对想定北京和广州发生输入性埃博拉疫情的计算实验研究

本次西非埃博拉疫情引起了世界范围内的高度重视,各国纷纷开展风险评估研究。我们采用仓室模型和基于Agent模型,对北京市和广州市想定发生输入性埃博拉疫情的后续疫情发展态势开展计算实验研究,对影响疫情发展的主要因素进行分析。结果显示,在严格执行埃博拉防控预案、尽快隔离传染性病例的情况下,埃博拉在两地暴发的风险很小。同时,以数据为驱动的计算流行病学也对公共卫生应急部门的基础数据准备工作提出了更高要求。     

埃博拉病毒受体的研究进展

埃博拉病毒能在人类和非人灵长类中引起严重的出血热疾病。1976年,国际上首次报道了埃博拉出血热病例,到2014年,非洲又爆发了历史上最严重的埃博拉疫情,然而,至今仍然没有明确的预防疫苗和治疗药物。与大多数病毒一样,埃博拉病毒需要入侵宿主细胞才能完成自身的复制。因此,找到埃博拉病毒入侵的受体并探究其入侵的过程和机制,对于开发病毒疫苗及新型治疗药物具有非常关键的作用。作者希望通过总结埃博拉病毒受体的研究进展,为埃博拉病毒疫苗及治疗药物的开发提供思路。     

序

<正>2014年2月,西非埃博拉出血热疫情暴发,来势汹汹,迅速蔓延,几内亚、利比里亚、塞拉利昂、尼日利亚……人们的恐慌情绪不断加剧,全世界都在焦灼于没有有效的抗埃博拉病毒药物。在灾难面前,人类不甘束手就范,各国医药研发机构和国际药企巨头纷纷加入了抗埃博拉疫苗和治疗药物的研发大军。埃博拉离我们并不遥远,在可能出现输入性埃博拉病例国家进行的预测排名中,中国排名16位。在抗击埃博拉疫情中,我国实现了国内防控"零输入"和中国埃博拉医疗队援非抗疫的"零感染"。     

关于西非埃博拉疫情态势预测研究的总结分析

西非埃博拉疫情态势预测作为计算流行病学的一次重要实践,显示出计算流行病学在应急资源配置、应急响应策略决策方面的重要价值。本文梳理回顾了2014年计算流行病学在西非埃博拉疫情态势预测方面的研究情况,对主要进展进行了总结分析,并对我国公共卫生应急能力建设提出了建议。     

中国埃博拉诊疗中心布局流程的设计与思考

为了应对西非埃博拉病毒病疫情,中国人民解放军援利医疗队在利比里亚建立并独立运营了埃博拉诊疗中心。中心严格按照传染病医院的防护要求和标准,设计科学合理的布局流程,实现有效的感染防控。详细说明了中国埃博拉诊疗中心的布局与流程设计,归纳阐述其特点,并对做好布局流程应把握的几个重点问题进行了探讨。     

关于在科学研究中防控埃博拉病毒的建议

自今年2月以来,从几内亚开始的新一轮埃博拉疫情正呈加速蔓延之势,截至9月7日,几内亚、利比里亚、塞拉利昂等国共报告埃博拉出血热病例4366例,死亡2218人。8月8日,WHO正式宣布,西非埃博拉疫情是＂国际关注的公共卫生突发紧急事件＂,是近40年来这类疫情最复杂的一次暴发。埃博拉病毒病（Ebola virus disease,EVD）是由埃博拉病毒（Ebola virus,EBOV）引起的一种急性出血性传染病。世界卫生组织已将EBOV列为对人类危害最严重的第4级病毒,按照中华人民共和国卫生部制定的《人间传染的病原微生物名录》中的要求,EBOV危害程度属于一类,     

关于埃博拉病毒核酸检测试剂应急审评的探讨

2014年埃博拉病毒出血热疫情引起了全世界的关注,为做好疫情监控,严防疫情输入,药监总局启动埃博拉病毒检测试剂应急审批程序,推动应急用体外诊断试剂产品尽快完成审批。本文就埃博拉病毒核酸检测试剂应急审评要求及审批条件进行解析和介绍,并结合此次应急审批工作提出了对应急审评的思考。     

埃博拉诊疗中心多维度质量管理体系的创建与实践

诊疗质量是评价埃博拉诊疗中心水平的关键指标。中国人民解放军首批援利医疗队在其运营管理的利比里亚中国埃博拉诊疗中心中,创建了一套特色的诊疗质量管理体系,从完善制度保证体系、建立联合诊疗机制、重视人性化关怀、实施信息化监管四个维度同步推进,有效提高了诊疗质量。实践表明,注重质量管理的多维性、发挥诊疗机制的协同性和扭住诊疗过程的关键点,是实施传染病诊疗质量管理的核心。     

