This table is a merger of lists of disease threats developed by the Defense Threats Reduction Agency (DTRA), Centers for Disease Control and Prevention (CDC), North Atlantic Treaty Organization (NATO), interviews with Russian experts, United States Army Medical Research Institute for Infectious Diseases (USAMRIID) and nationally notifiable diseases.
Diseases appearing on only one list (not included in the table): Nipah virus (CDC C list); coccidiomycosis and dengue (NATO); Machupo (USAMRIID); acquired immunodeficiency syndrome (AIDS), amebiasis, Campylobacter, carbon monoxide poisoning, Chlamydia trachomatis, congenital rubella syndrome, food poisoning, giardiasis, Haemophilus influenza type B (HIB), hepatitis A, hepatitis B, hepatitis C, Kawasaki syndrome, Legionnaires' disease, leptospirosis, Lyme disease, lymphogranuloma venereum, malaria, measles, meningitis, mumps, neisseria gonorrhea, neisseria meningitis in blood or cerebrospinal fluid, pertussis, poliomyelitis, rabies, Reye syndrome, rheumatic fever, rubella, syphilis, tetanus, toxic shock syndrome, toxoplasmosis, and trichinosis (Reportable List).
Reprinted from Journal of Biomedical Informatics, Vol. 36, Michael Wagner, Virginia Dato, John N. Dowling, and Michael Allswede, Representative Threats for Research in Public Health, pp. 177-188, Copyright 2003, with permission from Elsevier.
The Office International des Epizooties (OIE) is the world organization for animal health (see Chapter 7) The OIE sets guidelines and provides recommendations to minimize the risk of the spread of animal diseases and pests while facilitating trade between nations. The OIE develops policy, standards, and techniques that member countries can apply to help protect themselves from animal diseases by establishing valid import barriers for the trade of certain animals or animal products. The OIE documents these standards in the International Terrestrial Animal Health Code and the International Aquatic Animal Health Code (Office International des Epizooties, 2004a,b). These standards include lists of diseases, organized by priority.
Table 4.3 includes a selection of OIE diseases that produce high morbidity/mortality, spread rapidly, and can easily cross national boundaries. These diseases represent the greatest potential to disrupt international trade. These diseases (formerly called List A diseases) can produce significant socioeconomic upheaval or present a major public health risk; therefore, OIE establishes more stringent requirements for demonstrating freedom from the disease agent.
The OIE also lists diseases that cause significant socioeconomic disturbance or health risk within an affected country but generally do not cross national boundaries (Table 4.4). These diseases (formerly called List B diseases) are associated with requirements for reporting and demonstrating freedom from the disease or agent that are less severe than those for the pandemic agents described above; nonetheless, they are still quite restrictive.
Commercial farming and trade of aquatic animals is increasing dramatically. The aquatic environment provides unique transmission modes for disease. Therefore, the OIE has developed an Aquatic Animal Code (Table 4.5). OIE includes diseases based on the potential for international spread and the potential for transmission to humans.
5. REDUCING COMPLEXITY: THREAT PATTERNS_
Although to our knowledge no organization has attempted to develop functional requirements for an "all-biological threats'' system, it makes for an interesting gedanken experiment (thought experiment), which may reveal whether such a system can even be specified given the large number of organisms and variability in their presentation, or how such a specification might best be accomplished.
To design an all-threats system, a designer would have to speak with many disease experts to understand the requirements for each disease. In particular, the designer would have to understand the required timeliness of detection for each disease and the smallest size outbreak that should be detected. Just understanding these functional requirements for all biological agents would be an enormous undertaking and would only represent a first step in the development of a system specification, which would require additional analysis for each threat of the types of surveillance data and analytic methods that could satisfy the requirements at lowest cost and effort.
There is another way, however, to manage this design complexity, which is to identify a smaller number of general "patterns" that a biosurveillance system must be capable of recognizing. This idea is not terribly new; the field has appreciated the disease-independent value of looking for patterns ever since John Snow used a spatial pattern of cases to elucidate the cause of a cholera outbreak in London in 1854 (Snow, 1855). What is novel here is taking that idea to its logical conclusion, which entails systematically examining all threats (biological agents and their various presentations as outbreaks) to identify a set of patterns (more multidimensional than spatial patterns) that most or ideally represent all of the patterns that a biosurveillance system must be capable of recognizing.
