Validity of Antibodies in Lymphocyte Supernatant in Diagnosing Tuberculosis in Severely Malnourished Children Presenting with Pneumonia

Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Raqib, Rubhana; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Sharmin, Lazina; Ashraf, Hasan; Faruque, Abu Syed Golam; Bardhan, Pradip Kumar; Ahmed, Tahmeed

doi:10.1371/journal.pone.0126863

Cited by 8 publications

(8 citation statements)

References 15 publications

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“…Within the members of the control population, 22% demonstrated a positive MASC result yielding a specificity value of 78%. While this is lower than the 87% specificity initially reported in children from Bangladesh, it is much higher than the 51% specificity subsequently found among children Ͻ5 years of age admitted with radiographic pneumonia and severe acute malnutrition (8,9). We deemed these to be false-positive results for active TB because the control children in our study had no reported risk factors, symptoms, or clinical findings consistent with TB.…”

Section: Discussioncontrasting

confidence: 63%

“…Initial reports of this assay in childhood TB suggested a correlation with bacillary burden; serial measurements demonstrated reductions in ALS titers which correlated well with clinical treatment response among culture-confirmed TB cases (8,12). However, subsequent reports from studies performed with young malnourished children suggested that this assay did not outperform clinical scoring systems for diagnosis of disease in children with TB such as the Kenneth-Jones and WHO scoring criteria (9).…”

Section: Discussionmentioning

confidence: 98%

“…Initial studies suggested that the assay outperformed various clinical scoring systems in differentiating hospitalized children with TB from other causes of illness with 91% sensitivity and 87% specificity compared to a composite clinical reference standard (8). However, the level of performance was reduced among young children admitted with pneumonia in the setting of severe acute malnutrition (sensitivity of 67% and specificity of 51%) (9). The assay has not been evaluated among the members of an ambulatory pediatric population.…”

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confidence: 99%

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Antibody-Secreting Cells To Diagnose Mycobacterium tuberculosis Infection in Children in Pakistan

Iqbal

Ahmed

Qamar

et al. 2020

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Reliance on microbiologic methods to diagnose Mycobacterium tuberculosis infection is a suboptimal approach for children due in part to the paucibacillary nature of the disease. A blood-based biomarker assay, such as the mycobacterial-antibody-secreting cell (MASC) assay, could be a major advance for the field of study of pediatric tuberculosis (TB). Children <15 years of age with clinical concern for TB and age-matched children with no concern for TB were enrolled from outpatient clinics in Karachi, Pakistan. MASC, ferritin, and C-reactive protein (CRP) assays were performed, and results were compared among cases and controls, as well as among children with a case definition of “confirmed TB,” “probable TB,” or “possible TB.” MASC responses were significantly higher among children with TB than among controls (0.41 optical density [OD] versus 0.28 OD, respectively, P < 0.001), and the differences were largely driven by the data from children with confirmed TB (P = 0.002). Ferritin and CRP values were significantly higher among those with confirmed TB than among those with the other disease states and controls (P = 0.004 and P = 0.019, respectively). The use of the MASC assay as a blood-based biomarker for TB disease shows some promise among children with microbiologically confirmed disease; however, the performance characteristics for the majority of young children with unconfirmed TB were suboptimal in this cohort. IMPORTANCE Tuberculosis (TB) in children represents a missed opportunity for diagnosis and preventive therapy. The magnitude or burden of disease in children is not fully understood due to our limitations with respect to exploring sensitive diagnostic algorithms. In a setting of TB endemicity in Pakistan, we carried out a proof-of-concept study to evaluate for the first time the performance of B cell analyses by the use of well-defined diagnostic criteria and NIH consensus guidelines as “culture-confirmed,” “probable,” and “possible” TB groups. In contrast to detection of serum antibody, we focused on mycobacterial-antibody-secreting cell (MASC) detection as a marker of active disease in children with a strong suspicion of TB. Further work exploring a larger panel of inflammatory biomarkers and enrichment of B cells with the objective of increasing the sensitivity of the current MASC assay would lead to the development of a field-friendly assay for timely diagnosis of childhood TB.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Antibody-Secreting Cells To Diagnose Mycobacterium tuberculosis Infection in Children in Pakistan

Iqbal

Ahmed

Qamar

et al. 2020

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“…In recent studies, however, ALS assays have been successfully carried out in the pediatric population in the field using a small volume of blood samples (34,35).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Mucosal Immune Responses to Enterotoxigenic Escherichia coli Vaccine Antigens in a Human Challenge Model: Response Profiles after Primary Infection and Homologous Rechallenge with Strain H10407

