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Investigation of P. vivax elimination via mass drug administration: A simulation study 通过大规模给药消除间日疟原虫的研究:模拟研究
IF 3 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-09-01 DOI: 10.1016/j.epidem.2024.100789
Md Nurul Anwar , James M. McCaw , Alexander E. Zarebski , Roslyn I. Hickson , Jennifer A. Flegg

Plasmodium vivax is the most geographically widespread malaria parasite. P. vivax has the ability to remain dormant (as a hypnozoite) in the human liver and subsequently reactivate, which makes control efforts more difficult. Given the majority of P. vivax infections are due to hypnozoite reactivation, targeting the hypnozoite reservoir with a radical cure is crucial for achieving P. vivax elimination. Stochastic effects can strongly influence dynamics when disease prevalence is low or when the population size is small. Hence, it is important to account for this when modelling malaria elimination. We use a stochastic multiscale model of P. vivax transmission to study the impacts of multiple rounds of mass drug administration (MDA) with a radical cure, accounting for superinfection and hypnozoite dynamics. Our results indicate multiple rounds of MDA with a high-efficacy drug are needed to achieve a substantial probability of elimination. This work has the potential to help guide P. vivax elimination strategies by quantifying elimination probabilities for an MDA approach.

间日疟原虫是地域分布最广的疟疾寄生虫。间日疟原虫能够在人的肝脏中保持休眠(作为下生虫),随后重新活化,这就增加了控制工作的难度。鉴于大多数间日疟原虫感染都是由次原虫再活化引起的,因此针对次原虫库的根治方法对于消灭间日疟原虫至关重要。当疾病流行率较低或种群规模较小时,随机效应会对动力学产生很大影响。因此,在建立消除疟疾模型时必须考虑到这一点。我们利用间日疟传播的随机多尺度模型,研究了多轮大规模用药(MDA)和根治的影响,并考虑了超级感染和低佐虫动态。我们的研究结果表明,需要使用高效药物进行多轮大规模给药,才能达到很高的根除概率。这项研究通过量化 MDA 方法的消除概率,有可能帮助指导消灭间日疟原虫的战略。
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引用次数: 0
The utility of whole-genome sequencing to identify likely transmission pairs for pathogens with slow and variable evolution 全基因组测序在确定进化缓慢且多变的病原体的可能传播配对方面的作用
IF 3 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-08-23 DOI: 10.1016/j.epidem.2024.100787
A.J. Wood , C.H. Benton , R.J. Delahay , G. Marion , E. Palkopoulou , C.M. Pooley , G.C. Smith , R.R. Kao

Pathogen whole-genome sequencing (WGS) has been used to track the transmission of infectious diseases in extraordinary detail, especially for pathogens that undergo fast and steady evolution, as is the case with many RNA viruses. However, for other pathogens evolution is less predictable, making interpretation of these data to inform our understanding of their epidemiology more challenging and the value of densely collected pathogen genome data uncertain. Here, we assess the utility of WGS for one such pathogen, in the “who-infected-whom” identification problem. We study samples from hosts (130 cattle, 111 badgers) with confirmed infection of M. bovis (causing bovine Tuberculosis), which has an estimated clock rate as slow as 0.1–1 variations per year. For each potential pathway between hosts, we calculate the relative likelihood that such a transmission event occurred. This is informed by an epidemiological model of transmission, and host life history data. By including WGS data, we shrink the number of plausible pathways significantly, relative to those deemed likely on the basis of life history data alone. Despite our uncertainty relating to the evolution of M. bovis, the WGS data are therefore a valuable adjunct to epidemiological investigations, especially for wildlife species whose life history data are sparse.