Table 4.6 is the result of such an analysis conducted by Wagner et al. (2003b) for the diseases listed in Table 4.2. Note that the following discussion relates only the threats to human health. A similar analysis would be required for diseases that threaten only animals.
The analysis resulted in a final set of nine patterns, each of which represents a fundamentally different pattern recognition problem for a biosurveillance system. For example, large-scale aerosol releases, in general, have the same requirements for a large-scale aerosol release of B. anthracis described above. Building contaminations in general have the same requirements as described for a building contamination with B. anthracis. They also searched the literature for actual outbreaks of diseases in each category for which detailed descriptions were available for study by system designers.
The previous section on the functional requirements and specifications for anthrax biosurveillance already discussed the first three of the nine patterns in Table 4.5. We discuss the other six patterns in the following sections.
The fourth pattern is that produced by a continuous or intermittent release of an infectious agent or biologic toxin over time. Under such conditions, individuals entering a limited area develop disease over an extended period. The Philadelphia Legionnaires outbreak was of this type, as would have been the attempt by the Aum Shinrikyo cult to sicken the population of Tokyo by disseminating continuously liquid anthrax slurry over a period of 4 days from the rooftop of their building, had it succeeded (Mangold and Goldberg, 2000). Pets and birds were sickened, but no human cases were reported.
Early detection of this type of outbreak would require analysis of surveillance data both spatially and temporally, that is, searching for clusters of diseases or syndromes in both
TABLE 4.3 Selected Office International des Epizooties (OIE) Former List A Diseases
Distribution (see OIE HandiStatus at
http://www. oie. int7 hs27report.asp)
African horse sickness
African swine fever
Horses, mules, donkeys
Classical swine fever (hog cholera)
Contagious bovine pleuropneumonia
Foot and mouth disease (hoof and mouth disease)
Highly pathogenic avian influenza (fowl plague)
Sheep, goats, cattle, deer, bighorn sheep
Sub-Saharan Africa, occasional outbreaks in northern Africa, Middle East, and Europe Sub-Saharan Africa, Europe, South America, Caribbean
Africa, Middle East, China, United States, Mexico, southeast Asia, Australia, northern South America
Europe, Asia, Central and South America
Cattle, buffaloes, sheep, goats
Cattle, buffalo, signs highly pigs, sheep, goats, deer
Domestic poultry, waterfowl, wild game birds, pigs, humans
Africa, Asia, parts of Europe
Europe, Africa, Middle East, Asia, South America
Arthropod vector. Disease is not transmitted from animal to animal.
Direct transmission from infected animals. Virus can shed from animal for several months after recovery and contaminate environment.
Insect vector. Disease has seasonal occurrence based on conditions that promote vector survival.
Direct contact and fecal-oral route. Maintained in endemic areas by carrier animals. Transplacental infection can lead to chronically infected piglets that shed significant amount of virus over their lifetime.
Direct contact between animals. Agent does not persist in the environment.
Respiratory, mechanical transmission; virus can survive for weeks in bedding. Recovered animals may serve as carriers.
Direct contact with infected birds or material (e.g., feces, meat).
Lumpy skin disease Cattle Africa, one confirmed Transmission thought to outbreak in Israel be via insect vector, in 1989
Peracute disease generally produces death in absence of signs following 1- to 2-week incubation period. Acute, subacute, and chronic forms produce signs of varying severity that include abortion, fever, and inappetence. Incoordination, cyanosis, dyspnea, vomiting, and bloody diarrhea may develop in more severe cases.
Fever, facial edema, congestion, ulceration of mucous membranes. Tongue may become swollen and protrude from mouth. This hyperemia may extend to groin, axilla, and perineum. Signs in cattle are much milder.
Sudden fever, depression, and inappetence in acute cases. Vomiting and diarrhea develop along with skin blotching and ocular discharge. Mild cases may only present with abortion and failure to thrive.
Clinical signs can be confused with other diseases. Laboratory diagnosis essential. Serology. Culture of blood, spleen, lung, or lymph nodes.