西非防控埃博拉病毒病暴发和流行的分析

埃博拉出血热自1976年首次暴发以来,其高致死率引起了人们的高度重视。2014年的埃博拉病毒病疫情已造成6800多人死亡。其暴发流行既有病原学和流行病学因素,也与西非当地的政治、经济、文化、卫生现状及应对措施密切相关。因此,综合分析造成流行的因素,有利于尽快控制疫情的迅速蔓延。目前包括中国政府在内的国际社会给予了积极帮助,国际社会与西非本国防控力量的有效结合将在更短的时间内控制疫情,并为我国做好埃博拉病毒病疫情的相关防控提供新的思考。     

科研快讯

<正>《传染、遗传与进化》:埃博拉病毒研究获突破2014年在西非爆发的埃博拉病毒(Zaire ebolavirus,ZEBOV)疫情,到目前已造成2万多人感染,超过9000人死亡,是历史上规模最大、疫情最严重的一次爆发。尽管现在疫情得到了一定的控制,但再次爆发的风险仍然存在。中国科学院武汉病毒研究所研究员张波课题组对历年来所有埃博拉疫情中的ZEBOV进行了分子系统进化和全基因组选择压力的综合分析,在2014年西非爆发的ZEBOV分子进化研究中取得新进展,相关结果发表于国际传染性疾病研究期刊Infection Genetics and Evolution上。全     

The Impact of Contact Tracing in Clustered Populations

The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease.     

Measuring the unknown: An estimator and simulation study for assessing case reporting during epidemics

The fraction of cases reported, known as ‘reporting’, is a key performance indicator in an outbreak response, and an essential factor to consider when modelling epidemics and assessing their impact on populations. Unfortunately, its estimation is inherently difficult, as it relates to the part of an epidemic which is, by definition, not observed. We introduce a simple statistical method for estimating reporting, initially developed for the response to Ebola in Eastern Democratic Republic of the Congo (DRC), 2018–2020. This approach uses transmission chain data typically gathered through case investigation and contact tracing, and uses the proportion of investigated cases with a known, reported infector as a proxy for reporting. Using simulated epidemics, we study how this method performs for different outbreak sizes and reporting levels. Results suggest that our method has low bias, reasonable precision, and despite sub-optimal coverage, usually provides estimates within close range (5–10%) of the true value. Being fast and simple, this method could be useful for estimating reporting in real-time in settings where person-to-person transmission is the main driver of the epidemic, and where case investigation is routinely performed as part of surveillance and contact tracing activities.     

Contact tracing efficiency,transmission heterogeneity,and accelerating COVID-19 epidemics

Simultaneously controlling COVID-19 epidemics and limiting economic and societal impacts presents a difficult challenge, especially with limited public health budgets. Testing, contact tracing, and isolating/quarantining is a key strategy that has been used to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 and other pathogens. However, manual contact tracing is a time-consuming process and as case numbers increase a smaller fraction of cases’ contacts can be traced, leading to additional virus spread. Delays between symptom onset and being tested (and receiving results), and a low fraction of symptomatic cases being tested and traced can also reduce the impact of contact tracing on transmission. We examined the relationship between increasing cases and delays and the pathogen reproductive number R_t, and the implications for infection dynamics using deterministic and stochastic compartmental models of SARS-CoV-2. We found that R_t increased sigmoidally with the number of cases due to decreasing contact tracing efficacy. This relationship results in accelerating epidemics because R_t initially increases, rather than declines, as infections increase. Shifting contact tracers from locations with high and low case burdens relative to capacity to locations with intermediate case burdens maximizes their impact in reducing R_t (but minimizing total infections may be more complicated). Contact tracing efficacy decreased sharply with increasing delays between symptom onset and tracing and with lower fraction of symptomatic infections being tested. Finally, testing and tracing reductions in R_t can sometimes greatly delay epidemics due to the highly heterogeneous transmission dynamics of SARS-CoV-2. These results demonstrate the importance of having an expandable or mobile team of contact tracers that can be used to control surges in cases. They also highlight the synergistic value of high capacity, easy access testing and rapid turn-around of testing results, and outreach efforts to encourage symptomatic cases to be tested immediately after symptom onset.     