病原体全基因组测序(WGS)已被用于非常详细地追踪传染病的传播情况,特别是对于像许多 RNA 病毒那样经历快速而稳定进化的病原体。然而,对于其他病原体来说,进化的可预测性较低,这就使得解释这些数据以帮助我们了解其流行病学更具挑战性,而且密集收集的病原体基因组数据的价值也不确定。在此,我们评估了 WGS 在 "谁感染了谁 "的鉴定问题中对此类病原体的实用性。我们研究了宿主(130 头牛、111 只獾)的样本,这些宿主确诊感染了牛结核杆菌(导致牛结核病),据估计其时钟频率慢至每年 0.1-1 次变化。对于宿主之间的每种潜在途径,我们都会计算发生这种传播事件的相对可能性。这一计算参考了流行病学传播模型和宿主生活史数据。通过纳入 WGS 数据,我们大大减少了可能传播途径的数量,而不是仅根据生活史数据来计算。尽管我们对牛海绵状芽孢杆菌的进化存在不确定性,但 WGS 数据仍是流行病学调查的重要辅助工具,特别是对于生活史数据稀少的野生动物物种。
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引用次数: 0
Improving the contribution of mathematical modelling evidence to guidelines and policy: Experiences from tuberculosis 提高数学建模证据对指导方针和政策的贡献:结核病方面的经验。
IF 3 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-08-06 DOI: 10.1016/j.epidem.2024.100786
C. Finn McQuaid , Nicolas A. Menzies , Rein M.G.J. Houben , Gabriella B. Gomez , Anna Vassall , Nimalan Arinaminpathy , Peter J. Dodd , Richard G. White

We read with great interest the recent paper by Lo et al., who argue that there is an urgent need to ensure the quality of modelling evidence used to support international and national guideline development. Here we outline efforts by the Tuberculosis Modelling and Analysis Consortium, together with the World Health Organization Global Task Force on Tuberculosis Impact Measurement, to develop material to improve the quality and transparency of country-level tuberculosis modelling to inform decision-making.

我们饶有兴趣地阅读了 Lo 等人最近发表的论文,他们认为迫切需要确保用于支持国际和国家指导方针制定的建模证据的质量。在此,我们简要介绍了结核病建模与分析联合会与世界卫生组织结核病影响测量全球工作组一起,为提高国家级结核病建模的质量和透明度,为决策提供信息而开发材料所做的努力。
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引用次数: 0
Dynamics of Neisseria gonorrhoeae transmission among female sex workers and clients: A mathematical modeling study 淋病奈瑟菌在女性性工作者和嫖客中的传播动态:数学模型研究。
IF 3 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-08-05 DOI: 10.1016/j.epidem.2024.100785
Houssein H. Ayoub , Milan Tomy , Hiam Chemaitelly , Ryosuke Omori , Kent Buse , Nicola Low , Sarah Hawkes , Laith J. Abu-Raddad

Background

This study aimed to examine the transmission dynamics of Neisseria gonorrhoeae (NG) in heterosexual sex work networks (HSWNs) and the impact of variation in sexual behavior and interventions on NG epidemiology.

Methods

The study employed an individual-based mathematical model to simulate NG transmission dynamics in sexual networks involving female sex workers (FSWs) and their clients, primarily focusing on the Middle East and North Africa region. A deterministic model was also used to describe NG transmission from clients to their spouses.

Results

NG epidemiology in HSWNs displays two distinct patterns. In the common low-partner-number HSWNs, a significant proportion of NG incidence occurs among FSWs, with NG prevalence 13 times higher among FSWs than clients, and three times higher among clients than their spouses. Interventions substantially reduce incidence. Increasing condom use from 10 % to 50 % lowers NG prevalence among FSWs, clients, and their spouses from 12.2 % to 6.4 %, 1.2 % to 0.5 %, and 0.4 % to 0.2 %, respectively. Increasing symptomatic treatment coverage among FSWs from 0 % to 100 % decreases prevalence from 10.6 % to 4.5 %, 0.8 % to 0.4 %, and 0.3 % to 0.1 %, respectively. Increasing asymptomatic treatment coverage among FSWs from 0 % to 50 % decreases prevalence from 8.2 % to 0.4 %, 0.6 % to 0.1 %, and 0.2 % to 0.0 %, respectively, with very low prevalence when coverage exceeds 50 %. In high-partner-number HSWNs, prevalence among FSWs saturates at a high level, and the vast majority of incidence occurs among clients and their spouses, with a limited impact of incremental increases in interventions.

Conclusion

NG epidemiology in HSWNs is typically a "fragile epidemiology" that is responsive to a range of interventions even if the interventions are incremental, partially efficacious, and only applied to FSWs.

