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Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases (2005)

Chapter: 3 Assessment of Current Framework: Case Studies

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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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3
Assessment of Current Framework: Case Studies

INTRODUCTION

In this chapter, a series of case studies are examined to assess the capabilities and limitations of the framework in preventing, detecting, and diagnosing animal diseases. The analysis of disease events that have occurred nationally and abroad provides useful information on the responsiveness of the framework as a whole and lays the groundwork for Chapter 4, which identifies gaps and opportunities to strengthen the framework. This chapter does not attempt to provide a comprehensive analysis of all animal diseases, but examines a “cafeteria-style” sample of diseases that could have potentially large economic, human, and/or animal health impact. Box 3-1 lists the animal diseases and disease categories selected for analysis. The list is not based on diseases that are the most problematic or prevalent in the United States. (For example, food-borne diseases caused by Salmonella enteriditis and Escherichia coli O157:H7 are not on the list; they pose greater concerns for the health of humans than for animals.) Instead, the animal diseases or disease scenarios described here, from acute to chronic, endemic to exotic, naturally occurring to intentionally introduced, were selected to consider the breadth of issues that must be addressed by an inclusive infrastructure capable of detecting, diagnosing, and preventing a wide variety of events affecting animal and human health. The diseases selected involve each of the major animal types, namely food-animals, wildlife, and companion animals.

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

FOREIGN ANIMAL DISEASES: EXOTIC NEWCASTLE DISEASE AND FOOT-AND-MOUTH DISEASE

Exotic Newcastle Disease

Exotic Newcastle disease (END) is a contagious and fatal disease affecting all species of birds. Previously known as velogenic viscerotropic Newcastle disease (VVND), END is one of the most infectious diseases of poultry worldwide. A death rate of nearly 100 percent can occur in unvaccinated poultry flocks. The virus is so virulent that many birds die prior to showing clinical signs, and END infection can have high mortality even in vaccinated birds (University of Georgia, 2003).

END is classified as a foreign animal disease in the United States, historically causing severe economic losses when commercial poultry industries become infected, as occurred in a major outbreak of END in southern California in 1971. The disease threatened not only California poultry production, but it also had a significant economic impact on the entire U.S. poultry and egg industry. In all, 1,341 infected flocks were identified and 11.9 million birds were destroyed over a multiyear disease control effort. Disease eradication cost taxpayers $56 million (over $250 million in 2003 dollars), severely disrupted the operations of many producers, and increased the price of poultry and poultry products to U.S. consumers (Utterback, 1973; Davidson-York et al., 1998). It took 3 years to fully eradicate the disease, and nearly two decades before another outbreak of END occurred in U.S. commercial poultry. In the early 1990s, over 26,000 commercial turkeys were destroyed in North Dakota following detection of END. The virus is believed to have been transmitted to the turkeys from cormorants or other free-ranging birds. Hundreds of cormorants had previously died at a lake not far from the turkeys, in an outbreak that is believed to be the first documented Newcastle-related die-off of wild birds in the United States (Meteyer et al., 1997). Though END virus has not been detected in commercial birds in the United States since then, it is now known to exist in free-ranging wild birds, as well as in psitticine species. A variety of psitticine species enter the United States through the pet bird trade, generally traveling through USDA quarantine stations; however, illegal movements across U.S. borders also occur. END is detected nearly every year in California, primarily in psitticine and free-flying wild-bird species; however, in 1998, END was detected in urban gaming chickens in the state (Crespo et al., 1999). Subsequent to the 1971 outbreak, the presence of END has been detected numerous times through case submissions to the state’s diagnostic laboratory (passive surveillance), confirmed as END by the federal laboratory system, and rapidly

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

BOX 3-1
Animal Diseases Addressed in This Chapter

Foreign Animal Diseases. Important transmissible livestock or poultry diseases that are largely absent from the United States and its territories and that have the potential to cause significant health or economic impact should the causative agent be introduced. Foreign animal diseases discussed in this chapter include:

  • Exotic Newcastle disease (END)

  • Foot-and-mouth disease (FMD)

Recently Emergent Diseases. Infectious diseases for which the risk in animals has increased in the past two decades or threatens to increase in the near future. These diseases include:

  1. New infections resulting from changes or evolution of existing organisms or newly infectious particles (such as prions)

  2. Known infections spreading to new geographic areas or populations

  3. Previously unrecognized infections emerging in new geographic areas and human populations due to changing technologies and behaviors

  4. Old infections reemerging as a result of antimicrobial resistance in known agents or breakdowns in animal disease control measures.

The recently emergent diseases addressed in this chapter are:

  • Monkeypox

  • Bovine spongiform encephalopathy (BSE)

Previously Unknown Agents. Pathogens previously unrecognized that have recently (within the past decade) been transmitted from animals to humans. Included for discussion in this chapter:

  • Severe acute respiratory syndrome (SARS) coronavirus

eliminated by state regulatory authorities prior to spread of the disease (Molenda, 2003).

Detection and Diagnostic Methods

Despite the recognized and significant economic impacts of END introduction into the U.S. commercial poultry industry and the repeatedly observed risk of reintroduction in California, surveillance, detection, and diagnostic approaches were little changed in 2002 from those used in 1971. The accepted diagnostic standard was virus isolation in embryonated

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

Endemic Diseases. Animal-borne diseases that are native to or commonly found in the United States. Examples addressed here include:

  • Avian influenza

  • Chronic wasting disease

  • West Nile virus

While the committee recognizes that at one time these agents may have been considered as newly emergent, each of them has now become firmly established in North America and is considered endemic for the purposes of this report.


Novel Naturally Occurring Pathogens. Organisms previously unreported or infrequently associated with being a primary pathogen in a given host species. Novel naturally occurring pathogens may contain new genomic elements acquired through natural processes and not as the result of in vitro insertion.


Bioengineered Animal Pathogens. Organisms containing genomic elements that were acquired in vitro.


Diseases of Toxicological Origin. Diseases caused by exposure to toxic substance(s), including drug residues, in a concentration that alone or in combination meets either of the following criteria: (1) the animal(s) affected is/are a potential source of toxicological contamination to humans or other animals and/or (2) the source of the toxicological agent or exposure is potentially hazardous to humans or other animals.

eggs, a process requiring 2 to 7 days, followed by pathogenicity testing of the isolated virus by inoculation into chickens or direct nucleic acid sequence analysis of the virus’ pathogenicity marker. Isolation and characterization of the virus requires several days to several weeks, depending on the availability of eggs and experimental birds, access to containment and/or sequencing facilities, and technical resources at the federal laboratory. Though state and university veterinary diagnostic laboratories typically have virus isolation facilities with trained technical staff, consideration had not been given to using these resources; instead, the existing paradigm was for the federal laboratory to perform foreign animal dis-

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

ease testing. National technical training and proficiency evaluation for the isolation and characterization of foreign animal diseases, including END virus, did not exist, which limited possibilities for providing surge capacity needed in the face of an END outbreak. Proven technology that would allow surge capacity in the form of rapid and sensitive diagnostic assays had not yet been directed toward END detection, primarily because the U.S. Department of Agriculture (USDA) Cooperative State Research, Education, and Extension Service (CSREES), the major funding agency for animal health, discouraged allocation of competitive research dollars for projects solely targeting the development and validation of veterinary diagnostic assays.

However, in response to heightened biothreat awareness in early 2002, the USDA, in cooperation with the Department of Homeland Security, created a list of eight high-risk agriculture pathogens (USAHA, 2003a). Included in the $14 million funding allocated to the USDA Agricultural Research Service (ARS) for developing rapid diagnostics for the high-risk agricultural pathogens was $2.8 million for two poultry pathogens included in the list: highly pathogenic avian influenza (AI) virus and END virus (USDA, 2002f; USDA ARS, 2002). Months later, prior to the development or availability of rapid detection assays in the United States (though rapid END diagnostic approaches were documented in the international literature), END was again found in game fowls in southern California (Nolen, 2002). The END outbreak illustrates the following findings:

  • The animal health infrastructure lacked an analysis system for anticipating challenges to animal agriculture and a system for providing appropriate intervention or rapid detection strategies despite acknowledged risks of introduction of a high consequence pathogen into the United States.

  • The existing infrastructure did not support timely development, validation, and implementation of state-of-the-art technologies for prevention, detection, and diagnosis of recognized and economically threatening pathogens.

The 2002 END Outbreak

The timing and movement of the END outbreak in 2002–2003 followed a pattern eerily similar to the 1971 outbreak (see Table 3-1). In late September 2002, a game chicken was presented to the state’s animal health laboratory by a private veterinary practitioner on behalf of a southern California game fowl owner that had lost 200 birds (90 percent mortality) over a 5-day period. Two days later a veterinarian in a neighboring county contacted the state laboratory to report high mortality in a small backyard

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

flock of laying hens. Within the previous 6 months, two unrelated companion animal bird submissions with confirmed END infections had been traced to origins in southern California. In all cases the laboratory suspected END virus, and samples were transported to the federal laboratory in Ames, Iowa, as required for confirmation of END (Humanitarian Resource Institute, 2004). The END viruses isolated in the spring and fall of 2002 had identical genomic sequences, suggesting the virus may have entered bird populations in southern California at least 6 months before the declared outbreak. By the time the initial game fowl cases were detected by passive surveillance in late September, the disease had spread throughout the urban population of game and noncommercial poultry in southern California. The size and significance of the urban poultry population had clearly gone unrecognized, and the social and cultural barriers to effective surveillance within that population had not been addressed. Within the first week of the outbreak response alone, more than 5,000 noncommercial birds were depopulated and 30 backyard flocks placed under quarantine in a three-county area. Ultimately, nearly 300,000 premises were visited during the outbreak, and 90,000 of them had avian species, primarily poultry. Though trade partners had been notified by USDA of the END detected in game chickens on October 1, 2002, a federal emergency was not declared until January 6, 2003, by which time virus had been detected in 5 of the ultimate 22 infected commercial poultry flocks (USDA APHIS, 2003b).

Requests to the European Union for regionalization to protect U.S. trade and questions of federal and state authorities had, however, been initiated by USDA in late October and November (Rob Werge, personal communication, 2004). Heightened awareness of the disease resulted in the detection of END in neighboring Nevada game chickens in mid-January 2003, Arizona game chickens in early February, and an isolated incident of an unrelated END virus in Texas game chickens in early April. By the time the final END positive bird was detected 9 months later, 22 commercial premises and a total of 3.21 million birds had been depopulated at a cost of more than $160 million in federal control efforts. Up to 71 percent of USDA veterinary services staff—and a total of 7,690 state and federal employees—were recruited into the eradication effort (USDA APHIS, 2004a). Based on this review, the committee found:

  • The existing animal health infrastructure was designed to detect and respond to disease in commercial agriculture production systems, and was not appropriate for nontraditional species, management, or environments, effectively delaying both detection and response activities.

