Chapter 3 Bacterial zoonoses.
Cat-scratch disease (CSD) is a bacterial disease caused by Bartonella henselae and is spread through cat bites or scratches. Forty percent of cats are estimated to carry Ba. henselae at some time during their lives with kittens more likely to be infected than adult cats. The clinical syndrome of CSD was first documented by the Parisian physician, Robert Debre, in the early 1930s, but the etiologic agent has only recently been confirmed. For almost 50 years, a variety of microbial agents (including Pasteurella and Chlamydia) have been suspected as the causes of CSD. In 1983, Douglas Wear at the Armed Forces Institute of Pathology (AFIP) described the features of the cat-scratch agent using Warthin-Starry silver stain. By 1992 the name Afipia felis was proclaimed to be the agent causing CSD (Afipia is an acronym for the Armed Forces Institute of Pathology and felis refers to the vector of this infection). Some problems existed with the identification of Af. felis including the inability of other laboratories to isolate Af. felis from CSD patients and that CSD patients did not mount an immune response to Af. felis antigen. When human immunodeficiency virus (HIV) became more prevalent in the 1990s, a newly recognized disease called bacillary angiomatosis was recognized. Bacillary angiomatosis lesions contained bacillus bacteria visualized using Warthin-Starry stain. Since bacillary angiomatosis and CSD tissue sections contained bacillus organisms indistinguishable from each other many scientists believed that bacillary angiomatosis may be disseminated CSD in immunocompromised people. In time, polymerase chain reaction (PCR) amplification of ribosomal DNA was used to examine this bacterium and it became apparent that this organism was not Af. felis but was similar to Rochalimaea quintana (the agent of trench fever). The CSD causing bacterium was Rochalimaea-like and was named Ro. henselae after Diane Hensel, a microbiologist who isolated several of these bacteria. Shortly after this, sera from CSD-suspect patients were evaluated for the new Ro. henselae antibodies and 88% were positive. Several cat fleas combed from these bacteremic cats were also positive for Ro. henselae. Serologic data now existed that suggested that Ro. henselae was associated with CSD. In time, genotypic evaluation of members of the genus Rochalimaea demonstrated that they are related to Bartonella spp. and the genus designation of Bartonella is now applied to all species of the old genus Rochalimaea. Ba. henselae may progress to other diseases such as bacillary angiomatosis, bacillary peliosis, and Perinaud's oculogranular syndrome (a small sore on the conjunctiva, redness of the eye, and swollen lymph nodes in front of the ear). CSD should not be referred to as bartonellosis, a disease caused by Ba. bacilliformis.
It is generally accepted that most cases of CSD are caused by Ba. henselae with a small percentage being caused by Af. felis and Ba. clarridgeiae.
The bacterium that causes most cases of CSD is Ba. henselae, a short, slightly curved, gram-negative, oxidase-negative, aerobic, fastidious rod. Bartonella bacteria grow on chocolate agar, but not on blood agar or MacConkey agar. Many Bartonella species require long incubation periods in a humid, 37[degrees]C environment with increased levels of carbon dioxide. Bacteria belonging to the genus Bartonella have gone through extensive name changes and were once grouped with Rochalimaea genus bacteria with members of the family Rickettsiae. Bartonella and Rochalimaea are now one genus which currently includes 16 species; however, only 5 species are currently considered to cause disease in humans. All species of Bartonella are found in animals, but do not cause disease in animals (there are some reports that Ba. vinsonii causes endocarditis, lameness, and granulomatous lymphadenitis in dogs). Bartonella organisms are of a concern especially in immunocompromised people and recognized as causing clinical syndromes in immunocompromised and immunocompetent people.
Currently, there are six Bartonella species that infect humans: Ba. quintana, Ba. henselae, Ba. elizabethiae, Ba. clarridgeiae, Ba. vinsonii, and Ba. bacilliformis. Other than Ba. henselae causing CSD, the other major disease-causing species of Bartonella are Ba. bacilliformis and Ba. quintana. Ba. bacilliformis is the causative agent of bartonellosis, an often fatal disease causing fever, severe anemia, joint pain, and chronic skin infections that is transmitted by Phlebotomus flies (sand flies) in Peru, Ecuador, and Columbia. Ba. quintana is the causative agent of both trench fever (a louse-transmitted disease that varies from being asymptomatic to producing severe headaches, fever, and bone pain) and bacillary angiomatosis (a vascular disease of the skin and lymph nodes). Other species cause chronic asymptomatic bacteremia in a wide variety of mammalian hosts ranging from deer, wildcats, cattle, wild rodents, and the Norwegian rat. The full zoonotic potential of these species is unknown.
Epizootiology and Public Health Significance
CSD occurs only in humans and is not a disease of animals. CSD can be seen worldwide with Ba. henselae being endemic in Europe, Africa, Australia, and Japan. In the United States about 25,000 cases of CSD occur annually with 80% of those occurring in children and adolescents. In temperate climates, higher rates of CSD are reported in the autumn and winter (peak between September and March), which can be attributed to the seasonal breeding of the domestic cat. The highest levels of seropositive cats are seen in the southeastern states, coastal California, Hawaii, and the Pacific Northwest. There is only one genotype of Ba. henselae reported in North America. There are at least two genotypes of Ba. henselae reported in Europe.
The incidence of patients discharged from hospitals in the United States with a diagnosis of CSD is between 0.77 and 0.86 per 100,000 people per year. The estimated incidence of disease in outpatients is about 9 per 100,000 people per year. The estimated annual health care cost of CSD is thought to be more than $12 million.
The reservoir of Ba. henselae is domestic cats, which do not show clinical signs of disease but are bacteremic for extended periods of time. Ba. henselae has been isolated from bacteremic cats, with transmission among cats believed to be via the cat flea (Ctenocephalides felis). In regions with particularly high humidity and warm temperature, 40% to 70% of cats, especially feral cats, are carriers of Ba. henselae. Although other Bartonella species are transmitted by arthropod vectors, it is unlikely that the cat flea is involved directly in human infection, but plays a role in amplifying the bacteria in cats. Transmission of Ba. henselae to humans is believed to be via dried infected flea feces via the claws of cats by scratching (Figure 3-19).
Person-to-person transmission of CSD has not been documented; dogs have been implicated in 5% of CSD cases.
Bartonella infections have both intracellular and extracellular phases that may coexist causing a variety of clinical presentations in people. Typically, CSD causes regional lymphadenopathy in those lymph nodes that drain the inoculation site (area of the scratch in which bacteria are introduced) with the most common lymph nodes involved found in the upper extremities. Low-grade fever and lethargy occurs in up to 50% of patients with lymphadenopathy. Approximately 40% to 60% of patients report a cutaneous inoculation site of about 0.5 to 1.0 centimeters at the site of a cat scratch or bite. Skin lesions typically develop in 3 to 10 days after injury and progress to lymphadenopathy in one to two weeks. As the patient becomes bacteremic many organ systems become infected including the central nervous system, eyes, lungs, and bones. The affects on individual body systems include:
* Lymph nodes become enlarged in 1 to 2 weeks following exposure and are tender and occasionally fluid filled;
* Central nervous system involvement occurs in approximately 2% to 3% of patients abruptly and typically 1 to 6 weeks after lymphadenopathy occurs. CNS signs include disorientation, confusion, and seizures with deterioration to coma in some cases;
* Ocular involvement includes painless, unilateral vision loss with ophthalmoscopic examination revealing edematous optic discs and exudates surrounding the macula;
* Pulmonary involvement is rare developing in approximately 1 to 5 weeks after lymphadenopathy and presenting as pneumonia and pleural thickening and/or effusion;
* Angiomatosis involves angiogenesis in the skin, regional lymph nodes, and internal organs such as the liver, spleen, bones, and lungs. Angiomatosis typically occurs in immunocompromised people and the disease is termed bacillary angiomatosis. Lesions of the skin and lymph nodes will appear red and may ulcerate;
* Liver involvement is characterized by microscopic blood-filled cysts and is termed bacillary peliosis. Bacillary peliosis may also involve the spleen and lymph nodes. Patients with bacillary peliosis typically have symptoms such as fever, chills, and hepato- or splenomegaly.
[FIGURE 3-19 OMITTED]
Clinical Signs in Animals
Infected cats do not show signs of disease, but are bacteremic. Ba. vinsonii may cause endocarditis, lameness, and granulomatous lymphadenitis in dogs.
[FIGURE 3-20 OMITTED]
Clinical Signs in Humans
A cat scratch is typically the primary lesion with CSD and this lesion serves as the portal of entry for the bacteria (Figure 3-20). The skin lesion usually appears as an erythematous (red) papule (Figure 3-21). Following an incubation of 1 to 2 weeks, CSD usually presents as a self-limiting lymphadenopathy associated with a cat scratch or bite. The most common initial finding is subacute regional lymph node enlargement that may develop purulent discharge in 10% to 15% of cases. Generalized lymphadenopathy with CSD is rare. In up to 25% of cases systemic involvement may occur which includes ocular involvement, encephalopathy, hepatitis, and hepatosplenic infection.
[FIGURE 3-21 OMITTED]
Diagnosis in Animals
Diagnosis in cats is not done because this bacterium does not cause disease in cats.
