Nowak Julia, Ssanyu Jacquellyn Nambi, Namiiro Flavia, Mountford Nicola, Parducci Avery, Domijan Katarina, Daly Mandy, O'Brien Deirdre, Barden Eithne, Walshe Kieran, Doyle Sean, Waiswa Peter
Department of Biology, Maynooth University, Maynooth, Ireland.
Makerere University School of Public Health and Global Health, Kampala, Uganda.
PLoS One. 2025 Feb 12;20(2):e0314702. doi: 10.1371/journal.pone.0314702. eCollection 2025.
Sepsis is the overwhelming immunological response to infection, which if not treated can lead to multi-organ failure, shock and death. Specifically, neonatal sepsis results in 225,000 neonatal deaths globally per annum. Moreover, Uganda experiences one of the highest materno-fetal death rates (62,000 p.a.), with neonatal sepsis deaths at approximately 6,500 p.a.. The difficulty in diagnosing neonatal sepsis lies in the non-specific signs and symptoms associated with sepsis and an absence of definitive sepsis-specific biomarkers. However, serum amyloid A (SAA) detection has potential as a superior biomarker for the diagnosis of probable neonatal sepsis. Herein, in ethically-approved studies we have deployed a competitive lateral flow test (NeoSep-SAA (research-use only)) to detect SAA in whole blood at patient bedside in a resource-limited environment. Results are available within 10 minutes and test format is compatible with small blood volumes available from neonates (5 μl). NeoSep-SAA exhibited a high sensitivity and specificity for diagnosis of adult sepsis, and in neonates showed a sensitivity and specificity of 92% (89%, 95%) and 73% (68%, 77%) with PPV and NPV of 78% (75%, 81%) and 90% (86%, 93%), respectively (n = 714 individuals; 95% CI). NeoSep-SAA showed superior sensitivity for neonatal sepsis over C-Reactive Protein detection (sensitivity: 37%), albeit with some sacrifice of specificity. NeoSep-SAA enabled rapid diagnosis, which combined with minimally-invasive blood withdrawal, was less stressful for neonates. Overall, NeoSep-SAA can readily identify infection/inflammation and has the potential to enable rapid and informed clinical decisions to combat sepsis. This approach has potential to improve neonatal sepsis detection and reduce neonatal mortality in line with United Nations Sustainable Development Goal (SDG) 3.2 objectives.
脓毒症是机体对感染产生的过度免疫反应，若不加以治疗，可能会导致多器官功能衰竭、休克甚至死亡。具体而言，全球每年有22.5万例新生儿死于新生儿脓毒症。此外，乌干达是孕产妇和胎儿死亡率最高的国家之一（每年6.2万例），其中每年约有6500例死于新生儿脓毒症。新生儿脓毒症的诊断困难在于其相关体征和症状不具有特异性，且缺乏明确的脓毒症特异性生物标志物。然而，血清淀粉样蛋白A（SAA）检测有望成为诊断疑似新生儿脓毒症的优质生物标志物。在此，在经过伦理批准的研究中，我们采用了一种竞争性侧向流动检测法（NeoSep-SAA（仅用于研究）），以便在资源有限的环境中于患者床边检测全血中的SAA。10分钟内即可获得检测结果，且检测形式适用于新生儿可提供的少量血液（5微升）。NeoSep-SAA对成人脓毒症诊断具有较高的敏感性和特异性，在新生儿中，其敏感性和特异性分别为92%（89%，95%）和73%（68%，77%），阳性预测值和阴性预测值分别为78%（75%，81%）和90%（86%，93%）（n = 714人；95%置信区间）。与C反应蛋白检测相比，NeoSep-SAA对新生儿脓毒症表现出更高的敏感性（敏感性：37%），不过特异性有所牺牲。NeoSep-SAA能够实现快速诊断，再加上微创采血，对新生儿造成的压力较小。总体而言，NeoSep-SAA能够轻松识别感染/炎症，并有潜力促使临床做出快速且明智的决策以对抗脓毒症。这种方法有潜力改善新生儿脓毒症的检测，并根据联合国可持续发展目标（SDG）3.2的目标降低新生儿死亡率。
