Are carnivores universally good sentinels of plague?

Sylvatic plague, caused by the bacterium Yersinia pestis, is a flea-borne disease that primarily affects rodents but has been detected in over 200 mammal species worldwide. Mammalian carnivores are routinely surveyed as sentinels of local plague activity, since they can present antibodies to Y. pestis infection but show few clinical signs. In Boulder County, Colorado, USA, plague epizootic events are episodic and occur in black-tailed prairie dogs. Enzootic hosts are unidentified as are plague foci. For three years, we systematically sampled carnivores in two distinct habitat types to determine whether carnivores may play a role in maintenance or transmission of Y. pestis and to identify habitats associated with increased plague prevalence. We sampled 83 individuals representing six carnivore species and found only two that had been exposed to Y. pestis. The low overall rate of plague exposure in carnivores suggests that plague may be ephemeral in this study system, and thus we cannot draw any conclusions regarding habitat-associated plague foci or temporal changes in plague activity. Plague epizootics involving prairie dogs were confirmed in this study system during two of the three years of this study, and we therefore suggest that the targeting carnivores to survey for plague may not be appropriate in all ecological systems.     

Experimental model to evaluate the human body louse as a vector of plague

Yersinia pestis has been found in human body lice during plague outbreaks. To evaluate the role that the human body louse plays as a vector of plague, we allowed lice to feed on rabbits made bacteremic by intravenous inoculation of 10(9) colony-forming units of 3 strains of Y. pestis. High mortality rates were observed in all lice 2 and 3 days after infection. The lice remained infected with the strains for their life span and excreted viable organisms in their feces from day 1, although they were unable to lay eggs. The lice infected with 2 virulent strains of Y. pestis transmitted the organisms during feeding to uninfected rabbits, which became septicemic and died of plague (with 1 exception) 1 day later. Infections were transmitted to naive lice that were fed on these rabbits, showing that lice can be vectors of Y. pestis in an experimental model.     

Prompt laboratory diagnosis in timely containment of a plague outbreak in India

A focal outbreak of pneumonic plague occurred in a hamlet of village Hatkoti, district Shimla, Himachal Pradesh in the first fortnight of February, 2002. A total of 16 cases with 4 deaths were reported. Diagnosis of plague was confirmed by the laboratory in 10 (63%) cases. Y. pestis was isolated from clinical samples of 3 cases and confirmed by bacteriophage lysis. Molecular tests confirmed the presence of Y. pestis specific pla and F1 genes in 4 cases; DNA fingerprinting had identity with the known sequence of plague bacilli. Paired samples from 5 cases showed more than 4 fold rise and 1 case showed more than 4 fold fall in antibodies against F1 antigen of Y. pestis. The present communication emphasises that timely and systematic laboratory investigations give confirmatory diagnosis in shortest possible time which forms the backbone of the outbreak control in a timely fashion and prevents confusion and controversy.     

青海省鼠疫疫源地鼠疫耶尔森菌的基因型分布

目的研究青海省鼠疫耶尔森菌(鼠疫菌)基因型分布特征。方法对分离到的青海省148株鼠疫菌,根据已经证实的22个差异区段设计引物,每株鼠疫菌的每个基因差异区段都采用PCR技术进行验证。结果148株青海省鼠疫菌共包括8个基因型,即1、5、7、8、14型、新基因组型和Ype-ancestor型,其中以5型和8型为主。祁连山南麓和青海湖环湖地区的祁连、门源、刚察、海晏、共和、天峻等的菌株绝大多数属于基因型8型,占40．5％(60／148);位于青南高原的格尔木、玉树、扎多、治多、称多、囊谦和曲麻莱等的菌株,其基因型主要为5型,占31．8％(47／148)。青藏高原青海田鼠鼠疫疫源地鼠疫菌基因型全部为14型,占8．1％(12／148)。结论在青海省分离的鼠疫菌中,喜马托雅旱獭鼠疫疫源地鼠疫菌的基因型以5型和8型为主,青海田鼠疫源地鼠疫菌以基因型14型为主。     

