Antibiotics of the aminoglycoside group (gentamicin, sisomicin and amikacin) in the prevention and treatment of experimental plague]

Activity of aminoglycosides such as gentamicin, sisomicin and amikacin against plague microbe strains of natural origin was studied in vitro. It was also studied in prophylaxis and treatment of experimental plague infection in albino mice. The MAC of gentamicin and sisomicin for 50 strains of the plague microbe was 0.2-1.6 micrograms/ml. For the majority of the strains it was 0.4 micrograms/ml. The amikacin MICs were 0.4-3.2 and 0.8 micrograms/ml, respectively. High efficacy of gentamicin, sisomicin and amikacin was shown in prophylaxis and treatment of experimental plague infection in albino mice. The optimal doses of the antibiotics were determined. Under definite conditions such as the use of short-term regimens and higher intervals, advantages of sisomicin over gentamicin and amikacin in prophylaxis of experimental plague infection were observed.     

Further study of the effectiveness of oral immunization against plague in experiments on animals]

It was shown in comparative experiments on guinea pigs that the oral method of immunization with plague vaccine was much less effective than the inhalation and subcutaneous. Guinea pigs were found to be a poor model for studying the efficacy of oral immunization with dry live plague vaccine rehydrated before use: with the use of this preparation the animals were 46 times less resistant to aerosol plague infection than in application of strain EB cultured in agar.     

No evidence of persistent Yersina pestis infection at prairie dog colonies in north-central Montana

Sylvatic plague is a flea-borne zoonotic disease caused by the bacterium Yersinia pestis, which can cause extensive mortality among prairie dogs (Cynomys) in western North America. It is unclear whether the plague organism persists locally among resistant host species or elsewhere following epizootics. From June to August 2002 and 2003 we collected blood and flea samples from small mammals at prairie dog colonies with a history of plague, at prairie dog colonies with no history of plague, and from off-colony sites where plague history was unknown. Blood was screened for antibody to Y. pestis by means of enzyme-linked immunosorbent assay or passive hemagglutination assay and fleas were screened for Y. pestis DNA by polymerase chain reaction. All material was negative for Y. pestis including 156 blood samples and 553 fleas from colonies with a known history of plague. This and other studies provide evidence that Y. pestis may not persist at prairie dog colonies following an epizootic.     

Doxycycline in the prevention of experimental plague induced by plague microbe variants]

A comparative study was performed on the efficacy of doxycycline in experimental plague infection induced in albino mice by strain 231 of the plague microbe and its variant 231 Fra- deprived of the ability to produce the fraction I antigen. It was shown that the LD50 for strain 231 during animal treatment with doxycycline was significantly higher than that for variant 231 Fra-. Prophylaxis of the plague infection caused by the Fra- forms of the plague microbe required significantly higher doses of doxycycline (ED50) than that of the infection caused by the Fra+ forms. The use of the daily maximum permissible doses of doxycycline (50 to 100 mg/kg a day) for 10 days in treatment of albino mice infected with the strain Fra- did not provide animal survival at the level higher than 60 to 70 per cent while the survival rate in the animals infected with the strain Fra+ of the plague microbe and treated according to the same scheme amounted to 90-100 per cent. The lower therapeutic efficacy of doxycycline in the treatment of the infection caused by the fractionless variant of the plague microbe should be considered in development of rational schemes for prophylaxis and treatment of plague.     

Chromosomal resistance of plague agent to quinolones]

The nature of increasing chromosomal resistance to quinolones was studied in a model of the plague microbe. Five virulent strains of the natural plague microbe (Y. pestis) were used in the experiment: 363 (1/1479), 231, 2385, 2442 and 2444. The one-stage procedure for isolation of the mutants was applied. It was shown that the frequency of the one-stage mutants resistant to oxalinic acid, pefloxacin and ciprofloxacin amounted to 10(-9)-10(-11) and was 2 to 3 orders of magnitude lower than that of the mutants resistant to nalidixic acid. Two types of the plague microbe mutants resistant to the quinolones were detected: those resistant to the quinolones to the generations (Nalr-phenotype) and those resistant to the representatives of the 3rd generation quinolones (Nals-phenotype). The quinolones were not efficient in the treatment of albino mice with experimental plague caused by the quinolone-resistant forms of the plague microbe.     

