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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.

Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR tuberculosis are discussed.

A key challenge to greater progress in tuberculosis (TB) control is the reservoir of latent TB infection (LTBI), which represents a huge long-lived reservoir of potential TB disease. In parts of Africa, as many as 50% of 15-year-olds and 77%-89% of adults have evidence of LTBI. A second key challenge to TB control is the human immunodeficiency virus (HIV)-associated TB epidemic, and Africa alone accounts for one-quarter of the global burden of HIV-associated TB. HIV co-infection promotes both reactivation TB from LTBI and rapidly progressive primary TB following recent exposure to Mycobacterium tuberculosis. Preventing active TB and tackling latent infection in addition to the Directly Observed Treatment, Short-Course (DOTS) strategy could improve TB control in high-burden settings, especially where there is a high prevalence of HIV co-infection. Current strategies include intensified case finding (ICF), TB infection control, antiretroviral therapy (ART), and isoniazid preventive therapy (IPT). Although ART has been widely rolled out, ICF and IPT have not. A key factor limiting the rollout and effectiveness of IPT and ICF is the limitations of existing tools to both diagnose LTBI and identify those persons most at risk of progressing to active TB. In this review, we examine the obstacles and consider current progress toward the development of new tools to address this pressing global problem.