Epizoology and Response to the Bioweapon Use of the Organism, Yersinia pestls, in Commensal Rodents

JeO'N. Borchert Genesis Laboratories, Inc., Wellington, Colorado

ABsTRAcr: The increased·risk ofterrorism with biological agents has been well documented. In response, the United States has established an extensive infrastructure to counteract dehberate disease epidemics that would follow bioterrorism attacks. The plague organism, , has been identified as a Category A biological agent by the Centers for Disease Control and Prevention. The response to the use of Y. pestis as a bioweapon, aerosoli7.ed and released to a target population, would first involve the treatment and containment of the disease in humans. As the initial impacts of the first round of human infections occur, the possl'bility exists that the disease could infect commensal rodent populations. Ifthe disease were to pro~ in rodents, the rodents would suffer mortality and their plaguo-infected fleas would seek new hosts, potentially including human hosts, and cause a second disease epidemic in humans. This paper outlines the epizoology of the bioweapon use of Y. pestis to commensal rodents, identifies U.S. localities ofconcern, and suggests control and surveillance strategies in response to a biotem>rism attack of this nature.

KEY WORDS: bioterrorism, commensal rodents, piague, Rattus spp., Yersinia pestis

Proc. 21• Vertebr. Pest Conf. (RM. Tmun and W. P. Gon:nz.cl, Eds.) Published at Univ. of Calif., Davis. 2004. Pp. 209-216.

INTRODUCTION pandemic likely originated in East Africa, traveled north Plague, caused by the bacterial organism Yersinia along the Nile to Egypt, then to Palestine and throughout pestis, has been endemic in rodent populations United the Mediterranean region. Many believe that this States since the end of the 1911a Century and has the endemic was influential in the fall of the Roman Empire. potential to cause widespread epizootics in wild and This pandemic was spread by flea-borne (bubonic) commensal rodents. In humans, the disease is acutely transmission of the disease resulting from die-offs of febrile and has the potential to cause high mortality unless rodents (Politzer 1954, Gage 1998). The second promptly diagnosed and subsequently treated. There are ~demic, known as the "", occurred in the three clinical forms: the bubonic form, characterized by 14111 Century and was the cause of 50 million deaths, half swollen lymph nodes (buboes); the septicemic form, in Europe and half in Africa and Asia. This plague characterized by the proliferation of Y. pestis in the pandemic likely originated in Central Asia among bloodstream; and the pneumonic form, occurring as a marmots and spread to Europe along the Silk Road secondary complication of septicemic plague or as a (McEvedy 1988). Unlike the first pandemic, this result ofinhalation ofrespiratory droplets (Gage 1998). pandemic was driven not only by flea-borne transmission Bioterrorism is defined as the deliberate release of of the disease but also was driven by pneumonic transfer living organisms to inflict harm directly or indirectly to a of the disease among humans. This pandemic caused population (Meyerson and Reaser 2003). Yersinia pestis fundamental changes in European social and economic is defined as a Category A biological agent by the Centers systems and was the source of subsequent smaller plague for Disease Control and Prevention (CDC) and is outbreaks in Europe and Africa in the following centuries, considered to be one of the most serious, because of its often with equal ferocity (Politzer 1954, Gage 1998). The potential to cause widespread disease and death and to be last large pandemic, called the ''Modem Pandemic", spread person to person (CDC 2000, Rotz et al. 2002). If occurred in Hong Kong in 1894 and spread rapidly the plague organism were to be used as an agent of throughout the world, carried by commensal rats on bioterrorism against a human population, there exists the merchant steamships. Within 10 years, plague had chance that the organism could become established in entered 77 ports on 5 continents: 31 in Asia, 12 in rodent populations near the target human populations. Europe, 8 in Africa, 4 in North America, 15 in South After the initial implications ofthe human infection, ifthe America, and 7 in Australia. Epidemics resulted on every disease were to progress in rodent populations to affected continent and caused over 12 million deaths, epizootic capacity, there is the posstoility that a resulting most in India. Scientific study during this last pandemic "secondary" epidemic in humans could occur. resulted in the identification of the causative agent, Yersinia pestis, by Alexander Yersin in 1894 in Hong NATURALLY-OCCURRING PLAGUE Kong. Fleas also were identified as the primary vector of Throughout history, plague has been a devastating plague, and the role of commensal rats was recognized in disease that affected numerous people. The disease was the outbreaks of human plague (Politzer 1954, first characterized in the Bible (1 Samuel, ch. 5 - 