Effect of subinhibitory concentrations of antibiotics on catalase activity of plague microbes]

It was shown that the presence of subinhibitory concentrations of ampicillin, cefotaxime or gentamicin in the cultivation medium had a marked inhibitory effect on the catalase activity of plague microbe. The effect depended on the characteristic features of plague microbe strains and the incubation temperature. When the cells of a virulent strain of the plague microbe Y. pestis 1300 were cultivated at a temperature of 37 degrees C on a medium containing the subinhibitory concentrations of ampicillin or cefotaxime, the pathogen virulence for albino mice significantly decreased.     

青海省鼠疫的防控策略

鼠疫曾给人类带来3次世界性灾难,剥夺了上亿人的生命。作为危害人类健康最为严重的烈性传染病之一,鼠疫的防控工作显得尤为重要。新中国成立后,党和政府大力开展鼠疫防控工作,开展流行病调查,制定各项防控措施。虽然全国范围在较短的时间内遏制了鼠疫流行的猛烈势头,但在西部地区人间鼠疫时有发生。青海省地处我国西部,就其鼠疫流行特征制定了适合本地鼠疫的防控模式。本文就“青海模式”的工作机制、调查监测、宣传教育、人员培训、隐患排查等进行介绍,阐述青海省鼠疫防控工作的成效,为中国传染病防控策略发展提出新的思考。     

Draft Genome Sequence of Yersinia pestis Strain 2501, an Isolate from the Great Gerbil Plague Focus in Xinjiang, China

We deciphered the genome of Yersinia pestis strain 2501, isolated from the Junggar Basin, a newly discovered great gerbil plague focus in Xinjiang, China. The total length of assembly was 4,597,322 bp, and 4,265 coding sequences were predicted within the genome. It is the first Y. pestis genome from this plague focus.     

Host influence on the frequency of block formation in males and females of Citellophilus tesquorum altaicus Ioff, 1936 (Siphonaptera: Ceratophyllidae) and transmission the plague pathogen by these fleas

Data obtained during feeding of Citellophilus tesquorum aitaicus Ioff, 1936 infested females and males (Siphonaptera: Ceratophyllidae), the main vectors of plague in Tuva natural plague locus, on the natural host and laboratory animal was analyzed. It was found that sexual differences in fleas depended on the type of the host. Females fed more actively on the longtailed ground Citellus undulatus than on white mouse. Alimentary activity of males on these animals was similar. Higher mortality of fed females and males was noted during feeding on mice. Frequency of formation of the "block" and transmission of the pathogen in males was higher during bloodsucking on the ground squirrel; in females, during feeding on mice. Thus, differences in the transmission of the plague pathogen, revealed in laboratory on white mice, can be quite different in nature. So, extrapolation of experimental data on natural processes of interrelations between plague pathogen and ectoparasites must be performed taking into account revealed peculiarities.     

Broader investigation into the external environment of the specific antigen of the infectious agent in epizootiological observation and study of the structure of natural foci of plague.

The possibilities of detection of the infectious agent in natural foci of plague can be expanded to some extent by using the method of search for the specific FI capsular antigen of the plague microbe in such objects of the external environment which have not yet been subjected to laboratory analysis and serological analysis in particular. Such objects include soil from the burrow and the substrate of the nest of the rodent as well as the fleas of rodents and regurgitations of birds of prey.The effectivity and suitability of examination of these objects using immuno-adsorption reactions with standard erythrocyte diagnostics (passive haemagglutination reaction, antibody neutralization reaction) were demonstrated experimentally and confirmed under field conditions in various geographical and ecological zones of the Caucasus. Thus in 1971, an earlier unknown natural focus of plague was found in the Mount Elbrus massif by means of serological analysis of the substrate of the nest and of the soil from the burrows of rodents. It can be expected that broadened serological search for the FI antigen of plague will prove useful in the study of the structure of natural foci of plague, in the reconnaissance or retrospective investigation of poorly explored territories and in the solution of some questions concerning the epizootiology of plague, such as the survival of the infectious agent in the inter-epizootic period, telluric plague, etc.     