背景:本研究旨在探讨淋病奈瑟菌(NG)在异性性工作网络(HSWNs)中的传播动态,以及性行为和干预措施的变化对 NG 流行病学的影响:研究采用了基于个体的数学模型来模拟女性性工作者(FSWs)及其客户参与的性工作网络中的 NG 传播动态,主要侧重于中东和北非地区。此外,还使用了一个确定性模型来描述嫖客向其配偶传播 NG 的情况:性工作者中的 NG 流行病学显示出两种截然不同的模式。在常见的伴侣人数较少的 HSWNs 中,有很大一部分 NG 发生在 FSWs 中,FSWs 的 NG 感染率是客户的 13 倍,客户的 NG 感染率是其配偶的 3 倍。干预措施可大幅降低发病率。将安全套的使用率从 10% 提高到 50%,可将女性社会工作者、客户及其配偶的 NG 感染率分别从 12.2% 降至 6.4%、1.2% 降至 0.5%、0.4% 降至 0.2%。如果将女性外阴残割者的无症状治疗覆盖率从 0% 提高到 100%,感染率将分别从 10.6% 降至 4.5%、0.8% 降至 0.4%、0.3% 降至 0.1%。如果将对女性外阴残割者的无症状治疗覆盖率从 0% 提高到 50%,感染率将分别从 8.2% 降至 0.4%、0.6% 降至 0.1%、0.2% 降至 0.0%,当覆盖率超过 50%时,感染率将非常低。在性伴侣人数较多的 HSWN 中,FSW 的流行率在较高水平上达到饱和,绝大多数发病率发生在客户及其配偶中,干预措施的逐步增加影响有限:在 HSWNs 中,NG 流行病学是典型的 "脆弱流行病学",对一系列干预措施有反应,即使这些干预措施是渐进的、部分有效的,并且只适用于 FSWs。
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引用次数: 0
Inference of epidemic dynamics in the COVID-19 era and beyond COVID-19 时代及以后的流行病动态推断
IF 3 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-07-31 DOI: 10.1016/j.epidem.2024.100784
Anne Cori , Adam Kucharski

The COVID-19 pandemic demonstrated the key role that epidemiology and modelling play in analysing infectious threats and supporting decision making in real-time. Motivated by the unprecedented volume and breadth of data generated during the pandemic, we review modern opportunities for analysis to address questions that emerge during a major modern epidemic. Following the broad chronology of insights required — from understanding initial dynamics to retrospective evaluation of interventions, we describe the theoretical foundations of each approach and the underlying intuition. Through a series of case studies, we illustrate real life applications, and discuss implications for future work.

COVID-19 大流行表明,流行病学和建模在分析传染病威胁和支持实时决策方面发挥着关键作用。大流行期间产生的数据量之大、范围之广前所未有,在此激励下,我们回顾了现代分析的机遇,以解决现代大流行期间出现的问题。从了解最初的动态到对干预措施的回顾性评估,我们按照所需的洞察力的时间顺序,描述了每种方法的理论基础和基本直觉。通过一系列案例研究,我们阐述了现实生活中的应用,并讨论了对未来工作的影响。
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引用次数: 0
COVID-19 in Scottish care homes: A metapopulation model of spread among residents and staff 苏格兰护理院中的 COVID-19:居民和员工间传播的元种群模型
IF 3 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-07-05 DOI: 10.1016/j.epidem.2024.100781
Matthew Baister , Ewan McTaggart , Paul McMenemy , Itamar Megiddo , Adam Kleczkowski

