地理景观特征与鼠疫关系的研究概述

鼠疫是由鼠疫耶尔森菌引起的人兽共患的烈性传染病,鼠疫生态地理景观是形成自然疫源地的重要因素。疫源地地理景观类型多样,结构复杂,探讨地理景观特征与鼠疫的关系及其相关的研究技术,对阐明各类疫源地的适宜生境、鉴别地理生态环境系统的脆弱性及预防鼠疫的发生流行具有重要作用。     

白银市平川区黄鼠鼠疫疫源地宿主媒介生态调查

本文报道了甘肃省白银市平川区黄鼠鼠疫疫源地宿主动物阿拉善黄鼠（ｃｉｌｅｌｌｕｓ ａｌａｓｈａｎｉｃｕｓ，下称黄鼠）的地面活动期，活动范围，繁殖，密度变化及媒介的组成，黄鼠体蚤，洞干蚤，巢蚤的季节消长等生态学调查资料。     

2005-2017年个旧市动物鼠疫监测分析

目的分析2005—2017年云南省个旧市动物鼠疫宿主动物密度、媒介构成、种群变化和疫情态势。方法收集2005—2017年个旧市鼠疫监测资料,计算相关指标,应用描述流行病学方法进行分析。结果 2005—2017年共发现啮齿动物8种,年平均鼠密度在1.11%～3.42%波动,总平均鼠密度1.93%,其中优势鼠种是黄胸鼠(39.31%),次要鼠种是褐家鼠(33.66%);蚤类6种,总蚤指数及印鼠客蚤指数分别在0.19～0.57和0.04～0.35间波动,优势蚤种是印鼠客蚤(40.00%),其次是人蚤(30.70%);检测宿主动物6 207只、体外寄生虫2 140组和动物血清2 497份,结果均为阴性。结论目前个旧市处于鼠疫流行静息期,但结合自然环境、鼠疫流行史、优势鼠鼠密度和优势蚤蚤指数等因素综合分析,存在着鼠疫发生和流行的可能性;应继续认真开展和完成鼠疫监测等工作。     

鼠疫信息系统的建立

目的探索一种比较先进的方式来改变目前的鼠疫信息管理方式。方法结合信息管理相关理论,利用VB开发鼠疫信息数据库管理软件。结果鼠疫信息管理系统的建立,实现了鼠疫信息的科学化、规范化、标准化管理。结论该系统建立后能安全、高效的管理鼠疫信息,有推广意义。     

土壤保存鼠疫菌F1抗原的试验研究

本文报告利用放射免疫沉淀试验的竞争抑制原理,成功地从实验室保存了五年鼠疫菌的土壤中,检出F1抗原。检出F1抗原量可达340ng/ml。结果表明,该项试验较反向血凝方法敏感。     

吉林鼠疫监测技术和方法的研究

吉林省经过系统研究,建立了比较完善的鼠疫监测技术和方法。主要是:在50年代中期确定了主要储存宿主的基础上,60年代引进地理景观理论和方法;70年代提出了疫源地鉴定方法;80年代引进了数学模型及计算机技术;90年代提出了动物鼠疫监测标准,实施质量控制及对监测工作的科学评价。1 50年代 明确了吉林省鼠疫自然疫源地的疆界与分布。共分布16个县(市、区),面积5.64万hm~2,灭鼠面积398万hm~2。确定达乌尔黄鼠(以下简称黄鼠)为鼠疫的主要储存宿主,方形黄鼠蚤松     

平川区鼠疫防治现状及对策

平川区鼠疫自然疫源地属于甘宁黄土高原阿拉善黄鼠鼠疫自然疫源地的一部分，自1977年从阿拉善黄鼠和阿巴盖新蚤体内分离出鼠疫菌而被判定为疫源地以来，始终将严防发生人间鼠疫放在鼠疫防治工作的首位，坚持“三报、三不”制度，经过20多年的科学监测和调查研究，基本掌握了本区疫源地的自然景观、宿主动物、传播媒介动物等。     

鼠疫菌大质粒与生长关系的研究

本试验观察了携带大质粒和消除大质粒鼠疫菌株在28℃培养时的生长情况。结果证实消除大质粒的菌株比携带大质粒的菌株生长速度快。     

鼠疫坟茔尸骨检验结果分析

目的 检测死于50年前的鼠疫病人尸骨及尸骨周围土壤是否存在鼠疫菌。方法 利用鼠疫细菌学和血清学方法对尸骨和土壤进行检验。结果 尸骨及土壤中没有分离到鼠疫菌。结论 在尸体腐烂过程中其条件不利于鼠疫菌存活，加之50～60年风干的环境亦可导致鼠疫菌的死亡。     

