Predictive Value of Anemia for Tuberculosis in HIV-Infected Patients in Sub-Saharan Africa: An Indication for Routine Microbiological Investigation Using New Rapid Assays

Kerkhoff, Andrew D. MSc*,†; Wood, Robin MMed, FCP; Vogt, Monica DipMedTech; Lawn, Stephen D. MD, FRCP†,‡

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000091
Clinical Science

Background: The relationship between anemia and undiagnosed tuberculosis (TB) in patients living with HIV in sub-Saharan Africa is incompletely defined. We assessed the prevalence of TB among those with HIV-related anemia and evaluated new means of rapid TB diagnosis.

Methods: Blood hemoglobin levels were measured in unselected antiretroviral treatment–naive patients in Cape Town, South Africa, and anemia was classified according to World Health Organization criteria. All patients were screened for TB by testing paired sputum samples using liquid culture (reference standard), fluorescence microscopy, and Xpert MTB/RIF. Urine samples were tested for lipoarabinomannan (LAM) using the Determine TB-LAM diagnostic assay.

Results: Of 602 adults screened, 485 had complete results. Normal hemoglobin levels were found in 44.5% (n = 216) of patients, and mild, moderate, or severe anemia were present in 24.9% (n = 121), 25.4% (n = 123) and 5.2% (n = 25) of patients, respectively. Culture-confirmed pulmonary TB was diagnosed in 8.8% (19/216) of those without anemia compared with 16.5% (20/121), 26.0% (32/123), and 40.0% (10/25) among those with mild, moderate, or severe anemia, respectively (P < 0.001). Anemia was a strong independent predictor of TB. The sensitivities of diagnostic assays were much higher among those with moderate/severe anemia compared with those with no/mild anemia using sputum microscopy (42.9% vs 15.4%), urine LAM (54.8% vs 0%), sputum microscopy plus urine LAM (71.4% vs 15.4%), and sputum Xpert (73.8% vs 41.0%) (P < 0.01 for all).

Conclusions: A very high prevalence of undiagnosed TB was found in patients with moderate or severe anemia. Such patients should be prioritized for routine microbiological investigation using rapid diagnostic assays.

Author Information

*School of Medicine and Health Sciences, The George Washington University, Washington, DC;

Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; and

Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Correspondence to: Andrew D. Kerkhoff, MSc, School of Medicine and Health Sciences, The George Washington University, 2300 I Street NW, Washington, DC 20037 (e-mail:

S.D.L. is funded by the Wellcome Trust. R.W. was funded in part by the National Institutes of Health (NIH) through grants RO1 A1058736-01A1 and 5UO1A1069519-02. Alere provided the LAM assays free of charge.

The authors have no conflicts of interest to disclose.

S.D.L. and A.D.K. initiated and planned the study. S.D.L., R.W., and M.V. collected the data. S.D.L. and M.V. ran laboratory assays. A.D.K. did the data analysis. A.D.K. and S.D.L. wrote the article with input from R.W. All authors approved the final version of the article before submission.

None of these sources played any role in the design, conduct, analysis, interpretation, or decision to publish these data.

Received October 01, 2013

Accepted December 03, 2013

© 2014 by Lippincott Williams & Wilkins