The movement of populations between locations and activities can result in complex transmission dynamics, posing significant challenges in controlling infectious diseases like COVID-19. Notably, networks of care homes create an ecosystem where staff and visitor movement acts as a vector for disease transmission, contributing to the heightened risk for their vulnerable communities. Care homes in the UK were disproportionately affected by the first wave of the COVID-19 pandemic, accounting for almost half of COVID-19 deaths during the period of 6th March – 15th June 2020 and so there is a pressing need to explore modelling approaches suitable for such systems. We develop a generic compartmental Susceptible - Exposed - Infectious - Recovered - Dead (SEIRD) metapopulation model, with care home residents, care home workers, and the general population modelled as subpopulations, interacting on a network describing their mixing habits. We illustrate the model application by analysing the spread of COVID-19 over the first wave of the COVID-19 pandemic in the NHS Lothian health board, Scotland. We explicitly model the outbreak’s reproduction rate and care home visitation level over time for each subpopulation and execute a data fit and sensitivity analysis, focusing on parameters responsible for inter-subpopulation mixing: staff-sharing, staff shift patterns and visitation. The results from our sensitivity analysis show that restricting staff sharing between homes and staff interaction with the general public would significantly mitigate the disease burden. Our findings indicate that protecting care home staff from disease, coupled with reductions in staff-sharing across care homes and expedient cancellations of visitations, can significantly reduce the size of outbreaks in care home settings.

人口在不同地点和活动之间的流动会导致复杂的传播动态,给控制 COVID-19 等传染病带来巨大挑战。值得注意的是,护理院网络创造了一个生态系统,在这个系统中,工作人员和访客的流动成为疾病传播的媒介,导致其脆弱社区的风险增加。在第一波 COVID-19 大流行中,英国的护理院受到的影响尤为严重,在 2020 年 3 月 6 日至 6 月 15 日期间,护理院的死亡人数几乎占 COVID-19 死亡人数的一半,因此迫切需要探索适合此类系统的建模方法。我们建立了一个通用的分区易感-暴露-感染-康复-死亡(SEIRD)元种群模型,将护理院居民、护理院工作人员和普通人群作为子种群建模,并在描述其混合习惯的网络上进行互动。我们通过分析 COVID-19 在苏格兰 NHS Lothian 卫生局第一波大流行中的传播情况来说明该模型的应用。我们为每个亚群的疫情繁殖率和护理之家的探访水平建立了明确的模型,并进行了数据拟合和敏感性分析,重点关注造成亚群间混合的参数:人员共享、人员轮班模式和探访。敏感性分析的结果表明,限制安老院之间的人员共用以及员工与公众的互动将大大减轻疾病负担。我们的研究结果表明,保护护理院工作人员免受疾病侵袭,同时减少护理院之间的人员共用,并迅速取消探视,可以大大降低护理院环境中疫情爆发的规模。
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引用次数: 0
Social contact patterns following the COVID-19 pandemic: a snapshot of post-pandemic behaviour from the CoMix study COVID-19 大流行后的社会接触模式:来自 CoMix 研究的大流行后行为快照。
IF 3 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-06-29 DOI: 10.1016/j.epidem.2024.100778
Christopher I. Jarvis , Pietro Coletti , Jantien A. Backer , James D. Munday , Christel Faes , Philippe Beutels , Christian L. Althaus , Nicola Low , Jacco Wallinga , Niel Hens , W.John Edmunds

The COVID-19 pandemic led to unprecedented changes in behaviour. To estimate if these persisted, a final round of the CoMix social contact survey was conducted in four countries at a time when all societal restrictions had been lifted for several months. We conducted a survey on a nationally representative sample in the UK, Netherlands (NL), Belgium (BE), and Switzerland (CH). Participants were asked about their contacts and behaviours on the previous day. We calculated contact matrices and compared the contact levels to a pre-pandemic baseline to estimate R0. Data collection occurred from 17 November to 7 December 2022. 7477 participants were recruited. Some were asked to undertake the survey on behalf of their children. Only 14.4 % of all participants reported wearing a facemask on the previous day. Self-reported vaccination rates in adults were similar for each country at around 86 %. Trimmed mean recorded contacts were highest in NL with 9.9 (95 % confidence interval [CI] 9.0–10.8) contacts per person per day and lowest in CH at 6.0 (95 % CI 5.4–6.6). Contacts at work were lowest in the UK (1.4 contacts per person per day) and highest in NL at 2.8 contacts per person per day. Other contacts were also lower in the UK at 1.6 per person per day (95 % CI 1.4–1.9) and highest in NL at 3.4 recorded per person per day (95 % CI 43.0–4.0). The next-generation approach suggests that R0 for a close-contact disease would be roughly half pre-pandemic levels in the UK, 80 % in NL and intermediate in the other two countries. The pandemic appears to have resulted in lasting changes in contact patterns expected to have an impact on the epidemiology of many different pathogens. Further post-pandemic surveys are necessary to confirm this finding.

