Antibody-Secreting Cells To Diagnose Mycobacterium tuberculosis Infection in Children in Pakistan
Reliance on microbiologic methods to diagnose 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 ped...
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| Published in: | mSphere Vol. 5; no. 1 |
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| Main Authors: | , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
American Society for Microbiology
05-02-2020
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Reliance on microbiologic methods to diagnose
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,
< 0.001), and the differences were largely driven by the data from children with confirmed TB (
= 0.002). Ferritin and CRP values were significantly higher among those with confirmed TB than among those with the other disease states and controls (
= 0.004 and
= 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.
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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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Citation Iqbal NT, Ahmed K, Qamar FN, Shaheen F, Mehnaz A, Arif F, Saeed AA, Yousuf AM, Raza SF, Sultana S, Qureshi SM, Siddiqi SA, Houpt E, Thomas T. 2020. Antibody-secreting cells to diagnose Mycobacterium tuberculosis infection in children in Pakistan. mSphere 5:e00632-19. https://doi.org/10.1128/mSphere.00632-19. |
| ISSN: | 2379-5042 2379-5042 |
| DOI: | 10.1128/mSphere.00632-19 |