Diagnosis of opportunistic infections: HIV co-infections - tuberculosis

Abstract

Purpose of review: Tuberculosis (TB) incidence has declined ∼1.5% annually since 2000, but continued to affect 10.4 million individuals in 2015, with 1/3 remaining undiagnosed or underreported. The diagnosis of TB among those co-infected with HIV is challenging as TB remains the leading cause of death in such individuals. Accurate and rapid diagnosis of active TB will avert mortality in both adults and children, reduce transmission, and assist in timeous decisions for antiretroviral therapy initiation. This review describes advances in diagnosing TB, especially among HIV co-infected individuals, highlights national program's uptake, and impact on patient care.

Recent findings: The TB diagnostic landscape has been transformed over the last 5 years. Molecular diagnostics such as Xpert MTB/RIF, which simultaneously detects Mycobacterium tuberculosis (MTB) resistance to rifampicin, has revolutionized TB control programs. WHO endorsed the use of Xpert MTB/RIF in 2010 for use in HIV/TB co-infected patients, and later in 2013 for use as the initial diagnostic test for all adults and children with signs and symptoms of pulmonary TB. Line probe assays (LPAs) are recommended for the detection of rifampicin and isoniazid resistance in sputum smear-positive specimens and mycobacterial cultures. A second-line line probe assay has been recommended for the diagnosis of extensively drug-resistant (XDR)-TB Assays such as the urine lateral flow (LF)-lipoarabinomannan (LAM), can be used at the point of care (POC) and have a niche role to supplement the diagnosis of TB in seriously ill HIV-infected, hospitalized patients with low CD4 cell counts of less than 100 cells/μl. Polyvalent platforms such as the m2000 (Abbott Molecular) and GeneXpert (Cepheid) offer potential for integration of HIV and TB testing services. While the Research and Development (R&D) pipeline appears to be rich at first glance, there are actually few leads for true POC tests that would allow for earlier TB diagnosis or rapid, comprehensive drug susceptibility testing, especially when considering the very high attrition rates observed between biomarker discovery and product market entry.

Summary: In this review, we describe diagnostic strategies specifically for HIV and TB co-infected individuals. Molecular diagnostics in particular within the past 5 years have revolutionized and 'disrupted' this field. They lend themselves to integration of services with platforms capable of polyvalent testing. Impact on patient care is, however, still debatable. What has been highlighted is the need for health system strengthening and for true POC testing that can be used in active case finding.

Figure 1

A radar plot of the performance (represented as sensitivity values 0–100%) of Xpert MTB/RIF compared to liquid culture for various specimen types. PTB-pulmonary tuberculosis, BAL-bronchoalveolar lavage, EPTB, CSF-cerebrospinal fluid and TBM-tuberculosis meningitis. The solid radial arms illustrate sensitivity (%) of overall pooled data, and the dashed radial arms report studies among HIV/TB co-infected individuals. Adults Overall: n=27 studies (7 by HIV status), Smear Positive PTB: n=5 studies, Smear Negative PTB: n=5 studies [35]; BAL: n=1 study, centrifuged BAL [36]. Children Overall PTB (sputum): n=12 studies, Smear Positive PTB: n=6 studies, Smear Negative PTB: n=7 studies, Overall Gastic Lavage: n=7 studies [37]. EPTB Overall EPTB: n=36 studies [38]; Lymph Node Tissue/Aspirate: n=18 studies [39], n= 1 HIV positive cohort [40]; CFS(TBM): n=18 studies [39], n=1 HIV positive cohort, mixed CSF samples [41], n=1 HIV positive cohort, centrifuged CSF [42]; Pleural fluid: n=24 studies [43], n=1 high TB-HIV prevalence cohort [44]; Urine: n=1 hospitalised, HIV positive cohort [45].