with cough ≥2 weeks and suspected TB. Banked serum was tested for cryptococcal antigen. We compared demographic and clinical characteristics, and 2-month mortality in patients with and without cryptococcal antigenemia.

Results: Of 563 HIV-seropositive patients, 32 (5.7%) were cryptococcal antigen (CrAg) positive. None had Cryptococcus neoformans detected on fungal culture of bronchoalveolar lavage fluid (n = 116). CrAg-positive patients had a lower median CD4 count compared with CrAg-negative patients (25 vs. 55 cells/μL, P = 0.02), and a substantial proportion of CrAg-positive patients also had concurrent TB (31%). A positive CrAg test was not associated with increased mortality during the 2-month follow-up period (hazard ratio: 0.99, 95% confidence interval: 0.63 to 1.54, P = 0.95) after adjusting for CD4 count and antiretroviral therapy use at enrollment and/or follow-up.

Conclusions: Occult cryptococcal antigenemia occurs commonly among hospitalized HIV-seropositive patients with suspected TB. CrAg testing should be considered in hospitalized HIV-seropositive patients with CD4 count <50 cells/μL, coupled with longer follow-up to evaluate the diagnostic value of CrAg and therapeutic interventions in patients with asymptomatic cryptococcal antigenemia.

*Makerere University–University of California, San Francisco (MU-UCSF) Research Collaboration, Kampala, Uganda;

Department of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda;

Department of Medicine, Mulago National Referral Hospital, Kampala, Uganda;

§Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA;

Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Denver, Aurora, CO;

Health Tutors' College Mulago, Kampala, Uganda;

#Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA;

**HIV/AIDS Division, University of California, San Francisco, San Francisco, CA; and

††Division of Infectious Diseases and International Health, University of Minnesota, MN.

Correspondence to: Alfred O. Andama, MSc, Department of Medicine, School of Medicine, Makerere University College of Health Sciences, Old Mulago Hill Road, New Mulago Hospital Complex, P.O Box 7051, Kampala, Uganda (e-mail: andama.alf@gmail.com).

Supported by grant numbers K24 HL087713 (L. Huang), R01 HL 090335 (L. Huang), U01 AI089244-01 (COAT study), K23 AI080147 (J. L. Davis), K23 HL094141 (A. Cattamanchi) from the National Institutes of Health.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).

Received May 06, 2012

Accepted March 05, 2013

© 2013 by Lippincott Williams & Wilkins