Tuberculosis in antiretroviral treatment services in resource-limited settings: addressing the challenges of screening and diagnosis

Abstract

The high burden of tuberculosis (TB) among patients accessing antiretroviral treatment (ART) services in resource-limited settings is a major cause of morbidity and mortality and is associated with nosocomial transmission risk. These risks are greatly compounded by multidrug-resistant disease. Screening and diagnosis of TB in this clinical setting is difficult. However, progress has been made in defining a high-sensitivity, standardized symptom screening tool that assesses a combination of symptoms, rather than relying on report of cough alone. Moreover, newly emerging diagnostic tools show great promise in providing more rapid diagnosis of TB, which is predominantly sputum smear-negative. These include culture-based systems, simplified versions of nucleic acid amplification tests (such as the Xpert MTB/RIF assay), and detection of lipoarabinomannan antigen in urine. In addition, new molecular diagnostics now permit rapid detection of drug resistance. Further development and implementation of these tools is vital to permit rapid and effective screening for TB in ART services, which is an essential component of patient care.

Figure 1.

Tuberculosis (TB) incidence rates (cases/100 person-years and 95% confidence bands) and CD4 cell counts (cells/μL) in a South African cohort of HIV-infected patients before availability of antiretroviral therapy (ART; unshaded area) and during ART-induced immune recovery (shaded area). The shape of the curve at the time of ART initiation depends on the intensity of TB screening before ART initiation. Figure adapted from Lawn et al (2010) [8], and data originally adapted from Holmes et al (2006) [14] and Lawn et al (2009) [15].

Figure 2.

Total bacillary load of Mycobacterium tuberculosis in individuals showing progression from infection to development of symptomatic tuberculosis (TB) disease. After infection, patients may retain good immune control of the infection and low bacillary numbers (quiescent or latent infection). However, subsequent loss of immune control is associated with increasing bacillary load that initially remains as subclinical active infection. At some stage, symptoms develop, leading to presentation of active symptomatic disease. HIV infection greatly accelerates the progression toward active infection and disease. Figure adapted from Lawn et al (2010) [18].

Figure 3.

Sensitivity of a commercially available enzyme-linked immunosorbent assay (ELISA) to detect lipoarabinomannan (LAM) in urine samples for diagnosis of tuberculosis (TB) in a cohort of patients accessing antiretroviral treatment (ART) in a South African township. The sensitivity of sputum microscopy and the LAM ELISA are shown individually and combined (either positive), compared with a gold standard of automated liquid culture of 2 sputum samples. Data are stratified by CD4 cell count. Data are from Lawn et al (2009) [34].