苏丹埃博拉病毒病幸存者感染后2年的长期临床后遗症：一项匹配队列研究。

Long-term clinical sequelae among Sudan ebolavirus disease survivors 2 years post-infection: a matched cohort study.

作者信息

Muwonge Haruna, Nasimiyu Carolyne, Bakamutumaho Barnabas, Elyanu Peter, Joloba Moses L, Situma Silvia, Schieffelin John, Gunn Bronwyn, Bai Shuangyi, Breiman Robert F, Ssewanyana Isaac, Nabadda Susan, Lutwama Julius, Tegen Yonas, Muruta Allan, Kirenga Bruce, Olaro Charles, Aceng Jane Ruth, Bosa Henry Kyobe, Njenga M Kariuki

机构信息

Makerere University Medical School, Kampala, Uganda.

Center for Research in Emerging Infectious Diseases-East and Central Africa, Washington State University Global Health-Kenya, Nairobi, Kenya.

出版信息

BMC Med. 2025 Jul 18;23(1):432. doi: 10.1186/s12916-025-04271-z.

DOI:10.1186/s12916-025-04271-z

PMID:40682158

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12275283/

Abstract

BACKGROUND

The long-term health effects of ebolavirus disease (EVD) caused by the Sudan ebolavirus (SUDV) strain remain poorly characterized. Here, we assessed the nature, frequency, and persistence of post-EVD clinical symptoms among SUDV survivors 2 years after infection by comparing them with matched community controls.

METHODS

The primary objective was determining the prevalence of clinical symptoms over the 24-month period. Using a prospective matched cohort approach, 87 laboratory-confirmed SUDV survivors from the 2022-2023 Ugandan outbreak and 176 age-, sex- and village-matched controls were followed at 3, 9, 12, 15 and 24 months. Symptom data were collected through structured interviews and targeted clinical examinations. A secondary objective was investigating the duration of viral RNA shedding in semen and breast milk of survivors collected during follow-up, using the PCR test.

RESULTS

Of the 87 SUDV survivors, 57.5% reported significantly higher frequencies of clinical symptoms involving musculoskeletal (45.0%, P < 0.001), central nervous system (36.3%, p < 0.001), ophthalmologic (20%, P < 0.001), and respiratory (10%, P < 0.001) systems than those observed among controls. The risk ratio of occurrence was highest for ophthalmologic (20% vs 3.4%, RR = 5.9; p < 0.001) and central nervous systems symptoms (36.3% vs 6.8%, RR = 5.3, p < 0.001), and lowest for reproductive system (13.8% vs 8.5%; RR = 1.6; p > 0.005). Importantly, 50% of the survivors reported persistent multi-systemic symptoms, including low back pain, hand and feet numbness, confusion, and diarrhoea that resulted in an inability to perform basic activities of living. Viral RNA was detected in semen for up to 210 post-infection (median = 131 days, range: 111-210 days) and in breast milk for up to 199 days (median = 149 days, range: 111-199 days).

CONCLUSIONS

This study demonstrates that SUDV survivors develop long-term clinical sequelae characterized by persistent multi-systemic clinical symptoms. Detection of viral RNA in semen and breastmilk for up to 7 months post-infection suggests prolonged persistence, opening the possibility of latency and reactivation of the virus.

摘要

背景

由苏丹埃博拉病毒（SUDV）毒株引起的埃博拉病毒病（EVD）的长期健康影响仍未得到充分描述。在此，我们通过将苏丹埃博拉病毒感染幸存者与匹配的社区对照进行比较，评估了感染后2年这些幸存者中埃博拉病毒病后临床症状的性质、频率和持续性。

方法

主要目标是确定24个月期间临床症状的患病率。采用前瞻性匹配队列研究方法，对2022 - 2023年乌干达疫情中87名实验室确诊的苏丹埃博拉病毒幸存者以及176名年龄、性别和村庄匹配的对照进行3、9、12、15和24个月的随访。通过结构化访谈和针对性临床检查收集症状数据。次要目标是使用聚合酶链反应（PCR）检测随访期间收集的幸存者精液和母乳中病毒RNA的脱落持续时间。

结果

在87名苏丹埃博拉病毒幸存者中，57.5%报告称，涉及肌肉骨骼系统（45.0%，P < 0.001）、中枢神经系统（36.3%，P < 0.001）、眼科（20%，P < 0.001）和呼吸系统（10%，P < 0.001）的临床症状频率显著高于对照组。眼科症状（20%对3.4%，RR = 5.9；P < 0.001）和中枢神经系统症状（36.3%对6.8%，RR = 5.3，P < 0.001）的发生风险比最高，生殖系统症状（13.8%对8.5%；RR = 1.6；P > 0.005）的发生风险比最低。重要的是，50%的幸存者报告有持续的多系统症状，包括腰痛、手脚麻木、意识模糊和腹泻，导致无法进行基本生活活动。感染后长达210天在精液中检测到病毒RNA（中位数 = 131天，范围：111 - 210天），在母乳中长达199天检测到病毒RNA（中位数 = 149天，范围：111 - )199天）。