6) circa Tikhomirov 1999, Gage 1998). Overall, the incidence of 1320 B.C. The first large scale pandemic, known as plague has decreased since these epidemics, due to the Justinian's plague, occurred about 540 AD. in Asia, improvement of living standards in many nations of the Africa; and Europe and caused 40 million deaths. This world. In addition, the extensive use of insecticides for 209 the control of malaria may have played an important role the U.S., the most common wild rodents associated with in many countries as a means of indirectly controlling flea plague epizootics are ground squirrels of the genus populations (Akiev 1982). Spermophilus, prairie dogs of the genus Cynomys, chip­ The first two epidemics of plague in the U.S. occurred munks of the genus Tamias, and woodrats of the genus in San Francisco in 1900 (121 cases and 118 deaths) and Neotoma. Enzootic hosts include the deer mouse, 1907 (186 cases and 92 deaths), caused by both rat-borne Peromyscus maniculatus, and the vole, Microtus and pneumonic spread. Smaller plague epidemics in San ca/ifomicus (Gage et al. 1995, Gage 1998). Francisco and surrounding areas resulting from Rattus rattus continued to occur despite rodent and flea control YERSIMA PF.STIS AS A BIOWEAPON and public health campaigns. Rat-associated human Yersinia pestis is of great concern as a bioweapon outbreaks also occurred 7 times in 6 port cities along the because of its worldwide availability, capacity for mass West Coast and Gulf Coast (Link 1955, Politzer 1954). production, and the potential for it to be aerosolized. These outbreaks were both rat-borne and has the potential to cause hysteria in the target human-to-human transfer. Since the 1920s, there have population as evidenced by the 1994 outbreak of plague been no commensal rat-associated plague cases in the in India, which caused thousands ofpeople to flee the city United States (Gage 1998). Although introduced into and misinformation to flourish among citizens. Agents of ports on the eastern seaboard, the disease failed to bioterrorism can cause fear so extreme that social become established in urban or wild rodent populations or infrastructure can be disrupted, causing a crippling of a cause disease in humans (Antolin et al. 2002). nation's economy (Raza et al. 1997, Hall et al. 2003). The existence of epizootic plague in wild rodents was Recently, two human plague cases identified in New suspected as early as 1903 in California and eventually York City gained a national response and national became established in California ground squirrel reaction as a possible bioterrorism-related event. The (Spermophilus beecheyi) populations. A massive effort cases were later identified as being of sylvatic,;in origin, was undertaken to eradicate ground squirrels potentially contracted from the individuals' residence in ''New harboring the disease via rodenticides and vigorous Mexico (CDC 2003). shooting campaigns. Despite these efforts, by the 1940s Plague was first used as a bioweapon in the 14111 plague had become established throughout the American Centwy during a dispute between Muslims and Christians West (Link 1955). . in the port city of Crimea, in what is now the Ukraine. Plague is found routinely in Asia, Africa, and the Muslim Tartars became infected with plague and victims Americas and continues to cause epizootics and dying from the disease were catapulted at Christian epidemics in these areas. Although introduced, some­ sailors. The Christians subsequently fled back to Italy. times with ferocity, plague is no longer common in During the last centwy, plague was developed as a Europe. The disease failed to become established in potential bioweapon in the United States and other Australia and was never discovered in Antarctica. Areas countries. During the 1940s, Japan experimented with most commonly affected in the world include the tropics dropping plague-infected fleas (Pulex irritans) from and subtropics and warmer areas of temperate countries. airplanes as well as incorporating fleas into bombs. This From 1954-1997, human plague was recorded in 38 method was found to be ineffective, as the fleas suffered countries, 7 of which were affected virtually every year mortality during the explosions. During WWII, Japan (Tikhomirov 1999). During the periods of 1978-1997, dropped a mixture ofpaper, rice, cotton, wheat, and other Africa reported the largest numbers of plague cases and material (as well as presumably infected fleas) from deaths in the world. Madagascar, Kazakhstan, and Viet­ airplanes onto the city of Changteh in Hunan Province, nam are also endemic for plague (Tikhomirov 1999). In China, an area that had never previously experienced a the United States, plague affects the 12 western states of plague outbreak. Within two weeks, residents of the Arizona, California, Colorado, Idaho, Montana, Nevada, town began dying of plague. Likewise, two months after New Mexico, Oklahoma, Oregon, Texas, Utah, and the mysterious attack, rat populations began to die from Washington. The disease is concentrated in two