Evaluation of antigen-detecting and antibody-detecting diagnostic test combinations for diagnosing melioidosis.
Evaluation of antigen-detecting and antibody-detecting diagnostic test combinations for diagnosing melioidosis.
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DOI：
10.1371/journal.pntd.0009840
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发表时间：
2021-11
影响因子：
3.8
通讯作者：
Limmathurotsakul D
中科院分区：
文献类型：
--
作者：
Amornchai P;Hantrakun V;Wongsuvan G;Wuthiekanun V;Wongratanacheewin S;Teparrakkul P;West TE;AuCoin DP;Day NPJ;Brett PJ;Burtnick MN;Chantratitra N;Limmathurotsakul D
类鼻疽是由类鼻疽伯克霍尔德氏菌引起的一种传染病，在许多热带发展中国家是地方病，死亡率很高。在这里，我们评估了检测B的侧流免疫测定（LFI）的组合。类鼻疽荚膜多糖（CPS）和检测抗溶血素共调节蛋白（Hcp 1）或O-多糖（OPS）的抗体的酶联免疫吸附测定（ELISA）用于诊断类鼻疽。我们进行了一项基于队列的病例对照研究。病例和对照均来自泰国东北部社区获得性感染和脓毒症患者的前瞻性观察性研究（乌汶-脓毒症）。病例包括192例临床标本培养B阳性的患者。假鼻疽对照组包括502例血培养金黄色葡萄球菌、大肠杆菌或肺炎克雷伯菌阳性或聚合酶链反应检测疟疾或登革热阳性的患者。储存入院24小时内收集的血清样本，并使用CPS-LFI、Hcp 1-ELISA和OPS-ELISA进行检测。当评估诊断测试组合，结果被认为是积极的，如果任一测试是积极的。我们选择了对应于95%特异性的ELISA截止值。采用Hcp 1-ELISA的阳性截止值OD为2.912，CPS-LFI和Hcp 1-ELISA联合检测的敏感性为67.7%（130/192例患者），特异性为95.0%（477/502例对照患者）。联合检测的敏感性（67.7%）高于CPS-LFI（31.3%，p<0.001）和Hcp 1-ELISA（53.6%，p<0.001）。CPS-LFI和OPS-ELISA联用也观察到类似现象。在病例中，CPS-LFI阳性与症状持续时间短、改良序贯（脓毒症相关）器官衰竭评估（SOFA）评分高、菌血症和死亡结局相关，而Hcp 1-ELISA阳性与症状持续时间长、改良SOFA评分低、无菌血症和生存结局相关。抗原-抗体诊断试验的组合增加了类鼻疽诊断的灵敏度，同时保持了高特异性。应进一步开发和评价基于联合检测的类鼻疽即时检测。类鼻疽是由革兰氏阴性细菌类鼻疽伯克霍尔德氏菌引起的感染。目前还没有市售的可靠的类鼻疽即时诊断试验。我们以前证明，原型侧流免疫测定（LFI）开发检测B。假鼻疽荚膜多糖（CPS）诊断泰国东北部社区获得性感染或败血症患者类鼻疽的敏感性有限（31.3%），但特异性高（98.8%）。在这里，我们评估了CPS-LFI和酶联免疫吸附试验（ELISA）的组合，检测溶血素共调节蛋白（Hcp 1）或O-多糖（OPS）的抗体。当联合使用时，如果任一检测结果为阳性，则认为结果为阳性。我们选择了对应于95%特异性的ELISA截止值。我们的研究结果表明，抗原检测（CPS-LFI）和抗体检测（Hcp 1-ELISA或OPS-ELISA）检测的组合增加了诊断类鼻疽的灵敏度（分别为68%或63%），同时保持了高特异性（95%）。在病例患者中，CPS-LFI阳性与症状持续时间短、严重感染（通过器官衰竭评估评分测量）、菌血症和死亡结局相关，而Hcp 1-ELISA阳性与症状持续时间长、无菌血症和生存结局相关。根据我们的研究结果，我们建议应进一步开发和评估使用抗原和抗体检测组合的即时类鼻疽诊断测试。
Melioidosis, an infectious disease caused by Burkholderia pseudomallei, is endemic in many tropical developing countries and has a high mortality. Here we evaluated combinations of a lateral flow immunoassay (LFI) detecting B. pseudomallei capsular polysaccharide (CPS) and enzyme-linked immunosorbent assays (ELISA) detecting antibodies against hemolysin co-regulated protein (Hcp1) or O-polysaccharide (OPS) for diagnosing melioidosis. We conducted a cohort-based case-control study. Both cases and controls were derived from a prospective observational study of patients presenting with community-acquired infections and sepsis in northeast Thailand (Ubon-sepsis). Cases included 192 patients with a clinical specimen culture positive for B. pseudomallei. Controls included 502 patients who were blood culture positive for Staphylococcus aureus, Escherichia coli or Klebsiella pneumoniae or were polymerase chain reaction assay positive for malaria or dengue. Serum samples collected within 24 hours of admission were stored and tested using a CPS-LFI, Hcp1-ELISA and OPS-ELISA. When assessing diagnostic tests in combination, results were considered positive if either test was positive. We selected ELISA cut-offs corresponding to a specificity of 95%. Using a positive cut-off OD of 2.912 for Hcp1-ELISA, the combination of the CPS-LFI and Hcp1-ELISA had a sensitivity of 67.7% (130/192 case patients) and a specificity of 95.0% (477/502 control patients). The sensitivity of the combination (67.7%) was higher than that of the CPS-LFI