Early-phase transmission of Yersinia pestis by cat fleas (Ctenocephalides felis) and their potential role as vectors in a plague-endemic region of Uganda

In recent decades, the majority of human plague cases (caused by Yersinia pestis) have been reported from Africa. In northwest Uganda, which has had recent plague outbreaks, cat fleas (Ctenocephalides felis) have been reported as the most common fleas in the home environment, which is suspected to be a major exposure site for human plague in this country. In the past, C. felis has been viewed as only a nuisance-biting insect because limited laboratory studies suggested it is incapable of transmitting Y. pestis or is an inefficient vector. Our laboratory study shows that C. felis is a competent vector of plague bacteria, but that efficiency is low compared with another flea species collected in the same area: the oriental rat flea, Xenopsylla cheopis. On the other hand, despite its low vector efficiency, C. felis is the most common flea in human habitations in a plague-endemic region of Uganda (Arua and Nebbi Districts), and occasionally infests potential rodent reservoirs of Y. pestis such as the roof rat (Rattus rattus) or the Nile rat (Arvicanthis niloticus). Plague control programs in this region should remain focused on reducing rat flea populations, although our findings imply that cat fleas should not be ignored by these programs as they could play a significant role as secondary vectors.     

陕西省鼠疫耶尔森菌MLVA分型研究

目的 掌握陕西省鼠疫耶尔森菌分离株的MLVA基因分型特征,阐明不同疫情年份菌株间的遗传进化关系,为今后陕西省鼠疫的监测防治工作提供科学依据。方法 采用MLVA(14+12)方法,对分离自陕西省鼠疫疫源地的66株鼠疫耶尔森菌进行基因分型,利用BioNumerics(Version7.6)软件对分型结果进行聚类分析。结果 66株鼠疫耶尔森菌分为A、B、C群,根据分离时间聚集成为相应群,A群包含42株菌,其中39株菌分离自2000-2001年,B群包含16株菌,其中15株分离自2006年,C群含8株菌,其中6株分离自1987-1988年。基因型分为19种,8个基因型为多菌株基因型,其他型为单菌株基因型。结论 陕西省鼠疫菌MLVA基因型具有多态性,不同疫情年份菌株主导的基因型不同,MLVA分型能够很好区分陕西省不同年代鼠疫菌株,可用于鼠疫菌株的溯源分析。     

Quick control of bubonic plague outbreak in Uttar Kashi, India

A localized outbreak of bubonic plague occurred in village Dangud (population 332), district Uttar Kashi, Uttaranchal, India in the second week of October 2004. 8 cases were considered outbreak associated based on their clinical and epidemiological characteristics; 3 (27.3%) of them died within 48 hours of developing illness. All the 3 fatal cases and five surviving cases had enlargement of inguinal lymph nodes. None of them had pneumonia. The age of the cases ranged from 23-70 years and both sexes were affected. No such illness was reported from adjoining villages. The outbreak was fully contained within two weeks of its onset by supervised comprehensive chemoprophylaxis using tetracycline. A total of approximately 1250 persons were given chemoprophylaxis in three villages. There was no clear history of rat fall in the village. No flea was found on rodents or animals. 16 animal serum samples were found to be negative for antibodies against F-1 antigen of Y. pestis. However, Y. pestis was isolated from two rodents (Rattus rattus and Mus musculus) trapped in the village. One case and three animal sera showed borderline sero-positivity against rickettsial infection. The diagnosis of plague was confirmed by detection of four fold rise of antibody titre against F-1 antigen of Yersinia pestis in paired sera of three cases (one of the WHO approved criteria of diagnosis of confirmed plague). This outbreak and the occurrence of earlier outbreaks of plague in Surat (Gujarat) and Beed (Maharashtra) in 1994 and in district Shimla (Himachal Pradesh) in 2002 confirm that plague infection continue to exist in sylvatic foci in many parts of India which is transmitted to humans occasionally. Thus, there is a strong need for the States to monitor the plague activity in known sylvatic foci regularly and have a system of surveillance to facilitate prompt diagnosis and treatment of cases to control the disease. This investigation highlights that with high index of suspicion the disease can be diagnosed early and mounting of supervised comprehensive response can prevent the disease to proceed to pneumonic stage where man to man transmission gets established and outbreak assumes larger dimensions.     

Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis

Plague, one of the most devastating diseases of human history, is caused by Yersinia pestis. In this study, we analyzed the population genetic structure of Y. pestis and the two other pathogenic Yersinia species, Y. pseudotuberculosis and Y. enterocolitica. Fragments of five housekeeping genes and a gene involved in the synthesis of lipopolysaccharide were sequenced from 36 strains representing the global diversity of Y. pestis and from 12-13 strains from each of the other species. No sequence diversity was found in any Y. pestis gene, and these alleles were identical or nearly identical to alleles from Y. pseudotuberculosis. Thus, Y. pestis is a clone that evolved from Y. pseudotuberculosis 1,500-20,000 years ago, shortly before the first known pandemics of human plague. Three biovars (Antiqua, Medievalis, and Orientalis) have been distinguished by microbiologists within the Y. pestis clone. These biovars form distinct branches of a phylogenetic tree based on restriction fragment length polymorphisms of the locations of the IS100 insertion element. These data are consistent with previous inferences that Antiqua caused a plague pandemic in the sixth century, Medievalis caused the Black Death and subsequent epidemics during the second pandemic wave, and Orientalis caused the current plague pandemic.     

云南鼠疫耶尔森菌基因分型研究

目的通过对来自云南省鼠疫自然疫源地155株鼠疫菌进行基因分型,了解鼠疫菌的进化规律。方法根据22个差异区段(differentregions,DFR)设计引物,PCR扩增鼠疫菌的每个DFR。结果滇西山地闽广沿海居民区黄胸鼠鼠疫自然疫源地137株鼠疫菌的基因型均为9型。滇西山地齐氏姬鼠大绒鼠鼠疫自然疫源地18株鼠疫菌,有10株菌为7型,8株菌为9型。结论滇西山地齐氏姬鼠大绒鼠鼠疫自然疫源地鼠疫菌的基因型为7型和9型,而滇闽广沿海居民区黄胸鼠鼠疫自然疫源地鼠疫菌的基因型主要为9型。两疫源地鼠疫菌在遗传关系上有亲缘性,后者可能由前者进化而来。     

用4对引物聚合酶链式反应检测鼠疫耶尔森氏菌的实验研究

目的用4对引物聚合酶链式反应(以下简称4-Prim er-PCR)来检验鼠疫耶尔森氏菌,对于探索鼠疫的快速诊断方法将起到推动作用。方法选择不同疫源地的40株鼠疫耶尔森氏菌;目的基因选择于与鼠疫耶尔森氏菌毒力因子有关的FI抗原质粒基因cafI鼠疫杆菌素Ⅰ基因、与色素沉着有关的质粒基因hm s以及染色体基因inv。结果该法所有的鼠疫耶尔森氏菌全部出现4对引物的预期扩增带;该试验在4 h内完成;结论四对引物鼠疫PCR法具有快速、特异、敏感等优点,可以用于鼠疫的快速诊断和流行病学调查。     

环丙沙星治疗家兔实验感染鼠疫疗效观察

目的观察环丙沙星治疗实验感染动物鼠疫疗效。方法实验感染鼠疫24h后的新西兰白兔按每日每公斤体重0.04g,2次静脉注射环丙沙星。结果环丙沙星治疗组动物全部治愈,停药后9d处死,鼠疫细菌学培养阴性。结论环丙沙星可用于鼠疫的临床治疗。     