Differential plague susceptibility in species and populations of prairie dogs

Laboratory trials conducted over the past decade at U.S. Geological Survey National Wildlife Health Center indicate that wild populations of prairie dogs (Cynomys spp.) display different degrees of susceptibility to experimental challenge with fully virulent Yersinia pestis, the causative agent of plague. We evaluated patterns in prairie dog susceptibility to plague to determine whether the historical occurrence of plague at location of capture was related to survival times of prairie dogs challenged with Y. pestis. We found that black‐tailed prairie dogs (Cynomys ludovicianus) from South Dakota (captured prior to the detection of plague in the state), Gunnison's prairie dogs (Cynomys gunnisoni) from Colorado, and Utah prairie dogs (Cynomys parvidens) from Utah were most susceptible to plague. Though the susceptibility of black‐tailed prairie dogs in South Dakota compared with western locations supports our hypothesis regarding historical exposure, both Colorado and Utah prairie dogs have a long history of exposure to plague. It is possible that for these populations, genetic isolation/bottle necks have made them more susceptible to plague outbreaks.     

鼠疫的防控和抗菌治疗

鼠疫造成的危害极为严重,但随着抗生素的发明和广泛应用,其相关的病死率显著降低。对于鼠疫不必过于恐慌,只要做好个人防护,发病后及时就诊,就可获得痊愈。鼠疫的防控需要根据疫区或非疫区分别对待,才能够有效控制疫情播散。氟喹诺酮类、磺胺类等抗生素可有效控制病情,并可作为暴露后的预防用药。     

Detoxifying effect of antibiotics and their effectiveness in experimental plague at the stage of explicit intoxication]

The effect of antibiotics such as amikacin, rifampicin, doxycycline, polymyxin B and cefotaxime on the toxins of the plague microbe (lipopolysaccharide + fraction II according to Beiker) was studied in vitro and in vivo. The study on the antibiotic neutralization of plague toxins revealed that only polymyxin had toxin neutralizing capacity which depended on the dose. Investigation of the polymyxin effect at various stages of plague infection showed that when polymyxin in a dose of 1250 units and a mixture of plague toxins in lethal doses were administered simultaneously to albino mice, the positive effect amounted to 100 per cent. When the antibiotic was administered 30 or 60 minutes later, the antibiotic efficacy proved to be lower by 90 or 76.6 per cent, respectively. The intoxication in later periods (in 90-120 minutes) resulted in a decrease in animal survival up to 40-15 per cent. It was demonstrated on the model of the plague infection in albino mice that the use of amikacin, cefotaxime, rifampicin or doxycycline during polymyxin therapy at the stage of marked generalization of the infection provided a significant increase in the animal survival (60 to 80 per cent) as compared to that after the use of the same drugs alone (0 to 20 per cent).     

Sympatric speciation of the plague microbe <Emphasis Type="Italic">Yersinia pestis</Emphasis>: Monohostal specialization in the host–parasite marmot–flea (<Emphasis Type="Italic">Marmota sibirica–Oropsylla silantiewi</Emphasis>) system

An ecological scenario of the origin of the plague microbe that is interpreted in the light of modern Darwinism (synthetic theory of evolution) is presented. It is shown that the plague microbe emerged from a clone of the psychrophilic saprozoonotic pseudotuberculosis microbe Yersinia pseudotuberculosis O:1b in the mountain steppe landscapes of Central Asia in the Sartan time, 22000–15000 years ago, in the monohostal Mongolian marmot (Marmota sibirica)–flea (Oropsylla silantiewi) host–parasite system. It was noted that the evolutionary process described corresponds to the sympatric form of speciation by transition of the clone of migrant founders to a new, already-existing ecological niche. It was established that monohostal specialization of the plague microbe was made possible due to heterothermia (5–37°C) of marmots in the hibernation period. The factors of the speciation process—isolation, the struggle for existence, and natural selection—were analyzed.     