Diagnosis in Humans
The tissues infected with Bartonella bacteria vary in people and biopsies are typically not used in people to diagnose CSD. If biopsies are taken, the early stages of disease provide the better chance for microscopic detection of bacteria. Microscopy with Warthin-Starry silver stain and immunocytochemistry of blood smears is rarely positive as a result of the low density of bacteria in the blood. Diagnosis of CSD includes identifying the following clinical conditions: regional lymphadenopathy, contact with animals, and primary skin lesions. Positive culture results are optimal in diagnosing this disease, but may not occur because Ba. henselae is difficult to culture and may take up to 6 weeks to grow. Either serology or PCR tests are considered to be the best methods of detection. Anti-Ba. henselae IgG and IgM indirect fluorescence assay (IFA) or enzyme-linked immunosorbent assays (ELISA) tests exist for the diagnosis of CSD. IFA tests are up to 100% sensitive and ELISA tests for IgM are approximately 95% sensitive (Figure 3-22). Genetic variation occurs amongst Ba. henselae strains, which may explain the inconsistency of some diagnostic techniques and cross-reaction within the genus making species identification difficult. A separate serogroup (Marseilles) has been reported in a seronegative patient with CSD, and Ba. clarridgeiae and Af. felis have the potential to cause the disease which may also complicate the diagnosis of CSD. PCR tests are also available and typically coupled with serologic and histologic tests to increase the accuracy of diagnosis.
CSD is the most common cause of regional lymphadenopathy in children and young adults.
Histopathologic findings from involved lymph nodes depends on the stage of infection: early in the disease lymphoid hyperplasia is seen; as the disease progresses granulomas with areas of central necrosis are seen in the lymph nodes; late in the disease areas of necrosis in the lymph nodes start to coalesce. Bartonella bacteria can be seen on properly stained sections.
Skin tests can also be performed by preparing antigen by heating pus from affected lymph nodes and injecting 0.1 mL of the antigen intradermally in suspected patients. A positive result is at least 5 mm of induration after 48 and 72 hours. Skin testing is controversial as a result of the risk of disease transmission.
[FIGURE 3-22 OMITTED]
Treatment in Animals
Cats are not ill with this disease; therefore, no treatment is used in animals. Treatment of carrier animals is not warranted.
Treatment in Humans
The majority of CSD cases resolve spontaneously and do not require antibiotic treatment. Antipyretics and analgesics may be needed to reduce fever and pain in patients. In complicated CSD, treatment with trimethoprim-sulfamethoxazole, ciprofloxacin, doxycycline, or azithromycin is recommended as a result of their ability to achieve high intracellular concentrations. Aspiration of enlarged, fluid-filled lymph nodes may be recommended to relieve pain; however, incision and drainage leaves a scar and may spread the bacterium from one location to another.
Management and Control in Animals
There is no current management of bacteremic cats to control CSD. Flea control may help limit transmission between cats and reduce bacterial load in the reservoir host.
Management and Control in Humans
Prevention of CSD includes teaching people, especially children, how to handle pets gently to avoid scratches. Any scratch or bite from animals, especially cats, should be thoroughly washed immediately and monitored to make sure it resolves and that lymphadenopathy does not occur. Cats should not be allowed to lick open wounds. People who are immunocompromised, especially people with AIDS, have an increased risk of developing CSD and any skin lesion should be examined by medical professionals. Immunocompromised peoples should especially avoid contact with feral, flea-infested cats and kittens.
Cat-scratch disease (CSD) is a bacterial disease caused by Ba. henselae. Most people with CSD acquire the infection via a cat bite or scratch; the bacterium is spread amongst cats by fleas. Cats that carry Ba. henselae do not show signs of disease; people with CSD have swollen lymph nodes, fever, headache, fatigue, and anorexia. CSD may progress to a variety of different diseases including ocular involvement, encephalopathy, hepatitis, hepatosplenic infection, and bacillary angiomatosis. Ba. henselae is difficult and time consuming to culture; therefore, either serology or PCR tests are considered to be the best methods of detection. The majority of CSD cases resolve spontaneously and do not require antibiotic treatment. Flea control may help limit transmission between cats and reduce bacterial load in the reservoir host. Teaching people, especially children, how to handle pets gently to avoid scratches is also important in preventing CSD. Immunocompromised people should especially avoid contact with feral, flea-infested cats and kittens.
Clostridium bacteria are a large genus of anaerobic bacteria responsible for diseases such as botulism, tetanus, gas gangrene, and pseudomembranous colitis. Although there are over 100 species of Clostridium, only a few species are implicated in serious disease. Clostridium comes from the Greek word kloster meaning spindle and was thus named as a result of its large, almost rectangular morphology. This large genus of bacteria has varied habitats including soil, sewage, vegetation, organic debris, and as commensals of the intestinal tract of humans and animals. Clostridium bacteria were first identified by Louis Pasteur in 1861 (the first identified species was Cl. butyricum).
Cl. botulinum consists of seven members (four harmful) and was first discovered in 1793 when there were scattered cases of muscle weakness and respiratory failure linked to eating sausage in Germany, Scandinavia, and Russia. The word botulism is derived from the Latin word for sausage, botulus. In 1897, van Ermengem found the Clostridium organism in contaminated ham and discovered that the organism would only multiply in oxygen-free containers. He also discovered that Cl. botulinum produced a powerful toxin that could be inactivated by heat and the bacterium would not produce the toxin at all if the food was too salty. Botulism is a disease that is seen most frequently with home canning products, with cases peaking in the United States in the 1930s (about 35 cases per year). Cl. botulinum releases a gas that causes the tin cans used in food canning to bulge. Refrigeration and food preservation techniques (the use of nitrites in hot dogs and cold cuts is to prevent botulism) have made foodborne botulism rare today. More recent botulism outbreaks in the United States include a 1977 outbreak when 59 people got sick after eating improperly preserved jalapeno peppers, a 1993 outbreak when a restaurant in Georgia used contaminated canned cheese sauce, and another 1993 outbreak that occurred in a restaurant in Texas that served contaminated dip. Cl. botulinum can also cause infant botulism (when infants ingest the endospores and the toxin forms in the intestines in the absence of mature gastrointestinal normal flora) and wound botulism (where the bacterium multiplies in a wound and produces toxin which is absorbed into the bloodstream).
Horses are especially sensitive to tetanus and are used for commercial production of tetanus antitoxin.
Cl. tetani is the causative agent of tetanus, which comes from the Greek word tetanos meaning to stretch. Tetanus has been recognized since the time of Hippocrates in the 5th century B.C. In ancient Egypt, dung was a favored medicine to treat wounds. During wartime, lacerations and burns contaminated with Cl. tetani are a breeding ground for tetanus. Tetanus was not fully understood until the late 19th century when the Japanese bacteriologist Shibasaburo Kitasato demonstrated the damage done by this bacterium's toxin by injecting bacteria into the tips of mouse tails and chopping their tails off within an hour of injection. Even with this prompt "treatment," the mice died from the toxin. The discovery of tetanus toxoid (produced by inactivating the toxin with formaldehyde or other means) occurred during World War I when it was injected into French cavalry horses. Additionally, small amounts of toxin could be injected into animals enabling them to produce an antitoxin that could be used on humans. The discoveries of long-term immunization with tetanus toxoid and injection of tetanus antitoxin within a day or two following injury virtually wiped out tetanus. Most U.S. tetanus cases today are in people over fifty who are not up-to-date on their vaccinations. Cl. tetani also causes neonatal tetanus which results in hundreds of thousands of infant deaths in Asia and Africa where umbilical cords are cut with contaminated instruments or are packed with dirt.
Cl. perfringens is the cause of food poisoning (especially in cooked beef and poultry) and gas gangrene (named from the Greek term gangraina meaning eating sore). The Latin term perfringere means to break up and this bacterium is believed to be named because it produces necrotizing enzymes. Around 1892, Welch, Nuttall, and other scientists isolated a gram-positive anaerobic bacillus from gangrenous wounds. This organism was originally named Bacillus aerogenes capsulatus, then Bacillus perfringens, then Cl. welchii, and finally Cl. perfringens. Gas gangrene is typically associated with war injuries. In World War I, 6% of open fractures and 1% of open wounds were complicated with gas gangrene; in World War II these cases decreased to 0.7%; in the Korean War they decreased to 0.2%; in the Vietnam War they decreased to 0.002%; and were nonexistent during the war in the Falkland Islands in 1982.
Cl. difficile, an opportunistic bacterium of the gastrointestinal tract and potential zoonotic agent, is named because it is so difficult to culture. Cl. difficile causes antibiotic-associated diarrhea and pseudomembranous colitis in humans. Healthy people do not get Cl. difficile since it can be part of the normal gastrointestinal flora; however, people who have undergone gastrointestinal surgery, have serious underlying illness, or are immunocompromised are at risk of developing disease from this bacterium. Horses can develop Cl. difficile-associated diarrhea and may pose a zoonotic risk for this disease.
