YERSINIA PESTIS (a.k.a. Pasteurella pestis)

 
Table of contents :

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Epidemiology Genomics Proteomics Transmission Pathogenesis Symptoms & signs Laboratory examinations Therapy Prevention Web resources

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Epidemiology : > 2,000 years ago, a plague gripped the Greek city of Athens. Ultimately, as much as a third of the population succumbed and the devastation, which helped Sparta gain the upper hand in the nearly 30-year-long war between the city-states. That much Thucydides--an ancient historian, general in the war and plague victim who recovered--conveys in his History of the Peloponnesian War. But he did not leave a precise enough description to decide definitively whether the disease was bubonic plague, smallpox or a host of other ailments. Now DNA collected from teeth in an ancient burial pit points to typhoid fever. In 1994 researchers discovered a mass grave containing at least 150 bodies, including those of infants, deep beneath the Kerameikos cemetery in Athens. Contrary to Greek custom, the arrangement of the interred bodies grew progressively more haphazard as they were piled on top of one another and few burial offerings, which included a small number of vases, were left with the hastily buried corpses. Scientists dated the vases to roughly 430 B.C., which is coincident with Thucydides' report of when the plague broke out in the city. 3 random teeth samples were picked from the plague victims and extracted the dental pulp. This soft core under the hard tooth covering can store pathogens and other information about the body for centuries. The researchers also tested 2 modern teeth to make sure that no false results were indicated. Proceeding randomly through a list of possible causes, Papagrigorakis' team tested the pulp for the bacteria responsible for the bubonic plague, typhus, anthrax, tuberculosis, cowpox and catscratch disease before finding a match in Salmonella enterica serovar Typhi--the bacteria responsible for typhoid fever.
Typhoid fever--transmitted by contaminated food or water--causes fever, rash and diarrhea, all closely matching Thucydides' account of the terrible plague. The only thing that does not match up is the quick onset of the disease, because modern cases of typhoid fever typically take longer to gestate. This inconsistency may be explained by a possible evolution of typhoid fever over time. Considering the overcrowding and unsanitary conditions especially regarding the water supply within the walls of the besieged Athens, a typhoid epidemic would have been likely to break out^ref. In the 14^th century plague killed one third of Europe's population : around 1348, the population of England was estimated to be about 4 million, and within 2.5 years about 1/3 had died from plague, sometimes called The Great Dying. One third of the residents of Florence died in the first 6 months of the epidemic and as much as 75 percent died in a single year. Venice lost 60 percent of its population over 18 months that the epidemic raged. The last pandemics started in 19^th century in China and killed 12 millions people. In 2003, 9 countries reported 2118 cases and 182 deaths, almost all in Africa. Plague is still present in ... :

• Africa (where some people live in rat-infested villages, the death toll is the highest in the world) :
• Uganda : 19 cases, including 9 deaths, in Masindi district, Mutunda sub-county, in February 2007^ref
• Democratic Republic of the Congo : the first cases of plague in this country were reported in Ituri (632 cases during 1928 to 1959) and North Kivu (190 cases during 1938 to 1961). Plague is currently or recently endemic to Haut Zaire Province and Ituri Sub-region (Managi Administrative Zone). A graph of plague incidence and rates per 100,000 population in DRC^ref. Note that DRC has accounted for an increasing proportion of plague cases in Africa in recent years^ref. Notable outbreaks :
• 2004 : an outbreak (1042 suspect cases, 58 fatal) was reported in Ituri.
• 2005 : an outbreak (134 cases, 61 fatal) of pneumonic plague was reported in a diamond mining area of Zobia, Kisingani. Pneumonic plague affected 130 suspect cases, including 57 deaths, in Zobia (a town that was home to at least 7000 diamond miners, some 300 km (186 miles) north of the provincial capital Kisangani), Bas-Uele district, Oriental province in eastern Congo, since 15 Dec 2004 to Mar 2005. The disease might have spread when 4000 of the miners left Zobia and disappeared into the bush 2 weeks ago, fleeing the disease and clashes involving various factions of the security forces guarding the mining area^ref. As of 19 Jun 2006, WHO has received reports of 144 cases of suspected pneumonic plague, including 22 deaths in Ituri district, Oriental province. Suspected cases of bubonic plague have also been reported, but the total number is not known at this time. Ituri is known to be the most active focus of human plague worldwide, reporting around 1000 cases a year. The 1st cases in this outbreak occurred in a rural area, in the Zone de Sante of Linga, in mid-May 2006. There are now 12 zones in Ituri -- with total population of almost 100 000 -- affected by the plague outbreak. Bubonic plague, a less contagious form of the disease, is endemic to Ituri.^{ref1, ref2, ref3}.
• 2006 : outbreak of pneumonic plague in the northeast Orientale (also written Oriental or Eastern) province^ref. 1400 cases as of September, 600 of them in June and July, near Lake Albert in northeast Ituri district, where militias are still fighting 3 years after the end of Congo's 6-year war, the world's deadliest conflict since World War Two^{ref1, ref2}. Since 16 Aug to 4 Oct 2006, pneumonic plague claimed 29 lives and infected another 500 people in the Pawa and Wemba areas of Isiro District. A few cases were recorded in the Reti, Ringa and Zobia zones of the Bas-Uele District^ref. According to WHO, from 31 Jul to 8 Oct 2006, 626 suspected cases including 42 deaths have been reported  in 2 health zones in Haut-Uele district, the majority reported from Wamba health zone in Oriental province in the northern part of the country^ref. 24 cases and 6 deaths have been confirmed dead following a suspected outbreak of plague in Logiri sub-county, Arua district, inUganda, near the north-eastern Congolese border, a hotbed for the disease^{ref1, ref2}. As of 29 Sep 2006, WHO received reports of a suspected pneumonic