Experimental plague in the California ground squirrel

In experiments to determine the current susceptibility to plague, it was demonstrated that 256 Yersinia pestis (a local strain of high virulence) were required to produce a 50% infectious dose (ID50) in California ground squirrels (Spermophilus beecheyi) that had been collected in southeastern Monterey County, California; 6,070 Y. pestis were required to produce a 50% lethal dose (LD50). (The LD50 was about 24 times the ID50.) The frequency of serologic response to the specific fraction 1 antigen of Y. pestis and mortality were dose-related. Approximately half of the squirrels inoculated with six to 6,070 Y. pestis survived without seroconversion, whereas antibody to specific fraction 1 antigen was always observed in squirrels that survived challenges of greater than or equal to 60,700 Y. pestis. However, titers never exceeded 1:64. The implications of these data for enzootic and epizootic transmission of plague in resistant squirrel populations are examined.     

治疗鼠疫药物的筛选

目的筛选治疗鼠疫的新型抗生素。方法采用纸片扩散(K-B)法进行鼠疫菌药敏试验;用环丙沙星、诺氟沙星、头孢曲松钠治疗感染鼠疫实验动物疗效观察;将新型抗菌药物应用于人间鼠疫病例临床治疗。结果药敏试验表明鼠疫菌对所试30种抗菌药物有20种高度敏感,以β-内酰胺类的敏感性最好,喹诺酮类次之,氨基糖甙类尚可,大环内酯类则较差;环丙沙星和诺氟沙星治疗实验感染动物鼠疫的治愈率为100%,头孢曲松钠的疗效则依据剂量不同其效果也不同,400、150、50mg/kg组的治愈率分别为45.16%、80.00%、93.30%;新型抗菌药物应用于鼠疫病例治疗可痊愈并缩短病程。结论环丙沙星、诺氟沙星、头孢曲松钠治疗感染鼠疫实验动物有较好疗效,用于人间鼠疫病人的治疗可缩短病程,减少链霉素用量。     

四川省鼠疫耶尔森菌CRISPR基因分型及地区分布研究

目的 对四川省鼠疫耶尔森菌(Yersinia pestis)做规律成簇的间隔短回文重复序列(Clustered regularly interspaced short palindromic repeats CRSIPR)基因分型和地区分布研究,为四川鼠疫防治提供科学依据。方法 对132株鼠疫菌培养和提取核酸,应用3对CRISPR引物对被试菌株DNA进行PCR扩增、测序和分析,确定四川省鼠疫菌的CRSIPR基因型。结果 132株鼠疫菌共发现17种spacer,包括YPa 9种、YPb 5种、YPc 3种,新发现的1种space阵列。所有鼠疫菌株被分为2个CRISPR基因簇(Cc3',Ca7),3个基因型(37'型、22型和sc01型)。其中石渠县青海田鼠型菌株基因型为37'型,石渠县人间鼠疫的菌株为22型,德格县旱獭型菌株基因型为22型,巴塘县、理塘县、雅江县和新龙县旱獭菌株基因型为sc01型。结论 四川省鼠疫菌菌株具有明显的地区分布特征。     

云南省勐海县人间鼠疫的判定及分析

云南省勐海县在人间鼠间歇５２年后于１９９２年７～８月再次暴发流行。经病原学和血清学调查，结果共确诊腺鼠疫患者１０例，并从黄胸鼠体分离到鼠疫菌５３株，从印鼠客蚤分离到鼠疫菌４株，检出１０份家狗鼠疫Ｆ１抗体阳性。分析表明：该地可能存在着鼠疫自然疫源地。传染源为黄胸鼠，传播媒介为印鼠客蚤，该地鼠密度、蚤指数升高是促成此次鼠疫流行的重要因素。     

Plague dynamics are driven by climate variation

The bacterium Yersinia pestis causes bubonic plague. In Central Asia, where human plague is still reported regularly, the bacterium is common in natural populations of great gerbils. By using field data from 1949-1995 and previously undescribed statistical techniques, we show that Y. pestis prevalence in gerbils increases with warmer springs and wetter summers: A 1 degrees C increase in spring is predicted to lead to a >50% increase in prevalence. Climatic conditions favoring plague apparently existed in this region at the onset of the Black Death as well as when the most recent plague pandemic arose in the same region, and they are expected to continue or become more favorable as a result of climate change. Threats of outbreaks may thus be increasing where humans live in close contact with rodents and fleas (or other wildlife) harboring endemic plague.     