The genus Clostridium consists of large, obligate (strictly) anaerobic, gram-positive, endospore-forming bacilli that are found in almost all anaerobic habitats in nature where organic compounds are present (soil, aquatic sediments, and the gastrointestinal tracts of animals). Their resistance to environmental changes is a result of their ability to produce endospores and their virulence is a result of the vegetative cell's secretion of toxins. Clostridium bacteria produce oval to spherical endospores that swell the vegetative cell and the cells occur in single, paired, or chain arrangements. The main pathogenic species of Clostridium in humans are:
* Cl. botulinum. This species of Clostridium forms subterminal endospores and is commonly found in soil, decaying vegetation, and lake and pond sediments. The gastrointestinal tracts of birds, mammals, and fish may occasionally contain Cl. botulinum. Its endospores are able to survive improper food canning techniques and as the vegetative cell germinates they release neurotoxins into the container. Different strains of Cl. botulinum produce one of seven distinct neurotoxins (identified as A, B, C1, D, E, F, and G). In the United States type A is the most common cause of botulism (62% of cases). Types A, B, and E are most important in botulism in people; type B toxin causes botulism in horses and foals in the eastern United States; C1 in most animal species (wild ducks, pheasants, chickens, mink, cattle, and horses); D in cattle; type F has been responsible for two outbreaks in humans; type G (isolated from soil in Argentina) is not known to have been involved in any outbreak of botulism. Botulism neurotoxins affect the peripheral nervous system.
* Cl. tetani. This species of Clostridium is typically found in heavily-manured soils and in the gastrointestinal tracts and feces of many animals. There are 11 strains of Cl. tetani distinguished from each other on the basis of flagellar antigens. Cl. tetani produces terminal endospores within a swollen end giving it a tennis-racket appearance (Figure 3-23). Cl. tetani produces tetanospasmin, a neurotoxin that disrupts nerve impulses to muscles. This toxin is produced by vegetative cells and is released on cell lysis, which occurs naturally during germination.
@@@@@@@ * Cl. perfringens. Cl. perfringens is found in soil and dust, manure, in lakes and streams, on skin, and in the gastrointestinal tract. Cl. perfringens is nonmotile (most other species are motile) and produces subterminal endospores. This bacterium produces at least 12 different toxins and antigens and is divided into types A to E based on differences in the toxins. Important toxins include alpha (lethal toxin that is also hemolytic and necrotizing), beta (lethal toxin that is responsible for inflammation of the intestine and loss of mucosa), epsilon (lethal toxin that is necrotizing), itoa (lethal and necrotizing), delta (lethal and hemolyzing), kappa (lethal toxin that is a proteolytic enzyme that breaks down collagen), lambda (proteolytic enzyme that attacks hemoglobin), and mu (hydrolyzes hyaluronic acid). The toxin is deemed lethal as tested by injection in mice.
* Cl. difficile. This organism has a subterminal endospore and produces two toxins. Toxin A is an enterotoxin because it causes fluid accumulation in the intestines and toxin B is a cytopathic toxin that is extremely lethal. These two toxins destroy the intestinal lining causing diarrhea. In minor infections these lesions are self-limiting; in serious cases a life-threatening pseudomembranous colitis occurs in which large sections of the colon wall slough, potentially perforating the colon, leading to massive internal infection by fecal bacteria and possible death.
[FIGURE 3-23 OMITTED]
Selected Clostridium bacteria are summarized in Table 3-5.
Epizootiology and Public Health Significance
Thirty grams of pure botulism toxin could kill every U.S. citizen.
Clostridium spp. are ancient organisms and have worldwide distribution. Clostridium bacteria are found in soil and any other environment where organic compounds are found. Certain species may be more prevalent in some parts of the world and will be described with each disease.
Annual U.S. cases of botulism are about 25 with a 20% mortality rate (mortality rates used to be over 60% prior to the establishment of critical care). Typically the first person who contracts botulism in an outbreak has 25% mortality with subsequent cases being more rapidly diagnosed and treated carrying a 4% mortality rate. About 100 cases of infant botulism are reported annually in the United States. Since 1994, the use of black tar heroin by chronic IV drug users has led to a dramatic increase in wound botulism in the United States.
Over 1 million cases of tetanus occur annually worldwide, mostly in underdeveloped countries with inadequate health care and vaccination protocols. The mortality rate of tetanus is 50%; neonatal tetanus (usually from umbilical cord infection) has a 90% mortality rate. In the United States tetanus is uncommon as a result of the vaccine.
Gas gangrene is uncommon in the United States with only 1,000 to 3,000 cases occurring in the United States annually. The mortality rate with gas gangrene is about 40% even with therapy.
Cl. difficile infections among hospitalized patients are increasing. Studies from Canada indicate that between March 2000 and April 2004 the number of cases doubled (from about 3,300 to 7,000) with a 60% increase in deaths associated with Cl. difficile infection. Exact case numbers in the United States are not documented, but this increase is likely occurring in this country as well. Other than Cl. difficile infections which appear to be rising, clostridial diseases are uncommon in the United States.
The occurrence of Cl. tetani in the soil (and the resulting incidence of tetanus in man and horses) is higher in the warmer parts of the various continents.
Clostridial infections can be transmitted in a variety of ways including:
* Ingestion of preformed toxin in vegetable and meat-based foods for Cl. botulinum.
* Contamination of wounds or puncture of object contaminated with Cl. tetani, Cl. perfringens, and less commonly Cl. septicum and Cl. novyi.
* Colonization of gastrointestinal tract with toxin-producing bacterium for Cl. botulinum (infant botulism).
* Person-to-person spread for Cl. difficile.
* Potential zoonotic spread via fecal contaminated equipment for Cl. difficile. Pathogenesis
In foodborne botulism the toxin is ingested with contaminated food in which endospores have germinated and vegetative cells have multiplied. Foodborne botulism is a form of intoxication because the ingested food contains preformed toxin. In the upper gastrointestinal tract the toxin is absorbed, passes into the blood, and in time reaches the peripheral neuromuscular junction. The toxin binds to the presynaptic membrane and blocks the release of acetylcholine, a neurotransmitter required for muscle stimulation by a nerve. Botulism occurs from ingested uncooked foods and commonly is associated with home canning. Clinical signs of botulism occur 18 to 36 hours after toxin ingestion and include weakness, dizziness, and gastrointestinal signs like diarrhea and vomiting. Neurologic signs develop soon afterwards and include blurred vision, weakness of skeletal muscles, and respiratory paralysis.
The three most poisonous substances known are botulism toxin, tetanus toxin, and diphtheria toxin.
Infant botulism is caused by infection with Cl. botulinum and typically occurs in infants 5 to 20 weeks of age that have been exposed to solid foods containing endospores. Cl. botulinum establishes itself in the intestines of infants prior to development of competent normal flora. Bacteria produce toxin in the gastrointestinal tract which causes signs such as constipation and generalized weakness.
Most tetanus cases result from puncture wounds or lacerations that become contaminated with endospores that germinate in tissue and produce toxin. Infection is typically localized causing only minimal inflammation; however, because Cl. tetani is a strict anaerobe the endospores cannot germinate to vegetative cells unless the tissues are necrotic and have poor blood supply (lowers the oxygen tension). The tetanospasmin toxin is produced during cell growth and released upon cell lysis (occurs during vegetative growth and the production of endospores). The toxin moves along nerve pathways from the wound to the peripheral nerve endings. It travels within the axon to the spinal cord. In the spinal cord the toxin binds to specific sites on spinal neurons that are responsible for inhibiting skeletal muscle contraction. The tetanospasmin blocks the release of neuroinhibitors needed to regulate muscle contraction causing the muscles to contract uncontrollably. Larger muscle groups are initially affected such as the muscles of the jaw and then back (causing arching), arms, and legs. Respiratory paralysis is often the cause of death in severe cases.
Gas gangrene, also known as myonecrosis, is caused by a few species of Clostridium with Cl. perfringens being the most common etiologic agent. Cl. perfringens produces alpha toxin which causes red blood cell rupture, edema, and tissue damage. There are two forms of gas gangrene: anaerobic cellulitis in which previously injured necrotic tissue is infected with Cl. perfringens producing toxin and gas (infection remains localized and does not spread into healthy tissue) and myonecrosis in which toxins are produced in damaged tissue and are diffused into nearby healthy tissue (resulting in continued spread of disease as more tissue is destroyed producing gaseous bacterial waste products).
Cl. difficile produces two toxins: toxin A is an enterotoxin (causes fluid accumulation in the intestines) and toxin B is a cytopathic toxin (causes cell death). Typically following antibiotic treatment or in immunocompromised people, Cl. difficile endospores germinate in the intestine allowing it to predominant the normal flora. The toxins and enzymes produced by this bacterium produce hemorrhagic necrosis of the intestinal mucosa. In serious cases large sections of the colon will slough potentially causing bowel perforation and internal infection by fecal bacteria.
Clinical Signs in Animals
Clostridial infections in animals vary with the species of Clostridium and animal species. Some examples of resulting infections from select Clostridium species include (others can be found in Table 3-5):
* Cl. botulinum. This species of Clostridium causes botulism, a rapidly fatal motor paralysis in animals. The usual source of the toxin is decaying carcasses or contaminated vegetable materials such as decaying grass, hay, grain, or spoiled silage. In animals toxicoinfectious botulism occurs when Cl. botulinum grows in tissues of a living animal and produces toxins. Predisposing factors for the development of toxicoinfectious botulism include gastric ulcers, liver necrosis, navel and lung abscesses, skin and muscle wounds, and necrotic lesions of the gastrointestinal tract. The incidence of botulism in animals is unknown, but it is relatively low in cattle and horses, more frequent in chickens, and high in wild waterfowl (between 10,000 and 50,000 birds are lost annually in the United States, with losses reaching 1 million or more during outbreaks in the western United States). The zoonotic potential of botulism is minimal.