plague outbreak in 4 health zones in Haut-Uele district, Orientale province in the northeastern part of Congo DR. The local authorities on 11 Nov 2006 reported 1174 suspected cases, including 50 deaths. > 50 samples have been collected and analyzed; however, the diagnosis of plague has not been finally laboratory confirmed^ref
• Asia : carriers of plague in central Asia are often Camelidae getting their feet stuck in gerbil burrows, picking up the disease and passing it on to their owners
• endemic in Mongolia
• the last case of plague was registered in Russia in 1979
• Kazakhstan was the only former Soviet republic reporting plague : this is, in part, because the Soviet Union actively suppressed all reports of plague outbreaks. In fact, in 1949-50, there was a sizeable outbreak of pneumonic plague, which may have killed upwards of 100 people, according to Dr. Lev A. Melnikov, who was an eyewitness. Melnikov attributed the outbreak to the dangerous plague reservoir Rhombomys optimus (the great gerbil). The first reports were from 1989. In the 1989-1997 period, 11 cases with 4 deaths were reported from the Guriev and Kzyl-Orda regions^ref
• Turkmenistan : an epidemic of plague began in May 2004 : > 20 deaths (7 in Mari, Ashgabad ) after 25 years of absence
• Russia : In the Russian Federation, natural foci of plague in rodents have been recorded [historically] in several regions, namely the republics of Chechnya, Kabardino-Balkaria, Karachaevo-Cherkessia, Kalmykia and Dagestan, and the regions Stavropol and Astrakhan, all located in the