  • The lack of adequate surveillance for END, a foreign animal disease already known to enter the country periodically, allowed the virus to

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

TABLE 3-1 Timeline of 2002-2003 Exotic Newcastle Disease (END) Outbreak in Southern California

2002

March

Two unrelated companion animal birds diagnosed with END. Federal efforts trace origin of birds to Southern California.

 

September 25

Index case END outbreak game fowl submitted to state diagnostic laboratory by private practitioner.

 

September 27

Second case in backyard chickens submitted to state laboratory.

 

 

Task force formed. Urban door-to-door disease eradication efforts begin.

 

October 1

National Veterinary Services Laboratories (NVSL) confirms END virus. U.S. Department of Agriculture (USDA) notifies state veterinarians and trade partners. EU bans import of U.S. poultry.

 

 

USDA transfers $7.4 million in funds from Virginia LPAI to END ($5 million for state, $2.4 million for USDA VS).

 

 

Initial development of rapid diagnostic assay begins.

 

November

Prototype Real-time Reverse Transcriptase (RRT) Polymerase Chain Reaction (PCR) used in conjunction with virus isolation by state laboratory to detect END.

 

December 23

First detection of END in a commercial flock, presumptive diagnosis by state laboratory using virus isolation and RRT PCR, officially confirmed December 21 by USDA testing.

 

 

Secretary of Agriculture approves $121.8M fund request for END control.

2003

January

USDA declares extraordinary emergency.

 

 

Prototype RRT PCR used in federal laboratory.

 

 

END detected in Nevada game fowls (January 16, 2003). Nevada Task Force established. USDA declares extraordinary emergency for Nevada (January 17, 2003).

 

 

E.U. and Mexico agree to regionalize United States, restricting trade only with California, Nevada, and Arizona.

 

 

Arizona Task Force established due to proximity to California quarantine zones.

 

February 4

Arizona game fowl confirmed positive for END.

 

February 7

USDA declares extraordinary emergency for Arizona.

 

 

Virus isolation (egg inoculation) reaches peak laboratory capacity at ~4,000 samples per month.

 

March

Last detection of END in a commercial poultry flock.

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

 

April 9

END detected in Texan game fowl.

 

April 10

USDA declares extraordinary emergency for Texas and border state New Mexico.

 

 

USDA reports genomic sequence of Texas isolate differs from outbreak virus indicating introduction not due to spread from California, Nevada, and Arizona.

 

 

USDA officially validates USDA single-tube END RRT PCR. Test turn-around is 4–24 hours, laboratory capacity ~184 tests per day based on 3 cyclers and 3 technicians.

 

May

Final positive noncommercial bird detected.

 

 

State laboratory initiates use of modified high-throughput RRT PCR. Test turn-around is 4–24 hours, laboratory capacity ~1900 samples per day.

 

 

USDA lifts quarantines from all but original infection sites in Nevada and Arizona.

 

June

USDA lifts quarantine in Texas and New Mexico except for area around original positive premise.

 

July

Quarantines lifted from Arizona, Nevada, Texas, reduced areas in California.

 

August

E.U. lifts trade restrictions except for Southern Califonia, and original infection sites in Arizona, Nevada, and Texas.

 

 

California and Mexico sign agreement for regional plan for prevention and mitigation of future END outbreaks.

 

September

USDA approves $9.476 million for END surveillance.

 

 

USDA lifts California quarantine. Surveillance efforts directed toward avian health and mitigation continue.

 

 

Mexico and Canada lift END-related trade restrictions.

Final totals

19,146 premises quarantined

932 confirmed infected premises identified

3.21 million birds depopulated in four states

$160 million in control costs

7670 state and federal employees on the END task force

spread and become established in a relatively large animal population before detection.

In the absence of available rapid detection and diagnostic assays for END, the USDA and the state diagnostic laboratory, in a largely uncoordinated effort, initiated development of a molecular-based diagnostic ap-

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

proach to reduce from days to hours the time needed to obtain an END diagnosis. The federal approach was based on past experiences and successes with flock-based detection, while the state responded to the character of the current outbreak by focusing on high-throughput capacity and reliable detection in individual birds. Both groups used the established technology of real-time polymerase chain reaction (PCR). The state laboratory lacked significant fiscal resources specifically allocated for assay development and so relied on partnerships and collaborations with other federal agencies (such as the Department of Energy) and with commercial biotechnology equipment and reagent suppliers. The use of the extensive network of expertise located outside of the federal (and state) system allowed for timely development of a more cost-effective and rapid approach to detection and diagnosis of END, which was ultimately used on more than 81,000 samples during detection and control efforts by the state laboratory. The combination of real-time PCR with the high-throughput approach allowed a 10-fold increase in workload to more than 1,500 samples tested daily with results available within 4 to 24 hours, and is credited with supporting rapid and effective testing for disease eradication. The final END quarantines were lifted within 11 months of initial END detection in game fowls, despite earlier USDA Animal and Plant Health Inspection Service (APHIS) projections of a 3-year disease control effort (USDA APHIS, 2003c). The committee found the following:

  • Private industry, local and regional resources, and the willingness to capitalize on expertise located outside the centralized federal animal health system allowed a more timely, cost-effective, and reliable assay to be developed, validated, and implemented for disease detection and control.

Foot-and-Mouth Disease

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cattle, swine, and other cloven-hoofed species including sheep, goats, and deer. The disease is characterized by fever and blister-like lesions followed by erosions on the tongue and the lips, in the mouth, on the teats, and between the hooves. For some strains of the virus and host species, clinical signs of infection can be minimal or go clinically unrecognized. Most affected animals recover, but the disease can leave them debilitated and livestock herds can experience severe losses in production of meat and milk, providing the economic justification for including FMD virus among the OIE List A diseases (OIE, 2003). Pigs amplify most strains of FMD virus to high concentrations, so they transmit the disease readily, while cattle are generally considered the species most susceptible to infection. The virus can be transmitted readily to susceptible animals either by in-

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

gestion or inhalation of the virus from contagious animals or innate objects, such as contaminated vehicles, clothing, or feed or water. The virus is well known for its potential to spread widely and rapidly in the absence of obvious clinical signs that would trigger early detection and appropriate control measures.

FMDV in the United Kingdom

The United States has not had an incursion of FMD virus (FMDV) since 1929, but the devastating outbreak of FMD in the United Kingdom in 2001 (Box 3-2) has provided lessons about prevention, detection, and control of the disease in the United States. As in the United Kingdom, the United States does not permit the use of FMDV vaccine, creating a national population of FMDV-susceptible animals. Moreover, the United States has a large wildlife population—including feral swine, deer, and other susceptible cloven-hoofed animals—for which timely detection and prevention would be difficult, if not impossible. Establishment of infection in susceptible wildlife, such as feral swine, could result in widespread dissemination of the disease throughout the country. Prevention in both countries was and continues to be heavily reliant on federal policies restricting trade in animals and animal products from FMDV-endemic countries. Despite such policies, in early 2001 the FMDV entered the United Kingdom, most probably through an illegally imported meat product. By the time the disease was detected several weeks later, it had spread throughout the country and to as many as 79 premises primarily through animal movement (Mansley et al., 2003). Disease entry through import, either intentional or unintentional, is a similar risk for the United States, where a very small percentage of cargo and baggage is inspected. The USDA Safeguarding Review cites that 489 million passengers and pedestrians and 140 million conveyances crossed U.S. borders in 2000, and the review predicted this number to double in 2009 (NASDARF, 2001). In addition, approximately 38,000 animals were imported daily into the United States in 2000. The committee found that:

  • FMD prevention, and disease prevention in general, through exclusion of infected animals and animal products cannot be relied on as infallible and would require a significantly more effective infrastructure than currently exists at U.S. borders and ports of entry.

The lack of early detection following FMD virus introduction in the United Kingdom was responsible for the widespread dissemination of disease throughout the country and into neighboring countries (Haydon et al., 2004). Standard methods for testing clinical material (lesion swabs,

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

BOX 3-2
Foot-and-Mouth Disease Epidemic in Great Britain in 2001

On February 19, 2001, a routine inspection at an abattoir near London revealed “highly suspicious” signs of foot-and-mouth disease in 27 pigs. The Ministry of Agriculture confirmed the outbreak and the next day set up a 5-mile exclusion zone around the abattoir. With increasing numbers of FMD cases reported on cattle and sheep farms 5 days after the initial case, the government announced plans to slaughter pigs, sheep, and cattle in affected areas in an attempt to eliminate the disease. As the outbreak continued through the end of the month, the ban on movement of livestock was extended. By early March, neighboring countries had begun investigating their own suspected cases of FMD and enhanced precautionary measures were initiated to prevent FMD from entering their countries. The epidemic, however, extended beyond England to other European countries, with Scotland, Northern Ireland, France, Belgium, Denmark, Germany, and the Netherlands responding with programs to destroy animals in affected areas.

At a meeting of European ministers on March 6, a proposal was made to extend the ban on British livestock exports until March 27. Veterinary experts recommended against mass vaccination, and the E.U. agriculture ministers concurred with their advice. Despite extensive efforts, the number of new unconfirmed cases reached 1,000 by the beginning of April. On April 26, the government announced a change in policy, ending the practice of slaughtering healthy, unaffected livestock on farms neighboring farms with animals showing suspicious signs. By May 8, restrictions on livestock movement were eased across the European Union.

The British government killed 6.5 million animals during the epidemic: about 4 million for disease control and an additional 2.5 million for reasons of animal welfare. The epidemic lasted 214 days and involved over 10,000 herds and flocks. Annual festivals and international sporting events were cancelled due to the epidemic and tourism declined substantially. The epidemic incurred losses to agriculture and tourism estimated to be at least £6.3 billion.

SOURCES: Thompson et al., 2002; Haydon et al., 2004.

fluids, blood) from suspect animals, including virus isolation in cell culture and antibody detection by serum testing, were available in the United Kingdom and used with reportedly high accuracy. Had the government invested years earlier in the development of accurate and rapid real-time virus detection assays, it would have been very difficult for the govern-

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

ment then to ignore the need for diagnostic testing before animals were destroyed. Traditional FMDV control methods, targeting the killing of animals from infected premises and epidemiologically determined dangerous contact premises, were used through late March, after which time additional control measures were introduced. These measures included depopulation based only on suspicion of infection; destroying sheep, goats, and pigs within 3 kilometers of infected premises in some counties; and destroying animals on all premises contiguous to an infected premise within 48 hours regardless of health status of the animals. The 48-hour depopulation policy was and remains a controversial component of the U.K. control effort, and therefore was not consistently accepted. The policy, developed in large part based on computer model simulations of hypothetical disease transmission, has in retrospect been credited with the large number of noninfected animals destroyed during the 2001 epidemic and with the public’s negative response to the highly visible control efforts (Haydon et al., 2004). From the published lessons identified and formal recommendations in commissioned reports (National Audit Office, 2001; Royal Society, 2002), it can be concluded that:

  • The lack of early detection allowed FMD to become widespread in the United Kingdom.