primary the disease. Two additional releases of the plague foci in the U.S. The southwestern focus includes New organism may have occurred in China as the result of Mexico, northeast Arizona, southern Colorado, and similar attacks (McGovern and Friedlander 1997). southern Utah. The Pacific focus includes California and Although it signed the Biological and Toxin Weapons southern Oregon (Barnes 1982). For the period 1987 - Convention in 1972, the Soviet Union (and former Soviet 2001, 125 plague cases were reported in the U.S. (WHO Union countries) was especially active in developing 2003). The majority of cases in the U.S are reported from plague as a bioweapon, including the incorporation of the the tri-state area of Arizona, Colorado, and New Mexico, organism into warheads and the production of hundreds with most cases occurring in New Mexico (Craven et al. of tons of material (Kortepeter and Parker 1999, Davis 1993). Approximately 80% of U.S. plague exposures 1999). The U.S. ceased production of bioweapons in occurred in peridomestic environments, particularly those 1969 (Kortepeter and Parker 1999). The deleterious that provided food and harborage for rodents (CDC effects that bioweapons would have on wildlife 2003). Plague can affect numerous rodent species in the populations in the U.S. are discussed in detail in Dudley United States, but it seems to be maintained in complex and Woodford (2002) and indicate that the use of plague epizootic (amplification) and enzootic (maintenance) organisms would have serious effects on rodent and other transmission cycles involving certain species of rodents mammal populations. and the fleas that parasitize them (Gage et al. 1995). In The most likely form of attack using the plague 210 organism would come in the form of a dehberately­ release of Y. pestis into urban areas of Chicago. This released aerosol, causing the pneumonic phase of plague. exercise was conducted to test the new infrastructure that Epidemics of pneumonic plague are historically rare but has been implemented since the establishment of the have occurred in Manchuria, China and India in the early Department of Homeland Se.curity (U.S. Department of 1900s, in Los Angeles during the 1920s, Ecuador in Homeland Se.curity 2003). Both exercises demonstrated 1939, Manchwia in 1946, Madagascar in 1958, Vietnam how overwhelming a bioterrorism event could be when in 1967, and Tarmmia in 1968 (Gage 1998). In the U.S., the attack was localized; widespread use of aerosolized recent pneumonic cases of plague were contracted from plague would cause even greater damage. cats (CDC 1997, Levy and Gage 1999, Fritz et al. 1998). After use as a bioweapon, the primary pneumonic The spread of1 pneumonic plague is favored by crowded plague expected to occur would be clinically different conditions, resulting in greater potential of contact of from naturally-occurring plague and secondary infected individuals, as well as by cool environments with pneumonic plague. Indications of bioweapon use would high hmnidity, which allow the prolonged survival of include the occwrence of human cases not known to have respiratory droplets (Gage 1998). enzootic-acquired infection, occurrence in persons The World Health Organi7.ation (WHO) modeled the without known risk factors, and in human infection in the use of plague as a bioweapon; their model indicated that absence of rodent deaths that often precede human cases if SO kg of Y. pestis were released as an aerosol over a (Inglesby et al. 2000). It would also be recogni7.ed by the city of 5 million, pneumonic plague could occur in as sudden outbreak of illness presenting itself as pneumonia, many as 150,000 persons, of whom 36,000 would die. , and associated symptoms in many individuals The plague organism can remain viable as an aerosol for (Inglesby et al. 2000). Mortality associated with 1 hour and travel for a distance ofup to 10 km (Inglesby pneumonic plague is likely to be high and depends on et al. 2000). In 2001, the U.S. Congress directed the time of disease onset, rapid diagnosis, antibiotic Department of Justice to simulate a mock bioterrorism treatment, access to supportive care, and the dose of event. Called 10POFF (fop Officials), the exercise inhaled bacilli. Mortality appears to be especially high if simulated a release of an aerosol of Y. pestis in a Denver antibiotic treatment is delayed more than 24 hours after performing arts center, causing 783 cases of suspected onset ofsymptoms (Inglesby et al. 2000). pneumonic plague the following day. By Day 4, a Figure 1 outlines the enzootic cycle of plague and the projected 3,700 cases had occurred with 950 deaths (case possible exposure routes of the bioweapon use of plague. fatality rate of 27%). During the mock event, the The initial public health response would focus on human pneumonic form ofthe disease spread very quickly and at infection and possible pneumonic plague epidemic. The Day 4 was affecting othe.r states (Inglesby et al. 2001). In organism could be introduced into the sylvatic or urban 2003, 10POFF 2 was performed and simulated the cycles of plague as well...... • • :..:~" •A c::::::> · Sylvatic Cycle

