Lancet Infectious Diseases最新文献

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Lassa fever symptomatology, viral dynamics, and host immune response (PREPARE): a prospective, observational cohort study in Liberia. 拉沙热症状学、病毒动力学和宿主免疫反应（PREPARE）：利比里亚的一项前瞻性观察队列研究。

IF 31 1区医学 Q1 INFECTIOUS DISEASES

Lancet Infectious Diseases

Pub Date : 2026-01-07 DOI: 10.1016/S1473-3099(25)00725-X

David A Wohl, Carwolo Pewu, Chanhwa Lee, Emmanuel Kerkula, Martha Gayflowu, Nukal Doetein, Katie R Mollan, Taylor J Krajewski, Becky Straub, Alfred Flomo, Amara Fofana, Stanley Kerkula, Thomas Sumo, Alexander Sampson, Samuel Vouh, Fred Flomo, McKenzie A Colt, Thomas Remont, Eleanor Rose Watts, Marta Zizek, Catherine Nimely, Minnie Ricks, Jefferson Sibley, William A Fischer

Background: Lassa virus (LASV) is a persistent threat to public health in west Africa and beyond. LASV is endemic in west Africa and each year it is responsible for an estimated 2·7 million infections, 23 700 hospitalisations, and 5000 deaths. With over 32 reported cases of Lassa fever imported into non-endemic countries-one-third of which were fatal-the importance of enhanced detection and management of Lassa fever extends beyond west Africa.Methods: The prevalence, pathogenesis, and persistence (PREPARE) study was a prospective cohort study among patients admitted to two hospitals in a hyperendemic area of Liberia. Any patients aged 5 years or older with a febrile illness were eligible to enrol and be tested for Lassa fever. The study aimed to measure the prevalence of LASV infection and assess the signs and symptoms, LASV viral replication kinetics, and LASV-specific IgM and IgG responses longitudinally among adults and children with laboratory-confirmed Lassa fever.Findings: From July 10, 2018, to Aug 12, 2024, a total of 435 participants were enrolled, including 362 admitted with a febrile illness and 73 who were directly admitted with clinical suspicion for Lassa fever. Lassa fever was diagnosed by plasma LASV RT-PCR in 41 (11%) of 362 febrile participants and 47 (64%) of 73 participants directly admitted with suspected Lassa fever, resulting in a total of 88 cases of confirmed Lassa fever. At entry, anorexia (71 [81%] of 88 vs 178 [51%] of 347), severe fatigue or weakness (63 [72%] vs 178 [51%]), and nausea or vomiting (39 [44%] vs 95 [27%]) were more likely to be reported by participants with Lassa fever than by participants who tested LASV RNA negative. Among the participants with Lassa fever, 11 (13%) of 88 died after admission. Mental status changes, seizures, acute kidney failure, hyperkalaemia, and metabolic acidosis were more frequent in patients with Lassa fever who died than in patients who survived. Median cycle threshold values at study entry for glycoprotein complex gene (GPC) or polymerase gene (L) were lower in those who died (GPC cycle threshold 22·4 [IQR 20·0-27·9]; L cycle threshold 21·7 [19·0-27·7]) than in those who survived (GPC cycle threshold 31·5 [28·0-33·9]; L cycle threshold 32·3 [28·0-33·9]). Among the 70 participants with Lassa fever who consented to longitudinal follow-up through their hospitalisation, seven died and these participants tended to have lower cycle threshold values and lower IgM and IgG LASV responses compared with survivors.Interpretation: In a region of Liberia where it is endemic, Lassa fever is a prevalent cause of morbidity and mortality. Several symptoms were more likely in those with Lassa fever but overlap with those caused by other common infectious diseases. Compared with survivors, those who died during hospitalisation for Lassa fever tended to have evidence of organ dysfunction along with higher

背景：拉沙病毒（LASV）对西非及其他地区的公共卫生构成持续威胁。LASV在西非流行，每年估计造成270万人感染，2.37万人住院，5000人死亡。由于传入非流行国家的拉沙热报告病例超过32例，其中三分之一是致命的，因此加强拉沙热检测和管理的重要性超出了西非。方法：流行、发病机制和持续性（PREPARE）研究是一项前瞻性队列研究，研究对象是利比里亚高流行地区两家医院收治的患者。任何年龄在5岁或以上的发热性疾病患者都有资格参加并接受拉沙热检测。该研究旨在测量实验室确诊的拉沙热成人和儿童中LASV感染的流行程度，并纵向评估体征和症状、LASV病毒复制动力学以及LASV特异性IgM和IgG反应。结果：2018年7月10日至2024年8月12日，共纳入受试者435人，其中以发热性疾病入院362人，临床疑似拉沙热直接入院73人。362名发热参与者中有41人（11%）和73名直接确诊为拉沙热的参与者中有47人（64%）通过血浆LASV RT-PCR诊断出拉沙热，共确诊88例拉沙热。在入组时，与LASV RNA检测阴性的参与者相比，拉沙热参与者报告的厌食症（88人中的71人[81%]对347人中的178人[51%]）、严重疲劳或虚弱（63人[72%]对178人[51%]）和恶心或呕吐（39人[44%]对95人[27%]）的可能性更大。在88例拉沙热患者中，11例（13%）在入院后死亡。精神状态改变、癫痫发作、急性肾衰竭、高钾血症和代谢性酸中毒在死亡的拉沙热患者中比在存活的患者中更常见。研究进入时糖蛋白复合物基因（GPC）或聚合酶基因(L)的周期阈值中位数在死亡组（GPC周期阈值22.4 [IQR 20.0 - 27.9]； L周期阈值21.7[19.0 - 27.7]）低于存活组（GPC周期阈值31.5 [28.0 - 33.9]；L周期阈值33.2[28.0 - 33.9]）。在同意住院期间进行纵向随访的70名拉沙热患者中，有7人死亡，与幸存者相比，这些参与者往往具有较低的周期阈值和较低的IgM和IgG LASV反应。释义：在利比里亚流行拉沙热的一个地区，拉沙热是导致发病和死亡的普遍原因。拉沙热患者更可能出现几种症状，但与其他常见传染病引起的症状重叠。与幸存者相比，因拉沙热住院期间死亡的患者往往有器官功能障碍的证据，在研究开始时和随访期间病毒载量较高，在患病期间抗体水平较低，这表明体液免疫反应减弱可能是严重拉沙热发展的一个因素。资助：美国国家过敏和传染病研究所和国立卫生研究院。

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