环介导等温扩增技术检测鼠疫耶尔森菌的敏感性和特异性研究

为观察环介导等温扩增(loop-mediated isothermal amplification,LAMP)技术能否适用于我国不同疫源地鼠疫耶尔森菌所有基因组型的检测,本研究建立了一种基于3a靶序列设计特异性引物快速检测鼠疫耶尔森菌的LAMP方法.选择分离自我国11个鼠疫自然疫源地的65株野生代表性鼠疫耶尔森菌株,同...     

中国鼠疫宿主鼠类丰富度格局及疫区环境因子分析

鼠疫等媒介疾病地理分布规律的认识对于疫病防控具有重要意义,分析影响疾病地理分布的因素进而预测疾病发生趋势已经成为目前研究的热点。本文在分析鼠间鼠疫及其宿主鼠类地理分布数据以及相关环境数据的基础上,探讨了鼠疫宿主丰富度与环境因子的关系以及影响鼠间鼠疫发生的主要环境因素。我国的鼠疫宿主鼠类在干旱区和季风区过渡带的县级行政单元中物种丰富度最高,物种丰富度与高度差正相关性最高。发生鼠间鼠疫的地区,宿主鼠类丰富度较高,未发生鼠间鼠疫的地区,宿主鼠类丰富度较低。影响鼠间鼠疫发生的主要环境因子包括蚤类物种数、年均气温、年降雨量、年均相对湿度和年日照时数和气候因子,其次是包括高度差、植被类型数、土壤类型数和地貌类型数的景观因子,以及反映海拔和宿主鼠类物种数的地形和宿主鼠类因子。在未来全国气候变干变暖条件下,我国鼠间鼠疫发病区可能随宿主鼠类的迁移而扩展。     

Paper-Strip Blood-Sampling Technique for the Detection of Antibody to the Plague Organism Yersinia pestis

The paper-strip blood-sampling technique was evaluated for efficacy in plague passive hemagglutination tests. It is valuable for widespread serological surveys.     

Human plague in the USA: the importance of regional and local climate

A 56-year time series of human plague cases (Yersinia pestis) in the western United States was used to explore the effects of climatic patterns on plague levels. We found that the Pacific Decadal Oscillation (PDO), together with previous plague levels and above-normal temperatures, explained much of the plague variability. We propose that the PDO's impact on plague is conveyed via its effect on precipitation and temperature and the effect of precipitation and temperature on plague hosts and vectors: warmer and wetter climate leading to increased plague activity and thus an increased number of human cases. Our analysis furthermore provides insights into the consistency of plague mechanisms at larger scales.     

Experimental study of the antiviral properties of antibiotic 6734-21]

The effect of antibiotic 6734-21 on the viruses of variolovaccine, Herpes simplex, influenza and classical avian plague was studied on various experimental models. Antibiotic 6734-21 inhibited development of the variolovaccine virus in the tissue culture, in chick embryos, in rabbits with variolovaccine infection, as well as the development of the viruses of Herpes simplex, Aueski, and Newcastle diseases in the tissue culture. It had a virulicidic effect on the viruses of variolovaccine, influenza and classical avian plague.     

鼠疫耶尔森菌rV抗原单抗系统及其ELISA检测方法的建立

目的建立ELISA双抗体夹心法,测定重组毒力因子rV抗原含量。方法采用杂交瘤技术,制备鼠疫菌rV抗原的鼠单克隆抗体,对抗原表位和单抗特异性进行分析及鉴定,建立ELISA双抗体夹心法,并验证方法的专属性、准确性、精密度和线性范围。结果成功组建了鼠疫菌rV抗原诊断试剂,灵敏度最低检测值为10 ng/mL。结论该方法可用于免疫学检测鼠疫组分疫苗原液rV抗原含量及制备过程中抗原活性,是鼠疫组分疫苗制备中一种重要的质量控制手段,也为进一步开发鼠疫诊断试剂盒及其他相关研究奠定了基础。