\Mid .' c::::::> c1:y·~·. :~a i\onct~ ., .. · ~ ·~ / : : ··\ ' lnfdve • : : 1 lnfec:llve \\t , FIN ~ '. :~ w: Fl••, \ Don-* • ~ ., ·. ~·J J ',, ~· . \ Rodent ~>~~n•/ _ ...... r·~~W,n:- Pneumon1cP1aeue "\.~ · · · . LJ R=. < > ·~ ) Epidemic ' •• ¢:::::::l ...... ,, . .. Pa1hways ----"-' Flu '---~~ . ------Occulonal ·· · ···· '· · · · ~ Urban Cycle < > Y. pestls Introduction (Uaed wllh permlsllon, with modlficallons)

Figure 1. Enzootlc exposure routes of YetS/n/a pestJs used as a bloweapon. 211 EPIZOOLOGY OF Y. PESTISINFECTION IN host specificity ofthe rodent host. Low host specificity is RODENTS especially important for fleas in the role of transmitting The plague bacterium has been identified in >200 plague to humans (Gage 1998). species ofmammals and 150 species of fleas (Gage 1998, Regarding commensal rodents, the requirements for a Poland and Barnes 1979). Maintenance hosts are plague epizootic to occur, with subsequent risk for human characterized by the following traits: 1) moderately high disease, are: the presence of an adequate host, the resistance to plague morbidity and mortality, 2) broad presence of an efficient vector at a level high enough to heterogeneity to challenge with Y. pestis within a produce a rodent epizootic, favorable environmental population, 3) a long, multi-estrus breeding season with conditions (humid and mild, not hot), the successful successive multiple litters and high reproductive potential introduction of the organism to the rodent population via and 4) short natural life expectancy and a high a natural or bioterrorism event, and a human population replacement rate of individuals in a population. living in proximity to rodent and flea hosts. Rattus Amplifying hosts are characterized by the following norvegicus and R. rattus exhibit many of the previously traits: 1) low to moderate resistance to plague morbidity described characteristics of a competent epizootic host of and mortality, 2) relatively little population heterogeneity the disease. When introduced to the disease, these rats in response to challenge with Y. pestis, and 3) capability are very susceptible to infection and suffer high mortality of supporting vector populations under appropriate during epizootics. Likewise, the commensal rat flea external environmental conditions (Poland and Barnes Xenopsyl/a cheopis is an efficient vector of plague, has 1979). low host specificity, and will readily feed on other hosts, Although there are a large number of flea species including humans (Gage 1998). The risk of plague to known to be able to harbor or transmit plague, not all are humans increases greatly during epizootics ofrodents that efficient vectors of the disease. When fleas obtain a experience mortality, because as rodents die, their fleas blood meal from infected rodent hosts, Y. pestis begins to will seek alternate hosts (Gage 1998). The WHO defines collect and form colonies on the proventriculus of the a flea index (average number of fleas/rodent) of 1.0 or feeding flea, which typically shuts off while the flea is greater as the threshold level needed to support a rodent sucking but opens when ingested blood enters the epizootic of plague (Politzcr 1954). Based on modeling, stomach. h Y. pestis multiply, the proventriculus Keeling and Gilligan (2000) indicate that when rat eventually becomes blooked. h the flea continues to populations susceptible to plague are high, the arrival of feed, blood cannot enter the stomach but remains in the plague infection would be followed by a short-lived rat esophagus. When the flea stops sucking, the esophagus epizootic and a large force of infection directed at recoils and drives the into the bite wound, thus humans. House mice, Mus musculus, are affected by the infecting the animal. Fleas in this condition are described introduction of plague via the pneumonic form, but they as ''blocked". Fleas in this blocked condition begin to are not epizootic hosts of the disease because they lack starve, causing them to feed repeatedly on any available efficient flea vectors (Byrne et al. 1998, Mohr 1951). host h fleas attempt this voracious feeding, the bacteria Therefore, house mice would most likely not be involved are regmgitated in an attempt to clear its esophagus. with an epizootic of plague resulting from a bioterrorism Species in which ''blocking'' occurs are the most efficient event. vectors of plague (Gratz 1999). Other factors that make Major Noiway rat infestations have been documented certain fleas efficient vectors of plague are their in many major U.S. cities. A recent newspaper article abundance during seasons of plague transmission, reported that the rat population in New York City is geographical distribution, ability to survive off the rodent estimated at 70,000,000 (Alpert 2000) and, based on host when hosts die during epizootics, and the degree of complaints received from city dwelling residents, rat

Table 1. Hlstorlcal X. cheopls flea Index data from U.S. cities.