  • Outbreak planning with established, scientifically consistent policies and protocols defined prior to the outbreak or disease event are necessary for effective prevention, diagnosis, and response.

FMDV in Other Countries

Unlike the United Kingdom, the Netherlands chose to respond to the related 2001 incursion of FMDV into its herds with an emergency vaccination program (Tomasson et al., 2002; Bouma et al., 2003). The program was successful in the Netherlands and is cited as justification for the emergency use of FMDV vaccination during an outbreak, despite the after-affects of restricted trade when all vaccinated animals are not subsequently destroyed (Haydon et al., 2004). The criticisms of vaccinating in the face of an outbreak include the current lack of a validated assay or technology that would allow for the differentiation of animals exposed to FMD vaccine from those animals exposed to the live virus. The potential for an exposed and vaccinated animal to become a subclinical FMD virus carrier, capable of disease spread, is a significant concern for trade partners in FMD-free countries following an FMD outbreak in vaccinating countries. Technologies utilizing animal serum to test for their response to portions of the replicating FMD virus, termed nonstructural protein assays, have been developed in recent years but have not yet been evalu-

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

ated or approved for use in the United States. Likewise, technologies to produce effective vaccines that can rapidly and effectively protect an animal and also allow paired diagnostic tests to distinguish vaccinated from exposed animals (marker vaccines and diagnostics) exist for other animal diseases but are not yet developed or readily available for FMD control. The lessons reported from the 2001 U.K. FMD outbreak indicate that there is an immediate and ongoing need to provide for the development and critical evaluation of advancing technologies for vaccines, as well as detection and diagnostic assays for disease prevention, detection, and control.

RECENTLY EMERGENT DISEASES IN NORTH AMERICA: MONKEYPOX AND BOVINE SPONGIFORM ENCEPHALOPATHY

Monkeypox

Monkeypox is a rare viral disease that is found mostly in the rain forest countries of Central and West Africa. The disease is called “monkeypox” because it was first discovered in laboratory monkeys in 1958. Blood tests of animals in Africa later found evidence that monkeypox is primarily an infection of rodent species. The virus that causes monkeypox was recovered from an African squirrel, which may be the natural host. Laboratory studies showed that the virus can also infect rats, mice, and rabbits (Khodakevich et al., 1986; Hutin et al., 2001).

In 1970, monkeypox was identified as the cause of a rash illness in humans in remote African locations (Landyl et al., 1972; CDC, 2003b). Interestingly, in retrospect some monkeypox may have been misdiagnosed in humans prior to this time as mild smallpox but was easily identified as a separate disease after smallpox was eradicated (Ogden, 1987). In early June 2003, monkeypox was reported among several residents in the United States who became ill after having contact with sick companion animal prairie dogs. (See Box 3-3 for a description of the case.) This is the first evidence of monkeypox in the United States.

Prevention

There was no formal provision for monitoring monkeypox in these animals by an appropriately trained health professional at the point of origin in Ghana, at the importer, or from the importer on into the United States. Because of the lack of records, 178 (23 percent) of the original 762 African rodents could not be traced beyond the Texas importer (CDC, 2003e). Furthermore, there were no health examinations, certificates, or individual animal identification required for the prairie dogs exposed to

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

BOX 3-3
Recent Emergence of Monkeypox in the United States

On April 9, 2003, a shipment of 762 exotic rodents originating in Accra, Ghana, reached the United States. That shipment contained giant Gambian pouched rats (50 animals), rope squirrels (53), brushtail porcupines (2), tree squirrels (47), striped mice (100), and dormice (510). Accompanying these animals to Texas was an unexpected virus that eventually found its way into at least two other animal species in the United States (prairie dogs and humans) and spread to at least six other states. That unexpected agent, previously unseen in the United States, was a member of the orthopoxvirus group known as monkeypox (CDC, 2003b). It brought a scare to a public health and homeland security infrastructure, already in a state of heightened awareness for smallpox, and challenged the ability to address an emergent health threat in the United States that did not conveniently fall under the domain of any single federal agency.

In mid-May 2003, the first human cases of a febrile vesicular rash in the United States were examined by physicians in Illinois and Wisconsin. By June 10, a total of 53 cases were being investigated, 51 of which reported contact with a companion animal prairie dog. The Marshfield Clinic in Marshfield, Wisconsin, isolated and identified a virus from vesicular lesions of a human patient and from lymph nodes of the patient’s companion animal prairie dog. That virus, when examined by electron microscopy, resembled a poxvirus. The U.S. Centers for Disease Control and Prevention (CDC) subsequently identified it as monkeypox (CDC, 2003b). Spread of this poxvirus had peaked by early June, but in total over 70 cases from six states—Illinois, Wisconsin, Indiana, Kansas, Missouri, and Ohio—were reported over an approximately 3-month period. In Indiana, 28 children were exposed to a companion animal prairie dog, and seven became ill following this exposure (Langkop et al., 2003).

How did this virus make its way from exotic rodents in Ghana to a classroom in the heartland of the United States? Did it cause clinical signs in animals? Knowing that rodents in Africa carry monkeypox, why were these animals allowed into the United States, or at least not tested for the virus before entry? Who had responsibility for surveillance, identification, and response to this foreign zoonotic agent in exotic companion animals? These were some questions the committee asked while studying the monkeypox outbreak.

the monkeypox, which were distributed to eight states through “swap meets” where exotic animal aficionados gather to trade specimens.

Poor or no sales records are kept at swap meets, all of which complicated efforts to trace back and trace forward animals from the original

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
×

shipment and exposure contacts. At the time that the first human cases were being examined, the extent of the problem in animals was not understood, nor was it known that exposure to prairie dogs (and only prairie dogs) would turn out to be central to human cases. Also not known, at that time or at present, was the susceptibility of various animal species to monkeypox infection. Vendors of exotic companion animals often keep an impressive variety of species, many of which could have been susceptible. Once a definitive diagnosis was made, the Centers for Disease Control and Prevention (CDC) took a lead role in notifying regulatory officials of the outbreak.

On June 11, 2003, CDC and the Food and Drug Administration (FDA) issued a joint order that announced an immediate embargo on the importation of rodents from Africa and banned any sale, offering for distribution, transport, or release into the environment of prairie dogs and six genera of African rodents potentially involved in the spread of monkeypox in the United States (CDC, 2003b). CDC has jurisdiction over the importation section of the rule, while FDA has jurisdiction over movement of animals between and within states. On November 4, 2003, the joint order was replaced by an interim final rule that maintains the bans on importation of these rodents and their sale or distribution. These actions were taken by the Department of Health and Human Services under the authority granted in Section 361 of the Public Health Service Act (42 U.S.C. 264). Section 361 grants the Secretary of Health and Human Services the authority to make and enforce regulations to prevent the introduction, transmission, or spread of communicable disease from foreign countries into the United States or from one state to another. States are free, within their legal authority, to enact other regulations as long as those regulations do not conflict with the interim final rule. Enforcement of this rule relies on the CDC and FDA working collaboratively with other federal and state agencies. Many federal, state, and local agencies have authorities related to the animals involved, including the USDA and state departments of agriculture, which oversee the trade in these animals within the United States; and the Bureau of Customs and Border Protection of the Department of Homeland Security and the Fish and Wildlife Service of the Department of the Interior, which have statutory authority for enforcing importation embargos. The interim final rule addresses many of the issues surrounding importation and movement of exotic rodents into and within the United States. However, it does not ban the importation of all exotic animals.

The monkeypox outbreak revealed that:

  • The infrastructure that exists for preventing animal disease outbreaks is focused primarily on livestock, including poultry and farmed

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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aquatic animals. There is no equivalent federal responsibility and only an informal federal animal health infrastructure for addressing a zoonotic disease outbreak transmitted by a nonlivestock species.

Diagnostic Laboratory Capacity

State and academic veterinary diagnostic laboratories play a central role in diagnosing diseases such as monkeypox. As the monkeypox outbreak illustrates, the broad capabilities that exist in state and academic veterinary diagnostic laboratories and other local animal health infrastructure are currently underutilized and underconsulted by federal agencies and national organizations and by the public health community.

The monkeypox outbreak also points to weaknesses in the veterinary laboratory infrastructure in the United States. Far too few biosafety level 3 (BSL-3) laboratories and ABSL-3 animal facilities exist in the state laboratory system, universities, and industries (AAVMC, personal communication and informal survey, 2004). Rapid assays for zoonotic agents, whether endemic or exotic, have not been validated in animals. Assays validated for identification of exotic or bioterrorist agents in human samples (such as the non-variola rapid real-time polymerase chain reaction (PCR) assay used for diagnosis of monkeypox) do not have animal species or matrix controls. Further complicating this issue is that no federal agency has a mandate to develop and validate these assays. USDA is fully committed with livestock disease assay development and validation, and CDC is focused on development of additional assays for the broad array of high consequence pathogens affecting humans. The diagnosis of overlap agents in animals has fallen through the cracks. Good laboratory practice includes training and proficiency testing of laboratory staff in use of equipment and specific protocols, but neither the Laboratory Response Network for bioterrorism nor the National Animal Health Laboratory Network currently has responsibility for ensuring that these tenets of a quality system are in place in veterinary diagnostic laboratories. In summary, the monkeypox outbreak revealed significant gaps in prevention, problems with responsibilities, and coordination of response and in laboratory capacity, especially concerning delays in the development and validation of diagnostic assays.

Bovine Spongiform Encephalopathy

The diagnosis of bovine spongiform encephalopathy (BSE) in Canada and the United States in 2003 (see Box 3-4) and in 2005 carried with it a message that North America was not immune to the socioeconomic effects of what is commonly known as mad cow disease. Disruptions in the

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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BOX 3-4
Single Case of Bovine Spongiform Encephalopathy (BSE) in Washington State: An Unexpected Opportunity for Insight into Our Framework for Preventing, Detecting, and Diagnosing Animal Diseases

On the morning of December 25, 2003, the BSE World Reference Laboratory in Weybridge, England, confirmed USDA’s December 23 preliminary diagnosis of BSE in a single nonambulatory dairy cow that had been slaughtered on December 9 at Vern’s Moses Lake Meats in Washington State. USDA and Canadian officials worked together to confirm the identification of this cow through DNA testing and to establish that the animal was imported from Canada.

BSE (or “mad cow” disease) is a neurodegenerative disease transmitted to cattle through contaminated feed. It has an incubation period of 4–6 years. It is caused by an aberrant form of a protein called a prion and is in the family of diseases—all caused by prions—referred to as transmissible spongiform encephalopathies, or TSEs. The prion is an abnormally folded version of a normal cellular protein. The abnormal conformation results in a phenotype that is highly resistant to degradation and can persist in an infectious form during the rendering of contaminated bovine by-products for animal feeds, and the preparation of other products such as cosmetics and drugs using ingredients derived from cattle.