* Most affected birds are ducks, although loons, geese, and gulls also are susceptible. In birds, Cl. botulinum is commonly found in the gastrointestinal tract of poultry and wild birds and in litter, feed, and water in broiler chicken houses. Intoxications are sporadic in poultry, but massive mortality has occurred in waterfowl in western North America. Clinical signs in poultry and wild birds are similar and include flaccid paralysis of the legs, wings, eyelids, and neck (hence the term limberneck) (Figure 3-24), with paralytic signs progressing cranially from the legs to the wings, neck, and eyelids. In affected waterfowl, neck paralysis can lead to drowning.
* Dogs, cats, and pigs are comparatively resistant to most types of botulism toxin when administered orally. Botulism occurs sporadically in dogs as a result of type C toxin; botulism has not been reported in cats. Clinical signs of botulism include progressive motor paralysis, altered vision, difficulty in chewing and swallowing, and generalized weakness.
* Most cases of bovine botulism occurs in South Africa, where phosphorus-deficient cattle chew any bones they find on the range and intoxication occurs if these bones and flesh came from an animal that had been carrying type D strains of Cl. botulinum. As little as one gram of dried flesh from an infected carcass may contain enough toxin to kill mature cattle. Type C strains also cause botulism in cattle (this form is rare in the United States with only a few cases reported from Texas and referred to as loin disease). Cattle may drool, be unable to urinate, have dysphagia, and may be in sternal recumbency that progresses to lateral recumbency just before death. Clinical signs in cattle resemble milk fever, but the cows do not respond to calcium therapy. Death results from respiratory or cardiac paralysis. There are no characteristic lesions with botulism in cattle.
* Botulism in sheep has been reported in Australia, in sheep eating carcasses of rabbits and other small animals found on the range.
* Botulism in horses often results from forage contaminated with type C or D toxin. Foals with botulism, also known as shaker foal syndrome, are usually less than 4 weeks old and may be found dead without signs. The most common sign is progressive symmetrical motor paralysis; other signs include stilted gait, muscular tremors, dysphagia, constipation, mydriasis, frequent urination, dyspnea with extension of the head and neck, tachycardia, and respiratory arrest. Death occurs in foals within 24 and 72 hours after the onset of clinical signs.
* Botulism in unvaccinated mink occurs when mink eat raw meat diets. Mink botulism is typically caused by type C strains that have produced toxin in chopped raw meat or fish. Many mink are typically found dead within 24 hours of exposure to the toxin, whereas others show varying degrees of paralysis and dyspnea. Necropsy findings are nonspecific.
* Cl. tetani. Tetanus toxemia in animals is caused by a neurotoxin produced by Cl. tetani in necrotic tissue. Most mammals are susceptible to tetanus, although dogs, cats, and birds are relatively resistant. Horses are the most sensitive of all animal species. Tetanus in animals has a worldwide distribution, although in some areas, such as the northern Rocky Mountains of the United States, the bacterium is rarely found in the soil and tetanus is rare. Tetanus is seen following a puncture wound, a surgical procedure such as docking or castration, and occasionally the point of entry cannot be found because the wound is small or healed. The classic clinical sign is muscle rigidity and even minor stimulation of the affected animal may trigger muscle spasms. Muscle spasms affecting the larynx, diaphragm, and intercostal muscles may lead to respiratory failure. Involvement of the autonomic nervous system results in cardiac arrhythmias, tachycardia, and hypertension. Fever is rare, but may occur. The incubation period averages 10 to 14 days but can vary from 1 to several weeks (dogs and cats often have a longer incubation period). In most animals the first sign is localized stiffness, typically of the masseter muscles, muscles of the neck, hindlimbs, and the region of the infected wound, with generalized stiffness becoming pronounced a few days later with tonic spasms and hyperesthesia becoming evident. Hyperreflexia, general spasms, and difficulty in prehension and mastication of food (hence the common name lockjaw) are commonly seen.
* In horses, clinical signs include erect ears, stiff and extended tail, dilated anterior nares, prolapsed third eyelid, difficulty walking, turning, and backing, extension of the head and neck as a result of muscle spasms, a "sawhorse" stance, sweating, increased heart rate, rapid breathing, and congestion of mucous membranes (Figure 3-25).
* Sheep, goats, and pigs present with similar signs to horses and often fall to the ground and exhibit opisthotonos when startled. Mentation is not affected.
* In dogs and cats, localized tetanus presents as stiffness and rigidity in a limb with a wound. The stiffness progresses to the opposite limb and may advance cranially. Generalized tetanus in dogs and cats is similar to other animals except they may have a partially open mouth with the lips drawn back (as seen in humans).
* Cl. perfringens. This species of Clostridium is widely distributed in the soil and the gastrointestinal tract of animals. Five types of isolates (A, B, C, D, and E) have been identified.
** Type A strains of Cl. perfringens are commonly found as part of the normal intestinal flora of animals and do not have as destructive toxins as some other strains. Cl. perfringens type A produces necrotic enteritis in poultry and dogs (causing massive destruction of the villi and coagulation necrosis of the small intestine), colitis in horses, and diarrhea in pigs.
** Type B and C strains of Cl. perfringens produce highly necrotizing and lethal [beta] toxin (responsible for the severe intestinal damage) and cause severe enteritis, dysentery, toxemia, and high mortality in young lambs, calves, pigs, and foals. Cl. perfringens type C also causes enterotoxemia in adult cattle, sheep, and goats. Lamb dysentery is caused by Cl. perfringens type B in lambs up to 3 weeks of age (lambs stop nursing, become listless, and remain recumbent and commonly develop blood-tinged diarrhea with death occurring in a few days; some lambs may die before signs appear); calf enterotoxemia is caused by Cl. perfringens types B and C in well-fed calves up to 1 month of age (acute diarrhea, dysentery, abdominal pain, convulsions, and opisthotonos resulting in death in a few hours or in less severe cases recovery over a period of several days); pig enterotoxemia is caused by Cl. perfringens type C in piglets during the first few days of life (acute illness within a few days of birth with diarrhea, dysentery, reddening of the anus, and a high mortality rate typically within 12 hours); foal enterotoxemia is caused by Cl. perfringens type B in foals in the first week of life (acute dysentery, toxemia, and rapid death); and goat enterotoxemia caused by Cl. perfringens type C in adult goats (death is typically the only sign).
** Type D strain of Cl. perfringens causes an enterotoxemia of sheep (and to a rare extent goats and cattle). The main predisposing factor of this disease is ingestion of excessive amounts of feed or milk in the very young and grain in feedlot lambs (from where it gets it common name overeating disease). As starch intake increases it provides a suitable environment for bacterial growth and toxin production. This disease is commonly seen in lambs younger than 2 weeks of age or in weaned lambs on feedlot. The most common clinical sign is sudden death in the best conditioned lambs; in some cases excitement, incoordination, and seizures may be seen prior to death. Adult sheep may be affected occasionally showing similar signs.
** Type E strain of Cl. perfringens has not been linked to animal disease.
* Cl. difficile. Cl. difficile causes acute, sporadic gastrointestinal disease of horses characterized by diarrhea and colic. Clinical signs in horses range from mild and self-limiting to rapidly fatal. The factors that cause the disease are unknown; however, alteration in the normal flora allowing excessive multiplication of these bacteria, which are capable of producing toxins that cause intestinal damage and systemic effects, is believed to play a key role. Dietary change and antibiotic therapy likely play a role in disease development. Other host factors that may determine whether disease develops include age, immunity, and presence or absence of intestinal receptors for the clostridial toxins. Cl. difficile has been identified in foals with diarrhea, but not in healthy foals. Foals are more frequently affected, but adult horses may also get the disease. Clinical signs include dead horses without any signs, abdominal pain, diarrhea with or without blood, dehydration, toxemia, and shock. Cl. difficile has emerged in recent years as a cause of diarrhea and edema of the colon in neonatal swine (1- to 7-day-old pigs).
[FIGURE 3-24 OMITTED]
[FIGURE 3-25 OMITTED]
Clinical Signs in Humans
Clinical signs of botulism include weakness, dizziness, blurred vision, dry mouth, dilated pupils, constipation, and abdominal pain followed by progressive paralysis that ultimately affects the diaphragm. Death results from the inability to inhale. People remain alert when they have botulism. Babies with infant botulism excessively cry, have constipation, and fail to thrive. Paralysis and death with infant botulism is rare. Wound botulism is a rare disease and occurs when the endospores get into an open wound and multiply in an anaerobic environment (Figure 3-26). The symptoms produced are similar to those described above, but may take up to 2 weeks to appear.
[FIGURE 3-26 OMITTED]
[FIGURE 3-27 OMITTED]
Clinical signs of tetanus include the initial and diagnostic sign of tightening of the jaw and neck muscles, sweating, drooling, and back spasms (Figure 3-27). As the disease progresses irregular heart rate, changes in blood pressure, excessive sweating, and spasms spreading to other muscles such as those of the arms, fists, and feet. Death can occur as a result of the person's inability to exhale.