Chakraborty

Harro

DeNearing

et al. 2016

Clin Vaccine Immunol

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Enterotoxigenic Escherichia coli (ETEC) bacteria are the most common bacterial cause of diarrhea in children in resource-poor settings as well as in travelers. Although there are several approaches to develop an effective vaccine for ETEC, no licensed vaccines are currently available. A significant challenge to successful vaccine development is our poor understanding of the immune responses that correlate best with protection against ETEC illness. In this study, ETEC-specific mucosal immune responses were characterized and compared in subjects challenged with ETEC strain H10407 and in subjects rechallenged with the homologous organism. IgA responses to lipopolysaccharide (LPS), heat-labile toxin B subunit (LTB), and colonization factor antigen I (CFA/I) in antibody in lymphocyte supernatant (ALS), feces, lavage fluid, and saliva samples were evaluated. In all assay comparisons, ALS was the most sensitive indicator of a local immune response, but serum IgA was also a useful indirect marker of immune response to oral antigens. Volunteers challenged and then rechallenged with strain H10407 were protected from illness following rechallenge. Comparing mucosal antibody responses after primary and homologous rechallenge, protection against disease was reflected in reduced antibody responses to key ETEC antigens and in reduced fecal shedding of the H10407 challenge strain. Subjects challenged with strain H10407 mounted stronger antibody responses to LPS and LTB than subjects in the rechallenge group, while responses to CFA/I in the rechallenge group were higher than in the challenge group. We anticipate that this study will help provide an immunological benchmark for the evaluation of ETEC vaccines and immunization regimens in the future.

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“…The lesser performance of ALS in relation to MKJC scoring and the WHO criteria for the diagnosis of TB in our study population is interesting but critically important for the clinician in resource poor settings. The published data from the same cohort already revealed that ALS was not sufficiently accurate to improve the diagnosis of TB in severely malnourished children (15). However, that article did not reveal the comparative performance of ALS with MKJC scoring and the WHO criteria for the diagnosis of TB in our study population.…”

Section: Discussionmentioning

confidence: 99%

Comparative Performance of Modified Kenneth Jones Criteria Scoring, World Health Organization Criteria, and Antibodies in Lymphocyte Supernatant for Diagnosing Tuberculosis in Severely Malnourished Children Presenting With Pneumonia

et al. 2019

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Background: The diagnosis of childhood tuberculosis (TB) can be difficult in severely malnourished children. This is mainly due to the fact of our perceived notion that clinical signs of TB are often subtle in severely malnourished children and we may rely on laboratory investigation for the diagnosis. However, comparative data on the performance of clinical and laboratory diagnostics of TB in such population are also very limited.Objectives: To compare the performance of composite clinical criteria and a technique that measures antibodies in lymphocyte supernatant (ALS) for the diagnosis of TB in severely malnourished children with pneumonia.Methods: Severely malnourished children under five with radiological pneumonia admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh were enrolled consecutively following informed consent. We collected venous blood for ALS, gastric lavage fluid and induced sputum for microscopy, mycobacterial culture, and real-time PCR by Xpert MTB/RIF. We compared the sensitivity, specificity, positive, and negative predictive values, and accuracy of modified Kenneth Jones criteria (MKJC) score, World Health Organization (WHO) criteria, and ALS in diagnosing TB in severely malnourished children with pneumonia for “Confirmed TB” and “All TB” (“Confirmed TB” plus “Probable TB”) vs. “Not TB.”Results: Compared to culture confirmed TB, the sensitivity, and specificity (95% CI) for MKJC were 60 (27–86) and 84 (79–87)% and for WHO criteria were 40 (14–73) and 84 (80–87)%, respectively. Compared to culture and/or Xpert MTB/RIF positive TB, the sensitivity and specificity (95% CI) for the criteria were 37 (20–58) and 84 (79–87)%; and 22 (9–43) and 83 (79–87)%, respectively. For both these comparisons, the sensitivity and specificity of ALS were 50 (14–86) and 60 (53–67)%, respectively.Conclusion: Our data suggest that WHO criteria and MKJC scoring mainly based on clinical criteria are more useful than ALS in diagnosing TB in young severely malnourished children with pneumonia. The results underscore the importance of using clinical criteria for the diagnosis of TB in severely malnourished children that may help to minimize the chance of over treatment with anti-TB in such population, especially in resource limited TB endemic settings.

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Validity of Antibodies in Lymphocyte Supernatant in Diagnosing Tuberculosis in Severely Malnourished Children Presenting with Pneumonia

Cited by 8 publications

References 15 publications

Antibody-Secreting Cells To Diagnose Mycobacterium tuberculosis Infection in Children in Pakistan

Antibody-Secreting Cells To Diagnose Mycobacterium tuberculosis Infection in Children in Pakistan

Characterization of Mucosal Immune Responses to Enterotoxigenic Escherichia coli Vaccine Antigens in a Human Challenge Model: Response Profiles after Primary Infection and Homologous Rechallenge with Strain H10407

Comparative Performance of Modified Kenneth Jones Criteria Scoring, World Health Organization Criteria, and Antibodies in Lymphocyte Supernatant for Diagnosing Tuberculosis in Severely Malnourished Children Presenting With Pneumonia

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