Diagnostic Value of Elisa Serological Tests in Childhood Tuberculosis

Dayal, Rajeshwar; Sirohi, G.; Singh, Madhu; Mathur, P. P.; Agarwal, Bhumi; Katoch, Vishwa Mohan; Joshi, Beenu; Singh, Prashant Kumar; Singh, Haribhan

doi:10.1093/tropej/fml047

Cited by 8 publications

(9 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

“…Nevertheless, Ab detection assays may have adjunctive value in detecting these forms of extrapulmonary TB due to the extremely low yield for culturing M. tuberculosis from cerebrospinal or pleural fluid. For example, Dayal et al (21) detected serum IgG responses against the mycobacterial glycolipid PGLTb1 and the protein ESAT6 in 7/16 (44%) and 9/16 (56%) children with TB meningitis, respectively, in contrast to a positive cerebrospinal fluid culture in only 2/16 (13%). Thus, local Ab detection in such cases might have additional diagnostic value.…”

Section: Antibody Responses According To Type Of Tbmentioning

confidence: 99%

“…Third, many reported studies evaluating in-house Ab detection assays lacked a description of their assays (3,6,20,21,48,58). Furthermore, the use of crude mycobacterial antigen mixtures in Ab detection assays by many investigators introduced considerable data variability.…”

Section: Limitations Of and Aspects To Consider In Serological Studiementioning

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

View full text Add to dashboard Cite

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...

show abstract

Section: Mycobacterial Antigens Evaluated For Serodiagnosis In Childhmentioning

confidence: 99%

Section: Antibody Responses According To Type Of Tbmentioning

confidence: 99%

See 1 more Smart Citation

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

Achkar

Ziegenbalg

2012

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…However, antibody profile status to secreted antigens has not been investigated adequately in children. We have recently reported utility of ESAT-6 in paediatric patients [12]. Raja et al have found 30 kDa antigen to be highly sensitive and specific in the serological assay when IgG, IgM and IgA antibodies were measured for the diagnosis of tuberculosis in children [13].…”

Section: Introductionmentioning

confidence: 98%

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

et al. 2008

Self Cite

View full text Add to dashboard Cite

Childhood tuberculosis is difficult to diagnose. A rapid, simple and relatively inexpensive diagnostic test will be crucial to future control efforts. Therefore, efficacy and diagnostic potential of different secretory antigens of Mycobacterium tuberculosis (CFP‐10, Ag85complex, Ag85 A, B, C) and their combinations along with ESAT‐6 in the detection of antibody profiles of childhood tuberculosis cases were evaluated using ELISA technique and reactivity was compared with the gold standards (smear, culture and IS6110 targeted PCR). In the present study, 88 fresh, untreated childhood tuberculosis (TB) cases, 17 children undergoing anti‐tubercular therapy, 17 children having disease other than TB and 25 healthy children were included. ROC curve analysis was used to calculate the sensitivity and specificity of each antigen for antibody detection. Ag85C was found to be showing highest sensitivity of 89.77% and specificity of 92% among all the antigens used (P < 0.0001). Positivity with antigen was 95% in smear and culture negative patients. Antibody reactivity was noted in 92.62% of patients who were positive for IS6110 by PCR. Cocktail of all the antigens showed 67.1% sensitivity and 80% of specificity. Sensitivity of 29.55%, 57.95%, 64.77% and specificity of 80%, 72%, 64% was observed using CFP‐10, Ag85complex and Ag85B. Low reactivity of 31.82% in patients and least specificity of 24% was noted with Ag85A. Our finding demonstrates the potential of Ag85C in the detection of antibody in childhood TB cases and this antigen showed good concordance with PCR positivity.

show abstract

“…Radiographic changes in children can be quite variable (18). Serodiagnostic methods are generally low in sensitivity and specificity, especially for children, and seroreactivity data for pediatric TB are also limited (3,4,12,20,26,41). Recent studies evaluating multiple antigens by an enzymelinked immunosorbent assay (ELISA) or a multiantigen print immunoassay for the serodetection of M. tuberculosis infection appear to have potential but have not been tested on humans (13,15,16).…”

mentioning

confidence: 99%

Detection of Antibodies Secreted from CirculatingMycobacterium tuberculosis-Specific Plasma Cells in the Diagnosis of Pediatric Tuberculosis

Raqib

Mondal

Karim

et al. 2009

Clin Vaccine Immunol

View full text Add to dashboard Cite

Diagnosis of tuberculosis (TB) in children is difficult because symptoms are often nonspecific or absent in infected children, diagnostic specimens are difficult to obtain from younger children, and >50% have negative TB cultures. Thus, there is an urgent need for improved diagnosis of pediatric TB. This study aimed to evaluate the diagnostic value of a new serological method, the ALS (antibodies in lymphocyte supernatant) assay, for the diagnosis of active TB in children with clinically identified TB. The ALS test is based on the concept that antigen-specific plasma cells are present in the circulation only at times of acute infection and not in latency. A cross-sectional study of pediatric patients (age range, 11 to 167 months) who were clinically identified as TB (n ‫؍‬ 58) or non-TB (n ‫؍‬ 16) patients was conducted, and they were monitored for 6 months. Healthy children (n ‫؍‬ 58) were enrolled as controls. Spontaneous release of TB antigen-specific antibodies by in vitro-cultured, unstimulated peripheral blood mononuclear cells was assessed by an enzyme-linked immunosorbent assay using Mycobacterium bovis bacillus Calmette-Guérin ( According to World Health Organization (WHO) estimates, about 1 million children annually develop tuberculosis (TB) worldwide, accounting for about 11% of all TB cases (25,42,48). Bangladesh ranks 6th among the 22 high-TB-burden countries in the world; about 45% of its population is tuberculin positive at the age of 14 years (22, 48). Childhood TB is often not considered a priority by national TB control programs, because children acquire Mycobacterium tuberculosis infections from adults and do not contribute to disease transmission. However, failure to identify and treat TB in children can lead to death in a majority of Ͻ3-year-old children (14, 23).TB-infected children are often asymptomatic, and bacteriologic confirmation is rare, due to the difficulty of obtaining specimens (8, 31). Most pediatric TB cases are diagnosed using a combination of clinical and epidemiological features, which include characteristic chest radiographs (18), reactive tuberculin skin tests (TST), and a history of contact with active TB cases (31, 34); computed tomography and bronchoscopy are performed in industrialized countries (19). In areas where TB is endemic, most of the population acquires TB infection during childhood, and transmission is not restricted to the household (32,46). This situation limits the diagnostic contribution of documented household exposure and positive TST (10,47). Interpretation of TST reactivity is further complicated by the high prevalences of Mycobacterium bovis BCG vaccination and malnutrition. Radiographic changes in children can be quite variable (18). Serodiagnostic methods are generally low in sensitivity and specificity, especially for children, and seroreactivity data for pediatric TB are also limited (3,4,12,20,26,41). Recent studies evaluating multiple antigens by an enzymelinked immunosorbent assay (ELISA) or a multiantigen print immunoassay for the serodetect...

show abstract

Diagnostic Value of Elisa Serological Tests in Childhood Tuberculosis

Cited by 8 publications

References 7 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

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

Detection of Antibodies Secreted from CirculatingMycobacterium tuberculosis-Specific Plasma Cells in the Diagnosis of Pediatric Tuberculosis

Contact Info

Product

Resources

About