[FIGURE 3-28 OMITTED]
Clinical signs of gas gangrene include intense pain at the site of infection (as a result of tissue swelling and necrosis), the presence of gas in the tissues (as a result of bacterial waste products) (Figure 3-28), shock, kidney failure, and death.
Clinical signs of pseudomembranous colitis include a self-limiting explosive diarrhea in mild cases and in severe cases sloughing of the colon wall, intestinal perforation, sepsis, and possible death.
Diagnosis in Animals
Diagnosis of clostridial infections varies with the species of Clostridium.
* Botulism is diagnosed by clinical signs, eliminating other causes of motor paralysis, analyzing feed, detecting toxin in the blood (by mouse inoculation tests or ELISA testing), Gram stain, and anaerobic tissue culture.
* Tetanus is diagnosed by clinical signs and history of recent trauma, demonstrating the presence of tetanus toxin in serum, and demonstration of the bacterium in Gram-stained smears, and by anaerobic culture when a wound is apparent.
* Cl. perfringens infections can be diagnosed based on necropsy lesions (hemorrhagic enteritis with ulceration of the mucosa is the major lesion in all species), Gram-stained smears of intestinal contents, and toxin detection.
* Cl. difficile infections can be diagnosed based on lesions (necrotizing enterocolitis, loss of colonic and cecal mucosal epithelial cells, and thrombosis in capillaries of the intestinal mucosa), demonstration of toxins in feces or intestinal fluid, and demonstration of large numbers of the bacterium on Gram stain and through anaerobic culture.
Diagnosis in Humans
Diagnosis in people is similar to animals. Proper collection and transport of specimens for anaerobic culture are essential. Material for anaerobic culture is best obtained by tissue biopsy or fine needle aspirate. Swabs expose the specimen to drying, contamination, and retention of the organism to the swab fibers (although oxygenfree transport swabs are available). Some clostridial diseases (such as food-borne Cl. perfringens and Cl. botulinum and enteritis caused by Cl. difficile) must be sent to a public health laboratory for confirmation. Suitable anaerobic media include anaerobic blood agar, chopped meat broth, thioglycollate broth, and cycloserine cefoxitin fructose agar (CCFA), which is selective for Cl. difficile. Anaerobic incubation can be obtained by using anaerobe jars, holding jars, or an anaerobe chamber. Commercial identification methods are also available (Figure 3-29).
[FIGURE 3-29 OMITTED]
Treatment in Animals
Treatment of Clostridium infections includes the early use of antibiotics and antitoxin if available, removal of contaminated feed or material, and disinfection. Altering the anaerobic environment of contaminated wounds through debridement and antisepsis is also recommended.
The incidence of botulism in animals is relatively low in cattle and horses, somewhat frequent in chickens, and high in wild waterfowl. Probably 10,000 to 50,000 birds are lost annually in the United States with ducks being the bird most affected. Dogs, cats, and pigs are comparatively resistant to all types of botulinum toxin when administered orally. Botulism is treated with botulinum antitoxin in ducks and mink with type C antitoxin; however, such treatment is rarely used in cattle. Treatment with guanidine hydrochloride may ease paralysis caused by the toxin; however, it is not used extensively.
Tetanus is treated with curariform agents, tranquilizers, or barbiturate sedatives, in conjunction with tetanus antitoxin in horses. Draining and cleaning of wounds is also important in treating cases of tetanus. Keeping animals in a quiet, darkened area and assisting with ambulation are also important in the nursing care of animals with tetanus.
Treatment of Cl. perfringens infections is usually ineffective in animals because of the severity of the disease; however, specific hyperimmune serum and oral administration of antibiotics may be helpful.
Treatment of Cl. difficile in horses is oral metronidazole.
Treatment in Humans
Treatment of Clostridium infections in humans revolves around the proper use of antibiotics and antitoxin. Botulism is treated with antibiotics, antibodies against the botulism toxin (so that new toxin doesn't bind to neurons; any prior toxin binding is irreversible), and repeated washing of the intestinal tract to remove the bacterium. Tetanus is treated with antibiotics, passive immunization with antitoxin (binds to and neutralizes toxin before it can bind), cleansing of the wound to remove endospores, and active immunization with tetanus toxoid (stimulates the formation of antibodies that neutralize the toxin). As with botulism, bound tetanus toxin cannot be reversed. Sometimes sedatives or tranquilizers may be given to ease the spasms as well as keeping the person in a dark, quiet place. Gas gangrene is treated with antibiotics, administration of antitoxin, surgical debridement of the wound to eliminate the anaerobic environment, and sometimes hyperbaric oxygen treatment. Clostridial food poisoning is usually self-limiting. Treatment of Cl. difficile involves discontinuing the implicated antibiotic (mild cases) or treatment with vancomycin or metronidazole (severe cases where about one third of patients will relapse).
Management and Control in Animals
Control of Clostridium infections in animals includes proper disposal of carcasses, correcting any dietary deficiencies, avoiding overeating, removing contaminated grass or feed, proper surgical technique following strict guidelines for asepsis, using clean needles, and vaccination if available. Vaccines are available for cattle and sheep (a variety of combinations for Cl. chauvoei, Cl. septicum, Cl. novyi, Cl. sordelii, Cl. perfringens types C and D, Cl. tetani (toxoid and antitoxin), Cl. haemolyticum), mink (toxoid for botulism), horses (Cl. botulinum type B and Cl. tetani [toxoid and antitoxin]), and pigs (Cl. perfringens and Cl. tetani toxoid). In horses (who are especially sensitive to tetanus) the toxoid should be annually; mares should be vaccinated during the last 6 weeks of pregnancy and the foals vaccinated at 5 to 8 weeks of age, then repeated annually. If horses incur a deep wound after immunization, another injection of toxoid may be given to increase circulating antibody levels and repeated in 30 days. If the horse has not been immunized previously, it should be treated with tetanus antitoxin, which usually provides passive protection for up to 2 weeks. In high-risk areas, foals may be given tetanus antitoxin immediately after birth and every 2 to 3 weeks until they are 3 months of age, at which time they can be given toxoid. Vaccination of lambs, calves, and pigs depends on the prevalence of tetanus in the area.
Cl. difficile infections in horses can be reduced by judicial use of antibiotics (antibiotics such as metronidazole and chloramphenicol for oral administration is recommended for high-risk horses).
Management and Control in Humans
Clostridial infections in people can be controlled in a variety of ways. Botulism can be controlled by proper home canning techniques, preventing endospore germination by refrigeration or establishing an acidic environment, or destroying the toxin by heating to at least 80[degrees]C for at least 20 minutes. Infant botulism can be prevented by not feeding infants honey until they are over 1 year of age. Wound botulism can be avoided with proper wound cleaning. Tetanus can be controlled by vaccination with tetanus toxoid (part of the DTP or DT vaccine) as per CDC recommendations of three doses during the first year of life, a booster in about one year, a booster when entering elementary school, followed by a booster every 10 years of life. Gas gangrene infections are hard to control because the organism is so prevalent in the environment. Myonecrosis can be controlled with proper cleaning of wounds. Foodborne Cl. perfringens infections can be prevented through refrigeration of food and reheating of food to destroy any toxin present. Hot foods should be served immediately or held above 140[degrees]F. Refrigerated foods should be stored in small containers and reheated to 165[degrees]F prior to serving. Cl. difficile infections can be prevented with proper and limited use of antibiotics and proper hygiene to avoid nosocomial infections. Zoonotic potential can be reduced through the use of barrier precautions (gloves, gowns, and boots), personal hygiene, and disinfection of equipment with an appropriate disinfectant such as 5% to 10% bleach.
Clostridial infections are caused by bacteria in the genus Clostridium--large, strictly anaerobic, gram-positive, endospore-forming bacilli that are found in almost all anaerobic habitats in nature where organic compounds are present. Their resistance to environmental changes is a result of their ability to produce endospores and their virulence is a result of the vegetative cell's secretion of toxins. The main pathogenic species of Clostridium in humans are Cl. botulinum, Cl. tetani, Cl. perfringens, and Cl. difficile. Clostridium spp. are ancient organisms and have worldwide distribution. Clostridium bacteria are found in soil and any other environment where organic compounds are found. Clostridial infections can be transmitted in a variety of ways including ingestion of preformed toxin in vegetable and meat-based foods, contamination of wounds or puncture wounds, colonization of the gastrointestinal tract with toxin-producing bacteria, person-to-person spread, and potential zoonotic spread via fecal contaminated equipment. The pathogenesis of clostridial disease revolves around toxins and toxin production.