COVID-19 大流行导致了前所未有的行为变化。为了估计这些变化是否持续存在,我们在四个国家进行了最后一轮 CoMix 社会接触调查,当时所有社会限制均已解除数月。我们对英国、荷兰、比利时和瑞士的全国代表性样本进行了调查。调查询问了参与者前一天的接触情况和行为。我们计算了接触矩阵,并将接触水平与大流行前的基线进行比较,以估计 R0。数据收集时间为 2022 年 11 月 17 日至 12 月 7 日。共招募了 7477 名参与者。其中一些人被要求代表其子女参与调查。在所有参与者中,只有 14.4% 的人表示前一天戴过口罩。各国成人自我报告的疫苗接种率相似,都在 86% 左右。北荷兰记录的接触率最高,每人每天接触 9.9 次(95 % 置信区间 [CI] 9.0-10.8),中国最低,为 6.0 次(95 % 置信区间 [CI] 5.4-6.6)。英国的工作接触率最低(每人每天 1.4 次),荷兰最高,每人每天 2.8 次。其他接触在英国也较低,每人每天 1.6 次(95 % CI 1.4-1.9),在荷兰最高,每人每天 3.4 次(95 % CI 43.0-4.0)。下一代方法表明,密切接触疾病的 R0 在英国约为大流行前水平的一半,在荷兰为 80%,在其他两个国家处于中间水平。大流行似乎导致了接触模式的持久变化,预计将对许多不同病原体的流行病学产生影响。有必要在大流行后开展进一步调查,以证实这一结论。
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引用次数: 0
Role of heterogeneity: National scale data-driven agent-based modeling for the US COVID-19 Scenario Modeling Hub 异质性的作用:美国 COVID-19 情景建模中心的全国规模数据驱动代理建模
IF 3 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-06-27 DOI: 10.1016/j.epidem.2024.100779
Jiangzhuo Chen , Parantapa Bhattacharya , Stefan Hoops , Dustin Machi , Abhijin Adiga , Henning Mortveit , Srinivasan Venkatramanan , Bryan Lewis , Madhav Marathe

UVA-EpiHiper is a national scale agent-based model to support the US COVID-19 Scenario Modeling Hub (SMH). UVA-EpiHiper uses a detailed representation of the underlying social contact network along with data measured during the course of the pandemic to initialize and calibrate the model. In this paper, we study the role of heterogeneity on model complexity and resulting epidemic dynamics using UVA-EpiHiper. We discuss various sources of heterogeneity that we encounter in the use of UVA-EpiHiper to support modeling and analysis of epidemic dynamics under various scenarios. We also discuss how this affects model complexity and computational complexity of the corresponding simulations. Using round 13 of the SMH as an example, we discuss how UVA-EpiHiper was initialized and calibrated. We then discuss how the detailed output produced by UVA-EpiHiper can be analyzed to obtain interesting insights. We find that despite the complexity in the model, the software, and the computation incurred to an agent-based model in scenario modeling, it is capable of capturing various heterogeneities of real-world systems, especially those in networks and behaviors, and enables analyzing heterogeneities in epidemiological outcomes between different demographic, geographic, and social cohorts. In applying UVA-EpiHiper to round 13 scenario modeling, we find that disease outcomes are different between and within states, and between demographic groups, which can be attributed to heterogeneities in population demographics, network structures, and initial immunity.

