Progress in Serodiagnosis of Mycobacterium tuberculosis Infection

Abstract

One‐third of the world population is estimated to have Mycobacterium tuberculosis infection. Accurate and timely identification of infected individuals is critical for treatment and control. The current diagnostic methods lack the desired sensitivity and specificity, require sophisticated equipment and skilled workforce or take weeks to yield results. Diagnosis of extrapulmonary TB, TB‐HIV co‐infection, childhood TB and sputum smear‐negative pulmonary TB pose serious challenges. Interest in developing serodiagnostic methods is increasing because detection of antibody is rapid, simple and relatively inexpensive, and does not require a living cell for detection. Three types of tests, namely screening tests to overcome diagnostic delay, specific tests for diagnosis of extrapulmonary TB and other bacteriologically negative cases, and tests for vaccine‐induced immunity need critical consideration. Several factors must be considered to develop serodiagnostic methods for TB. Antigen recognition by infected individuals is highly heterogeneous due to stage of disease, differences in HLA types, strain of the bacilli, health of the patient and bacillary load. With advances in molecular biological techniques, a number of novel antigens have been identified. Some of these antigens have proven valuable in detecting specific antibodies in some of the most challenging TB patients. The best example is a fusion protein containing several M. tuberculosis proteins (e.g. CFP‐10, MTB8, MTB48, MTB81 and the 38‐kDa protein) which showed encouraging results in detecting antibodies in sera of patients, including TB‐HIV co‐infection. This review presents progress made in the serodiagnosis of TB during the last decade.

Mycobacterium tuberculosis adhesins: potential biomarkers as anti-tuberculosis therapeutic and diagnostic targets

“…With regard to the onset of the immune response, methylation of HBHA appears to be crucial for the induction of T-cell antigenicity and protective immunity against M. tuberculosis (Temmerman et al, 2004). Methylated HBHA may thus be a suitable diagnostic marker for identifying individuals with active TB (Abebe et al, 2007).…”

“…Several M. tuberculosis antigenic proteins have been evaluated as serological markers, particularly culture filtrate proteins, although surface-exposed proteins appear to be more effective (Abebe et al, 2007).…”

“…The anchorless adhesin malate synthase is a surrogate marker for TB infection in HIVseropositive individuals (Abebe et al, 2007), with 57 % of TB-infected and 92 % of TB-HIV-co-infected patients in Uganda and South Africa, respectively, showing reactivity to this antigen (Hendrickson et al, 2000). The 30 kDa antigen (antigen 85B or a-antigen) binds to fibronectin and is regarded as a potential M. tuberculosis adhesin (Ratliff et al, 1988).…”

Immunologic evaluation and validation of methods using synthetic peptides derived from Mycobacterium tuberculosis for the diagnosis of tuberculosis infection

“…Rapid, inexpensive diagnostic tests would aid these countries in limiting the spread of infection within their communities (WHO 2009). In addition, molecular methods based on nucleic acid amplification to diagnose TB infection are rapid, highly specific and more sensitive than microscopic examination of smears, but are less sensitive compared to culture assays for smear-negative TB cases (Abebe et al 2007).Serological tests that rely on the detection of antibodies against Mycobacterium tuberculosis-specific antigens possess several advantages: they are simple, inexpensive and feasible for the diagnosis of TB. Potential M. tuberculosis antigens were recently reviewed in a metaanalysis.…”

“…These results indicated that highly specific tests frequently exhibited poor sensitivity, which limited the use of these antigens when a single antigen was used in the assay (Steingart et al 2009). Recently, there has been renewed interest in the development of antibody-based diagnostic assays that utilise multiple antigens to achieve high sensitivity and specificity (Abebe et al 2007). Many attempts to develop a serologic TB test have been made.…”