Optimal mix of screening and contact tracing for endemic diseases

Two common means of controlling infectious diseases are screening and contact tracing. Which should be used, and when? We consider the problem of determining the cheapest mix of screening and contact tracing necessary to achieve a desired endemic prevalence of a disease or to identify a specified number of cases. We perform a partial equilibrium analysis of small-scale interventions, assuming that prevalence is unaffected by the intervention; we develop a full equilibrium analysis where we compare the long-term cost of various combinations of screening and contact tracing needed to achieve a given equilibrium prevalence; and we solve the problem of minimizing the total costs of identifying and treating disease cases plus the cost of untreated disease cases. Our analysis provides several insights. First, contact tracing is only cost effective when prevalence is below a threshold value. This threshold depends on the relative cost per case found by screening versus contact tracing. Second, for a given contact tracing policy, the screening rate needed to achieve a given prevalence or identify a specified number of cases is a decreasing function of disease prevalence. As prevalence increases above the threshold (and contact tracing is discontinued), the screening rate jumps discontinuously to a higher level. Third, these qualitative results hold when we consider unchanged or changed prevalence, and short-term or long-term costs.     

The long-term effect of current and new interventions on the new case detection of leprosy: a modeling study

Background

Although the number of newly detected leprosy cases has decreased globally, a quarter of a million new cases are detected annually and eradication remains far away. Current options for leprosy prevention are contact tracing and BCG vaccination of infants. Future options may include chemoprophylaxis and early diagnosis of subclinical infections. This study compared the predicted trends in leprosy case detection of future intervention strategies.

Methods

Seven leprosy intervention scenarios were investigated with a microsimulation model (SIMCOLEP) to predict future leprosy trends. The baseline scenario consisted of passive case detection, multidrug therapy, contact tracing, and BCG vaccination of infants. The other six scenarios were modifications of the baseline, as follows: no contact tracing; with chemoprophylaxis; with early diagnosis of subclinical infections; replacement of the BCG vaccine with a new tuberculosis vaccine ineffective against Mycobacterium leprae (“no BCG”); no BCG with chemoprophylaxis; and no BCG with early diagnosis.

Findings

Without contact tracing, the model predicted an initial drop in the new case detection rate due to a delay in detecting clinical cases among contacts. Eventually, this scenario would lead to new case detection rates higher than the baseline program. Both chemoprophylaxis and early diagnosis would prevent new cases due to a reduction of the infectious period of subclinical cases by detection and cure of these cases. Also, replacing BCG would increase the new case detection rate of leprosy, but this effect could be offset with either chemoprophylaxis or early diagnosis.

Conclusions

This study showed that the leprosy incidence would be reduced substantially by good BCG vaccine coverage and the combined strategies of contact tracing, early diagnosis, and treatment of infection and/or chemoprophylaxis among household contacts. To effectively interrupt the transmission of M. leprae, it is crucial to continue developing immuno- and chemoprophylaxis strategies and an effective test for diagnosing subclinical infections.     

Epidemic management and control through risk-dependent individual contact interventions

Testing, contact tracing, and isolation (TTI) is an epidemic management and control approach that is difficult to implement at scale because it relies on manual tracing of contacts. Exposure notification apps have been developed to digitally scale up TTI by harnessing contact data obtained from mobile devices; however, exposure notification apps provide users only with limited binary information when they have been directly exposed to a known infection source. Here we demonstrate a scalable improvement to TTI and exposure notification apps that uses data assimilation (DA) on a contact network. Network DA exploits diverse sources of health data together with the proximity data from mobile devices that exposure notification apps rely upon. It provides users with continuously assessed individual risks of exposure and infection, which can form the basis for targeting individual contact interventions. Simulations of the early COVID-19 epidemic in New York City are used to establish proof-of-concept. In the simulations, network DA identifies up to a factor 2 more infections than contact tracing when both harness the same contact data and diagnostic test data. This remains true even when only a relatively small fraction of the population uses network DA. When a sufficiently large fraction of the population (≳ 75%) uses network DA and complies with individual contact interventions, targeting contact interventions with network DA reduces deaths by up to a factor 4 relative to TTI. Network DA can be implemented by expanding the computational backend of existing exposure notification apps, thus greatly enhancing their capabilities. Implemented at scale, it has the potential to precisely and effectively control future epidemics while minimizing economic disruption.     