Unlike other agents (such as FMD virus), the prion is not contagious. Although it is considered “infectious,” it is not spread directly from one animal to another. It carries a low risk of spreading to animals in the United States (Harvard risk assessment). The overall public health risk of develop-

supply of meat can shake consumer confidence, resulting in reduced demand, and can significantly disrupt trade of meat and meat products for a prolonged period. Establishing countrywide disease-free status once a case is diagnosed can be extremely difficult. According to a panel of experts from the European Association for Animal Production, the estimated total cost of BSE in Europe is €92 billion, nearly $115 billion dollars (EAAP, 2003). It had been estimated that a single case of BSE in either Canada or the United States would cost their respective beef industries $3.3 billion CAD and $6 billion USD, respectively (CBC News, 2003; Presley, 2004).

The onset of BSE in Great Britain led the United States to carry out an extensive analysis and forge policies based on risk factors associated with the disease, even though the disease was not present; this marked a significant departure from the past (USDA APHIS-VS, 1991). Trade in animal feed has been extensive in North America. Rendered by-products

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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ing variant Creutzfeldt-Jakob disease (vCJD, the human variant of the disease, which is acquired through consumption of prion-contaminated meats) from a few cases in the bovine population or through blood transfusion is extremely, almost infinitesimally small.

At present, immunohistochemistry and immunoblot are widely considered in the international community the two gold standards to test for BSE.

The key to prevention is to ensure that high-risk materials from cattle are not incorporated into the feed supply. Enforcement is critical to the success of this approach. When enforcement cannot be guaranteed, a complete ban on feeding of ruminant by-products may be necessary.

In this case, the USDA Food Safety and Inspection Service recalled over 10,000 pounds of meat to prevent human food contamination. The recall involved by-products from 20 BSE-infected cattle, including 2,000 tons of potentially infectious feed, which had already been processed and exported to foreign ports. Over 700 animals were slaughtered during the traceback and traceforward investigation, while the U.S. beef industry continued to see a loss of export markets.

Lessons identified from the BSE experience included the following:

  • The U.S. animal health community realized that BSE can no longer be considered a problem only for other nations.

  • In contrast to traceback required for a highly contagious diseases like FMD and classical swine fever, comprehensive tracing required for a disease like BSE, with such a prolonged incubation period and likely exposure as a young calf, was nearly impossible within the current U.S. system of animal tracking and identification.

from the United Kingdom were freely imported into North America prior to an understanding of the potential of these products to transmit BSE. In addition, U.S. and Canadian restrictions that ban feeding of ruminant by-products to other ruminants were not implemented until 1997, and even then compliance, at least in the United States, may not have been optimal. Thus, the advanced age (6½ years) of the BSE-infected animal in the United States placed her, and her birth cohorts, at risk of exposure to BSE-contaminated ruminant by-products as a calf.

The BSE prion (PrPres) concentrates almost exclusively in nervous tissue in cattle and is found in highest concentrations in the brain, eyeballs, spinal cord, and dorsal root ganglia. In younger animals, the distal ileum, or last segment of the small intestine, can also harbor PrPres. This is the basis for concentrating on control of these so-called specified risk materials (SRMs). Appropriate quality control can ensure that these mate-

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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rials are not used for ruminant feed or human food. An added level of assurance can be provided by a complete ban on feeding of ruminant products back to ruminants, while complete assurance can only be provided by a complete ban on the use of ruminant by-products. In examining the 2003 BSE case, the committee concluded the following:

  • The key to preventing an accidental introduction of BSE into the United States, as well as preventing subsequent transmission to other animals and humans, is recognition of the sources of infection and means of spread. Control of import, production, and distribution of ruminant by-products for feed, food, drugs, and cosmetics is essential.

  • A risk-based approach is best used to determine what level of control should be implemented. The World Animal Health Organization provides a model for risk analysis.

In the United States, several additional control steps were taken following the discovery of the BSE-infected animal in December 2003. They included prohibition of all nonambulatory, or “downer,” cattle and SRMs (skull, brain, trigeminal ganglia, eyes, vertebral column, spinal cord, and dorsal root ganglia of cattle over 30 months of age and a portion of the small intestine of cattle of all ages) from the human food chain; prohibition of a meat label for dorsal root ganglia that might be present in products obtained through advanced meat recovery processes; prohibition of air injection stunning of cattle at slaughter; prohibition of mechanically separated meat in human food; holding product from BSE-tested animals until a final diagnosis has been made; and immediate implementation of a national animal identification system. These new rules were published in the Federal Register on January 12, 2004.

BSE does not generate a typical host immune response. To date there has been no demonstration of antibodies generated to the abnormal prion variant in any affected species. Thus, traditional methods of infectious disease control by vaccination hold little if any promise for BSE. Perhaps it is possible to stop infection of cattle by means other than preventing exposure. To address this possibility, further research on the process of uptake and dissemination of the abnormal prion and conversion of normal prion to the abnormal variant is necessary. With a better understanding of the pathogenesis of these unique agents may come novel methods of prevention through blocking of transmission or disease progression, which leads to the following conclusion:

  • Early detection of BSE relies on recognition of clinical signs and testing of the appropriate, high-risk population of animals.

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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While a thorough discussion of surveillance is not within the scope of this report, the committee recognizes that surveillance of high-risk animals (nonambulatory, with or without central nervous system signs) provides the highest sensitivity of early detection of BSE. The surveillance program implemented by the United States in June 2004 is designed to detect a level of BSE as low as five cases in the U.S. high-risk group.

At the time of publication of this report, a second BSE case had just been confirmed in the United States. A downer cow initially tested “inconclusive” for BSE via enzyme-linked immunosorbent assay (ELISA) rapid screening and immunohistochemical (IHC) tests in November 2004, but a later immunoblot (Western blot) test resulted in a “weak positive.” The sample was retested in June 2005 at the world reference laboratory for BSE in Weybridge, England, and was confirmed positive using a combination of rapid, Western blot, and IHC tests (USDA, 2005). This case raises questions about the type and accuracy of diagnostic tests used by USDA to confirm an initial reactor in the ELISA assay.

Diagnosis of BSE relies on the use of ELISA assays, Western blots, or IHC tests. Each of these assays requires sampling of brain from dead animals and demonstrates through antibody binding the presence of the abnormal prion, PrPres. All of the currently approved assays have excellent sensitivity in older animals (30 months and older). However, in younger animals, the prion is either not present or is present at such low levels in the target tissues that it cannot be detected. The decision on which assay is used depends upon test purpose and the fitness of each assay for that purpose. High throughput formats are most commonly used for surveillance purposes to facilitate testing of large numbers of animals. Immunohistochemistry, in which the presence of the abnormal prion is visualized under the microscope in a section of brain by a trained pathologist, and Western blots, in which the abnormal prion in the brain can be visualized and its approximate molecular weight determined after separation from other proteins in the brain based on its size and resistance to enzymes, are widely considered gold standard tests. Immunohistochemistry, however, cannot be used for high throughput testing, in which rapid turnaround is required, as results typically are not available for 2–4 days, leading to this lesson learned:

  • There is no available method for diagnosing BSE in young calves, when infection first occurs, or in live animals.

At the time of this writing, additional tests were in the process of approval in the United States. Most of these assays have been used extensively in Europe, but the USDA had not comprehensively adopted these assays before the 2003 occurrence of BSE in North America. However, a

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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gap in all testing procedures is the reliance on a sample of brain taken from an older, dead animal. Since infection of cattle occurs in young calves, the ability to sensitively detect young infected calves using a sample from a live animal would be a significant advance. Current research on diagnostics focuses on the development of a sensitive live animal test. Unfortunately, this is a challenge in BSE, since experimental data suggest that the abnormal BSE prion is either not present or is rarely and inconsistently present in blood and lymphoid tissue, unlike scrapie which is present in both blood and lymphoid tissue or chronic wasting disease (CWD), which is consistently present in lymphoid tissue (Hunter et al., 2002; Hibler et al., 2003). For this reason, current research focuses on finding surrogate markers of BSE infection by understanding the host response that leads to conversion of the normal prion to the abnormal variant.

PREVIOUSLY UNKNOWN AGENTS

Severe Acute Respiratory Syndrome (SARS) Coronavirus

Severe acute respiratory syndrome (SARS) is a viral respiratory illness caused by the SARS coronavirus (SARS CoV). SARS was first reported in Asia in February 2003. Over the next few months, the illness spread to more than two dozen countries in North America, South America, Europe, and Asia before the SARS global outbreak was contained. (See Box 3-5 for a description of the outbreak.) According to the World Health Organization (WHO), a total of 8,098 people worldwide became sick with SARS during the 2003 outbreak. Of these, 774 died. In the United States, only eight people had laboratory evidence of SARS-CoV infection. However, in addition to the direct health costs of treating those people and testing others, as with FMDV and other exotic diseases, SARS had devastating effects on both global travel and trade, and its social and economic global impacts were disproportionate to the number of actual fatalities. Due to concern about spread of the disease, there were increased medical facility costs to prevent the spread of the highly contagious disease, altered travel plans (both business and pleasure), and additional precautions taken in airline travel. The infection of large numbers of health care workers, coupled with exhausting demands on the remaining staff, created additional burdens for the severely stressed health care systems. Economists have estimated the global economic loss from SARS at close to $40 billion in 2003 (Lee and McKibbin, 2004).

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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International Collaboration, Coordination, and Outreach

Lacking the research and investigative capacity to control the SARS epidemic, WHO elicited public health service partners from countries such as the United States, the United Kingdom, Germany, and France. WHO’s international Global Alert and Response Network (GOARN) is a virtual network of 11 leading, well-equipped, and high biosecurity infectious disease labs in nine countries established primarily to address influenza outbreaks. GOARN was instrumental in spearheading laboratory efforts: these labs were connected by secure web sites and daily teleconferences to identify the causative agent of SARS, develop diagnostic tests, and collect and analyze clinical and epidemiological data on SARS. The U.S. CDC established other virtual teams in the United States, eliciting advice from medical experts, epidemiologists, and virologists, including both biomedical and veterinary coronavirus experts. Highly trained personnel from the CDC were dispatched to outbreak areas to assist in infection control, and numerous CDC employees were involved in all aspects of the response to SARS. To educate the public by countering rumors with reliable information, both WHO and the CDC provided factual information on SARS through updated web sites, satellite broadcasts, frequent presentations to the news media, and public response hotlines for clinicians and the general public.

These exceptional international laboratory efforts led to the rapid identification of a new coronavirus as the causative agent of SARS by April 16, 2003, only about 1 month after the initial WHO global alert (Drosten et al., 2003; Ksiazek et al., 2003; Peiris et al., 2003; Poutanen et al., 2003). Although vaccines or antivirals to prevent or control SARS infections were lacking, the SARS epidemic was countered by classical infection control and containment methods. These included screening of individuals for symptoms (fevers) with isolation, quarantine, and effective clinical management of symptomatic patients, followed by contact tracing and 10-day quarantine of known contacts. Implementation of effective surveillance measures, identification of the causative agent of SARS as a coronavirus, and containment of the SARS epidemic were attributed to this unparalleled level of global cooperation. Two features of the global SARS outbreaks include the following:

  • SARS had devastating social and economic global impacts disproportionate to the number of actual fatalities and affecting both global travel and trade.

