Rapid Capsular Antigen Immunoassay for Diagnosis of Inhalational Anthrax: Preclinical Studies and Evaluation in a Nonhuman Primate Model.

Rapid Capsular Antigen Immunoassay for Diagnosis of Inhalational Anthrax: Preclinical Studies and Evaluation in a Nonhuman Primate Model.
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DOI:
10.1128/mbio.00931-22
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发表时间:
2022-06-28
期刊:
影响因子:
6.4
通讯作者:
Kozel, Thomas R.
Kozel, Thomas R.
中科院分区:
生物学1区
文献类型:
--
作者:
Gates-Hollingsworth, Marcellene A.;Kolton, Cari B.;Hoffmaster, Alex R.;Meister, Gabriel T.;Moore, Addie E.;Green, Heather R.;Pogoda, Janice M.;Pillai, Segaran P.;Kozel, Thomas R.

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吸入性炭疽是一种致命的传染病。快速有效的治疗关键取决于早期准确的诊断。血培养、随后的鉴定和确认可能需要几天的时间才能提供临床相关信息。相比之下,针对脱落抗原、荚膜多肽 γ-d-聚谷氨酸 (γDPGA) 的免疫测定可以在护理时提供快速结果。在本研究中,在稳健的非人灵长类吸入性炭疽模型中评估了 γDPGA 的侧流免疫分析。结果显示,使用血清或血液作为临床样本的快速检测获得阳性结果的时间与感染后血培养呈阳性的时间相似。体外测试表明,该测试对炭疽杆菌三个主要分支的培养物同样敏感。来自其他芽孢杆菌属的培养物。已知可产生 γDPGA 的化合物也产生了积极的结果。来自 200 名正常受试者和 45 名经培养证实患有非炭疽细菌或真菌败血症的受试者的人类血清检测结果呈阴性。综上所述,结果表明,γDPGA 免疫测定是相关食蟹猴吸入性炭疽模型中血培养的有效替代方法。该测试将有助于炭疽的早期诊断,这对于快速干预和积极的结果至关重要。使用该测试可以促进在大规模接触事件中以及在实验室资源不易获得的资源匮乏环境中对有炭疽体征和症状的患者进行分类。
Inhalational anthrax is a fatal infectious disease. Rapid and effective treatment is critically dependent on early and accurate diagnosis. Blood culture followed by identification and confirmation may take days to provide clinically relevant information. In contrast, immunoassay for a shed antigen, the capsular polypeptide gamma-d-polyglutamate (γDPGA), can provide rapid results at the point of care. In this study, a lateral flow immunoassay for γDPGA was evaluated in a robust nonhuman primate model of inhalational anthrax. The results showed that the time to a positive result with the rapid test using either serum or blood as a clinical specimen was similar to the time after infection when a blood culture became positive. In vitro testing showed that the test was equally sensitive with cultures of the three major clades of Bacillus anthracis. Cultures from other Bacillus spp. that are known to produce γDPGA also produced positive results. The test was negative with human sera from 200 normal subjects and 45 subjects with culture-confirmed nonanthrax bacterial or fungal sepsis. Taken together, the results showed that immunoassay for γDPGA is an effective surrogate for blood culture in a relevant cynomolgus monkey model of inhalational anthrax. The test would be a valuable aid in early diagnosis of anthrax, which is critical for rapid intervention and a positive outcome. Use of the test could facilitate triage of patients with signs and symptoms of anthrax in a mass-exposure incident and in low-resource settings where laboratory resources are not readily available.
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