Clostridial infections in animals vary with the species of Clostridium and the animal species. Some examples of resulting infections from select Clostridium spp. include Cl. botulinum (causes botulism, a rapidly fatal motor paralysis in animals), Cl. tetani (causes tetanus toxemia in animals as a result of a neurotoxin produced in necrotic tissue that results in muscle rigidity and spasms), Cl. perfringens (causes wound contamination and gastroenteritis in animals), and Cl. difficile (causes acute, sporadic gastrointestinal disease of horses characterized by diarrhea and colic). In people, clostridial infections cause botulism (signs include weakness, dizziness, blurred vision, dry mouth, dilated pupils, constipation, and abdominal pain followed by progressive paralysis that ultimately affects the diaphragm), tetanus (signs include the initial and diagnostic sign of tightening of the jaw and neck muscles, sweating, drooling, and back spasms, progressing to irregular heart rate, changes in blood pressure, excessive sweating, and spasms spreading to other muscles such as those of the arms, fists, and feet), gas gangrene (signs include intense pain at the site of infection (as a result of tissue swelling and necrosis), the presence of gas in the tissues (as a result of bacterial waste products), shock, kidney failure, and death), and pseudomembranous colitis (signs include a self-limiting explosive diarrhea in mild cases and in severe cases sloughing of the colon wall, intestinal perforation, sepsis, and possible death). Clostridial infections are typically diagnosed via clinical signs, toxin detection, Gram stain, and anaerobic tissue culture. Treatment of clostridial infections includes the early use of antibiotics and antitoxin if available, removal of contaminated feed or material, and disinfection. Altering the anaerobic environment of contaminated wounds through debridement and antisepsis is also recommended. Control of clostridial infections in animals includes proper disposal of carcasses, correcting any dietary deficiencies, avoiding overeating, removing contaminated grass or feed, proper surgical technique following strict guideline for asepsis, and vaccination if available. Vaccines are available for cattle and sheep (a variety of combinations for Cl. chauvoei, Cl. septicum, Cl. novyi, Cl. sordelii, Cl. perfringens types C and D, Cl. tetani (toxoid and antitoxin), Cl. haemolyticum, mink [(toxoid for botulism)], horses (Cl. botulinum type B) and Cl. tetani (toxoid and antitoxin)), and pigs (Cl. perfringens and Cl. tetani toxoid). In people, botulism can be controlled by proper home canning techniques and by not feeding infants honey until they are older than 1 year of age. Wound botulism can be avoided with proper wound cleaning. Tetanus can be controlled by vaccination with tetanus toxoid. Gas gangrene infections can be controlled with proper cleaning of wounds. Foodborne Cl. perfringens infections can be prevented through refrigeration of food and reheating of food to destroy any toxin present. Cl. difficile infections can be prevented with proper and limited use of antibiotics and proper hygiene to avoid nosocomial infections. Zoonotic potential can be reduced through the use of barrier precautions, personal hygiene, and disinfection of equipment with an appropriate disinfectant.
Erysipeloid is a disease of traumatized skin consisting of fever, vesicles of the hands and feet, and inflammation of the mucous membranes caused by Erysipelothrix rhusiopathiae (from the Greek words erythros for red, pella for skin, thrix for hair). The taxonomic name Er. rhusiopathiae literally means erysipelas thread of red disease. Er. rhusiopathiae (formerly known as Er. insidiosa) was first isolated by Koch in 1878. In 1886 it was described by Loeffler as the etiologic agent of swine erysipelas. Erysipeloid was first described in humans by William Morrant Baker in 1873. In 1909, Rosenbach isolated the bacterium from a human patient with localized cutaneous lesions thus establishing it as a human pathogen. Rosenbach used the term erysipeloid to avoid confusion with the cutaneous lesions of human erysipelas (caused by Streptococcus pyogenes). Joseph Victor Klauder in 1917 published the first account in English.
Erysipeloid is known by a variety of other names such as Baker-Rosenbach syndrome, Klauder's syndrome, Rosenbach's erysipeloid, crab dermatitis, ectodermosis erosiva pluriorifacialis, fish-handlers' disease, and swine erysipelas in man. The eponym Rosenbach's disease is used in describing the mild form of the disease, whereas Klauder's form is used to describe a syndrome of severe systemic involvement. Erysipeloid appears most commonly in kitchen workers, butchers, fishermen, and other persons coming in contact with contaminated meat, animal products, or animal carcasses.
Er. rhusiopathiae is a straight or slightly curved, thin, nonmotile, nonendospore forming, gram-positive bacillus that is facultatively anaerobic. There is no capsule or flagellum. There are two forms of this bacterium based on cellular morphology. Bacteria isolated from tissues during acute infection or from smooth (S) colonies (small, circular, transparent colonies on BAP with a smooth glistening surface and edge) are straight or slightly curved small rods that may occur in short chains. Bacteria from older cultures or rough (R) colonies (larger, flatter, colonies on BAP with a matte surface and jagged edge) tend to become filamentous and may be confused with fungal mycelia. The S form prefers alkaline environments, whereas the R form prefers acidic environments.
Infection by Er. rhusiopathiae in humans is known as erysipeloid. Erysipelas is the name given to an infection in animals caused by the bacterium Er. rhusiopathiae. Erysipelas in humans is an acute Streptococcus bacterial skin infection (historically known as St. Anthony's fire as a result of its red lesions).
There are 24 serotypes (designated 1 through 24) of Er. rhusiopathiae based on heat-stable antigens. No correlation has been shown to exist between the serotype and the manifestation of the septicemic, urticarial, or endocardial forms of the disease. Er. rhusiopathiae is the only pathogenic species in the genus Erysipelothrix (recently a nonpathogenic species Er. tonsillarum has been identified as normal flora in the tonsils of healthy pigs and in surface waters but is not considered zoonotic).
Over 50 animal species may be infected with Er. rhusiopathiae, but it is especially common in domesticated pigs. Adult pigs, and especially nursing sows, are more susceptible than others.
Epizootiology and Public Health Significance
Infection with Er. rhusiopathiae occurs worldwide in a variety of animals, especially hogs (the major reservoir of this bacterium), but is also found in sheep, horses, cattle, chickens, crabs, fish, dogs, and cats.
Erysipeloid is an occupational disease seen more commonly among farmers, butchers, cooks, housewives, and fishermen. The infection is more likely to occur during the summer or early fall. Since it is not a reportable disease in the United States there are limited statistics on its prevalence.
Both animals and humans are infected with Er. rhusiopathiae through contact with infected animals, fish, or their products allowing bacteria to gain access through skin wounds and abrasions (including mucous membrane damage during insemination). In endemic areas, pigs are exposed naturally to the organism when they are young and have maternal antibodies (thus they have some immunity and do not show overt clinical signs). Infection may occur in animals by ingestion of contaminated foodstuffs (particularly cannibalism of infected carcasses). Rarely, human infections have been reported to occur through dog bites or the consumption of contaminated meat. Rodents may serve as reservoirs. Insect vectors and ticks may transmit the bacteria mechanically.
Er. rhusiopathiae is shed in the feces of infected (and perhaps carrier) animals contaminating the soil. This bacterium may survive for long periods depending on the environmental temperature and soil pH. Seasonal changes in climate (especially cold, rainy weather) have been associated with disease outbreaks.
Er. rhusiopathiae is excreted by infected animals and survives for short periods in moist soil.
Er. rhusiopathiae typically enters the skin through scratches or open wounds. In the skin, the bacterium produces enzymes that dissect tissues allowing the organism to move through these dissected areas. Er. rhusiopathiae also produces a hyaluronidase (the significance of which is not known) and a neuraminidase (its level of activity correlates with virulence). The neuraminidase breaks links in neuraminic acid located on the surface of host cells helping the bacterium invade tissues. Two adhesive surface proteins (RspA and RspB) are also produced by this bacterium that help the microorganism bind to biotic (living) and abiotic (nonliving) surfaces.
Er. rhusiopathiae can survive in meat even after smoking, pickling, or salting.
There are several forms of the disease and these forms may occur separately, in sequence, or together. The erysipeloid lesions are the result of thrombotic vasculitis.
Clinical Signs in Animals
Erysipelas occurs in many animals; however, the main reservoirs are pigs. Clinical signs vary in different animal species and include:
* Swine. Er. rhusiopathiae can be found in 30% to 50% of healthy swine (typically in the pharynx, feces, urine, or oronasal secretions). The bacterium can also be isolated from the environment. There are three basic forms of erysipelas in swine that represent different progressive stages of the disease.
** Acute septicemia. Pigs with acute septicemia may die suddenly without clinical signs. Acute septicemia occurs most frequently in finishing pigs (100 to 200 pounds). Clinical signs include fever (104[degrees]F to 108[degrees]F), stiff gait (walking up on their toes), anorexia, vomiting, and lying in sternal recumbency separately rather than piling in groups. Hemorrhages may be found in a variety of organs. Mortality is 0% to 100% and death may occur up to 6 days after the first signs of illness. Acutely affected pregnant sows may abort and suckling sows may stop milk production. Untreated pigs may progress to the other stages.
** Cutaneous form (also known as diamond skin disease). Skin discoloration varies from widespread erythema (redness) and purplish discoloration of the ears, snout, and abdomen, to diamond-shaped skin lesions anywhere on the body, but particularly on the abdomen (Figure 3-30). Skin lesions become raised and firm to the touch within 2 to 3 days of illness. In untreated cases, skin lesions become necrotic and large areas of skin can separate. In addition to skin lesions, lymph nodes are usually enlarged, the spleen is swollen, and the lungs are congested. Petechiael hemorrhages may be found in the kidneys and heart.
** Chronic arthritis. This is the most common form of chronic infection producing mild to severe lameness (Figure 3-31). Affected joints tend to become visibly enlarged and firm. Mortality in chronic cases is low, but growth in these animals is slowed.
