Poor Performance of Serological Tests in the Diagnosis of Pulmonary Tuberculosis: Evidence from a Contact Tracing Field Study

Clinical Microbiology Division, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India.
PLoS ONE (Impact Factor: 3.23). 07/2012; 7(7):e40213. DOI: 10.1371/journal.pone.0040213
Source: PubMed


Delayed or missed diagnosis of TB continues to fuel the global TB epidemic, especially in resource limited settings. Use of serology for the diagnosis of tuberculosis, commonly used in India, is another factor. In the present study a commercially available serodiagnostic assay was assessed for its diagnostic value in combination with smear, culture and clinical manifestations.
A total of 2300 subjects were recruited for the study, but 1041 subjects were excluded for various reasons. Thus 1259 subjects were included in the study of which 470 were pulmonary tuberculosis cases (440 of 470 were culture-positive) and 789 were their asymptomatic contacts. A house-to-house survey method was used. Blood samples were tested for IgM, IgA, and IgG antibodies using the Pathozyme Myco M (IgM), Myco A (IgA) and Myco G (IgG) enzyme immunoassay (EIA). Out of 470 PTB cases, BCG scar was positive in 82.34%. The Mantoux test and smear positivity rates in PTB cases were 94.3% (430/456), and 65.32% (307/470), respectively. Among the asymptomatic contacts, BCG scar was positive in 95.3% and Mantoux test was positive in 80.66% (442/548) contacts. No contact was found falsely smear positive. The sensitivity of IgM, IgA, and IgG EIA tests was 48.7%, 25.7% and 24.4%, respectively, while the specificity was 71.5%, 80.5%, 76.6%, respectively. Performance of EIAs was not affected by the previous BCG vaccination. However, prior BCG vaccination was statistically significantly (p = 0.005) associated with Mantoux test positivity in PTB cases but not in contacts (p = 0.127). The agreement between serology and Mantoux test was not significant.
The commercial serological test evaluated showed poor sensitivity and specificity and suggests no utility for detection of pulmonary tuberculosis.

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    • "The rapid and accurate diagnosis of infected individuals is the basis of any TB control program. The sensitivity and specificity of immunological tests tend to show variation in different demographic characteristics or geographical background due to different levels of immunological responses [9] [17]. This study, conducted in a homogeneous population of both microscopically confirmed cases and non-TB controls, showed that MT is better in terms of sensitivity and specificity "
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    ABSTRACT: Objective Bangladesh is a high tuberculosis burden country. It is always challenging to diagnose active pulmonary tuberculosis (PTB) cases in rural areas where the setting up of conventional microscopic and cultural diagnostic tools is difficult. The objective of the present study is to find a feasible, reliable and easily accessible alternative diagnostic approach for PTB in the rural areas of Bangladesh. Methods A total of 86 sputum samples were collected from clinically suspected PTB patients of Anantapur village, an underdeveloped remote area of Netrokona district, Bangladesh. Sputum samples were screened by Ziehl-Neelsen (Z-N) and fluorescence staining methods and were categorized as smear-positive active PTB cases (n = 50) and smear-negative controls (n = 36); then the performance of three popular immunological tests were evaluated, including ICT, ELISA and Mantoux tests (MT). Results The sensitivity of ICT, ELISA, and MT (10 mm induration size) was 68%, 84% and 96%, respectively, and the specificity of these tests was 94.4%, 80.6% and 52.8%, respectively. When the cut-off size of induration in MT was changed from 10 to ⩾15 mm, the sensitivity and specificity of MT became 92% and 83.3%, respectively. It was also found that the interpretation of MT was not significantly affected by BCG vaccination when ⩾15 mm induration was taken as a cut-off value. Conclusion Considering the resource-constraints of rural and remote areas, the Mantoux test could be an alternative tool for the diagnosis of active PTB.
    International Journal of Mycobacteriology 06/2014; 3(2). DOI:10.1016/j.ijmyco.2014.03.003
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    • "Serological tools are likely to detect extrapulmonary and smear-negative pulmonary tuberculosis cases that are usually missed by routine sputum smear microscopy. Employing the principle of EIA, though a number of point-of-care diagnostic tools have been developed (Liao et al., 2011; Lawn, 2012; Nabity et al., 2012; Litster et al., 2013; Rasooly et al., 2013), these often exhibit low sensitivity and specificity (Singh et al., 2012). Studies have shown that excretory-secretory proteins, EST-DE1 and ESAS-7 of M. tuberculosis H37Ra antigenic fraction have a good potential for the diagnosis of different forms of TB (Banerjee et al., Contents lists available at SciVerse ScienceDirect "
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    ABSTRACT: Tuberculosis (TB) is one of the most important diseases of humans and major public health problem worldwide. Early and accurate diagnosis of TB is necessary for the treatment, prevention, and control of TB. Therefore, it is important to identify suitable antigens that can differentiate active tuberculosis patients from BCG-vaccinated individuals. In the present study, we have used Rv0256c (PPE2) protein of M. tuberculosis to screen the sera of infected patients belonging to different clinical TB presentations, and BCG-vaccinated clinically healthy individuals by enzyme immunoassay. Our results demonstrated that Rv0256c displayed stronger and specific immunoreactivity against the sera obtained from clinically active tuberculosis patients compared to PPD and ESAT-6 and could differentiate the TB-patients from the BCG-vaccinated controls. Importantly, Rv0256c was also found to detect even the extrapulmonary and smear-negative pulmonary cases which often are tedious and difficult to detect using conventional diagnostic methods. This study suggests that Rv0256c can be used as a potential marker for the serodiagnosis of tuberculosis patients.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 07/2013; 22. DOI:10.1016/j.meegid.2013.06.023 · 3.02 Impact Factor
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    • "Three immunoglobulin based ELISA kits (PATHOZYME® MYCO IgG, IgA, and IgM) were used to check levels of antimycobacterial antibodies against two antigens in the serum of diseased and controls. The ELISA tests were performed according to the instructions in kits’ manual (Omega Diagnostics Limited, Scotland, UK) and repeated three times as published earlier.[7] "
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    ABSTRACT: Antibody based serodiagnosis tests for tuberculosis (TB) was used widely in developed and developing countries. Pathozyme Myco(®) immunoglobulin (Ig) M, IgA, and IgG were evaluated in pulmonary TB in many studies. In this study we assessed this commercially available kit in detecting extrapulmonary TB (EPTB). A total of 354 subjects were recruited for the study, of which 217 (61.2%) were EPTB patients and 137 (38.7%) were subjects with no suggestive TB. The mean age was 29.7 ± 13.7 and 31.2 ± 15.2 years, respectively for two groups. Serum samples were tested for IgM, IgA, and IgG using Pathozyme Myco(®) IgM, IgA, and IgG kit. The individual specificity rates of IgM, IgA, and IgG were 70.8% (95% confidence interval (CI): 62.7-77.7), 77.3% (95% CI: 68.6-83.5), and 68.6%. (95% CI: 60.4-75.7); while their sensitivity was 29% (95% CI: 23.4-35.4), 24.4% (95% CI: 19.1-30.5), and 34.5% (95% CI: 28.5-41.1); respectively. The serological tests either singly or in combination failed or performed poorly to diagnose EPTB.
    Journal of laboratory physicians 03/2013; 5(1):11-6. DOI:10.4103/0974-2727.115902
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