South Federal District of Russia. Cases have also been observed in the republics of Tyva and Gorniy Altay. Since 1984, no plague cases have been recorded in humans in Russia^ref. However, abnormally warm weather and a sharp increase in the rodent population enhance the danger of an epidemic in pets and humans in many regions of the country
• rural Americas (< 1.4% of world cases annually) :
• North America : southwestern USA. The introduction of plague into the US via California in 1900^{Lipson LG, 303-310} led to the spread of the infection eastward across about halfway across the country, but it did not reach the east coast : however, person-to-person transmission is extremely rare; the last such transmission in the USA was reported in 1925. During 1990-2005, a total of 107 cases of plague were reported in the USA (CDC, unpublished data, 2006), a median of 7 cases per year. The increased plague activity in 2006 is consistent with the predicted relationship between climate and the frequency of human plague in the southwestern USA. 2 consecutive Feb-Mar periods with high precipitation and an intervening cool summer predicts increased cases of plague the next summer; this effect is thought to lead to increased reproduction and survival rates among rodents and fleas^ref. During 1990-2005, a total of 81 (76%) of 107 plague cases in the USA were classified as primary bubonic plague, 19 (18 %) as primary septicemic plague, and 5 (5%) as primary pneumonic plague; 2 (2%) were not classified (CDC, unpublished data, 2006). 11 (10%) cases were fatal. In 2006, 5 (38%) of the 13 patients had primary septicemic plague, underscoring the need for clinicians to consider this diagnosis in patients who do not have an obvious bubo. Although endemic in rodent populations the western USA, plague is most commonly seen in 2 regions:
• firstly :
• New Mexico (northern) : 246 cases of human plague, including 31 fatalities, since 1949, an average of 6 cases per year with a range of 0 to 27 cases. The last plague fatality occurred in 1994 in a Rio Arriba County child. 1 case was reported in Torrance County in 2003 and 2 cases were reported in 2002 in Santa Fe County. There were no reported cases of human plague in the state in 2004. There have been cases of plague in animals reported in 2005 in Rio Arriba, Santa Fe, Taos, Los Alamos, Colfax and Bernalillo Counties : an adolescent from Santa Fe County was affected by bubonic plague in July 2005 (rock squirrels collected in the vicinity of the patient's home were heavily infested with fleas, and fleas were collected from burrows in the area). 7 cases in 2006^ref. 4 cases in 2007 (a man from San Juan County who recovered in late April 2007, a woman from Torrance County who is still hospitalized, a 3 year old Bernalillo County boy who died of bubonic plague in June^ref, and a 50-year-old woman who has recovered after hospitalization^ref)
• northern Arizona
• southern Colorado :
• 2001-2003 : absent
• 2004 : 3 cases (1 death), none in La Plata County
• 2005, 2 of the 3 cases in the state were found in La Plata County
• 2006 : 4 cases in humans^{ref1, ref2}, 43 cases in animals^ref
• Utah
• Texas : the last recorded human case of plague was in 1993 in a Kent County resident : in 2004 it has been isolated near the Midland-Glasscock counties border in West Texas and in fleas from wild prairie dogs in Dallam County in the Texas Panhandle. 1 case in 2006^ref
• secondly, California (2 cases in 2006^ref), southern Oregon, and western Nevada^ref
The last urban plague epidemic in the USA occurred in Los Angeles in 1924-25. Since then, human plague in the USA has occurred as mostly scattered cases in rural areas (an average of 10 to 15 persons each year).
The FBI and CDC are investigating the disappearance from a New Jersey research lab of at least 3 mice carrying a deadly strain of plague. The rodents have been missing for 2 weeks. Sources say FBI agents and bioterrorism experts are interviewing and polygraphing employees at the University of Medicine and Dentistry in Newark, N.J., the location of the lab run by the Public Health Research Institute, a leading center for research on infectious diseases. There are no indications of terrorism. The FBI responded to the matter, and we dedicated a great number of agents as well as a large number of resources to the investigation, which is still ongoing : we're satisfied that there is no public safety risk and there doesn't seem to be any nexus to criminal activity or terrorism. New Jersey officials also are downplaying the health risk. They believe the infected mice probably died quickly. However, some government officials are deeply concerned about what the case says about security of some of the most deadly infectious disease projects and research labs. One source admitted that while officials are saying there is minimal health risk, no one can be entirely certain. There is minimal information provided, but "3 mice" possibly represents only a single box of such animals in a BSL-3 facility. Occam's razor would indicate a stupid mistake, but as the loss was noted 2 weeks ago, all probable explanations will have been investigated and the answer is still being sought. If the mice had died, been incinerated, and the box emptied, cleaned, and sterilized, all traces will have been lost, along with any memories of what had happened. But the card for the box should have been kept along with any comments. If this were a break-in by Friends of the Earth, there would have been ancillary damage unless this has been suppressed. They have the experience to carry out such a "raid" -- if raid it was. Clearly those involved are assuming that the mice have died, if they were removed. Odd, but those with experience of such facilities probably have plenty of pre-Homeland Security war stories.
3 mice infected with the bacteria that cause bubonic plague have gone missing from a laboratory in Newark, New Jersey. Authorities have launched a search for the animals and an investigation into how they might have escaped. But researchers are quick to add that the mice, even if they are on the loose, pose little risk to the public. At this point we are satisfied that there is no public-safety risk, but the investigation is ongoing. The mice, which carried Yersinia pestis, were being studied at the Public Health Research Institute as part of a vaccine experiment. The institute, which handles about 10,000 mice a year, had a total of 24 plague mice in this experiment. Eight of these had not been vaccinated, 8 had been given the best current vaccine, and 8 had an experimental version: each group is missing a mouse, and has been for the past two-and-a-half weeks. There are many potential explanations. The rodents could have been stolen or accidentally incinerated along with bedding from the cages. It is even possible that they ate each other, as mice are known to do this when they have plague. The institute's director, David Perlin, acknowledges the possibility of theft, but says he thinks it is more likely to be an honest mistake. Some estimate that research into plague and plague vaccines has tripled in the United States following fears of bioterrorism sparked by the 11 September 2001 attacks. This trend means there are more infected animals scattered about the country that could, potentially, go missing. But experts have expressed surprise that such mice could actually escape. Research on plague takes place under tight security, in labs categorized as BSL3 and the entire lab is under video surveillance. The CDC is working with the FBI and local officials to see what happened. If the mice did actually escape from the lab, they would have quickly died from the disease. And the animals' bodies wouldn't be expected to pose a risk after decomposing for several days. Having plague running wild is not as unusual as some might think
A Los Angeles woman is being treated for bubonic plague, the 1st case of the age-old pestilence in the county since 1984, health officials announced Tue 18 Apr 2006. She may have contracted the disease from fleas in the area around her Country Club Park neighborhood. Although human cases of the plague are uncommon, it is endemic to ground squirrels and some rodents in parts of the Angeles National Forest, Tehachapi, Lake Isabella and Frazier Park.^ref
• South America :
• Peru : northern
• Bolivia : in the Department of La Paz
• Brazil : several areas in northeastern
• Ecuador : the Chimborazo Province since 1977^ref. 200-350 cases per year were reported from 1961 to 1966. 2 outbreaks of pneumonic plague occurred in Guamote county/canton, Ecuador in 1998 (160 cases^{ref1, ref2}) and 2004. Plague has been reported in this general region since first reports of cases in Chimborazo in 1977. There was a major outbreak in 1998 (approximately 160 cases) and 14 cases reported in 1999^ref