** Endocarditis. Heart lesions usually result in large, irregular masses on the mitral valve. In long standing cases, hypertrophy of affected ventricles occurs in an attempt to keep blood flow at adequate levels.
** Birds. Erysipelas or fowl erysipelas occurs worldwide in poultry of all ages typically as an acute septicemia. Signs consist of acute death without any other clinical signs. Outbreaks occur suddenly with a few birds dying one day followed by increasing mortality on subsequent days. Mortality rates may range from <1% to 50% depending on vaccination status of the flock. Prior to death, some birds may appear droopy, with an unsteady gait. Chronic clinical disease in a flock is rare and if occurs produces cutaneous lesions and swollen hocks. Turkeys may develop vegetative endocarditis without showing clinical signs and may die suddenly. Clinical signs in chickens include general weakness, depression, diarrhea, decreased egg production in hens, and sudden death. Erysipelas may affect the fertility of the male and may contribute to production losses. Generalized or diffuse darkening of the skin is common. At necropsy the liver and spleen are usually enlarged, friable, and mottled. Turkeys are the most frequent poultry species affected, but outbreaks have also occurred in chickens, ducks, and geese.
Although the acute septicemic form of swine erysipelas may cause death, the greatest economic loss probably occurs from the chronic, nonfatal forms of the disease. Erysipelas can occur in sheep flocks that have been artificially inseminated 4 to 5 days prior to an episode of death without clinical signs.
** Sheep. Er. rhusiopathiae in sheep occurs as an extension of a focal cutaneous infection typically around the hoof resulting in laminitis (adults) or as arthritis (lambs). In adults, infection begins after dipping in a solution with bacteriostatic activity that has become contaminated with Er. rhusiopathiae. When animals are dipped, small skin abrasions occur near the hoof and fetlock joint when their legs scrape against the sides of the vat resulting in lameness of one or more legs. The affected leg appears normal except that the hoof and pastern are hot and painful. In sheep clinical signs appear 2 to 4 days after dipping with most sheep recovering spontaneously in 2 to 4 weeks. In lambs Er. rhusiopathiae enters the body through wounds that occur during docking and castration. Lambs develop septicemia which leads to joint infection (the entry site does not appear infected). The characteristic lesion in lambs is an acute, nonsuppurative (without pus) arthritis manifested by heat, pain, and slight joint swelling (typically involving the hock, stifle, elbow, and carpus). In lambs the clinical signs appear 9 to 19 days after the operation (docking or castration) with all cases developing in a 5-day period. Morbidity is 10% to 50%.
** Calves. Calves can develop arthritis similar to lambs.
** Reptiles, amphibians, marine mammals, and fish. Erysipelas has also been reported in reptiles, amphibians, marine mammals, and fish and typically presents without clinical signs (reptiles, amphibians, fish) or as peracute, acute, or chronic forms typically having septicemia and skin lesions (marine mammals). The organism has been isolated from the surface slime of fish, which may serve as a source of infection for other species.
Er. rhusiopathiae is carried in the pharynx of subclinically infected pigs and shed in feces, urine, and oronasal secretions of up to 30% of pigs.
[FIGURE 3-30 OMITTED]
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Clinical Signs in Humans
The disease caused by Er. rhusiopathiae in man is erysipeloid and presents itself in three ways:
* Localized cutaneous form (also known as erysipeloid of Rosenbach). The most common and least severe form of erysipeloid is the localized form that manifests itself cutaneously. Typical lesions are clearly defined bright red to purple lesions with smooth shiny surfaces that slowly expand over a few days to develop sharp or curvaceous borders. Tiny blisters may be present. Skin lesions produce local burning, intense pruritus or pain at lesion sites, and may be warm and tender to the touch. Most skin lesions occur on the hands, forearms, or any other exposed area of the body and leave a brownish discoloration on the skin when resolving. Occasionally patients may experience mild fever, regional lymphadenopathy, chills, and malaise. This form is self-limiting.
* Generalized (diffuse) cutaneous form. Multiple, well-demarcated lesions appear on various parts of the body. Lesions appear as plaques with an advancing border and central clearing. Cellulitis may develop extending proximal to the initial infection site.
* Septicemic form. Rarely, a severe systemic form of erysipeloid may develop where skin lesions may not be apparent. If skin lesions are present they appear as localized areas of swelling surrounding a necrotic center or may present as several follicular, erythematous papules. In the septicemic form other organs are infected, such as the heart (endocarditis), brain, joints, and lungs. People with systemic disease may experience symptoms such as chills, fever, headache, cough, joint pain, and weight loss.
Diagnosis in Animals
In swine, the diamond-shaped skin lesions are diagnostic for erysipelas. At necropsy, demonstration of the bacterium in stained smears or cultures confirms the diagnosis. In chronic arthritis cases, organisms may not be cultured making diagnosis difficult. Typical necropsy lesions include large, irregularly shaped masses on the mitral valve projecting into the lumen of the left ventricle, thickened joint capsules with folding synovial membranes, and cutaneous lesions that appear rectangular in shape.
In all animal species, Er. rhusiopathiae can be definitively identified via Gram stain, culture, and serology. Er. rhusiopathiae is a gram-positive, short rod with long filaments. It can be isolated on BAP (blood agar plates) from spleen, kidney, and long bone samples of acutely sick animals and from the tonsils and lymph nodes of many apparently normal animals. Its colonies may present as large and rough or small, smooth, and translucent on BAP with alpha hemolysis with both forms after prolonged incubation. Bacterial culture may require specialized media (such as Fletcher, Stuart, Ellinghausen combined with neomycin to control growth of other bacteria). Er. rhusiopathiae is the only catalase-negative, gram-positive, nonendospore forming rod that produces hydrogen sulfide when inoculated on triple sugar iron (TSI) agar.
Serology is available for identification of Er. rhusiopathiae but can prove unreliable. A rising titer in an agglutination test (with controls) is available as well as a complement fixation test. Identification can be made by fluorescent antibody staining or a mouse protection test.
Diagnosis in Humans
Laboratory diagnosis of Er. rhusiopathiae requires culture of the organism (using blood, CSF, or urine). If blood cultures are negative, an aspirate of the center or edge of the cellulitis lesion may be used to isolate the bacterium. Bacterial culture on BAP and specialized media may be needed and was previously described. Serologic conversion by the micro-agglutination (MA) test requires a fourfold or greater rise in titer between the acute and convalescent sample for diagnosis. The MA test is difficult to perform and is usually done by reference laboratories. Several rapid serologic tests such as the indirect hemagglutination assay (IHA) have been developed that are reliable and commercially available. Many feel serologic tests for Er. rhusiopathiae are not reliable. A PCR test has also been developed.
Treatment in Animals
* Swine. In treating acute cases in an unvaccinated swine herd, antiserum may be administered to protect uninfected pigs. Penicillin, cephalosporin, or tetracycline antibiotics may also be given to exposed pigs in an attempt to provide prophylaxis. Penicillin and erythromycin are effective in acutely affected pigs (with or without concurrent antiserum administration). Treatment of swine with chronic infection is ineffective and these animals should be culled.
* Birds. Penicillin is the drug of choice for treating birds along with a full dose of erysipelas bacterin. Broad-spectrum antibiotics like erythromycin are also effective. Vaccination with a bacterin helps protect those birds in the flock not yet infected. Neither antibiotic therapy nor vaccination eliminates the carrier state.
* Sheep. Lambs are treated with penicillin as early as possible in the disease course. Most adult sheep recover spontaneously in 2 to 4 weeks. * Cattle. Penicillin and cephalosporin antibiotics have been used in cattle to treat Erysipelothrix infections. Antibiotic withdrawal times need to be adhered to in food-producing animals.
* Reptiles, fish, and marine mammals. Penicillin and cephalosporin antibiotics are used to threat Erysipelothrix infections in these animals.
Treatment in Humans
In humans cutaneous infection resolves spontaneously in 3 to 4 weeks after disease onset. Antibiotics such as penicillin and cephalosporin will speed resolution of the disease. Er. rhusiopathiae is resistant to vancomycin and its failure may be used to diagnose this type of infection. Invasive disease with septicemia and endocarditis requires IV penicillin for 4 to 6 weeks, whereas milder forms can be treated with oral antibiotics.
Management and Control in Animals
Ways to reduce the incidence of erysipelas in animals includes elimination of carriers, good sanitation practice including prompt waste removal, and establishment of a vaccination program. Individual species variation includes:
* Swine. Killed bacterins are used to vaccinate pigs in the United States, whereas live-culture strains of low virulence are used in other countries. The formal-in-killed, aluminum-hydroxide-adsorbed bacterin provides immunity that protects growing pigs from acute disease until market age. An oral vaccine of low virulence is also available. Young breeding stock should be vaccinated twice at the recommended interval, and then revaccinated every 6 months or after each litter. Vaccination of pregnant sows is not recommended. Although vaccination raises the level of immunity it does not provide complete protection and acute cases may develop after periods of stress. Antigenic variation exists between bacterial strains, so a vaccine may not be effective against all wild strains of the bacterium.