  • International collaboration and communication among agencies and with scientists in established laboratory networks with prior working relationships and access to state-of-the-art equipment and the required biosecurity level were key elements for rapid and successful SARS diagnosis and control.

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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BOX 3-5
The 2003 SARS Outbreak

Atypical pneumonia cases, later characterized as SARS, first occurred in the Guangdong Province of China in mid-November 2002. Early data suggested a possible zoonosis, with the earliest SARS cases detected among workers dealing with exotic food animals. In subsequent studies, SARS-like coronaviruses were detected or isolated from two wild animal species in live animal markets, the masked palm civets (Paguma larvata) and raccoon dogs (Nyctereutes procyonoides), although the natural animal reservoir remains uncertain. Further studies have documented that nonhuman primates, ferrets, domestic cats, mice, and hamsters are also susceptible to experimental SARS coronavirus (Fouchier et al., 2003; Guan et al., 2003; Martina et al., 2003; Glass et al., 2004; McAuliffe et al., 2004; Roberts et al., 2005); pigs in China were naturally infected with a human-like SARS strain lacking the 29-nt insertion (Chen et al., 2005). Conversely, civets are susceptible to infection and disease with at least two human strains of SARS CoVs: one early human isolate (GZ01) with the 29-nt insertion like the civet strains, and one later human strain (BJ01) without the 29-nt insertion (Wu et al., 2005). Similar exotic animal markets also provided a breeding ground for recent influenza outbreaks in Hong Kong. The unsanitary conditions in live animal markets in China (and elsewhere) foster an environment conducive to the emergence of new zoonotic and animal diseases and likely played a role in SARS transmission from animals to humans (Peiris et al., 2004; Xu et al., 2004).

Global spread of the SARS epidemic was triggered on February 21, 2003, by a superspreading event in the Metropole Hotel in Hong Kong by an infected physician from Zhongshan University in China. Within 24 hours, he infected others at the hotel, who then carried SARS to Singapore, Vietnam, Canada, Ireland, and the United States, besides elsewhere in Hong Kong. Based on WHO estimates, this superspreader initiated a chain of infection involving nearly half of the 8,000 cases in more than 30 countries. On March 12, 2003, the World Health Organization (WHO) issued a global alert describing atypical pneumonia cases (severe acute respiratory syndrome or SARS) in Hong Kong and Vietnam and initiated worldwide surveillance. In an unprecedented move on March 15, WHO issued a travel advisory regarding high-risk areas where SARS outbreaks had been detected. The agency continued to issue travel advisories and advise airline passenger screening from high-risk areas through mid-April 2003.

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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From mid-March to April 2003, a second major outbreak of SARS occurred in another location in Hong Kong, the Amoy Gardens Apartments, with 321 people ultimately infected (Chim et al., 2003). This outbreak was more severe clinically, with more diarrhea cases (73 percent), higher intensive care unit admissions (32 percent), and higher mortality rates (13 percent) than in the Metropole Hotel outbreak. Environmental factors (in a faulty sewage system) were postulated to have contributed to the virus spread in the Amoy Gardens via aerosolized fecal material.

SARS did not spare developed countries, even ones with modern public health systems and significant resources. Canada had an outbreak of SARS on February 23, 2003, imported from Hong Kong. A second outbreak followed in mid-May 2003 after a lapse in infection control. Also because of a delayed initial response, SARS was not controlled in China until late June 2003. By that time, over 5,000 cases had been reported. On July 5, 2003, after control of a Taiwan outbreak, WHO reported that the global SARS epidemic had been contained. However on September 8, 2003, a single case of SARS was reported in Singapore (confirmed by the CDC). This individual likely became infected via laboratory-acquired exposure to SARS coronavirus, illustrating the need for strict adherence to laboratory safety procedures required for work with BSL-3 level pathogens. The widespread distribution of SARS coronavirus samples in international labs highlights the need for vigilance in the inventory of these virus stocks. Also, adequate laboratory supervision and facilities are required to avoid future laboratory acquired infections as a possible source of new SARS outbreaks.

In December 2003–January 2004, several new SARS cases reemerged in Guangdong Province, China (Normile, 2004). For at least one case, no risk factor was identified such as a link to civets. Other postulated reservoirs including rats and cats were tested, but no final conclusions were drawn concerning the origin of this reemergent case. However, sequence data suggested that the reemerged SARS coronavirus strains were more like the civet isolates (Normile, 2004), and China ordered the destruction of large numbers of civets in its wildlife markets (Watts, 2004). Recent data based on serology suggest that some SARS antibody seropositives occurred in Hong Kong in 2001 before the documented SARS outbreaks, suggesting that low numbers of subclinical SARS infections likely occur (Zheng et al., 2004). Thus both animal reservoirs and subclinically infected humans remain potential sources for the reemergence of SARS.

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Links between Veterinary Research and Public Health

The veterinary coronavirus (CoV) research community provided important resources and an extensive background perspective on coronavirus biology, contributing to an improved understanding of SARS evolution and infections. From the isolation of genetically similar CoV from civets and raccoon dogs in live animal markets in China, scientists postulate that SARS evolved from a wild animal host (Guan et al., 2003). Many of the earliest SARS cases and SARS antibody detections occurred among workers who had contact with exotic food animals in Guangdong animal markets (Guan et al., 2003; Xu et al., 2004). The unsanitary and crowded conditions, with multiple species in close contact in live animal markets in China (and elsewhere), fosters an environment conducive to the emergence of new zoonotic and animal diseases and likely played a role in the putative transmission of SARS from animals to humans. The published evidence and epidemiological data suggest that SARS was a probable zoonosis (Guan et al., 2003; Peiris et al., 2004; Xu et al., 2004; Wu et al., 2005). These markets also provided a breeding ground for the 1997 avian influenza outbreaks in humans in Hong Kong (Hampton, 2004). Prior studies of animal CoVs have shown that interspecies transmission of CoVs is not unprecedented (Tsunemitsu et al., 1995; Ismail et al., 2001). However, the determinants of CoV host-range specificity and the potential of wildlife as reservoirs for emergence of other CoV strains of potential threat to public or animal health are unknown.

In addition, respiratory and enteric CoV infections in the natural animal host (swine, cattle, poultry) have provided important information on CoV disease pathogenesis and possible potentiators for increased disease severity applicable to SARS CoV infections. Enteric CoV infections alone frequently cause fatal infections in young animals. However in adults, respiratory CoV infections are more severe or often fatal when they are combined with other factors including stress and transport of animals (shipping fever of cattle), high exposure doses, aerosols, treatment with corticosteroids, and other respiratory co-infections (viruses, bacteria, bacterial lipopolysaccharides) (Saif, 2004). Such variables may influence the severity of SARS or contribute to the phenomena of superspreaders.

Thus coronaviruses, largely ignored by the biomedical research community and public health funding agencies because of low-impact human infections, are a recognized and significant cause of potentially fatal respiratory and intestinal infections in animals. This knowledge base of animal coronavirus pathogenesis, vaccines, and basic studies of coronavirus replication strategies and development of infectious clones contributed to rapid progress in characterization of SARS coronavirus and is critical for

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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future SARS vaccine and antiviral strategies. Lessons of the global SARS outbreaks include the following:

  • Wild animals transported from their native habitat or forms and introduced into live animal markets may harbor unknown disease agents such as SARS that are transmissible to humans.

  • Veterinary science research contributed to the understanding of SARS CoV pathogenesis, particularly its potential for interspecies transmission and fatal disease, which had significant implications for public health.

  • There is a need for greater collaboration between the animal health and medical research communities in studying the pathogenesis of previously unknown and likely zoonotic agents such as SARS. In the case of SARS, research ties and interagency funding and cooperation are lacking to promote collaborative infectious and zoonotic disease research between biomedical and veterinary scientists and to provide trained biomedical and veterinary public health personnel. Furthermore, funds are lacking to study disease pathogenesis in the appropriate animal host and to investigate zoonotic diseases including identifying animal reservoirs and the mechanisms and chain of interspecies transmission.

Diagnostic Techniques

Classical virological techniques (such as electron microscopy [EM], cell culture, and immunofluorescence), as well as new molecular approaches (microarray) were essential for identification of the previously unrecognized SARS coronavirus. Many diagnostic labs are phasing out EM and/or cell culture facilities because of costs or lack of trained personnel and putting more emphasis on molecular techniques. However, most current molecular approaches (RT-PCR with specific primers) or serology are designed to detect known, but not unknown or new, pathogens. In addition, the focus of public health agencies (CDC, WHO) is on development and validation of diagnostic tests for SARS applicable to humans. These tests, especially antibody assays, lack validation for use in various animal species or lack animal coronavirus controls, creating difficulties for assay development and interpretation of results from testing wild or domestic animals. Little funding is available from federal agencies to stimulate development of new or improved diagnostic assays for humans and animals, including ones targeted to identification of microbial nucleic acid signatures, or to study the relationships of pathogens common to animals and humans or their disease mechanisms or persistence in the animal host. Development and availability of standardized validated test protocols, reagents, and controls is essential for reliable diagnostic tests to

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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monitor SARS cases in the early stages of infection. Accurate tests also require reagents and testing of both human and animal CoV strains as controls to eliminate confounding cross-reactivities and to identify the animal reservoir for SARS.

ENDEMIC DISEASES: AVIAN INFLUENZA, CHRONIC WASTING DISEASE, AND WEST NILE VIRUS

A large array of indigenous diseases could serve as case studies in the category of endemic disease. The committee selected three diseases, including avian influenza (AI), which it chose for four reasons: (1) it has been a recurring disease problem that has caused significant economic loss to the poultry industry in the United States; (2) strains of the influenza virus that could cause a human pandemic can emerge; (3) it occurs in many countries; and (4) strains are harbored in migratory waterfowl. The committee looked at chronic wasting disease (CWD) to illustrate the potential of wildlife disease to decimate wildlife populations, the danger of translocation of animals in spreading diseases, and public concern about transmissible spongiform encephalopathies (TSEs). CWD was selected as an example of a serious disease that is, at this point, exclusively a problem of wildlife and game farms, specifically elk and deer (cervids) in North America. Diseases of wildlife are a concern, not only because wild animal populations can be depleted by diseases (with potential ramifications for biodiversity and ecological integrity), but also because wild animals can be reservoirs of indigenous and exotic infectious diseases of domestic animals and reservoirs of human zoonoses. Game animals can be a source of infectious disease agents into the human food chain. The third disease selected for analysis, West Nile virus (WNV), is an example of a disease that will likely persist in North American wildlife and remain a constant threat to domestic animals and people. All of these diseases illustrate the consequences of increasing biological connectedness in today’s world. At one time these agents may have been considered as newly emergent, but they have now become firmly established in North America and for the purposes of this report are considered endemic.