Serology. Clinical signs and gross pathology (e.g., hemorrhages in organs and lesions seen in reticuloendothelial system) are suggestive.
Serology. Culture of infected tissue.
Serology. Hemorrhages and necrosis within the gut are common. Lesions are seen in reticuloendothelial system.
Anorexia, fever, dyspnea, cough, and nasal discharge. Clinical signs not always present.
Fever, depression, inappetence, and vesicle emergence followed by painful ulcers.
Serology. Culture from nasal discharge, pleural fluid or bronchial washings, lung tissue.
Serology, clinical signs highly suggestive of disease.
Sudden increases in death rates within flocks before signs appear. Clinically affected birds are depressed and have raffled feathers, inappetence, fever, and generalized weakness. Birds will also develop profuse diarrhea, their combs will become swollen, and they will have respiratory signs.
Can be subclinical. In acute animals, persistence fever with nasal and ocular discharge. Lactating cattle will have a marked reduction in milk production. Nodules develop on head, neck, udder, and perineum. Swollen lymph nodes and animal may be reluctant to move.
Necrotic foci in the spleen, liver, kidney, and lungs. Exudate may be present in air sacs. Virus can be isolated from tracheal and cloacal cultures.
Serology. Identification of capripox virions in biopsy material.
Peste des petit ruminants
Rift valley fever
Sheep pox and goat pox
Domestic poultry, waterfowl, wild game birds, infrequently in humans
Small ruminants, especially goats; white-tailed deer have been infected experimentally
Ruminants, dogs, cats, monkeys, humans
Cattle, buffalo, sheep, goats, pigs
Swine vesicular disease
Vesicular stomatitis (Indiana fever)
Cattle, horses, pigs, sheep, wild animals, and rarely goats
Africa, Arabian Peninsula, Middle East, southwest Asia
Africa, Middle East. Potential spread to other parts of world given wide host and vector range.
North Africa, Middle East, India, parts of Asia
Africa, Middle East, Asia
Asian and European countries
Contact with carrier bird or contaminated items (e.g., equipment, feed, personnel).
Transmitted from animal to animal via aerosol transmission.
Disease in animals usually by mosquito vector. Human infection most commonly arises from contact with contaminated tissue and discharge.
Respiratory, feces, and urine. Introduction of infected animal to naive population generally results in explosive outbreak with high morbidity.
Direct contact with infected animal saliva, nasal secretions, feces, or lesions. Inhalation of aerosols. Indirect via contaminated objects (e.g., vehicles, litter). Virus can survive for years in dried scabs.
Contact with infected animal, ingestion of raw waste and feed containing infected products. Transport in contaminated vehicle.
Ecology of agents not well understood. Arthropod-involved transmission cycle may be likely.
Marked depression, inappetence, decreased production, recumbency, and death. Edema of the comb and diarrhea are common. A nervous form may present with limb paralysis, head tremors, dyspnea, and coughing.
Resembles rinderpest in cattle. Fever, ocular and nasal discharge, diarrhea, pneumonia, stomatitis. Oral lesions develop with excessive salivation. Does not produce clinical disease in cattle.
Sever fever, vomiting, nasal discharge, bloody diarrhea beginning after 1 day after exposure, with 95 % mortality in young animals. Adult animals often present with less severe signs. Severe influenza-like signs common in humans.
Nasal and ocular discharge followed by high fever, depression, restlessness, inappetence, and decreased production. Progresses with oral, respiratory, and gastrointestinal ulcers. Death typically 6 to 12 days after onset of signs.
Cases may be subclinical. Fever, depression, conjunctivitis, nasal discharge, and swelling of eyelids. Lesions evolving into papules form, beginning on hair/wool-free parts of body. Cough develops as papules in lungs cause pneumonia.
Sudden lameness in close animal groups. Slight fever. Development of vesicles on the snout, coronary band, and interdigital spaces. Young pigs may lose the horny hoof following vesicle rupture.
Very similar to foot and mouth disease. Brief febrile period and formation of papules and vesicles in mouth, udder, and coronary band. Profuse salivation.
