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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:

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.

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Received May 06, 2012

Accepted March 05, 2013

© 2013 by Lippincott Williams & Wilkins