UVA-EpiHiper 是一个基于国家规模代理的模型,用于支持美国 COVID-19 场景建模中心 (SMH)。UVA-EpiHiper 使用底层社会接触网络的详细表示法以及大流行期间测量的数据来初始化和校准模型。在本文中,我们使用 UVA-EpiHiper 研究了异质性对模型复杂性和由此产生的流行动态的作用。我们讨论了在使用 UVA-EpiHiper 支持各种情景下流行病动态建模和分析时遇到的各种异质性来源。我们还讨论了这如何影响模型复杂性和相应模拟的计算复杂性。以第13轮SMH为例,我们讨论了如何对UVA-EpiHiper进行初始化和校准。然后,我们讨论如何分析 UVA-EpiHiper 产生的详细输出,以获得有趣的见解。我们发现,尽管基于代理的模型在情景建模中需要复杂的模型、软件和计算,但它能够捕捉现实世界系统的各种异质性,尤其是网络和行为中的异质性,并能分析不同人口、地理和社会群组之间流行病学结果的异质性。在应用 UVA-EpiHiper 进行第 13 轮情景建模时,我们发现各州之间、各州内部以及不同人口群体之间的疾病结果是不同的,这可归因于人口统计、网络结构和初始免疫力的异质性。
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引用次数: 0
Assessing the impact of autologous virus neutralizing antibodies on viral rebound time in postnatally SHIV-infected ART-treated infant rhesus macaques 评估自体病毒中和抗体对产后感染 SHIV 并接受抗逆转录病毒疗法治疗的猕猴幼鼠病毒反弹时间的影响。
IF 3 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-06-27 DOI: 10.1016/j.epidem.2024.100780
Ellie Mainou , Stella J. Berendam , Veronica Obregon-Perko , Emilie A. Uffman , Caroline T. Phan , George M. Shaw , Katharine J. Bar , Mithra R. Kumar , Emily J. Fray , Janet M. Siliciano , Robert F. Siliciano , Guido Silvestri , Sallie R. Permar , Genevieve G. Fouda , Janice McCarthy , Ann Chahroudi , Jessica M. Conway , Cliburn Chan

While the benefits of early antiretroviral therapy (ART) initiation in perinatally infected infants are well documented, early initiation is not always possible in postnatal pediatric HIV infections. The timing of ART initiation is likely to affect the size of the latent viral reservoir established, as well as the development of adaptive immune responses, such as the generation of neutralizing antibody responses against the virus. How these parameters impact the ability of infants to control viremia and the time to viral rebound after ART interruption is unclear and has never been modeled in infants. To investigate this question we used an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Infant Rhesus macaques (RMs) were orally challenged with SHIV.C.CH505 375H dCT and either given ART at 4-7 days post-infection (early ART condition), at 2 weeks post-infection (intermediate ART condition), or at 8 weeks post-infection (late ART condition). These infants were then monitored for up to 60 months post-infection with serial viral load and immune measurements. To gain insight into early after analytic treatment interruption (ATI), we constructed mathematical models to investigate the effect of time of ART initiation in delaying viral rebound when treatment is interrupted, focusing on the relative contributions of latent reservoir size and autologous virus neutralizing antibody responses. We developed a stochastic mathematical model to investigate the joint effect of latent reservoir size, the autologous neutralizing antibody potency, and CD4+ T cell levels on the time to viral rebound for RMs rebounding up to 60 days post-ATI. We find that the latent reservoir size is an important determinant in explaining time to viral rebound in infant macaques by affecting the growth rate of the virus. The presence of neutralizing antibodies can also delay rebound, but we find this effect for high potency antibody responses only. Finally, we discuss the therapeutic implications of our findings.