Necrosis and hemorrhage of gastrointestinal tract. Microscopic changes to brain. Virus isolated from cloacal culture of live birds.
Serology. Tentative diagnosis based upon clinical signs. Linear hemorrhages (zebra stripes) present in large intestine. Necrotic enteritis, enlarged lymph nodes, necrotic lesions on spleen, and apical pneumonia.
Liver of ruminants is enlarged, focally necrotic, and friable at necropsy. Serology.
Clinical signs are highly suggestive. Confirmed by serology in early stage of disease.
Serology. Identification of agent from full skin biopsy or lung lesions needed to differentiate from lumpy skin disease.
Serology. Culture of vesicular fluid, blood, or feces. Clinical signs easily confused with foot and mouth disease.
Serology. Rapid laboratory diagnosis of animal disease important to distinguish from foot and mouth disease.
Transmissible diseases that have the potential for very serious and rapid spread, irrespective of national borders, that are of serious socioeconomic or public health consequences, and that are of major importance in the international trade of animals and animal products.
TABLE 4.4 Selected Office International des Epizooties (OIE) former List B Diseases
(See OIE HandiStatus at
http://www. oie. int7 hs27report.asp)
(woolsorter's disease, malignant pustule, malignant carbuncle) Echinococcosis
(cowdriosis, malkopsiekte) Johne's disease (paratuberculosis)
(Chiclero ulcer, buba, oriental sore, Aleppo boil, Baghdad sore, espundia)
(Weil's disease, swineherd's disease, cane-cutter's fever, mud fever, Stuttgart disease)
New and Old World screwworm (traumatic myiasis)
Cattle, sheep, goats, deer, horses, fogs, pigs, humans
Dog, cattle, sheep, pigs, goats, camels, horses, humans
All domestic and wild ruminants
All domestic and wild ruminants, horses, pigs, deer, alpaca, rabbits, foxs, weasels
Cattle, pigs, horses, sheep, goats, dogs, many wild animals, including rodents
Mammals, birds (rarely)
Africa, Madagascar, Caribbean Worldwide
Southern Mexico to northern Argentina, Dominican Republic, South America, Middle East, Asia, northern China, northwest India, Africa Worldwide
Old World: Africa, Gulf countries, Indian subcontinent, and southeast Asia to Papua New Guinea New World: southern United States to northern Argentina (area contracts in winter and expands in summer)
Spores from soil. Eating undercooked meat from infected animals, exposure to hide/wool of infected animals.
Infection via fecal oral route. Dog is definitive host, shedding Echinococcus cestodes. Intermediate host infected via ingestion of contaminated water, food, or soil.
Transmitted by Amblyomma ticks. Wild animals could play role as reservoir.
Under natural conditions, ingestion of agent from contaminated environment. Infection can be spread to unborn fetus. Calves contract infection through milk of infected cow.
Vector-borne parasite. Rodents are reservoir. Once inside vertebrate host, organism invades cutaneous macrophages.
Environment is contaminated through infected animal's urine. Direct or indirect transmission through abraded skin or mucosa. Ingestion of contaminated water, soil, or foods.
Female screwworm flies lay eggs on edges of wounds on live animals. Eggs laid on mucous membranes can result in infections of natural openings. Larvae burrow into flesh upon emerging. Larvae leave wound after maturing and purpurate in the soil where they further develop into an adult fly.
Fever, behavioral changes, seizures, hematuria, gastroenteritis, pharyngeal edema, In horses; colic, enteritis, followed by edema, hemorrhage and death.
Identification of etiologic agent in stained smears or culture of blood or aspirate from pustules.
After ingestion, cestodes hatch and larvae encyst primarily in lungs or liver. Location, size, and number of cysts will dictate signs. Symptoms usually those associated with slow-growing tumor.
Identification of larval cyst in affected organ of intermediate host via sonogram or necropsy/ autopsy. Identification of cestodes in dog feces.
Sudden high fever (drops shortly before death), inappetence, diarrhea, lung edema; nervous signs develop gradually.
Slowly progressive wasting. Diarrhea that progressively becomes more severe. Diarrhea is less common in smaller ruminants.