鼠疫治疗策略进展

鼠疫是自然疫源性疾病,起病急、病程短、传染性强、病死率高,给人民生命安全和社会稳定带来严重威胁。鼠疫疫源地分布于世界各地,至今,部分地区疫情流行仍很活跃,导致鼠疫这种人兽共患病的防控形势十分严峻。以链霉素为首选的抗生素疗法是传统的方案,在各型鼠疫的治疗中发挥关键作用,但随之而来的耐药性报道,促使了新策略的研发和实践。文章就不同种类抗生素的治疗效应、鼠疫疫苗的研究进展、噬菌体疗法的研究进展作一综述,以期为今后鼠疫治疗提供参考。     

Stone Age Yersinia pestis genomes shed light on the early evolution,diversity, and ecology of plague

The bacterial pathogen Yersinia pestis gave rise to devastating outbreaks throughout human history, and ancient DNA evidence has shown it afflicted human populations as far back as the Neolithic. Y. pestis genomes recovered from the Eurasian Late Neolithic/Early Bronze Age (LNBA) period have uncovered key evolutionary steps that led to its emergence from a Yersinia pseudotuberculosis-like progenitor; however, the number of reconstructed LNBA genomes are too few to explore its diversity during this critical period of development. Here, we present 17 Y. pestis genomes dating to 5,000 to 2,500 y BP from a wide geographic expanse across Eurasia. This increased dataset enabled us to explore correlations between temporal, geographical, and genetic distance. Our results suggest a nonflea-adapted and potentially extinct single lineage that persisted over millennia without significant parallel diversification, accompanied by rapid dispersal across continents throughout this period, a trend not observed in other pathogens for which ancient genomes are available. A stepwise pattern of gene loss provides further clues on its early evolution and potential adaptation. We also discover the presence of the flea-adapted form of Y. pestis in Bronze Age Iberia, previously only identified in in the Caucasus and the Volga regions, suggesting a much wider geographic spread of this form of Y. pestis. Together, these data reveal the dynamic nature of plague’s formative years in terms of its early evolution and ecology.

The earliest known cases of human infection with the plague pathogen, Yersinia pestis, date to around 5,000 y ago (1–4). Analyses of ancient Y. pestis genomes from this period suggest that the time window between 6,000 and 4,000 y ago was critical and formative for the evolution and ecology of Y. pestis as we know it today. Four ancient Y. pestis lineages have been identified so far, which can be genomically distinguished based on their adaptations to the flea, the main vector of modern plague. Today, fleas are known to play a central role in the transmission of plague within rodent populations, which can act as reservoirs from where spillovers to human populations typically occur (5, 6). The transmission of Y. pestis by the flea is either facilitated by a blockage of the foregut (proventriculus), where the bacterium produces a biofilm (7), or in a biofilm-independent manner, also known as early-phase transmission (8, 9). The oldest lineages of Y. pestis (2, 4) (hereafter referred to as preLNBA−), and the Late Neolithic and Early Bronze Age (LNBA−) lineage (1, 3) present a genetic background that has been interpreted as being incompatible with flea transmission via the blockage of the foregut (indicated in the naming by the minus sign). While a recently identified ancient lineage also dating to the Bronze Age presents all the genetic adaptations for this highly efficient form of flea transmission (10) (LNBA+; the plus sign indicates the adaptation to the flea vector). Intriguingly, both variants coexisted for millenia and they might have occupied different niches. However, it remains unclear how the different forms of Y. pestis infected humans during prehistory and how the resulting diseases manifested in the human population. Whether plague ecology and transmission as we know it today can serve as a model to understand its manifestation in the past remains also unknown.Elucidating the ecology and transmission will be crucial for understanding how the LNBA+/− lineages of plague, which were widespread across Eurasia for thousands of years (1, 3, 10, 11), have impacted human societies, and how changes in human subsistence and economy have shaped the early evolution of this pathogen. It is currently unknown whether and which types of animal populations served as potential reservoirs of the disease and their identification will be essential for characterizing past Y. pestis transmission dynamics. The absence of an adaptation to the flea vector in some plague lineages suggests that the transmission dynamics were complex. Today, the flea-mediated model is not the only documented form of plague transmission: pneumonic plague can be acquired via respiratory droplets from close human-to-human contact. However, only a few reported outbreaks have been attributed to this transmission mode and usually in contexts of poor ventilation and direct contact with infected individuals (12–17). Additionally, plague has been documented in humans who handled or ingested parts of infected animals (18–22).Changes in human behavior may also have contributed to a higher risk of plague infection. During the LNBA period, archeological evidence attests to technological advances, such as the spread of oxen-drawn carts and wagons (23) and horse domestication (24), which enabled increased human mobility and exploitation of new habitats, such as the Eurasian steppe belt. This ultimately led to the establishment of long-distance networks, in which raw materials such as copper were circulated (25, 26). However, periods of unrest and war could also have played a role in the extended human mobility during the LNBA period. While earlier studies hypothesized that increased mobility was the cause for an early spread of Y. pestis across Eurasia (1, 3), it could also have been its effect. It is also during this period that animal husbandry and mobile pastoralism intensified in the steppe (27), thus facilitating the overlap of ecological niches for zoonoses to occur. The aforementioned changes could have played a role in the likelihood of transmission to humans and the long-distance spread of plague during its early evolution.Here we expand the number of Y. pestis genomes from the LNBA period to offer a higher genomic resolution for important stages in the evolution of the bacterium, as well as its diversity and geographical distribution in the past. By linking the genomic evidence with the available archeological context, we discuss potential transmission mechanisms of plague during its early evolution.     