NewYork,NY 1923-1924 Rattus sp. 0.3 Monthly Sampling Mohr 1951 New York. NY 1924-1925 Rattus sp. 0.0 Monthly Sampling Mohr 1951 Phlladelphla, PA 1933 Rattus sp. 1.0 Monthly Sampling Mohr 1951 Norfolk, VA 1927-1928 Rattus sp. 2.7 Monthly Sam piing Mohr 1951 Boston, MA 1922-1923 Rattussp. 0.4 Monthly Sampling Fox and Sullivan 1925 SavaMah, GA 1933 Rattus sp. 6.0 Monthly Sampling Mohr 1951 Jacksonville, FL 1934 Rattus sp. 3.8 Monthly Sampling Mohr 1951 Moblle,AL 1934 Rattus sp. 4.8 Monthly Sampling Mohr 1951 Dothan, AL 1933-1934 Rattussp. 5.1 Monthly Sampling Mohr 1951 New Orleans, LA 1915-18 Rattussp. 2.4 Monthly Sampling Mohr 1951 New Orleans, LA 1922-1923 Rattus sp. 1.7 Monthly Sampling Fox and Sullivan 1925 Seattle, WA 1930-1932 Rattussp. 0.4 Monthly Sampling Mohr 1951 Los Angeles, CA 1935 Rattussp. <1.0 19 Months Trimble 1935 Los Angeles, CA 1984-1985 Rattussp. 5.8 Monthly Sampling Nelson etal.1986 San Bernardino, CA 1971 Rattussp. 7.3, 5.3 7 SampUng Months Ryckman 1971 Honolulu. HI 1934 Rattus sp. 3.1 Monthly Sampling Mohr 1951

212 problems exist in Philadelphia, Baltimore, Washington dead rodents, monitoring activity of potentially affected D.C., and Detroit (NIAID 1996). Urban rodent control rodents, and trapping rodents for necropsy, blood, tissue, programs exist in many other cities including Los and ectoparasite collection and analysis (Gage 1999). Angeles, Chicago, Atlanta, San Francisco, and Denver Ectoparasites are collected from trapped, anesthetized (Genesis Laboratories, unpubl. data). rodents by combing their fur "against the grain" while Many areas in the U.S. have environmental conditions they are suspended over a collection pan. Such combing adequate for X cheopis proliferation. Table 1 causes fleas to fall into the pan for collection. Blood summarizes flea index data from references during the samples are collected via retro-orbital or cardiac puncture 20dl Century. In the early part of last century, flea index technique. Collected blood or sera samples can be placed data were collected because of the possibility of potential onto paper collection strips and dried for later analysis. plague or flea-borne typhus epidemics occurring (Mohr Rodent sera are analyzed by many techniques including 1951). X cheopis infestations of Rattus spp. have been complement fixation, passive hemagglutination, latex found in the following major U.S. cities: Honolulu ID, agglutination, and enzyme immunoassays (Gage 1998, Jacksonville FL, Boston MA, New York NY, 1999). A rapid test for plague in rats using sera is Philadelphia PA, New Orleans LA, Seattle WA, San currently being tested as well (Thullier et al. 2003). Bernardino CA, Norfolk VA, Savannah GA, Dothan AL, Tissues collected during necropsy should include liver, and Mobile AL. Los Angeles CA was also described as spleen, kidney, and lung. Y. pestis is detected in the having a high infestation of flea-infested rats in the tissues of animals by direct immunofluorescence assay, downtown area. The density of X cheopis on Noiway agglutination, enzyme-linked immunosorbent assays, or rats in the older residential and commercial sections of by isolating the organism in culture (Gage 1999). downtown and the central city was termed "alarming'' Collection of ectoparasites from rodent burrows is and posed a high potential risk for human epidemics, if performed by attaching a 12 x 12-inch piece of white plague were to enter the Noiway rat population (Nelson flannel cloth to the end of a flexible plumber's snake and and Madon 1986). With the exception of fairly recent inserting it into the rodent burrow. Once removed, the references regarding flea indices from southern flannel and fleas (if present) are placed in a zip-lock bag California, there were not many recent, published for later identification and laboratory analysis by poly­ refeimces located pertaining to the flea index of U.S. merase chain reaction (PCR) techniques (Gage 1999). urban rats. Data, ifcollected by municipalities, appears to remain internal. Although