..., causing 1,000-4,000 deaths per year. Worldwide, there were nearly 2,700 human cases and 175 deaths from plague in 2001. The following children's' rhyme (of unclear origin) has elements that can be interpreted as being related to plague, epidemic in the Middle Ages.

Ring around the rosies,
A pocket full of posies,
Ashes, ashes!
We all fall down

Rosies represent rosary beads, used to (hopefully) provide divine intervention against the disease. Plague victims may emit a rather strong and objectionable odor; flowers (posies) could be carried to mask the smell.  Ashes are all that was left of a burnt corpse (in the Middle Ages). "All fall down" reflects the profound death rate. Alternatively, for the last 2 lines of the rhyme: The 3rd line can be replaced with "A Tishoo, a tishoo," which represents the sneezes of the victims of pneumonic plague which are infectious to others. To be sneezed on by them was a sure death sentence for all. The death rate for those who acquire pneumonic plague directly is almost 100%.
Genomics : as many as 13% of Y. pseudotuberculosis genes no longer function in Y. pestis. The number of insertion sequence (IS) elements (DNA sequences capable of interfering with gene expression) has dramatically expanded in Y. pestis, delineating the probable role of IS expansion in the elimination and modification of preexisting gene expression pathways
Proteomics :

3 biovars :
• antiqua
• orientalis
• medievalis
microcapsule, no flagella.
• PLD is required for survival in the midgut of rat flea.
• > 19 different antigenic components. Virulence factors (all plasmid-encoded) :
• fraction 1 (F1) capsular antigen is the principal antigen involved with both virulence and immunity. Although some experts consider a titer of antibody to F1 (determined by PHA) of at least 1:32 to be indicative of protection, the U.S. ACIP states that the minimum titer of antibody to F1 capsular antigen (determined by PHA) indicative of adequate protection against plague infection is 1:128 in animals.
• V antigen
• W antigen
• exotoxin
• endotoxin
• pesticin
• protease
• coagulase
• fibrinolysin

Transmission : a zooanthroponosis :