鹤庆新发野鼠鼠疫疫源地中鼠疫噬菌体的分离及其裂解谱测定

目的 查明鹤庆新发野鼠鼠疫疫源地内是否存在鼠疫噬菌体,并对所离分鼠疫噬菌体进行形态鉴定及噬菌谱分析。方法 以鹤庆县马厂村为核心,选择5 km范围内的自然村为采样点,采用鼠铗法进行捕鼠,实验室中取鼠盲肠置入改良PBS中,采用双层平皿对样本进行筛选、纯化得到噬菌体,观察噬菌斑形态,电镜检查噬菌体形态,并在22 ℃、24 ℃、28 ℃及37 ℃对21株鼠疫菌与115株非鼠疫菌进行裂解特性分析。结果 采集的354份标本,分离到2株鼠疫噬菌体;2株噬菌体在高于24 ℃温度下可裂解鼠疫菌,低于24 ℃不能裂解鼠疫菌,而非鼠疫菌在4个温度下均不裂解;电镜形态检测2株噬菌体均属于肌尾噬菌体。结论 鹤庆新发野鼠疫疫源地内存在着鼠疫噬菌体,且所分鼠疫噬菌体只有在高于24 ℃时才裂解鼠疫菌,此特性与鼠疫菌在鹤庆县的长期存在相关,且两株噬菌体存在裂解谱较窄,特异性良好,可用于备用诊断噬菌体的筛选株。     

鼠疫历史疫情的考古微生物学研究进展

鼠疫是由鼠疫耶尔森氏菌(简称鼠疫菌)引发的烈性传染病,人类历史上曾发生3次大规模的鼠疫大流行。近年来,考古微生物学得到长足发展,使得研究人员可以对历史上的鼠疫疫情进行探索,为鼠疫的起源、传播以及鼠疫菌的进化等关键问题提供更为深刻的理解。本文就关于考古微生物学方法在古代鼠疫疫情研究领域取得的进展进行简单综述:包括基于PCR、蛋白质分析以及基因组序列测定在内的考古微生物学研究技术方法;基于以上技术确认查士丁尼瘟疫和黑死病的病原体为鼠疫菌;新石器时代晚期至青铜时代就已经存在人类感染鼠疫菌的病例;通过分子钟分析将鼠疫菌的物种形成时间确定为5000-7500年前。考古微生物学方法不仅可以继续推进鼠疫和鼠疫菌的相关研究,也将为其他历史传染病的研究提供有益借鉴。     

梁河家鼠鼠疫疫源地鼠疫噬菌体的分离及其流行病学意义

目的 调查梁河县家鼠鼠疫疫源地宿主动物中是否携带鼠疫噬菌体,并探讨其流行病学意义。方法 2017年采集梁河家鼠鼠疫疫源地4个曾流行过鼠疫乡镇的鼠类标本,以鼠疫疫苗株EV76为饲养菌,采用双层平板法分离鼠疫噬菌体,同时挑取部分噬菌体进行电镜扫描。结果 共获得338份标本(黄胸鼠234只,臭鼩鼱43只,其余61只),分离到29株鼠疫噬菌体,总分离率为8.58%(29/338),其中19株分离自黄胸鼠,分离率为8.12%(19/234),8株分离自臭鼩鼱,分离率为18.6%(8/43);4个乡镇全部有分离到鼠疫噬菌体,其中遮岛镇分离率最高为16.13%(5/31);初次分离这些鼠疫噬菌体时,其噬斑在双层平板上表现为大(直径≥2.0 mm)、中(≥1.0 mm,≤2.0 mm)及小(≤1.0 mm)3种噬斑;2株有代表性噬菌体皆为肌尾病毒科噬菌体。结论 梁河家鼠鼠疫疫源地中普遍存在鼠疫噬菌体,黄胸鼠是主要的携带宿主,所分鼠疫噬菌体为肌尾病毒科噬菌体且具有多态性,值得进一步研究。     

动物鼠疫周期流行的生态位影响因素研究进展

鼠疫是由鼠疫耶尔森菌引发的烈性传染病,曾在历史上发生过3次大规模的流行,导致数亿人死亡.作为鼠疫自然疫源地最丰富的国家之一,中国拥有独特的鼠疫研究资源.在鼠疫自然疫源地中,动物间鼠疫呈现流行与静息周期性交替的特征.了解其转换机制对鼠疫防控具有重要意义.现有研究表明,疫源地生态位变化是导致动物间流行周期性转换的可能触发因...     