Culture of capillary endothelial cells of brain. Brain smears for dead animals.
Fecal smears. Fecal/tissue culture. Serology. Lesions in small intestine. Lesions progress to occur in cecum, colon, and mesenteric lymph nodes as disease progresses.
Begins as itchy lesion then forms papules and painless ulcers. Lesions may persist for a year or more.
Identification of parasite through lesion scraping or aspiration.
May remain subclinical. Sudden onset of fever, Culture of agent from blood anorexia, birth of weak/stillborn animals. (early) or urine. Serology
Infertility. Some may present with jaundice. requires repeated samples.
Chronic phase of disease may last months after clinical recovery.
Extensive tissue destruction from burrowing larvae. Severe infections can result in death.
Identification of larvae collected from the deepest part of the wound
(Aujesky's disease, mad itch)
Q-fever (Balkan influenza, coxiellosis, abattoir fever, nine-mile fever)
All mammals, especially pigs, except humans and tailless apes
Sheep, cattle, goats, cats, rabbits, dogs, humans (has been found in almost all domestic and wild animal species)
Worldwide except Canada and Oceania
Pigs, rats, bears, other flesh-eating mammals, including humans
All continents (except Oceania) with many rabies-free countries, including Japan, Ireland, the Netherlands, Portugal, Spain, and the United Kingdom
Worldwide, not confirmed in Australia or several tropical countries in Africa, Latin America, and Asia
Pigs are natural host and will remain latently infected after clinical recovery. Raccoons in the United States and wild boar in Europe may be healthy carriers. Airborne transmission possible.
Domestic cycle of disease mainly exists in cattle, sheep, and goats. Infection through inhalation of aerosols from contaminated placenta, amniotic fluid, and excreta. In natural setting, agent is circulated between wild animals and ticks.
Inoculation (e.g., bite) or Infection can be obtained through inhalation of agent. Exposure to infected material.
Ingestion of cyst in contaminated meat. Larvae can live for months in badly decayed flesh.
Abortions and stillbirths. Nervous signs (young animals), respiratory disease (older animals). Intense itching.
Spontaneous abortion and fever. Otherwise clinically inapparent. In man, sudden onset of fever, chills, profuse sweating, myalgia, and malaise following a 2- to 5.5-week incubation. Acute hepatitis also possible. Chronic disease mainly affects the cardiovascular system.
Incubation period may be affected by amount of virus introduced. Reported as long as years. Anxious feeling, sensory alteration, headache, slight fever followed by extreme sensitivity to light, increased salivation, and pupil dilation. Liquids are violently rejected by muscular contractions as disease progresses. May prevail until death or develop generalized paralysis until death.
No clinical disease in wild animals. Anorexia, nausea, vomiting, diarrhea. Followed by fever, muscle pain, swollen eyelids, headache and chills. Muscle pain may last several months.
Culture of agent from nasal fluid or tonsil biopsy from live animals, brain tissue from dead. Affected animals, other than pigs, do not survive long enough for marked seroconversion.
Serology since few laboratoriess have adequate installations and equipment to safely isolate the agent (Coxiella burnetii).
Diagnosis can only be made in laboratories utilizing brain tissue to identify Negri bodies microscopically or virus nucleocapsid antigen via ELISA techniques.
Muscle biopsy. Identification of larvae. Clinical diagnosis difficult owing to nonspecific signs.
Transmissible diseases that are considered to be of socioeconomic and/or public health importance within countries and that are significant in the international trade of animals and animal products. ELISA indicates enzyme-linked immunosorbent assay.
Epizootic hematopoietic necrosis Infectious hematopoietic necrosis Oncorhynchus masou virus disease Spring viremia of carp Viral haemorrhagica septicemia Channel catfish virus disease Viral encephalopathy and retinopathy Infectious pancreatic necrosis Infectious salmon anaemia Epizootic ulcerative syndrome
Bacterial kidney disease (Renibacterium salmoninarum) Enteric septicemia of catfish (Edwardsiella ictaluri) Piscirickettsiosis (Piscirickettsia salmonis) Gyrodactylosis (Gyrodactylus salaris) Red sea bream iridoviral disease White sturgeon iridoviral disease
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