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

Abstract

The World Health Organization (WHO) lists tuberculosis (TB) as the most important fatal infection worldwide (WHO 2009). The development of a new diagnostic test for TB infection is an important component of the Global Plan to Stop TB and the WHO Stop TB Strategy. In 2005 alone, an estimated 8.8 million individuals were infected with TB and 1.6 million people died of the disease (WHO 2009). Importantly, less than one half of the total 8.8 million estimated cases were diagnosed as smear-positive; the diagnosis of smear-negative patients has proven to be more challenging. Currently, a definitive diagnosis of both pulmonary TB (PTB) and extrapulmonary TB (EPTB) relies on the time consuming culture of mycobacteria. A vast majority of TB cases occur in developing countries that have limited resources. 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. A total of 254 studies were identified that encompassed nine native proteins, 27 recombinant proteins, 15 lipid-derived antigens and 30 combination antigen targets. 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. These assays need to discriminate active from latent infection, avoid cross-reactivity with Bacillus Calmette-

Diagnostic utility of 99mTc-EDDA-tricine-HYNIC-Tyr3-octreotate SPECT for differentiation of active from inactive pulmonary tuberculosis

“…However, this is timeconsuming and needs 2-8 weeks before achieving a proper final result. Although various modern tests are being developed for fast and precise diagnosis of pulmonary tuberculosis, these techniques are not widely accepted because of their cost and complexity [8][9][10][11].…”

Evaluation of multi-antigen serological screening for active tuberculosis among people living with HIV

“…Rv0934-P38, also known as PstS1 or 38 kDa antigen, is a phosphate binding protein that has been combined with other antigens for TB diagnosis, though none of these combinations achieved target performance [21,23,38,39]. Ag85A is a secreted protein that is thought to have an important role in M. tuberculosis pathogenicity [40], and Ag85A peptide sequences have been found to be specific to pulmonary TB [41]. Rv2031-HSPX, also known as alpha-crystallin or 16 kDa antigen, is induced in a hypoxic state, and has been shown to be higher in pulmonary TB compared to household contacts or community controls [39,42,43].…”

Synthetic Peptides as an Alternative Tool for the Diagnosis of Cryptococcosis

“…Some of the tests that are already available on the market include tests for Epstein-Barr virus, which examines various epitopes on the capsid protein; hepatitis C virus, which includes synthetic peptides that mimic its structural and nonstructural regions (NS4 and NS5); coronavirus, which is composed of synthetic peptides derived from epitopes of the nucleocapsid and spike proteins and can detect the presence of antibodies from human serum and plasma specimens; Chlamydia trachomatis, which has three ELISA diagnostic tests available on the market; and rheumatoid arthritis, with three generations of diagnostic tests based on the detection of antibodies by synthetic peptides [94][95][96][97]. Despite the existence of various diagnostic tests using synthetic peptides and the prevalence of studies reporting the use of synthetic peptides for the diagnosis of various pathologies, particularly those of medical importance, such as tuberculosis, Chagas disease, and leishmaniasis, little has evolved in this area with respect to systemic mycoses [98][99][100][101][102][103].…”