Diagnostic Potential of Ag85C in Comparison to Various Secretory Antigens for Childhood Tuberculosis

Kumar, Gyanendra; Dagur, Pradeep K.; Singh, Manoj Kumar; Yadav, V. S.; Dayal, Rajeshwar; Singh, Haribhan; Katoch, V. M.; Sengupta, Utpal; Joshi, Beenu

doi:10.1111/j.1365-3083.2008.02133.x

Cited by 21 publications

(21 citation statements)

References 24 publications

(29 reference statements)

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“…Of these antigens, only ESAT-6 and CFP10 are M. tuberculosis complex specific, while the other antigens can be found in several other mycobacteria. As in adult TB, Ab responses to ESAT-6 and CFP10 were lower than those against several other antigens in pediatric TB (31,57,71). Sensitivities and specificities for the reported studies varied widely (Table 2), influenced by the factors discussed in detail.…”

Section: Mycobacterial Antigens Evaluated For Serodiagnosis In Childhmentioning

confidence: 98%

“…Sensitivities and specificities for the reported studies varied widely (Table 2), influenced by the factors discussed in detail. Of note, most investigators evaluating in-house Ab detection assays used the same groups of cases and controls to determine cutoff values and estimate sensitivity and specificity values (30,31,47,74). In addition, many studies lacked a description of their assays, making data interpretation not possible (3,6,20,21,48).…”

Section: Mycobacterial Antigens Evaluated For Serodiagnosis In Childhmentioning

confidence: 99%

“…Furthermore, the use of crude mycobacterial antigen mixtures in Ab detection assays by many investigators introduced considerable data variability. In addition, several investigators used the same groups of cases and controls to determine cutoff values and estimate sensitivity and specificity values (30,31,47,74). This approach, although valid in pilot studies, limits the reproducibility of data and is likely to have contributed to the wide variability of reported Ab responses.…”

Section: Limitations Of and Aspects To Consider In Serological Studiementioning

confidence: 99%

“…Ab responses to further mycobacterial antigens evaluated via an in-house ELISA included (i) antigen 5 (Ag5)/the 38-kDa protein (2), (ii) the 30-kDa antigen, a culture filtrate protein, more commonly known as antigen 85B (47,74), (iii) fractions 4 and 5 of polar lipids belonging to the lipo-oligosaccharide family (LOS) (58), (iv) 2,3-diacyl trehalose, formerly also referred to as 2,3-diacyl-trehalose-2=-sulfate (SLIV) antigen (DAT) (58), (v) the glycolipid antigen triglycosyl phenol phthiocerol dimycocerosate (PGLTb1) (58), (vi) the 16-kDa heat shock protein (30,47), (vii) the 60-kDa heat shock protein (HSP60) (3), (viii) the excretorysecretory antigen (ES-31) (6), (ix) the early secretory antigen 6 (ESAT-6) (21, 31), (x) the antigen 85 complex consisting of the proteins Ag85A, 85B, and 85C (Ag85 complex) (20,31), and (xi) culture filtrate protein 10 (CFP10) (31). Of these antigens, only ESAT-6 and CFP10 are M. tuberculosis complex specific, while the other antigens can be found in several other mycobacteria.…”

Section: Mycobacterial Antigens Evaluated For Serodiagnosis In Childhmentioning

confidence: 99%

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Antibody Responses to Mycobacterial Antigens in Children with Tuberculosis: Challenges and Potential Diagnostic Value

Achkar

Ziegenbalg

2012

Clin Vaccine Immunol

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The identification of easily detectable biomarkers for active tuberculosis (TB) is a global health priority. Such biomarkers would be of particular value in childhood TB, which poses greater diagnostic challenges than adult TB. Serum antibodies can be detected by simple formats that provide extremely rapid results. However, attempts to develop accurate serodiagnostic tests for TB have been unsuccessful. Whereas antibody responses to mycobacterial antigens in adult TB have been studied extensively and reviewed, the same cannot be said for serologic data in pediatric populations. Here we appraise studies on serological responses in childhood TB and discuss findings and limitations in the context of the developing immune system, the age range, and the spectrum of TB manifestations. We found that the antibody responses to mycobacterial antigens in childhood TB can vary widely, with sensitivities and specificities ranging from 14% to 85% and from 86% to 100%, respectively. We conclude that the limitations in serodiagnostic studies of childhood TB are manifold, thereby restricting the interpretation of currently available data. Concerns about the methodology used in published studies suggest that conclusions about the eventual value of serodiagnosis cannot be made at this time. However, the available data suggest a potential adjunctive value for serology in the diagnosis of childhood TB. Despite the difficulties noted in this field, there is optimism that the application of novel antigens and the integration of those factors which contribute to the serological responses in childhood TB can lead to useful future diagnostics.A ctive tuberculosis (TB) is a major cause of morbidity and mortality in children, especially in resource-limited countries, in which children under the age of 15 years account for approximately 15 to 20% of the disease burden (19,39). Infection with Mycobacterium tuberculosis in children is generally the consequence of household transmission from an adult incident case. Thus, it is not surprising that 75% of the estimated 1 million annual pediatric TB cases occur in the 22 high-burden countries (69). While adult TB is commonly due to reactivation, pediatric TB is typically a primary disease. In addition, there are considerable differences in host immune responses between adults and young children. The results are a more atypical clinical manifestation with a paucity of classical signs and symptoms in pediatric TB, resulting in considerably higher challenges to establish TB diagnosis than in adults.In young children, TB frequently disseminates and can be rapidly progressive early in life before immune competency is fully developed (36). Therefore, diagnostic delay quickly leads to increased morbidity and mortality, and rapid diagnosis becomes particularly important. However, the differences in disease manifestation of pediatric and adult TB result in reduced sensitivities for TB diagnostic tests. For example, cavitary disease is uncommon in children while up to 30% have extrapulmonary manifestations...