Disease contact tracing in random and clustered networks

The efficacy of contact tracing, be it between individuals (e.g. sexually transmitted diseases or severe acute respiratory syndrome) or between groups of individuals (e.g. foot-and-mouth disease; FMD), is difficult to evaluate without precise knowledge of the underlying contact structure; i.e. who is connected to whom? Motivated by the 2001 FMD epidemic in the UK, we determine, using stochastic simulations and deterministic 'moment closure' models of disease transmission on networks of premises (nodes), network and disease properties that are important for contact tracing efficiency. For random networks with a high average number of connections per node, little clustering of connections and short latency periods, contact tracing is typically ineffective. In this case, isolation of infected nodes is the dominant factor in determining disease epidemic size and duration. If the latency period is longer and the average number of connections per node small, or if the network is spatially clustered, then the contact tracing performs better and an overall reduction in the proportion of nodes that are removed during an epidemic is observed.     

Outbreak of tuberculosis after minimal exposure to infection.

The identification of a case of respiratory tuberculosis in a swimming-baths attendant whose sputum was smear positive was followed by intensive contact tracing of children aged 8-11 years who had visited the baths. An outbreak was discovered that otherwise might not have been detected. Out of 3764 children, 108 (2.9%) had evidence of infection: there were 16 cases of tuberculosis, of which 11 were symptomless but showed lesions on chest radiography, and a further 92 with tine test grade 3 or 4 without clinical or radiological signs. The contact of these children with the index case was apparently minimal. Early detection, isolation, and treatment of infectious cases of respiratory tuberculosis and vigorous contact tracing should be given more priority in tuberculosis control.     

Leprosy New Case Detection Trends and the Future Effect of Preventive Interventions in Pará State,Brazil: A Modelling Study

BackgroundLeprosy remains a public health problem in Brazil. Although the overall number of new cases is declining, there are still areas with a high disease burden, such as Pará State in the north of the country. We aim to predict future trends in new case detection rate (NCDR) and explore the potential impact of contact tracing and chemoprophylaxis on NCDR in Pará State.MethodsWe used SIMCOLEP, an existing individual-based model for the transmission and control of M. leprae, in a population structured by households. The model was quantified to simulate the population and observed NCDR of leprosy in Pará State for the period 1990 to 2014. The baseline scenario was the current control program, consisting of multidrug therapy, passive case detection, and active case detection from 2003 onwards. Future projections of the NCDR were made until 2050 given the continuation of the current control program (i.e. baseline). We further investigated the potential impact of two scenarios for future control of leprosy: 1) discontinuation of contact tracing; and 2) continuation of current control in combination with chemoprophylaxis. Both scenarios started in 2015 and were projected until 2050.ResultsThe modelled NCDR in Pará State after 2014 shows a continuous downward trend, reaching the official elimination target of 10 cases per 100,000 population by 2030. The cessation of systematic contact tracing would not result in a higher NCDR in the long run. Systematic contact tracing in combination with chemoprophylaxis for contacts would reduce the NCDR by 40% and bring attainment of the elimination target two years forward to 2028.ConclusionThe NCDR of leprosy continues to decrease in Pará State. Elimination of leprosy as a public health problem could possibly be achieved around 2030, if the current control program is maintained. Providing chemoprophylaxis would decrease the NCDR further and would bring elimination forward by two years.     

Innovative Technological Approach to Ebola Virus Disease Outbreak Response in Nigeria Using the Open Data Kit and Form Hub Technology

The recent outbreak of Ebola Virus Disease (EVD) in West Africa has ravaged many lives. Effective containment of this outbreak relies on prompt and effective coordination and communication across various interventions; early detection and response being critical to successful control. The use of information and communications technology (ICT) in active surveillance has proved to be effective but its use in Ebola outbreak response has been limited. Due to the need for timeliness in reporting and communication for early discovery of new EVD cases and promptness in response; it became imperative to empower the response team members with technologies and solutions which would enable smooth and rapid data flow. The Open Data Kit and Form Hub technology were used in combination with the Dashboard technology and ArcGIS mapping for follow up of contacts, identification of cases, case investigation and management and also for strategic planning during the response. A remarkable improvement was recorded in the reporting of daily follow-up of contacts after the deployment of the integrated real time technology. The turnaround time between identification of symptomatic contacts and evacuation to the isolation facility and also for receipt of laboratory results was reduced and informed decisions could be taken by all concerned. Accountability in contact tracing was ensured by the use of a GPS enabled device. The use of innovative technologies in the response of the EVD outbreak in Nigeria contributed significantly to the prompt control of the outbreak and containment of the disease by providing a valuable platform for early warning and guiding early actions.