the methods used to collect FLEA CONTROL data appearing in Table 1 were not standardized, the table Flea control is imperative when controlling a plague indicates that X cheopis populations appear to be outbreak. Because the transmission of plague requires a restricted to warm and humid areas but are inconsistent minimum threshold of the number of fleas per rodent with arid and colder areas. X cheopis populations are (flea index), decreasing the number of potential flea highest when the mean January temperature is >4°C and vectors will intenupt the rodent-flea-rodent transfer and the average humidity in July is -37%. This includes the decrease the potential risk to humans. Recommended gulf coast and the west coast. Urban areas of Los methods for controlling fleas are by application of an Angeles appear to be especially favorable (Mohr 1951). EPA-registered insecticide to rodent burrows or runways, and host-targeted techniques using bait stations to apply ENVIRONMENTAL DECONTAMINATION insecticidal dust or liquids to rodents (Gage et al. 1995, The response to the use of Y. pestis in a bioterrorism Gage 1998). The insecticidal powders chlorpyrifos and event includes epidemiologic investigation of disease, diazinon have been shown to be effective for the control medical treatment, possible quarantine, and prophylaxis of plague vector fleas of the western chipmunk (Tamias for affected persons. Environmental decontamination senex) when applied to burrows (Smith and Lusk 1990). measures would also be necessary. Animal-based Permethrin dust was effective against the fleas of the surv~ce to determine Y. pestis infection in mammaJs golden-mantled ground squirrel (Spermophilus lateralis) and fleas would be required as well as the initiation of and the black-tailed prairie dog (Cynomys ludovicianus) disease prevention and environmental decontamination (Smith and Lusk 1990, Beard et al. 1992). Deltamethrin measures, including the control of both fleas and dust has been used to control the fleas of C. ludovicianus potentially affected rodents (Gage 1999, Gratz 1999, and R rattus (Seery et al. 2003, Rotovonjato and CDC 2000). These control measures could prevent a Duchemin 2001). Dimicron (a microencapsulated secondary round ofinfections in humans that would result formulation of the organophosphate insecticide diazinon) from the infection becoming established in commensal was successful in reducing flea populations on R rattus rodents. as (Rotovonjato and Duchemin 2001 ). Regarding liquid insecticides, Bronson and Smith ANIMAL-BASED SURVEII..LANCE (2002) described the success of liquid deltamethrin in The collection of rodents and ectoparasites is an host-targeted bait tubes for the control of fleas on S. essential part of animal-based plague surveillance. The /ateralis and on the chipmunks T. amoenus and T. senex. primary goal of surveillance is to collect .and test Metzger and Rust (2002) evaluated the effectiveness of sufficient numbers of the rodent population affected to the insecticides fipronil and imidacloprid (commercial deten:nine the extent of Y. pestis infection in rodents and veterinary formulas) against the flea Oropsyl/a montana thereby the potential risk to humans. The surveillance of when applied topically to wild-caught California ground rodents potentially exposed to plague involves collecting squirrels (Spermophilus beecheyi) at a dosage rate of 15 213 mg/kg. Topically-applied fipronil was effective at population in an area. Similar methods could be utilized producing flea mortality on squirrels for at least 10 to for routine smveillance of urban flea index. More weeks, but imidacloprid was effective for only 2 weeks importantly, establishing the lack of risk from secondary after application. In addition, liquid pennethrin was infection resulting from the deliberate use of Y. pestis as effective against the fleas of the Mexican woodrat an agent of bioterrorism could be determined. (Neotoma mexicana) (Gage et al. 1997). ACKNOWLEDGEMENTS RODENT CONTROL I c:mnd my