Munira Sira J, Islam Nahidul, Prithe Nowshin T, Sarkar Anik, Esfandiari Javan, Gunasekera Dhammika, Islam Shuborno, Akter Tanjila, Garrett Denise O, Saha Samir K, Andrews Jason R, Saha Senjuti, Charles Richelle C
Child Health Research Foundation, Dhaka, Bangladesh.
Chembio Diagnostics Systems, Medford, NY USA.
Lancet Microbe. 2025 Mar;6(3):100983. doi: 10.1016/j.lanmic.2024.100983. Epub 2024 Dec 17.
There is a shortage of rapid, accurate, and low-cost assays for diagnosing enteric fever. The dual-path platform for typhoid (DPPT) assay had high accuracy in retrospective studies with banked plasma samples. We aimed to evaluate the diagnostic accuracy of the DPPT assay in a prospective study using fingerstick capillary blood.
For this prospective diagnostic accuracy study, we enrolled children younger than 18 years, who presented at the Bangladesh Shishu Hospital and Institute (Dhaka, Bangladesh) with at least 3 days of fever. We collected blood and nasal swabs, and did the following assays to assess the accuracy of DPPT: blood culture, serological assays for typhoid fever (DPPT assay, Widal, and Test-it), and molecular assays to identify alternative aetiologies (eg, respiratory syncytial virus [RSV], influenza, dengue virus, and Rickettsia spp). The primary outcomes of the study were the sensitivity and specificity of the DPPT assay for diagnosis of enteric fever. We evaluated the accuracy of combined anti-haemolysin E and anti-lipopolysaccharide IgA readings using the DPPT assay in distinguishing culture-confirmed enteric fever from alternative aetiologies using receiver operating characteristic area under the curve (AUC). Given the imperfect reference standard diagnostics for enteric fever, we used Bayesian latent class models, incorporating results from the typhoid and alternative aetiology diagnostics, to estimate the sensitivity and specificity of the DPPT assay. We also did subgroup analyses for the assay across multiple biological variables.
Between Aug 17, 2021, and July 16, 2022, we enrolled 501 participants who presented with at least 3 days of fever. 223 (45%) of 501 participants were female and 278 (55%) were male. 77 participants had culture-confirmed enteric fever (62 Salmonella enterica serotype Typhi and 15 Salmonella enterica serotype Paratyphi A) and 70 were culture-negative with PCR-confirmed alternative aetiology (34 influenza A or B, 22 dengue virus, seven Rickettsia spp, six RSV, and one participant co-infected with RSV and dengue virus). The AUC for DPPT on fingerstick capillary blood in distinguishing typhoid from alternative aetiologies was 0·969 (95% CI 0·943-0·994). In latent class analysis, the sensitivity of DPPT was 93% (95% credible interval [CrI] 87-97) and specificity was 89% (85-93). The balanced accuracy was higher for DPPT (91%, 95% CrI 87-94) than blood culture (81%, 78-85), Test-it (77%, 74-79), or Widal (70%, 67-73). Assay performance did not vary by sex, age, duration of fever at presentation, antibiotic use before presentation, Salmonella serotype, or sample type.
The point-of-care DPPT assay achieved high diagnostic accuracy for enteric fever in a highly endemic community. This assay has the potential to improve clinical outcomes for enteric fever, allowing rapid diagnosis and treatment, and could facilitate more appropriate antimicrobial use.
National Institute of Health, Bill & Melinda Gates Foundation, and Child Health Research Foundation.
目前缺乏快速、准确且低成本的伤寒热诊断检测方法。伤寒双路径平台（DPPT）检测法在对储存血浆样本的回顾性研究中具有较高的准确性。我们旨在通过一项使用指尖毛细血管血的前瞻性研究来评估DPPT检测法的诊断准确性。
在这项前瞻性诊断准确性研究中，我们纳入了年龄小于18岁、在孟加拉国儿童医院及研究所（达卡，孟加拉国）出现至少3天发热症状的儿童。我们采集了血液和鼻拭子，并进行以下检测以评估DPPT的准确性：血培养、伤寒热血清学检测（DPPT检测法、维达试验和Test-it）以及用于识别其他病因的分子检测（例如呼吸道合胞病毒[RSV]、流感、登革热病毒和立克次体属）。该研究的主要结局是DPPT检测法诊断伤寒热的敏感性和特异性。我们使用DPPT检测法评估抗溶血素E和抗脂多糖IgA联合读数在区分培养确诊的伤寒热与其他病因方面的准确性，采用曲线下面积（AUC）的受试者工作特征曲线进行评估。鉴于伤寒热的参考标准诊断并不完美，我们使用贝叶斯潜在类别模型，纳入伤寒和其他病因诊断的结果，来估计DPPT检测法的敏感性和特异性。我们还针对多个生物学变量对该检测法进行了亚组分析。
在2021年8月17日至2022年7月16日期间，我们纳入了501名出现至少3天发热症状的参与者。501名参与者中223名（45%）为女性，278名（55%）为男性。77名参与者血培养确诊为伤寒热（62例伤寒沙门菌血清型伤寒杆菌和15例甲型副伤寒沙门菌），70名血培养阴性但PCR确诊为其他病因（34例甲型或乙型流感、22例登革热病毒、7例立克次体属、6例RSV以及1例同时感染RSV和登革热病毒的参与者）。DPPT对指尖毛细血管血中伤寒与其他病因的区分AUC为0.969（95%CI 0.943 - 0.994）。在潜在类别分析中，DPPT的敏感性为93%（95%可信区间[CrI] 87 - 97），特异性为89%（85 - 93）。DPPT的平衡准确性（91%，95% CrI 87 - 94）高于血培养（81%，78 - 85）、Test-it（77%，74 - 79）或维达试验（70%，67 - 73）。检测性能在性别、年龄、就诊时发热持续时间、就诊前抗生素使用情况、沙门菌血清型或样本类型方面没有差异。
即时检测的DPPT检测法在高度流行社区中对伤寒热实现了较高的诊断准确性。该检测法有可能改善伤寒热的临床结局，实现快速诊断和治疗，并有助于更合理地使用抗菌药物。
美国国立卫生研究院、比尔及梅琳达·盖茨基金会和儿童健康研究基金会。