• reservoir :
• Rattus rattus and Rattus norvegicus, great gerbils (Rhombomys opimus)
• less commonly other animals may be exposed to plague infection either by feeding on infected carcasses or by becoming infested with infected fleas
• Lynx rufus
• Felis catus (extremely sensitive : when sylvatic outbreaks occur in rodent populations, domestic cats can be infected by fleas on the rodents or by direct contact with infected rodent tissues as they chomp on squirrels or other rodents. The incubation period in cats may be short, a day or 2, and marked by a fever of up to 41.5°C and lymphadenopathy. Typical buboes often occur in the head and neck, which can be mistaken for cat fight abscesses. Bubonic plague is of zoonotic concern as individuals may contract disease from either infected fleas or contact with purulent discharges from ruptured bubos or blood from the cat. An even greater threat occurs when the disease in cats progresses to pneumonic plague. This has been documented in cats, including transmission to veterinarians and owners. Antibiotic treatment is effective in cats, but the threat of plague is only one of many reasons that people should keep their pets free of fleas. There are many good flea control products and methods of eliminating fleas from the animal as well as the yard.  If an animal owner is having trouble with fleas, a visit to the veterinarian may be in order. If an animal has a swelling, extra caution should be taken by the animal owner as well as the veterinarian. The swellings may rupture and expose the owner and/or the veterinarian to the plague agent. The disease is treatable with antibiotics, so a trip to the veterinarian may be in order)
• Canis familiaris (considered to be less susceptible than cat), ground squirrels (sylvatic plague in the western United States)
• marmots
• Canis latrans
• Odocoileus hemionus
• Cynomys parvidens (often considered sentinel animals because of their susceptibility to the organism)
• Oryctolagus cuniculus (contact with infected rabbit carcasses has been a significant source of infection for man during the winter)
• Sylvilagus audubonii
• Neotoma spp.
• of the domestic animals, Bos taurus, Equus caballus, Ovis aries and Sus scrofaare not known to develop plague
• Capra hircus and Camelidae have reportedly developed clinical illness, and there have been several human outbreaks of plague attributable to ingestion of camel meat infected with Yersinia pestis in Middle Eastern and Central Asian countries^ref
• rock squirrels (Spermophilus variegates) are closely related to California ground squirrels and are the most significant plague host in Colorado. Their principal flea Diamanus montanus is an aggressive parasite and will readily bite other animals and people. One human case was reported in conjunction with a previous outbreak of plague among urban populations of fox squirrels (Scirus niger) in Denver during 1968.
• bite of infected vectors : Xenopsylla cheopis, Nosopsylla fasciatus, Leptopsyllaspp., Pulex irritans, Anomiopsyllus nudatus, Aetheca wagneriand Pulex simulans. Fleas become infected upon feeding on the blood of a rodent suffering from bacteremic infection. The bacteria are restricted to the alimentary tract of the flea, where they multiply in the midgut. The bacteria may form large brown clumps that extend throughout the midgut, esophagus and proventriculus, a valve-like chamber situated between the esophagus and the midgut. The clumps increase in mass over a few days until the proventriculus is blocked. The "blocked" flea then feeds on blood, but the meal is unable to pass into the stomach. The flea continues to attempt to feed, but as it futilely sucks blood from the host, the blood meal, mixed with bacteria from the foregut, is regurgitated into the mammal. As many as 24 000 bacilli may be transmitted in a single attempted feeding (Burroughs, AL: Sylvatic plague studies. The vector efficiency of nine species of plague compared with Xenopsylla cheopis. J Hyg 1947;45:371-96)
• contact with breath or ingestion of infected reservoirs
• human-to-human infection usually occurs by inhalation of plague bacilli–laden droplet aerosols

Pathogenesis : plague bacteria are thought to inject so called effector Yops via the type III pathway into host cells. The identity of host cells targeted for injection during plague infection is unknown. Using Yop b-lactamase hybrids and fluorescent staining of live cells from plague infected animals, it was found that Y. pestis selected immune cells for injection. In vivo, dendritic cells, macrophages and neutrophils were injected most frequently, whereas B and T lymphocytes were rarely selected. Thus, it appears that Y. pestis disable these cell populations to annihilate host immune responses during plague^ref. Y. pestis is able to replicate in macrophages that are activated with IFN-g after infection (postactivated). A region of chromosomal DNA known as the pigmentation (pgm) locus was required for replication in postactivated macrophages, and this replication was associated with reduced nitric oxide (NO) levels but not with reduced iNOS expression. Y. pestis pgm replicated in iNOS^-/- macrophages that were postactivated with IFN-g, suggesting that killing of Dpgm Y. pestis is NO-dependent. A specific genetic locus within pgm, which shares similarity to a pathogenicity island in Salmonella, was shown to be required for replication of Y. pestis and restriction of NO levels in postactivated macrophages. Intracellular Y. pestis can evade killing by macrophages that are exposed to IFN-g and identify a potential virulence gene encoded in the pgm locus that is required for this activity^ref.