Avian Influenza

Of the diseases examined in this chapter, AI (also called “bird-flu”) could arguably be the most representative for evaluating comprehensiveness of the animal health infrastructure. The virus has the potential to impact public health, production animals (e.g., poultry and swine industries), and wildlife (e.g., waterfowl and migratory birds). It is on the list of potential biothreat agents, and the CDC and state departments of public

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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health address it annually in their Pandemic Disease Plans. Enhanced government awareness of biological threats and the associated “culture of fear” following the September 11, 2001, attacks and the terrorist anthrax letters is still very apparent in the public media, yet the most probable and real threat, that of a pandemic due to influenza virus, has received relatively little attention beyond the scientific community. Since the 1997 H5N1 avian influenza virus adapted to humans, the academic and public health communities have warned of the potential for an influenza pandemic, a global outbreak that could mimic the 1918 Spanish flu outbreak. The 1918 Spanish flu caused the single deadliest epidemic in history, killing between 20 and 50 million people in just half a year (IOM, 2003, 2005). In 2004, a virulent strain of H5N1 avian influenza virus spread through numerous Asian countries. The virus jumped species 6 months into the outbreak, making humans susceptible to infection (CDC, 2004c). By January 2005, the situation in Southeast Asia had worsened as the H5N1 virus continued to spread into the human and bird populations. As of January 2005, the H5N1 avian influenza virus killed 34 of 47 infected humans and resulted in the death and depopulation of over 100 million birds, primarily commercial poultry, as well as uncounted numbers of wild birds. More significantly, in September 2004, AI apparently spread not from a bird to a human, but directly from an infected child to her mother (Ungchusak et al., 2005). The demonstrated ability of the virus to spread from one human to another makes the possibility of a pandemic a significant threat.

Influenza prevention measures for susceptible animals, primarily swine and poultry, rely on vaccination, quarantine, and depopulation. These measures failed to contain the 2004 spread of Asian H5N1 influenza. In the public health domain, an October 2004 announcement that 48 million of the expected 250 million global doses of influenza vaccine would not be available due to closure of a vaccine producer’s facility clearly amplifies the threat of unchecked spread should the virus establish itself in humans (HHS, 2004).

Nature of the Pathogen

Avian influenza viruses are endemic in wild bird and migratory waterfowl populations and can be transmitted to domestic poultry. Table 3-2 provides a summary of key events linked to the identification and spread of the disease. Some influenza subtypes are also capable of infecting mammalian species, in particular swine and humans. The pathogenicity of these viruses (of which there are 15 known subtypes identified as H1–H15) can be classified as low to high, dependent on the severity of disease caused. Of the 15 avian influenza virus subtypes, H5N1 is of particular

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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TABLE 3-2 Timeline of Key Influenza Events

1878

Fowl plague (FP) was described as a serious disease in chickens in Italy.

1918

Spanish flu (influenza A) pandemic claimed 20 to 50 million lives worldwide in less than a year and ranks among the worst disasters in human history. In the United States alone, an estimated 1 in 4 people became ill and 675,000 people died (Crosby, 1989). Recent studies now suggest this historic pandemic was associated with interspecies transmission of an avian influenza virus (Hampton, 2004; Stevens et al., 2004).

1955

Fowl plague virus was determined to be one of the influenza viruses.

1984-1985

Outbreak of avian influenza virus H5N2 in poultry in the Northeast United States. It initially caused low mortality, but within 6 months had mutated to a highly pathogenic virus causing nearly 90 percent mortality. The outbreak cost over $65 million and resulted in the destruction of 17 million birds.

1992

An avian influenza virus H5N2, identified as “low pathogenecity” in Mexico, mutated to a highly pathogenic form and continued to spread until 1995. In 1999, an Italian H7N1 virus had a similar pattern of mutation over a 9-month period and was not controlled until 2001. The 2001 Italian losses are estimated at 13 million birds.

1997

The first documented AI infection of humans occurred in Hong Kong when the H5N1 strain caused severe respiratory disease in 18 humans, of whom 6 died. Extensive investigation determined that close contact with live infected poultry was the source of the human infection. Studies at the genetic level further determined that the virus had jumped directly from birds to humans but had only very limited human-to-human spread.

concern because it mutates rapidly and has a documented propensity to acquire genes from viruses infecting other animal species (WHO, 2004). The majority of avian influenza viruses have low pathogenicity, typically causing little or no clinical disease in infected birds, particularly migratory waterfowl, which serve as a reservoir of the virus. The highly pathogenic strains may be associated with mortality close to 100 percent (Easterday et al., 1997; WHO, 2004). The highly pathogenic influenza virus subtypes can cause significant economic losses to poultry, impinge on international trade, and, if transmitted to humans, pose public health risks with the potential to initiate deadly human influenza pandemics. The virus is additionally considered a potential biothreat agent based on its abil-

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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2003

A 57-year-old veterinarian who visited a poultry farm affected by the H7N7 strain died on April 17, 2003, of acute respiratory distress syndrome in the Netherlands. H7N7 influenza virus was isolated from the patient. No other respiratory pathogen was detected in a series of laboratory tests (WHO, 2003).

 

West Virginia initiated preemptive disease eradication efforts in cooperation with the USDA after observing mutation of a circulating low pathogenecity H7N2 virus toward high pathogenecity. Texas initiated similar control efforts directed at low pathogenic avian influenza a few years earlier.

2004

In early 2004, a similar situation played out in the Northeast United States associated with a rapidly spreading, low pathogenecity H7N2 influenza variant. More than 400,000 chickens in two states were destroyed, and additional farms quarantined following detection of the H7N2 influenza virus. International trade restrictions were also imposed on the United States within days of the first cases being reported.

 

In Canada, at least 17 million poultry died or were destroyed to contain the spread of Canada’s first reported detection of highly pathogenic influenza, an H7N3 virus, which also occurred as a low pathogenic form of the virus on the same farm.

 

In Texas, 8,900 chickens were destroyed following detection of a highly pathogenic variant of H5N2, which was the first detection of a highly pathogenic strain since 1984 in the United States.

 

Thijs Kuiken and colleagues at the Erasmus Medical Centre in the Netherlands found that cats could become infected and spread the avian influenza virus H5N1 (Kuiken et al., 2004).

 

Beginning in January 2004 and continuing into 2005, an outbreak of highly pathogenic H5N1 avian influenza spread through 11 Southeast Asian countries, affecting millions of birds, including multiple avian species. By January 2005, the outbreak had resulted in the deaths of 34 of 47 people infected in two different countries (WHO, 2005).

ity to spread easily and rapidly as a respiratory infection in both animal and human populations. Influenza virus outbreaks can directly involve federal, state, and local agencies as diverse as those that deal with homeland security, public health, agriculture, interior, commerce and trade, natural resources, and environmental quality.

Interspecies Transmission (Particularly to Humans)

In 1997, the first documented case of avian influenza transmission to humans occurred in Hong Kong, affecting 18 people, killing 6, and resulting in the destruction of 1.5 million birds in efforts to eliminate the variant

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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virus. Since 1997 several instances of bird-to-human transmission have occurred, and recent studies suggest that the historic Spanish flu pandemic of 1918 was associated with interspecies transmission of an avian influenza virus (Hampton, 2004). In 1999 (Hong Kong and China H9N2), 2003 (Hong Kong H5N1, Netherlands H7N7, Hong Kong H9N2), and 2004 (Viet Nam and Thailand H5N1), avian influenza was transmitted from birds to humans, in some cases resulting in death of infected individuals. In the recent bird-to-human scenarios, little transmission of the avian influenza virus from human to human was detected. However, public heath officials fear the possibility of a human influenza virus and an avian influenza virus infecting the same individual and “reassorting” or trading genes, to produce a highly lethal virus capable of rapidly spreading in the human population.

Cause for Concern—Possibility for Human-to-Human Transmission and Mutations of Low-Pathogenic Viruses

Should an avian influenza virus unfamiliar to the human population gain the ability for human-to-human transmission, the predicted outcome is a pandemic with serious disease and death globally. In the three influenza pandemics that occurred during the past 100 years, all spread worldwide within 1 year, causing significant social and economic disruption. (The 1918 Spanish flu resulted in nearly 675,000 deaths in the United States, the 1957 Asian flu caused 70,000 deaths, and the 1968 Hong Kong flu caused 34,000 deaths.) Once established in the human population, influenza viruses tend to persist and significantly affect human health for years. The CDC and WHO continuously monitor and react to influenza viruses, with the primary goal to watch spread and determine vaccine strains, but also with the goal of preventing or controlling the emergence of a new and potentially pandemic influenza virus.

As the 1984–1985, 1992, and 2001 outbreaks in poultry illustrate, influenza viruses of low pathogenicity have the capacity to mutate into highly pathogenic strains, sometimes after very short periods of circulation in poultry populations. Aggressive surveillance, detection, and disease control, generally including total depopulation of poultry in the area, are considered critical to minimize transmission, control economic losses, and eliminate the public health risks associated with human exposure to highly pathogenic avian influenza viruses. As Table 3-2 indicates, individual states have initiated preemptive disease eradication efforts in cooperation with USDA APHIS and their poultry industries after observing mutation of a circulating low pathogenecity H7N2 virus toward high pathogenecity. Though effective, the low pathogenecity influenza eradi-

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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cation programs were initially hindered by lack of defined USDA regulatory authority for endemic diseases and absence of an established indemnity program for the depopulated birds.

In February 2004, prompted by the H5 avian influenza outbreaks in Southeast Asia, HHS and USDA officials cooperatively announced a ban on importation of birds from eight Asian countries. Globally, public health as well as animal health agencies have closely followed the appearance and movement in 2004 of H5 avian influenza viruses in poultry and are particularly concerned about its rapid spread through Asia, where acceptance or compliance with slaughter-based control efforts is considered not economically feasible or socially acceptable. The millions of affected birds, commingling of different avian and mammalian species, difficulty in protecting poultry workers from respiratory exposure, and the recognition of bird-to-human transmission have placed the global community on high alert for the potential evolution of a pandemic influenza virus. The committee drew the following conclusions regarding AI:

  • Gaps in scientific knowledge, focused and applied research, understanding of disease risks, and lack of access to validated rapid detection methodologies have complicated and jeopardized effective and timely responses to AI.

  • Lack of a standardized reporting mechanism among animal health agencies has delayed laboratory findings and epidemiological investigations.

  • Though clearly defined for highly pathogenic avian influenza, the regulatory lines of authority are not defined for endemic (low pathogenecity) avian influenza, hindering the nation’s ability to prevent a potentially devastating disease situation.

Chronic Wasting Disease

As a prion-associated transmissible spongiform encephalopathy (TSE), CWD belongs to a group of diseases that merit careful study and monitoring (NRC, 2004a). Over a relatively short time span, CWD has become a major problem in some U.S. western and midwestern states, affecting both farmed and wild cervids, thus impacting the markets for farmed cervids and cervid products and for wildlife-related recreation and aesthetics. While there is no conclusive evidence to date that a CWD prion has caused naturally occurring disease in domestic animals or people, research needs to continue to determine whether this disease is a threat to other than cervid species (Belay et al., 2004).