Hereditary hemochromatosis restores the virulence of plague vaccine strains

Nonpigmented Yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout (Hjv(-/-)) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis. Unlike wild-type mice, Hjv(-/-) mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv(-/-) mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines.     

Plasmid composition and virulence-associated factors of Yersinia pestis isolates from a plague outbreak at the Paraiba State, Brazil

Pathogenic Yersinia pestis isolates were collected during a plague outbreak at the Paraiba State in 1986. The Y. pestis isolates were investigated for the presence of virulence-associated factors and plasmid content. All strains analysed were proficient in the expression of the VW and fraction 1 antigens, pigment adsorption and pesticin-fibrinolysin-coagulase production. A similar plasmid profile composed by four plasmid with molecular weight of 60, 44, 14.9, and 6.4 Megadaltons (MD) was found in all strains. DNA cleavage with EcoRI restriction enzyme further demonstrated the uniform plasmid content of the Y. pestis isolates. Seven additional Y. pestis strains, previously isolated in the same region but in an endemic state, showed the same plasmid fingerprint. The lack of any detectable difference between epidemic and endemic isolates as well as the value of plasmid fingerprints in epidemiology of Y. pestis is discussed.     

Pulmonic plague

One hundred years after Yersin discovered Yersinia pestis during the plague epidemic in Hong Kong in 1894, human plague still has not been eliminated. The epidemic in 1994 in India, a country where no cases had been observed since 1996, raised great concern. Plague is an epizootic bacterial infection caused by a Gram negative coccobacillus, Y. pestis, transmitted by the bite of infected fleas. Bubonic plague is the most common form. Other clinical presentations include asymptomatic plague, abortive plague, pharyngeal plague, septicemic plague, meningeal plague, and primary or secondary pneumonic plague which is observed in 5 to 20% of cases. Plague is a highly communicable disease between humans despite antibiotic therapy which has reduced mortality by 80%. The prognosis depends on early diagnosis. Streptomycin and cyclines are the gold standard treatment.     

1975-2007年青海省藏系绵羊鼠疫流行病学分析

目的 分析青海省1975-2007年来藏系绵羊鼠疫流行特征,为预防和控制绵羊鼠疫提供科学依据.方法 对1975-2007年青海省鼠疫监测报告、人间鼠疫疫情病例等资料进行回顾性总结、分析.结果 1975-2007年从藏系绵羊体内共分离出鼠疫菌14株,其中玉树县分离出10株,囊谦县2株,治多县和德令哈市各1株;1975年和1979年分离鼠疫菌各2株,1996-2007年共分离10株.由藏系绵羊作为传染源引起人间鼠疫10起,鼠疫病例25例,死亡13例,其中玉树县、玛多县、囊谦县、杂多县、玛沁县分别发生3、2、2、2、1起,发病人数分别为6、6、8、4、1人,死亡人数分别为4、4、1、4、0人,其他县(市)无病例报告;其中腺鼠疫9例,肺鼠疫6例,败血型鼠疫3例,肠鼠疫1例,其他继发性鼠疫病例为6例.在25例病例中,1例为汉族农民外,其他24例均为藏族牧民,感染方式中为剥、食病死于鼠疫的绵羊20例,接触病人5例.发病季节为6-11月份,其中11月份发病11例.结论 从1996年开始,绵羊鼠疫流行与旱獭鼠疫一致,呈明显的上升趋势,局部地区牧场出现鼠疫爆发流行.近10年来虽然没有藏系绵羊引起人间鼠疫,但绵羊间鼠疫波及人间的可能性仍然存在.因此,及时、有效的处理和控制旱獭鼠疫,普遍提高牧民群众防病意识和自我保健能力是预防绵羊和人间鼠疫发生的关键.