Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Centre on Climate Change and Planetary Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.
PLoS Negl Trop Dis. 2022 Jun 13;16(6):e0010506. doi: 10.1371/journal.pntd.0010506. eCollection 2022 Jun.
Leptospirosis is a zoonotic disease prevalent throughout the world, but with particularly high burden in Oceania (including the Pacific Island Countries and Territories). Leptospirosis is endemic in Fiji, with outbreaks often occurring following heavy rainfall and flooding. As a result of non-specific clinical manifestation and diagnostic challenges, cases are often misdiagnosed or under-ascertained. Furthermore, little is known about the duration of persistence of antibodies to leptospirosis, which has important clinical and epidemiological implications.
Using the results from a serosurvey conducted in Fiji in 2013, we fitted serocatalytic models to estimate the duration of antibody positivity and the force of infection (FOI, the rate at which susceptible individuals acquire infection or seroconversion), whilst accounting for seroreversion. Additionally, we estimated the most likely timing of infection. Using the reverse catalytic model, we estimated the duration of antibody persistence to be 8.33 years (4.76-12.50; assuming constant FOI) and 7.25 years (3.36-11.36; assuming time-varying FOI), which is longer than previous estimates. Using population age-structured seroprevalence data alone, we were not able to distinguish between these two models. However, by bringing in additional longitudinal data on antibody kinetics we were able to estimate the most likely time of infection, lending support to the time-varying FOI model. We found that most individuals who were antibody-positive in the 2013 serosurvey were likely to have been infected within the previous two years, and this finding is consistent with surveillance data showing high numbers of cases reported in 2012 and 2013.
This is the first study to use serocatalytic models to estimate the FOI and seroreversion rate for Leptospira infection. As well as providing an estimate for the duration of antibody positivity, we also present a novel method to estimate the most likely time of infection from seroprevalence data. These approaches can allow for richer, longitudinal information to be inferred from cross-sectional studies, and could be applied to other endemic diseases where antibody waning occurs.
钩端螺旋体病是一种流行于世界各地的人畜共患疾病,但在大洋洲(包括太平洋岛国和地区)的负担尤其沉重。钩端螺旋体病在斐济流行,大雨和洪水过后经常爆发疫情。由于临床表现不具特异性和诊断挑战,病例经常被误诊或漏诊。此外,人们对钩端螺旋体病抗体的持续时间知之甚少,这具有重要的临床和流行病学意义。
利用 2013 年在斐济进行的血清学调查结果,我们拟合了血清催化模型来估计抗体阳性的持续时间和感染力(FOI,即易感个体感染或血清转化的速率),同时考虑了血清转化。此外,我们还估计了最有可能的感染时间。使用反向催化模型,我们估计抗体持续存在的时间为 8.33 年(4.76-12.50;假设 FOI 不变)和 7.25 年(3.36-11.36;假设 FOI 随时间变化),这比以前的估计时间更长。仅使用人群年龄结构血清流行率数据,我们无法区分这两种模型。然而,通过引入关于抗体动力学的额外纵向数据,我们能够估计最有可能的感染时间,这支持了随时间变化的 FOI 模型。我们发现,2013 年血清学调查中抗体阳性的大多数人很可能在过去两年内感染了该病毒,这一发现与监测数据显示 2012 年和 2013 年报告的大量病例相符。
这是第一项使用血清催化模型来估计钩端螺旋体感染的 FOI 和血清转化率的研究。除了提供抗体阳性持续时间的估计值外,我们还提出了一种从血清流行率数据估计最有可能感染时间的新方法。这些方法可以从横断面研究中推断出更丰富的纵向信息,并且可以应用于其他发生抗体衰减的地方性疾病。