Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka.
Department of Microbiology, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka.
PLoS Negl Trop Dis. 2022 Apr 4;16(4):e0010331. doi: 10.1371/journal.pntd.0010331. eCollection 2022 Apr.
Leptospirosis has globally significant human mortality and morbidity, yet estimating the clinical and public health burden of leptospirosis is challenging because timely diagnosis remains limited. The goal of the present study was to evaluate leptospirosis undercounting by current standard methods in both clinical and epidemiological study settings.
METHODOLOGY/PRINCIPAL FINDINGS: A prospective hospital-based study was conducted in multiple hospitals in Sri Lanka from 2016 to 2019. Culture, whole blood, and urine samples were collected from clinically suspected leptospirosis cases and patients with undifferentiated fever. Analysis of biological samples from 1,734 subjects confirmed 591 (34.1%) cases as leptospirosis and 297 (17.1%) were classified as "probable" leptospirosis cases. Whole blood quantitative PCR (qPCR) did identify the most cases (322/540(60%)) but missed 40%. Cases missed by each method include; urine qPCR, 70% (153/220); acute sample microscopic agglutination test (MAT), 80% (409/510); paired serum sample MAT, 58% (98/170); and surveillance clinical case definition, 53% (265/496). qPCR of negative culture samples after six months of observation was of diagnostic value retrospectively with but missed 58% of positives (109/353).
Leptospirosis disease burden estimates should consider the limitations of standard diagnostic tests. qPCR of multiple sample types should be used as a leading standard test for diagnosing acute leptospirosis.
钩端螺旋体病在全球范围内对人类的死亡率和发病率都有重大影响，但由于及时诊断仍然有限，因此评估钩端螺旋体病的临床和公共卫生负担具有挑战性。本研究的目的是评估当前临床和流行病学研究环境中标准方法对钩端螺旋体病的漏报情况。
方法/主要发现：本前瞻性医院基于研究于 2016 年至 2019 年在斯里兰卡的多家医院进行。从临床疑似钩端螺旋体病病例和不明原因发热患者中采集培养物、全血和尿液样本。对 1734 名受试者的生物样本进行分析，证实 591 例（34.1%）为钩端螺旋体病，297 例（17.1%）为“可能”钩端螺旋体病病例。全血定量 PCR（qPCR）确实可以确定最多的病例（322/540（60%）），但也漏诊了 40%。每种方法漏诊的病例包括：尿液 qPCR，70%（153/220）；急性样本显微镜凝集试验（MAT），80%（409/510）；配对血清样本 MAT，58%（98/170）；以及监测临床病例定义，53%（265/496）。在观察六个月后对阴性培养物样本进行 qPCR 具有诊断价值，但也漏诊了 58%的阳性病例（109/353）。
钩端螺旋体病疾病负担的估计应考虑标准诊断测试的局限性。应将多种样本类型的 qPCR 作为诊断急性钩端螺旋体病的主要标准测试。