appreciation to Ors. ~ Enscore and Kenndh Controlling rodent populations in an infected area Gage at the COC Division of Vector-Borne Infectious Diseucs for could be performed via rodenticides. When implement­ their insight regarding the mataial in this paper, and to Dr. Neil ing plague control strategies, direct control of the rodents Ouunbcrlain at the Kirksville College of Osteopalhic Medicine, is not recommended until flea control measures have been Kirlcsvitlc, MO, for use of the diagram detailing the enzootic c:ycle of implemented and demonstrated to be effective. Lethally plague, which I modified. controlling rodents prior to controlling fleas could create an increased risk of plague to humans, as many fleas are LITERATURE CITED released into the environment after widespread rodent AKIEV, AK.. 1982. F.pidcmiology and incidence of plague in deaths occur, a situation that is similar to what would the world, 1958-1979. Bull of the WHO 60(2):165-169. occur during a rat di~ff (Gage et al. 1995). An example Afj)ERT, L. I. 2000. 70 million rats might throng big apple. of this occurred in Tani;mia, where an epidemic of The Denver Post, July 10, 2000, Denver, CO. human plague was reported to be preceded by rodent ANroUN, M. F., P. GoBER, B. LucE, D. E. BIGGINS, W. E. VAN control operations in which the indiscriminate use of PELT, D. B. SEERY, M. LocKHAR.T, AND M. BAU.. 2002. rodenticides caused fleas to be released into the The influence of on North American environment and subsequently parasitized humans wildlife at a landscape level, with special emphasis on (Kilonzo 1994). For lethal control, many rodenticide black-footed ferret and prairi~ conservation. Trans. N. baits, traps, and fumigants are commercially available for Am. Wtldl. Nat Res. Conf. 67:104-127. the control of R. norvegicus and R. rattus (fimm 1994, BARNPS, AM. 1982. Surveillance and control of bubonic Marsh 1994, Gratz 1999). As a preventative measure, plague in the United States. Symp. ZooL Soc. Lond. 50: non-lethal control of rat infestations can be accomplished 237-270. by exclusion, repellents, habitat modification, improving BEARD, M. L., S. T. ROSE, A M. BARNPS, AND J. A the sanitation of an area (foodstuff and trash storage) and MONTENIERI. 1992. Control of Oropsylla hirsute, a plague the alteration of landscape (fimm 1994, Marsh 1994, vector by treatment of prairie dog burrows with 0.5% Colvin et al. 1996). Many large U.S. cities are currently permethrin dust. J. Med. EntomoL 29(1):25-29. practicing larg~scale rodent control measures. BRONSON, L. R, AND c. R SMIIH. 2002. Use of liquid Therefore, the infrastructure for larg~scale rodent control dcltamctbrin in modified, host-targeted bait tubes for control campaigns is already available. These currently practiced of fleas on sciurid rodents in northern California. J. Vector methods should be continued as a means of mitigating F.coL 27(1):55-62. potential risk in metropolitan areas. BYRNE, W. R, S. L. WELK.OS, M. L. Prrr, K.. J. DAVIS, RF. BRUF.CKNER, J. W. E7zEI 1 , G. 0. NELWN, J. R VACCARO, DISCUSSION LC. BATIERSBY, AND AM. FRIEDLANDER. 1998. Antibi­ The deliberate exposure of Y. pestis to a human otic treatment of experimental pncumonic plague in mice. population to would have devastating consequences. The Antimicrob. Agents and Chemothcnpy 42(3):675-681. establishment of the disease in urban Rattus populations CDC (CENrERs FOR DISEASE CONTROL AND PRliVENttON). is a possible secondary consequence as well. Potential 1997. Fatal human plague-Arimna and Colorado, 1996. risk exists in areas where rats are living in close proximity MMWR46(27):617-620. to humans (especially unsanitary areas), areas with CDC (CEm'ERS FOR DISEASE CONI'ROL AND PRliVENttON. favorable environmental conditions, and in areas where 2000. Biological and chemical terrorism: strategic plan for the flea index on rodents is high enough to support an preparedness and response. Recommendations and ieports. epizootic. MMWR49:RR-4. 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