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Section: Mycobacterial Antigens Evaluated For Serodiagnosis In Childhmentioning

confidence: 98%

Section: Mycobacterial Antigens Evaluated For Serodiagnosis In Childhmentioning

confidence: 99%

Section: Limitations Of and Aspects To Consider In Serological Studiementioning

confidence: 99%

Section: Mycobacterial Antigens Evaluated For Serodiagnosis In Childhmentioning

confidence: 99%

See 2 more Smart Citations

Antibody Responses to Mycobacterial Antigens in Children with Tuberculosis: Challenges and Potential Diagnostic Value

Achkar

Ziegenbalg

2012

Clin Vaccine Immunol

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“…A successful serodiagnostic test for TB hinges on the capacity of the assay to detect the pauci and multibacillary forms of TB, paediatric TB cases and TB-infected patients coinfected with human immunodeficiency virus (HIV) (Mabey et al 2004, Tiwari et al 2007). Many reports have proposed utilising several combinations of antigens or specific antibodies for a serological assay for the diagnosis of TB (Araujo et al 2004, Kumar et al 2008, He et al 2011.…”

mentioning

confidence: 99%

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

Araujo¹,

Giampietro²,

Bochichio³

et al. 2013

Mem. Inst. Oswaldo Cruz

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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-

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Serodiagnostic Efficacy of Mycobacterium tuberculosis 30/32-kDa Mycolyl Transferase Complex, ESAT-6, and CFP-10 in Patients with Active Tuberculosis

Kumar

Dagur

Singh

et al. 2010

Arch. Immunol. Ther. Exp.

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Elimination of tuberculosis (TB) largely depends upon definitive rapid diagnosis and treatment. Widely used diagnostic tests do not qualify for use in a developing country due to lack of either desired accuracy or their cost. In the present study an enzyme-linked immunosorbent assay was used to evaluate the diagnostic potential of an immuno-dominant 30/32-kDa mycolyl transferase complex (Ag85 complex) and Mycobacterium tuberculosis-specific proteins (ESAT-6 and CFP-10) of the RD1 region. Higher sensitivity (84.1%) with Ag85 complex was observed compared with ESAT-6 (64.9%) and CFP-10 (66%), with almost similar specificity (Ag85: 85.2%, ESAT-6: 88.9%, CFP-10: 85.2%), whereas the individual components of Ag85 complex, i.e. Ag85A, Ag85B, and Ag85C, showed sensitivities of 44.6, 34, and 80.9% and specificities of 55.6, 74.1, and 40.7% respectively. A cocktail of Ag85 complex, ESAT-6, CFP-10, Ag85A, Ag85B, and Ag85C antigens also could not help in increasing either sensitivity (51.1%) or specificity (85.2%). Furthermore, immunoblot analysis using clinical isolates as well as a standard strain (H37Rv) of M. tuberculosis also showed strong reactivity of sera from TB patients to Ag85 complex and, to a lesser extent, also to ESAT-6. To conclude, use of Ag85 complex along with ESAT-6 and CFP-10 seems to be promising in minimizing the heterogeneous sero-responses of adult TB cases.

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Diagnostic Potential of Ag85C in Comparison to Various Secretory Antigens for Childhood Tuberculosis

Cited by 21 publications

References 24 publications

Antibody Responses to Mycobacterial Antigens in Children with Tuberculosis: Challenges and Potential Diagnostic Value

Antibody Responses to Mycobacterial Antigens in Children with Tuberculosis: Challenges and Potential Diagnostic Value

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

Serodiagnostic Efficacy of Mycobacterium tuberculosis 30/32-kDa Mycolyl Transferase Complex, ESAT-6, and CFP-10 in Patients with Active Tuberculosis

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