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Occurrence and Transmission

CWD was first identified as a disease syndrome in 1967 in a mule deer in a research facility in Colorado that had been populated by wild deer captured in that state (Williams and Young, 1980). It is likely the disease existed in nature but went unrecognized. About 10 years later CWD was determined to be a TSE (Williams and Young, 1980; Williams et al., 2002; Belay et al., 2004).

CWD occurs in free-ranging native elk, mule deer, and white-tailed deer and was first reported in northeast Colorado and southeast Wyoming in the 1980s. Its prevalence in this area over the period 1996–1999 was found to be about 5 percent in mule deer, 2 percent in white-tailed deer, and less than 1 percent in elk (Miller et al., 2000). Since 2002, the wider application of testing of hunter-killed or other animals has uncovered endemic loci of infected animals in western Colorado, Nebraska, New Mexico, South Dakota, Utah, Wyoming, Wisconsin, Illinois, and New York, and in Saskatchewan, Canada. The prevalence of CWD in endemic areas has been estimated to be less than 1 percent for elk and to vary from less than 1 percent to 15 percent for mule deer (Williams et al., 2002).

CWD has been a major problem for the cervid farming industry. The first diagnosis on an elk farm occurred in South Dakota in 1997 and marked the beginning of more widespread testing (USDA APHIS-VS, 2005). Subsequently the disease has been found on a substantial number of game farms in other parts of the United States (Colorado, Kansas, Minnesota, Montana, Nebraska, New York, Oklahoma, and Wisconsin) and Canada (Alberta and Saskatchewan) (AVMA, 2005; Belay et al., 2004). It is reasonable to assume that CWD has been spread in large part through trade associated with the growth and development of the game farming industry. Spread from game farms to free-living cervids appears to have occurred in at least some but not all situations where game farms have been established. The widespread dissemination of CWD among game farms in Canada resulting from importation of infected elk is beyond dispute (Bollinger et al., 2004). However it occurred, CWD has emerged as an immediate and serious threat to wildlife resources that generally are highly prized by society and serve as the basis for substantial economic activity.

Pathogenesis

CWD is associated with the accumulation of abnormal prions in brain and lymphatic tissue. While not yet universally accepted, the “infectious” agent is believed to be an abnormal prion (Belay et al., 2004). The disease has a long incubation period, probably 15 months or more before the ap-

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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pearance of clinical signs (Belay et al., 2004). Affected animals lose weight and may show neurological signs. Definitive diagnosis is based on direct laboratory examination of brain or lymphatic tissue by immunodiagnostic techniques that can determine the presence of the agent in clinically normal animals as well as those showing signs. These tests are the basis of epidemiological surveys for prevalence of the disease in culled and hunter-killed animals.

It is likely that CWD is transmitted among cervids by urine, feces, and saliva (Miller et al., 2004). The CWD agent remains infective in contaminated premises for at least 2 years and presumably this would also be true in the natural environment (Miller et al., 2004). No evidence suggests that other species can acquire CWD under natural circumstances or when housed in direct contact with affected deer or on contaminated premises. There is no known risk to humans from consuming meat from deer or elk, but prudence makes consumption of meat or nervous tissue from animals known to be infected unwise until more is known about this disease (Belay et al., 2004).

APHIS has developed procedures to validate and approve testing procedures for diagnosing CWD. There is a danger of moving animals to new habitats in the absence of the means to certify their health with a high level of assurance or guarantee of their quarantine in the new location. The history of CWD illustrates that controlling the translocation of captive wildlife is of paramount importance in preventing the spread of wildlife disease.

The national response to CWD has been guided since 2002 by a Plan for Assisting State and Federal Agencies and Tribes in Managing CWD in Wild and Captive Cervids (USDA APHIS, 2002), developed by a task force of federal and state wildlife management agencies. Subsequently a group representing a broad constituency of universities, professional organizations, and interest groups developed action items. The task force has directed attention to six broad areas of activity: communications, dissemination of technical information (including education), diagnostic methodology, disease management, research, and surveillance. Both USDA and DOI have provided funding for CWD programs (FYs 2003–2005). Implementation of the plan has been coordinated through the Multi-States CWD Working Group, U.S. Animal Health Association, and the International Association of Fish and Wildlife Agencies. The DOI (NPS, USGS, FWS) and USDA (APHIS, CSREES) have established interagency work groups to deal with specific issues. Interested nongovernment organizations have banded together to form the CWD Alliance to keep stakeholders appraised of developments. The formation of the CWD Alliance by conservation organizations and the development of its web site (www.cwd-info.org) have been particularly effective in pro-

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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viding a source for accurate information among nonexperts. Also, a substantial number of continuing education programs for biologists and others working on CWD have been developed or are in preparation by agencies involved in the Plan.

Diagnosis

Immunohistochemistry (IHC) tests of tissue samples remain the approved means for definitive diagnosis of CWD. ELISA based methods have been developed for screening samples more rapidly, but positives must be verified by IHC. Research continues on developing methods that could be used to diagnose infection in live animals or be more cost-effective. By April 2003, the NVSL had approved 26 university or state diagnostic laboratories to provide CWD testing, a number that accommodated demand prior to the onset of BSE surveillance. Currently the system is stretched to or somewhat beyond capacity, and additional laboratories may be approved.

Prevention

Steps are being taken to prevent or limit the spread of CWD. All 50 states and several federal and tribal agencies have conducted monitoring and management activities partially funded by APHIS through cooperative agreements. As of June 2004, 24 state wildlife management agencies adopted a policy set out in Multi-state Guidelines for Chronic Wasting Disease Management in Free-ranging White-tailed Deer, Mule Deer and Elk. The APHIS-proposed rule, Chronic Wasting Disease (CWD) Herd Certification Program and Interstate Movement of Captive Deer and Elk, is pending. Some states have put restrictions on baiting and feeding of free-ranging cervids.

Experience in both the United States and Canada indicates that eradication of CWD in farmed cervids should be possible (Bollinger et al., 2004). On the other hand, containing CWD in free-living cervids and preventing its spread to contiguous regions free of the disease will be extraordinarily difficult (Gross and Miller, 2001). Of paramount importance is controlling the translocation of animals or infected material. It has been recognized this will require not only appropriate regulations, but also an educated public that will not be tempted to ignore restrictions on the movement of cervids.

Containing CWD will require a well-coordinated management program supported by an aggressive research program that defines the population density, buffer zone size, and time required to render contaminated environments free of infectivity to arrest spread to contiguous areas. It

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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has been suggested that deer densities of less than 1 square kilometer of critical habitat will likely have to be maintained for prolonged periods of up to 10 years or more to create such buffer zones and prevent spread from endemic areas (Bollinger et al., 2004). Through an examination of CWD, the committee learned that:

  • The infrastructure to detect, diagnose, and prevent wildlife diseases is an essential element in the nation’s framework for dealing with animal diseases and its consequences. In the past, it has been flawed by inadequate (1) coordination of relevant agencies, (2) diagnostic expertise, (3) research support, and (4) education and training of professionals. Experience with CWD, and other diseases of wildlife such as WNV or the pathogens they may harbor, such as avian influenza, has highlighted these deficiencies and provided the motivation to correct these inadequacies.

  • In purely biomedical terms, the discovery of CWD has provided a research opportunity in comparative medicine for gaining greater insight into the pathogenesis of TSEs. The recent creation by the White House of an interagency working group on disease-causing prions to identify gaps in knowledge is timely.

  • The spread of CWD, taken together with the history of the spread of raccoon rabies and of monkeypox, provides compelling contemporary evidence of the need for much more effective control of translocation of wild animals in preventing the spread of animal disease. It reaffirms an essential strategy for disease control that has been recognized since the establishment of the first U.S. national animal health agency, the Bureau of Animal Industry, in 1884. The translocation of wildlife, both indigenous and exotic, is fraught with every bit as much risk as translocation of domestic animals, especially since organisms that are symbiotic in wildlife may be pathogenic in people and/or domestic animals.

West Nile Virus

The introduction and rapid spread of WNV (caused by a single stranded RNA flavivirus) across the North American continent is a simple and powerful illustration of the growing importance of a zoonotic disease that is harbored and spread in wildlife in an increasingly interconnected world. The disease was first described in Uganda in 1937. Since that time it has become endemic in other parts of Africa, Southwest Asia, and Europe, where it appears to cause relatively few cases of disease in people, domestic animals (horses and geese), or wildlife.

WNV appeared in New York in 1999 from an unknown source. By 2003 it had spread across the continent in a naive bird population that sustained the infection and allowed it to be spread by mosquitoes that

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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feed largely on birds. While WNV primarily infects birds, and while most species are apparently resistant, corvids are particularly susceptible and many died from the infection. Surveillance for the virus in dead crows proved to be a better indicator of looming human and animal infection than isolation of the virus from trapped mosquitoes or sentinel flocks of chickens. Humans and horses become infected when species of mosquitoes that feed on both mammals and birds (e.g., some Culex spp) are favored by climatic circumstances. About 80 percent of the people who become infected with WNV will have no symptoms and the vast majority of the remaining 20 percent will have mild disease symptoms (CDC, 2004e). Unfortunately, a few acquire encephalitis that can be fatal. In 2002 and 2003, WNV infected 15,300 and 5,200 horses in North America, respectively (USDA APHIS, 2004b). It can be expected that the disease will become entrenched permanently in some North American ecosystems. The industrial and research establishment in the United States responded to this outbreak by developing an effective vaccine to protect horses and a rapid screening test that provided for efficient and cost-effective presumptive diagnosis. The committee found that globalization brings increasing risk from diseases such as WNV that have hitherto not been present in the United States but are transmissible to people and domestic animals by wildlife. It is unlikely that all such diseases can be prevented from entering and staying in the country.

North America has large, pristine, nonimmune populations of animal hosts, humans, multiple efficient and competent vectors, and a favorable environment for disease transmission and spread. The introduction of WNV became the key catalyst and final element needed to produce one of this country’s most significant epidemics. Every year since 1999 has led to new information about this epidemic.

West Nile virus has an extremely broad host range replicating in birds, reptiles, amphibians, mammals, and numerous mosquito vectors. While WNV is primarily a vector-borne zoonotic disease that is maintained through a bird-to-bird transmission cycle via mosquito vectors, new information has also revealed that this flavivirus can be transmitted by other means: for example, contaminated blood products, organ transplantation, maternal transmission via breast milk and intrauterine, percutaneous exposure in a lab setting, and, at least experimentally, direct horizontal transmission between and among birds due to exposures via fecal shedding.

The WNV epidemic is still evolving and not well understood. The recent recognition of a very large host range, numerous potential vectors, nonvector modes of transmission, and the potential movement into Central and South America via bird migrations has revealed that WNV is a much greater threat and more difficult to control than initially realized. There is every indication that WNV is becoming established as an en-

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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demic zoonosis and will be a permanent part of the animal and human medical landscapes in the United States and beyond for many years to come.