尽管早期开始抗逆转录病毒疗法(ART)对围产期感染婴儿的益处已得到充分证实,但对于产后感染艾滋病病毒的儿科患者来说,早期开始抗逆转录病毒疗法并不总是可行的。开始抗逆转录病毒疗法的时机可能会影响潜伏病毒库的规模,以及适应性免疫反应的发展,如产生针对病毒的中和抗体反应。这些参数如何影响婴儿控制病毒血症的能力以及抗逆转录病毒疗法中断后病毒反弹的时间尚不清楚,也从未在婴儿中模拟过。为了研究这个问题,我们使用了非人灵长类猿猴/人类免疫缺陷病毒(SHIV)婴儿感染模型。婴儿猕猴(RMs)口服 SHIV.C.CH505 375H dCT,并在感染后 4-7 天(早期抗逆转录病毒疗法条件)、感染后 2 周(中期抗逆转录病毒疗法条件)或感染后 8 周(晚期抗逆转录病毒疗法条件)接受抗逆转录病毒疗法。然后对这些婴儿进行长达 60 个月的病毒载量和免疫测定监测。为了深入了解分析性治疗中断 (ATI) 后的早期情况,我们构建了数学模型来研究开始抗逆转录病毒疗法的时间对治疗中断后延缓病毒反弹的影响,重点是潜伏库规模和自体病毒中和抗体反应的相对贡献。我们建立了一个随机数学模型,以研究潜伏库规模、自体中和抗体效价和 CD4+ T 细胞水平对急性抗逆转录病毒治疗后 60 天内反弹的 RM 病毒反弹时间的共同影响。我们发现,潜伏库的大小会影响病毒的生长速度,是解释婴儿猕猴病毒反弹时间的重要决定因素。中和抗体的存在也会延缓反弹,但我们发现只有高效力抗体反应才会产生这种效应。最后,我们讨论了研究结果的治疗意义。
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引用次数: 0
Assessing population-level target product profiles of universal human influenza A vaccines 评估通用型人类甲型流感疫苗的人群目标产品特征。
IF 3 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-06-25 DOI: 10.1016/j.epidem.2024.100776
Qiqi Yang , Sang Woo Park , Chadi M. Saad-Roy , Isa Ahmad , Cécile Viboud , Nimalan Arinaminpathy , Bryan T. Grenfell

Influenza A has two hemagglutinin groups, with stronger cross-immunity to reinfection within than between groups. Here, we explore the implications of this heterogeneity for proposed cross-protective influenza vaccines that may offer broad, but not universal, protection. While the development goal for the breadth of human influenza A vaccine is to provide cross-group protection, vaccines in current development stages may provide better protection against target groups than non-target groups. To evaluate vaccine formulation and strategies, we propose a novel perspective: a vaccine population-level target product profile (PTPP). Under this perspective, we use dynamical models to quantify the epidemiological impacts of future influenza A vaccines as a function of their properties. Our results show that the interplay of natural and vaccine-induced immunity could strongly affect seasonal subtype dynamics. A broadly protective bivalent vaccine could lower the incidence of both groups and achieve elimination with sufficient vaccination coverage. However, a univalent vaccine at low vaccination rates could permit a resurgence of the non-target group when the vaccine provides weaker immunity than natural infection. Moreover, as a proxy for pandemic simulation, we analyze the invasion of a variant that evades natural immunity. We find that a future vaccine providing sufficiently broad and long-lived cross-group protection at a sufficiently high vaccination rate, could prevent pandemic emergence and lower the pandemic burden. This study highlights that as well as effectiveness, breadth and duration should be considered in epidemiologically informed TPPs for future human influenza A vaccines.

甲型流感有两个血凝素群,群内再感染的交叉免疫比群间更强。在此,我们探讨了这种异质性对拟议的交叉保护性流感疫苗的影响,这种疫苗可提供广泛但非普遍的保护。虽然人类甲型流感疫苗的研发目标是提供跨群体保护,但目前处于研发阶段的疫苗对目标群体的保护效果可能优于非目标群体。为了评估疫苗配方和策略,我们提出了一个新的视角:疫苗群体级目标产品谱(PTPP)。在这一视角下,我们使用动态模型量化未来甲型流感疫苗对流行病学的影响,并将其作为疫苗特性的函数。我们的研究结果表明,自然免疫和疫苗诱导免疫的相互作用会强烈影响季节性亚型的动态变化。具有广泛保护作用的二价疫苗可以降低两类人群的发病率,并在足够的疫苗接种覆盖率下实现消灭。然而,当疫苗提供的免疫力弱于自然感染时,接种率较低的单价疫苗可能会导致非目标群体重新出现。此外,作为大流行模拟的替代方案,我们分析了逃避自然免疫的变种的入侵情况。我们发现,未来的疫苗如果能在足够高的接种率下提供足够广泛和持久的跨群体保护,就能防止大流行的出现并降低大流行的负担。这项研究强调,在根据流行病学制定未来人类甲型流感疫苗的技术选择方案时,不仅要考虑有效性,还要考虑广度和持续时间。
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Epidemics
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