=> plague / pest / pestis :

• bubonic or glandular plague / pestis bubonica (85-90% : incidence : 1,000-3,000 / yr ; lethality : 15-30%, none if treated with antibiotics) : 2-15 days incubation => abrupt onset of fever, chills, weakness, and headache, followed by regional lymphadenitis (malignant buboes => secondary buboes undergo necrolysis => hemorrhages), most often the femoral > inguinal (90%), axillary, and cervical nodes => suppuration, associated with a marked hemorrhagic tendency (hemorrhagic plague) and the development of DIC and necrotic purpura and extensive symmetrical gangrene (which may have led to the epithet “black death”). Local bacterial proliferation is sometimes evident (4-10% of cases) in the form of an abscess or ulcer at the site of infection. Usually heralded by very severe pain within 6-8 hours after the onset of constitutional symptoms, the bubo becomes evident within 24 hours. The bubo may be so tender that semicomatose patients will posture in a way to attempt to decrease pressure on the swelling. The bubo may not be evident in the 1st few days of symptoms. Furthermore, involvement of deeper lymph nodes may not be visible. In these cases, abdominal pain suggestive of appendicitis, colitis, enteritis or cholecystitis may be described. In such cases, tenderness upon abdominal palpitation will be misleading and may result in hazardous exploratory surgery and a potentially lethal delay in specific antimicrobial therapy (McGovern, T. W. and Friedlander A. M. Plague. In Zajtchuk R. and Bellamy R.F. (eds.) Textbook of Military Medicine: Medical Aspects of Chemical and Biological Warfare. Office of the Surgeon General, Borden Institute, Washington, D.C., pp 479-502)

Therapy : IM streptomycin is the first line treatment, though IM or IV gentamicin is frequently used. IV or po chloramphenicol, tetracycline or doxycycline are also used over a 7-10 day period, reducing mortality from 60% to less than 15% => recovery (expecially from pestis minor / ambulatory plague / parapestis / pestis ambulans : a mild form of bubonic plague, usually occurring only in endemic areas, with lymphadenitis, fever, headache, prostration, and a short course) or hematogenous dissemination => suppurative foci throughout the body =>
• septicemic plague / pesticemia / pestis siderans / plague septicemia / siderating pestis / pestis fulminans / pestis major : acute fulminating, high-density bacteraemia occurring in the acute stage of bubonic plague (within day 6-7), or as a so-called primary infection that may present and result in death before the appearance of buboes or of pulmonic manifestations
• meningeal plague / plague meningitis => coma vigil / "typhoid status"
• secondary plague alveolar pneumonia, which is also the contagion source for ...
• primary pulmonic or pneumonic plague / plague pneumonia (1% of natural plague presentations) : a rapidly progressive, highly contagious alveolar pneumonia due to inhalation of droplet nuclei expelled during coughing (from infected animals or other humans with pneumonic plague) in which there is extensive involvement of the lungs and productive cough with mucoid, blood-stained (hemoptysis), foamy, plague bacillus–laden sputum, with incubation period ranging from some hrs up to 5 days => 100% lethality in < 4 dd due to septic shock => coma if antibiotics aren't administered within 24 hours. Patients with primary pneumonic plague generate large quantities of infectious aerosols that pose a significant risk to close contacts. CDC guidelines identify contacts within 2 meters as being at greatest risk and do not consider the organism likely to be carried through air ducts or vents. Persons who have been in contact with pneumonic plague patients or handling potentially infectious body fluids or tissues without appropriate protection should receive preventive antimicrobial therapy with tetracyclines, quinolones, or chloramphenicol
• pharyngeal plague / plague pharyngitis

It is considered by CDC as a category A biological weapon.
Laboratory examinations : dipstrip rapid detection test (RDT) for F1 antigen in blood, bubo pus, or phlegm
Prevention :

• local officials could simply assess numbers of great gerbils (Rhombomys opimus)  and cull them during an upswing, rather than capturing the animals and performing expensive lab tests as they now do. As shown in Kazakhstan You could know about an outbreak 2 years in advance upswing, rather than capturing the animals and performing expensive lab tests as they now do^ref. The disease tends to crop up around 18 months after a heavy winter rainfalls that could have fed the plants on which rodents nibble
• killed vaccine

Web resources :

• Plague at eMedicine
• Plague at CDC and DVBID