Immunoassays for Extrapulmonary Tuberculosis Need Improvement

The diagnosis of extrapulmonary tuberculosis (EPTB) is challenging as routine methods for diagnosis, such as smear for acid-fast bacilli (AFB) and culture of Mycobacterium tuberculosis on solid media, have poor sensitivity.

Nucleic acid amplification test and liquid culture methods are costly and required sophisticated infrastructure and therefore antibody based serodiagnosis tests for tuberculosis (TB) are used widely in developed and developing countries.


Scientists at the All India Institute of Medical Sciences (New Delhi, India) evaluated the diagnostic performance of commercially available enzyme-linked immunosorbent assay (ELISA) kit in the diagnosis of EPTB. They prospectively enrolled 354 patients, of whom 217 (61.2%) were EPTB patients and 137 (38.7%) were subjects with no suggestive TB, between 2007 and 2011. The mean age was 29.7 years for the EPTB patients and 31.2 years for the controls. Before culture inoculation, all samples were examined microscopically after Zeihl-Neelsen stain. All the isolates were confirmed as M. tuberculosis by species-specific in-house multiplex polymerase chain reaction (PCR) and phenotypic methods.

Three immunoglobulin based ELISA kits, PATHOZYME MYCO IgG, IgA, and IgM (Omega Diagnostics Limited; Alva, Scotland, UK) were used to check levels of antimycobacterial antibodies against two antigens in the serum of diseased and controls. The individual and overall sensitivity rates of IgM, IgA, and IgG assays were 29%, 24.4%, and 34.5%, respectively, while their specificities were 70.8%, 77.3%, and 68.6%, respectively. Not all TB patients produce antibodies against all antigenic epitopes in the cell walls of the tubercle bacilli, which infers on the inconsistency in specificity of antibody-based assays among different patient groups like gender, age, ethnicity, and geographical distribution.

The authors concluded that even though the specificity of the Pathozyme Myco IgA, IgM, and IgG was significantly better and acceptable as compared to pulmonary TB, the sensitivity of these kits was less than can be expected, and they did not recommend their use for diagnosis of EPTB. While a negative result by any one of these tests would be useful in helping to exclude disease in a population with a low prevalence of tuberculosis, a positive result may aid in clinical decision making when applied to symptomatic patients being evaluated for active tuberculosis. The study was published on August 1, 2013, in the Journal of Laboratory Physicians.

Related Links:
All India Institute of Medical Sciences
Omega Diagnostics Limited