alone (31.3%, p<0.001) and that of Hcp1-ELISA alone (53.6%, p<0.001). A similar phenomenon was also observed for the combination of CPS-LFI and OPS-ELISA. In case patients, positivity of the CPS-LFI was associated with a short duration of symptoms, high modified Sequential (sepsis-related) Organ Failure Assessment (SOFA) score, bacteraemia and mortality outcome, while positivity of Hcp1-ELISA was associated with a longer duration of symptoms, low modified SOFA score, non-bacteraemia and survival outcome. A combination of antigen-antibody diagnostic tests increased the sensitivity of melioidosis diagnosis over individual tests while preserving high specificity. Point-of-care tests for melioidosis based on the use of combination assays should be further developed and evaluated. Melioidosis is an infection caused by the Gram-negative bacterium Burkholderia pseudomallei. There are currently no commercially available and reliable point-of-care diagnostic tests for melioidosis. We previously demonstrated that a prototype lateral flow immunoassay (LFI) developed to detect B. pseudomallei capsular polysaccharide (CPS) had limited sensitivity (31.3%) but high specificity (98.8%) for diagnosing melioidosis among patients presenting with community-acquired infection or sepsis in northeast Thailand. Here, we evaluated combinations of the CPS-LFI and enzyme-linked immunosorbent assays (ELISA) that detect antibodies against hemolysin co-regulated protein (Hcp1) or O-polysaccharide (OPS). When used in combination, results were considered positive if either test was positive. We selected ELISA cut-offs corresponding to a specificity of 95%. Our results demonstrated that a combination of antigen-detection (CPS-LFI) and antibody-detection (Hcp1-ELISA or OPS-ELISA) tests increased the sensitivity for diagnosis of melioidosis (68% or 63%, respectively) over any single test, while maintaining high specificity (95%). In case patients, positivity of the CPS-LFI was associated with a short duration of symptoms, severe infections (as measured by an organ failure assessment score), bacteraemia and mortality outcome, while positivity of Hcp1-ELISA was associated with a long duration of symptoms, non-bacteraemia and survival outcome. Based on our findings, we propose that point-of-care melioidosis diagnostic tests using combinations of antigen- and antibody-detection should be further developed and evaluated.
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DOI：
10.1161/circgenetics.110.957928
发表时间：
2011-04
期刊：
Circulation. Cardiovascular genetics
影响因子：
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作者：
Anderson CD;Nalls MA;Biffi A;Rost NS;Greenberg SM;Singleton AB;Meschia JF;Rosand J
通讯作者：
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影响因子：
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作者：
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通讯作者：
Limmathurotsakul, Direk
影响因子：
3
作者：
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Norton, Robert
DOI：
10.4269/ajtmh.17-0998
发表时间：
2018-12
期刊：
The American journal of tropical medicine and hygiene
影响因子：
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作者：
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通讯作者：
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影响因子：
2.5
作者：
Diefenbach-Elstob, Tanya R.;Graves, Patricia M.;Warner, Jeffrey M.
通讯作者：
Warner, Jeffrey M.