No evidence for persistent natural plague reservoirs in historical and modern Europe

Caused by Yersinia pestis, plague ravaged the world through three known pandemics: the First or the Justinianic (6th–8th century); the Second (beginning with the Black Death during c.1338–1353 and lasting until the 19th century); and the Third (which became global in 1894). It is debatable whether Y. pestis persisted in European wildlife reservoirs or was repeatedly introduced from outside Europe (as covered by European Union and the British Isles). Here, we analyze environmental data (soil characteristics and climate) from active Chinese plague reservoirs to assess whether such environmental conditions in Europe had ever supported “natural plague reservoirs”. We have used new statistical methods which are validated through predicting the presence of modern plague reservoirs in the western United States. We find no support for persistent natural plague reservoirs in either historical or modern Europe. Two factors make Europe unfavorable for long-term plague reservoirs: 1) Soil texture and biochemistry and 2) low rodent diversity. By comparing rodent communities in Europe with those in China and the United States, we conclude that a lack of suitable host species might be the main reason for the absence of plague reservoirs in Europe today. These findings support the hypothesis that long-term plague reservoirs did not exist in Europe and therefore question the importance of wildlife rodent species as the primary plague hosts in Europe.

The plague’s agent, Yersinia pestis, is primarily found in wildlife mammals but occasionally spills over to human populations. Its wildlife host species typically consist of a range of burrow-dwelling rodents (1), comprising of 279 species. Human infections usually occur after rodent–host populations remain above certain population thresholds for a few years before collapsing (2). Between high prevalence of the bacterium in the wild and subsequent plague outbreaks in humans, the bacteria can survive in what is typically described as a “natural plague reservoir,” i.e., a place where suitable rodent hosts, their flea vectors, and the pathogen (either within or outside their hosts and vectors) can exist indefinitely.Yersinia pestis has caused at least three extensive human plague pandemics (3–7): the First Plague Pandemic starting with the Justinianic Plague from 541-2 to ca. 750 CE; the Second Plague Pandemic begun with the Black Death of c.1338–1353 and was followed by numerous outbreaks until the mid-19th century CE; and the Third Plague Pandemic (8) that started in 1772 as a local epidemic in Yunnan but became a global pandemic only in 1894 and continues today in various parts of the world. Plague has been reported historically to be present on all continents, except Antarctica (9). It remains contested, however, whether plague reservoirs existed in Europe in the past (2, 10–12). It has been argued that medium-term plague reservoirs may have existed in Europe, such as the one hypothesized for South-Central Germany in the later 14th century and another in Central Europe (possibly the Alps) in the late 15th- early 17th centuries, before becoming extinct (see 13–16). However, it is not clear whether the plague bacterium settled within Europe during the late Middle Ages or was repeatedly reintroduced (through human transport) from beyond its borders (possibly from the same region) (11).Table 1.Previously proposed localities for putative plague reservoirs in Western–Central Europe in the past

蛋白质芯片在鼠疫患者血清抗体谱检测中的应用

目的检测鼠疫患者血清抗体谱,为鼠疫的疫苗研究奠定基础。方法利用鼠疫耶尔森氏菌毒流力相关蛋白的蛋白质芯片检测鼠疫患者血清抗体谱。结果利用一个包含145个鼠疫菌毒力相关蛋白的蛋白质芯片,在鼠疫患者血清中检测到37种鼠疫菌蛋白相应的抗体。结论通过对鼠疫患者血清抗体谱的分析,寻找到新的能在人体内产生体液免疫的蛋白。     

腺鼠疫患者血清抗体谱的研究

目的检测腺鼠疫患者血清抗体谱及抗体随时间变化趋势。方法利用一包含145个鼠疫耶尔森氏菌毒力相关蛋白质的蛋白芯片检测云南腺鼠疫患者血清抗体谱及抗体随时间变化趋势。结果在腺鼠疫患者体内检测到32种蛋白相应的抗体。结论FI抗体产生的速度最快、幅度最高、持续的时间最长;YopM、YopH、YopE抗体升高不明显;V抗体在患者体内未检测到;在发病后14 d才检测到pH6抗原的抗体,3个月时抗体荧光值没有下降,可持续半年。YopD的抗体在部分患者体内明显升高,但在半年后下降到正常水平。