دورية أكاديمية
Assessment and translation of the antibody-in-lymphocyte supernatant (ALS) assay to improve the diagnosis of enteric fever in two controlled human infection models and an endemic area of Nepal
| العنوان: | Assessment and translation of the antibody-in-lymphocyte supernatant (ALS) assay to improve the diagnosis of enteric fever in two controlled human infection models and an endemic area of Nepal |
|---|---|
| المؤلفون: | Darton, TC, Jones, C, Dongol, S, Voysey, M, Blohmke, CJ, Shrestha, R, Karkey, A, Shakya, M, Arjyal, A, Waddington, CS, Gibani, M, Carter, MJ, Basnyat, B, Baker, S, Pollard, AJ |
| المصدر: | 13 ; 1 |
| بيانات النشر: | Frontiers Media |
| سنة النشر: | 2017 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Microbiology, enteric fever, Salmonella Typhi, Salmonella Paratyphi A, diagnostic test, antibody-in-lymphocyte supernatant assay, febrile illness, resource-limited settings, bacteremia, TYPHOID-FEVER, LABORATORY DIAGNOSIS, TESTS, EPIDEMIOLOGY, RESISTANCE, 0502 Environmental Science and Management, 0503 Soil Sciences, 0605 Microbiology |
| الوصف: | New diagnostic tests for enteric fever are urgently needed to assist with timely antimicrobial treatment of patients and to measure the efficacy of prevention measures such as vaccination. In a novel translational approach, here we use two recently developed controlled human infection models (CHIM) of enteric fever to evaluate an antibody-in-lymphocyte supernatant (ALS) assay, which can detect recent IgA antibody production by circulating B cells in ex vivo mononuclear cell culture. We calculated the discriminative ability of the ALS assay to distinguish diagnosed cases in the two CHIM studies in Oxford, prior to evaluating blood culture-confirmed diagnoses of patients presenting with fever to hospital in an endemic areas of Kathmandu, Nepal. Antibody responses to membrane preparations and lipopolysaccharide provided good sensitivity (>90%) for diagnosing systemic infection after oral challenge with Salmonella Typhi or S. Paratyphi A. Assay specificity was moderate (~60%) due to imperfect sensitivity of blood culture as the reference standard and likely unrecognized subclinical infection. These findings were augmented through the translation of the assay into the endemic setting in Nepal. Anti-MP IgA responses again exhibited good sensitivity (86%) but poor specificity (51%) for detecting blood culture-confirmed enteric fever cases (ROC AUC 0.79, 95%CI 0.70–0.88). Patients with anti-MP IgA ALS titers in the upper quartile exhibited a clinical syndrome synonymous with enteric fever. While better reference standards are need to assess enteric fever diagnostics, routine use of this ALS assay could be used to rule out infection and has the potential to double the laboratory detection rate of enteric fever in this setting over blood culture alone. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1664-302X |
| العلاقة: | Frontiers in Microbiology; http://hdl.handle.net/10044/1/83916Test |
| DOI: | 10.3389/fmicb.2017.02031 |
| الإتاحة: | https://doi.org/10.3389/fmicb.2017.02031Test http://hdl.handle.net/10044/1/83916Test |
| حقوق: | © 2017 Darton, Jones, Dongol, Voysey, Blohmke, Shrestha, Karkey, Shakya, Arjyal, Waddington, Gibani, Carter, Basnyat, Baker and Pollard. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.C4FC0DA2 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 1664302X |
|---|---|
| DOI: | 10.3389/fmicb.2017.02031 |