The scope, scale, intensity, and consequences of this ongoing disease problem are unprecedented for an arbovirus (an arthropod-spread virus). WNV is a remarkable example of an emerging zoonosis that involves the dynamic and complex interface among domestic animals, humans, and wildlife species. The United States was an ideal setting for this epidemic, and the virus continues to adapt and move into new ecological settings that produce new selective pressures and exposures to new hosts and vectors that constantly change the nature of this disease. The final chapter on this disease has not been written because the story continues to unfold and will continue to do so in unprecedented ways.

Important lessons to be learned from the WNV epidemic include the following:

  • With the propitious epidemiological conditions for arboviruses in the United States, epidemic events can result in long-term endemic disease problems in multiple sites and species. The ease of spread of WNV also provides a living model and example of what a purposeful introduction of a vector-borne zoonotic disease might do. Rift Valley fever, for example, has epidemiological similarities to WNV that should be of serious concern.

  • There is a need for a better understanding of most aspects of WNV, including its adaptations, environmental survival, host and vector range, and nonvector transmission modes. Ecology, wildlife dynamics, and epidemiology are among the scientific disciplines that need to be addressed by the animal health framework in the future.

  • WNV offers further evidence that the veterinary profession and animal health organizations must develop the expertise, knowledge, and skills needed to address the implications of zoonotic diseases.

  • The epidemic illustrates the need for strategic and collaborative partnerships between government agencies, and especially among animal and human health officials and communities. Those partnerships also need to extend globally.

The confluences of human and animal health, along with wildlife, create new opportunities for pathogens to emerge and reemerge. Microbes will adapt, gain competitive ecological advantages, and threaten populations in novel and dangerous ways. WNV is a wakeup call to both human and animal health officials and organizations—it is a clarion suggesting that the past systems and operations in both of these communities will need to reconsider how and with whom they work.

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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NOVEL AND BIOENGINEERED PATHOGENS

The past two decades have witnessed the evolution and emergence of new strains or entirely new groups of animal or human pathogens. Many of these are thought to have emerged from interspecies transmission or as variants of established strains with new tissue tropisms. In this respect, emergent RNA viruses are notorious because of the presence of quasispecies or “swarms of virus within a viral population,” high mutation rates due to lack of proofreading mechanisms for RNA polymerases, and the ability to generate genetic recombinant or reassortant viruses. Recent examples include the emergence of several RNA viruses in swine such as:

  • The porcine respiratory and reproductive syndrome virus (PRRSV), an economically important arterivirus first isolated in 1991 in Europe and in 1992 in the United States, but with no known previous host and no prior serological evidence of previous infection detected in swine (Benfield et al., 1999).

  • The porcine respiratory coronavirus (isolated in Europe in 1984 and the United States in 1989), an emergent virus that acquired a new tissue tropism (respiratory) and is a naturally occurring deletion mutant of TGEV, common, widespread swine intestinal coronavirus (Saif and Wesley, 1999).

  • The porcine epidemic diarrhea virus (PEDV), a new group I coronavirus, which was reported initially in Europe in 1978 and in Asia in the 1990s as a major cause of diarrheal deaths in piglets, but still has not been detected in the United States (Pensaert, 1999).

These new viruses appear to have emerged independently in swine in Europe and the United States, suggesting that they have separate evolutionary origins. Equally troubling was the recent emergence in Malaysia of the new swine RNA virus, the Nipah virus, a zoonotic paramyxovirus that was transmitted to humans, necessitating the precautionary slaughter of large numbers of pigs (Chua, 2003). This latter virus was acquired by swine through interspecies infections, presumably from fruit bats. The identification of these novel porcine viruses required the use of classical (EM, cell culture) virological techniques, as well as molecular approaches, such as reverse transcriptase-polymerase chain reaction (RT-PCR).

If the challenge of diagnosing new, naturally occurring diseases were not already difficult enough, the prospect of identifying an intentionally-introduced recombinant (bioengineered) pathogen presents an even greater challenge. A bioengineered disease agent might, for example, be a chimera formed from unrelated pathogens that would confuse diagnostic

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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tests by causing multiple reactivities. Specific antigen sites or genetic regions of a pathogen could be masked or deleted so that serological or genetic tests would result in false negatives. Therefore, a broad array of diagnostic tests with a wide spectrum of agent detection capabilities may be required to identify both novel pathogens, whether naturally occurring or intentionally engineered.

Identification of Novel Pathogens

Classical virological techniques and the fulfillment of Koch’s postulates (for example, verifying a causative agent by using it to reproduce a similar disease syndrome in susceptible animal models) will remain important tools in disease diagnosis. However, rapid and unambiguous diagnostic tools are needed for early intervention in the event of a bioterrorism-related national crisis or for identifying novel pathogens. New molecular assays are evolving to meet those needs.

For example, the SARS coronavirus was identified using microarray technology that targeted consensus regions of gene expression within distinct virus families (Ksiazek et al., 2003). Pathogen specific detection methods using gene probes derived by genome mining, in conjunction with target or signal amplification, can yield methods sensitive enough to detect just a few organisms in suspect materials. The same technologies in combination with sequencing or microarrays can aid in genotyping pathogens, specifically in the diagnosis of antimicrobial agent resistance (Hamels et al., 2001). Of particular interest are microarrays designed to enable detection of major classes and families of organisms based on intergenic and polymorphic loci. Once such classification has been worked out, family-specific arrays may be used to scan for homologies and major differences to identify new pathogens. Another example is the use of mass spectroscopy and high-performance liquid chromatography methods on whole microorganism (bacteria, viruses, and protozoa) extracts to define protein profiles that can be matched to an existing database of fingerprints. This may enable classification of organisms into major families that can be used to further design molecular probes for a finer degree of discrimination (Bernardo et al., 2002; Huang et al., 2002; Frazier et al., 2003).

Rapid Monitoring of the Host Response to Pathogens

Serology (monitoring serum antibody responses to pathogens) is important in assessing seroresponders and the seroprevalence of infections to determine levels of exposure of the populations. However, it is inadequate for rapid disease diagnosis because antibody development usually takes 2–3 weeks.

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Recognition of the rapid response (hours or days) in immunomodulatory factors such as cytokines in the blood to various pathogens suggests that microorganism-specific cytokine tests may permit more rapid monitoring of host-specific responses. An example is the adoption of assays to monitor for mycobacteria-specific antigen-induced secretion of the cytokine interferon-gamma in blood mononuclear cells as a more rapid diagnostic assay than slower cultivation protocols (weeks) required for isolation of Mycobacterium bovis from cattle (Stabel, 1996). Such tests could also provide rapid data on new immunosuppressive pathogens, naturally occurring or bioengineered, by revealing significant decreases in certain cytokine levels. Another example is the recognition that some immunomodulatory factors (the cytokine IL-4) coexpressed with a virus may increase the virulence of certain viruses (mousepox) in the host (Jackson et al., 2001). Monitoring of a dramatically up-regulated single cytokine level could signal the presence of such a bioengineered pathogen-cytokine recombinant or guide treatment with antibodies to the relevant cytokine or counter-regulatory cytokines. Besides of diagnostic value, innate immune factors (such as cytokines and interferons) occurring early (hours or first days) after infection, and preceding the acquired immune responses, might be manipulated as treatment modalities to reduce or prevent infection of contact or susceptible animals. Early innate immunomodulator intervention strategies might block or reduce pathogen infection and shedding, decreasing transmission to other animals or making contact animals more resistant to infection.

INTENTIONALLY INTRODUCED PATHOGENS AND DISEASES OF TOXICOLOGICAL ORIGIN

Of course, an act of bioterrorism need not involve a bioengineered pathogen. The intentional spread of known microorganisms or microbial toxins can be accomplished using the same routes as accidental introductions, which occur when disease agents are brought to new areas via the movement of air and water, fomites, vectors, infected animals, or animal products.

Currently, if naturally occurring, endemic agents were intentionally introduced into a new locale, investigatory agencies would be reliant solely on the pattern of outbreak to distinguish an attack, since there is currently no methodology to distinguish between intentionally versus accidentally introduced. The purposeful introduction of an exotic disease through channels of international commerce could also be disguised, since such an occurrence could as easily be the result of an accident as not. In the 2003 National Research Council report Countering Agricultural Bioterrorism, the Committee on Biological Threats to Agricultural Plants

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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and Animals offered advice about animal diseases and animal disease vectors that could be used as agents of agricultural bioterrorism. Because the report discusses themes that are relevant to both intentionally introduced and naturally occurring disease and the potentially devastating consequences of a failure of the animal health network, we have included the conclusions of the report as Appendix D.

In addition to pathogens, toxins, chemicals, and radiological weapons might also be used to purposefully threaten animal health. These topics are outside the focus of this report. However, the committee acknowledges that toxic diseases (such as botulism and domoic acid) are an important concern for animal and human health. Diseases of toxicological origin present challenges different from those of other types of animal diseases. Domestic and wild animals are subject to toxins that occur naturally, for example in plants, or that are the result of human activity. Paralytic shellfish poisoning, domoic acid, Pfeisteria outbreaks, and related phenomena appear tied to coastal pollution and have the potential to make poisonous and inedible a growing proportion of the country’s protein food supply. Therefore toxicology is an essential element in any program addressing animal disease.

SUMMARY

The lessons of past disease outbreaks and the prospects of future epidemics suggest that the animal health framework faces a formidable challenge in preventing, detecting, and diagnosing the spectrum of animal diseases, some of which have direct consequences for humans as well as animals. The challenge is multifaceted and includes planning for outbreaks; conducting multidisciplinary research across species; developing new vaccines and rapid diagnostic tools; effectively using the broad capabilities of university, industry, state veterinary diagnostic laboratories; and ensuring that an appropriate and state-of-the-art infrastructure exists to accomplish diagnosis. More than ever, there is a need to develop strong connections between public health and animal health officials, both domestically and internationally, and to expand the scope of animal disease concern to include wild and exotic animals.

Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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Suggested Citation:"3 Assessment of Current Framework: Case Studies." National Research Council. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases. Washington, DC: The National Academies Press. doi: 10.17226/11365.
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The confirmed case of "mad cow" disease (BSE) in June 2005 illustrates the economic impact of disease outbreaks, as additional countries closed their markets to U.S. beef and beef products. Emerging diseases also threaten public health--11 out of 12 of the major global disease outbreaks over the last decade were from zoonotic agents (that spread from animals to humans).

Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Diseases finds that, in general, the U.S. animal health framework has been slow to take advantage of state-of-the-art technologies being used now to protect public health; better diagnostic tests for identifying all animal diseases should be made a priority. The report also recommends that the nation establish a high-level, authoritative, and accountable coordinating mechanism to engage and enhance partnerships among local, state, and federal agencies, and the private sector.

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