* Birds. Both inactivated and live vaccines are available for use in turkeys. The use of bacterins in flocks used for meat is useful but labor intensive and should be given every 2 to 4 months in breeding stock. The use of live vaccines administered in the drinking water does not require handling each bird; however, it cannot be guaranteed that all birds are inoculated.
* Sheep. There is not a vaccine commonly used in the United States for preventing erysipelas in sheep. In Australia there is a vaccine that is used to vaccinate ewes prior to lambing (the vaccine is given once and then repeated 4 to 6 weeks later, and at least 4 weeks prior to lambing in previously unvaccinated sheep). Annual boosters are recommended. Lambs are vaccinated prior to mulsing (extensive tail docking where a dinner plate size area of skin is removed by the tail). Prevention includes using copper sulfate in dipping wash to prevent bacterial growth and using strict antiseptic techniques when docking and castrating lambs.
* Cattle. There is not a vaccine for preventing erysipelas in cattle.
* Marine mammals. There is a commercially available bacterin for marine mammals such as dolphins. The bacterin is followed by a modified live vaccine in 6 months. Annual revaccination is recommended. The vaccine is typically given in the dorsal musculature using a long needle to assure that the vaccine is placed in the muscle.
Er. rhusiopathiae is not readily destroyed by the usual laboratory disinfectants (it may survive in litter or soil for various lengths of time) making disinfection of premises difficult. It is inactivated by a 1:1000 concentration of bichloride of mercury, 0.5% sodium hydroxide solution, 3.5% liquid cresol, or a 5% solution of phenol.
Management and Control in Humans
Preventing Er. rhusiopathiae infection in people includes avoiding direct contact with animal tissues, animal secretions/excretions, and/or contaminated soil. People handling animals should wear gloves as barrier protection. Frequent hand washing with an antiseptic soap and prompt medical treatment of cuts and abrasions can also prevent erysipeloid.
Er. rhusiopathiae is a gram-positive, facultatively anaerobic, nonmotile rod found worldwide that can survive in water, soil, decaying organic matter, slime on the bodies of fish, and carcasses, even after processing. Er. rhusiopathiae usually enters the body through traumatized skin and in animals causes swine erysipelas, nonsuppurative arthritis in lambs, postdipping lameness in sheep, and acute septicemia in poultry. In humans the infection may be localized, generalized, or systemic and is termed erysipeloid. Erysipeloid should not be confused with erysipelas in man, a form of cellulitis caused by Streptococcus pyogenes. This bacterium is typically diagnosed with Gram stain and culture. Serologic tests are available providing variable results. Treatment consists of antibiotics such as penicillin, cephalosporins, tetracyclines, and erythromycin. Vaccines are available for swine, poultry, and marine mammals. People can avoid contracting the organism by avoiding direct contact with animal tissues, animal secretions/excretions, and/or contaminated soil.
Erysipeloid is a not a nationally reportable disease in the United States; however, many states require notification of erysipeloid.
E. COLI INFECTION
Escherichia coli, more commonly known as E. coli, is a coliform bacterium (coliforms are gram-negative normal intestinal flora which ferment lactose within 48 hours) originally known as Bacterium coli commune. E. coli belongs to the family Enterobacteriaceae and was first isolated and described in 1885 by the German bacteriologist and pediatrician, Theodor von Escherich. Most E. coli strains are harmless to animals and humans. Their ability to multiply quickly has helped the scientific community through their use in the biotechnology field; however, their ability to multiply quickly has also resulted in the production of disease especially in the young and old.
Historically, E. coli has been associated with many disease forms including enteritis, cystitis, and meningitis. Infantile diarrhea, known by a number of synonyms including griping in the guts, cholera infantum, and summer diarrhea, was a term used to describe the clincial signs of an infection that had been noted for a number of centuries. Over the past four centuries, infantile diarrhea was a major problem worldwide, with high morbidity and mortality. The isolation of E. coli from cases of infantile summer diarrhea had already been noted as early as 1889 when it was suggested that there were both pathogenic and nonpathogenic strains of E. coli. The term enteropathogenic E. coli (EPEC) was introduced in 1955 to describe strains of E. coli implicated epidemiologically with infantile diarrhea.
Even though E. coli is a single species of bacteria, there are many different strains of the species including the dangerous pathogen E. coli O157:H7. E. coli O157:H7 is a mutation discovered in 1982 that has at least 62 subtypes and causes an acute bloody diarrhea. Enterohemorrhagic E. coli infection, also called hemorrhagic colitis that may lead to hemolytic uremic syndrome (HUS), is an infectious disease caused by the microbe E. coli O157:H7. It is found in feces and fecal-contaminated meat (contaminated meat is the primary source of infection). When milk, cider, water, sawdust, and air come in contact with cattle feces they too may become contaminated with bacteria. Drinking or swimming in sewage-contaminated water may also be a source of pathogenic E. coli as well as some vegetables rinsed or watered with contaminated water. Since the first outbreak in 1982, there have been several E. coli O157:H7 outbreaks in the United States: in June and July 1997, E. coli O157:H7 infection outbreaks occurred in Michigan and Virginia associated with the consumption of alfalfa sprouts grown from the same seed lot; in October 1996, there were simultaneous outbreaks in California, Colorado, and Washington linked to the consumption of unpasteurized apple juice; in July 2002, 28 reported infections in Colorado were all linked to consuming contaminated beef products produced and later recalled by ConAgra Beef Company; in the Spring and Fall of 2000, an outbreak of E. coli O157:H7 was reported among school children in Pennsylvania and Washington when they became infected after having direct contact with animals during farm visits with their families and/or school. Many of the infections resulted in the development of HUS. HUS was first described in 1955 by a Swiss pediatrician and is now the leading cause of kidney failure in children (approximately 10% of all hemorrhagic colitis cases end in HUS and nearly 5% of all HUS cases lead to death). E. coli O157:H7 causes 90% of all HUS cases and it is the only known cause of HUS in children.
[FIGURE 3-32 OMITTED]
E. coli are motile, gram-negative, rod-shaped bacteria of the family Enterobacteriaceae (Figure 3-32). All Enterobacteriaceae, including the genus Escherichia, have three kinds of major antigens: somatic or cell wall (O), surface or envelope (K), and flagellar (H) (Figure 3-60). Some strains of E. coli are virulent pathogens and are distinguished from each other by two of the types of antigens they produce (these antigens are then assigned numbers). One of these antigens is designated O for outer membrane and the other is designated H for flagellum. Some E. coli antigens such as O157, O111, H8, and H7 are associated with virulence. Virulent strains have genes for fimbriae, adhesions, and a variety of exotoxins that allow these strains to colonize animal tissue and cause disease. Pathogenic strains of E. coli can adhere to animal cells, invade tissue, and produce toxin. The set of virulence factors that a pathogenic strain possesses determines whether it is classified as enterohemorrhagic, enteropathogenic, enterotoxigenic, enteroinvasive, or enteroaggregative (Table 3-6).
* Enterotoxigenic strains of E. coli are the primary cause of traveler's diarrhea and infant diarrhea in developing countries. These strains produce two enterotoxins: one heat-labile toxin (destroyed by heat) and the other heat-stable toxin (not destroyed by heat). The heat-labile toxin is similar to the toxin that causes cholera because it stimulates intestinal secretion and fluid loss. This strain is typically spread by poor sanitation in developing countries.
* Enteroinvasive strains of E. coli cause dysentery similar to shigellosis. These bacteria produce proteins that allow invasion into cells; however, they are not as virulent as Shigella bacteria and larger numbers of bacteria are needed to initiate infection. This strain causes an inflammatory disease that involves invasion and ulceration of the large intestinal mucosa.
* Enteropathogenic strains of E. coli cause diarrhea in infants. This strain attaches to mucosal cells of the small intestine and destroys the microvilli of the intestinal epithelium.
* Enteroaggregative strains of E. coli cause chronic watery diarrhea in infants as a result of their adherence to animal cells most likely by pili. This strain is also believed to produce hemolysis-like toxins, although the exact mechanism of pathology is unknown.
* Enterohemorrhagic strains of E. coli produce bloody diarrhea that may lead to a life-threatening condition called hemolytic uremic syndrome (HUS). The virulence of E. coli O157:H7 is a result of the production of shiga-like toxin (also called Vero toxin) that this strain of E. coli may have acquired through plasmid transfer from a strain of Shigella. This strain of E. coli is resistant to the acidity of gastric secretions and is able to attach to intestinal cells and disrupt their cell structure.
E. coli can survive and grow in the presence or absence of oxygen making it a useful experimental bacterial model in the laboratory.
Epizootiology and Public Health Significance
E. coli is widespread in nature (including soil and water) and is found worldwide with some endemic areas present in developing countries. Most strains are commensals of the gastrointestinal tract of animals and help protect against infection by enteric pathogens. E. coli is important to animal health because it manufactures vitamins [B.sub.12] and K from undigested food in the large intestine. In animals, particularly ruminants, E. coli does not cause disease (except in the very young) and animals tend to be carriers and excretors of this bacterium. In terms of global public health, enteropathogenic E. coli is the most widespread diarrhea-causing E. coli. However, since 1982, enterohemorrhagic E. coli has emerged as a cause of sporadic or epidemic disease in North and South America, Europe, Asia, and Africa. The annual incidence of enterohemorrhagic E. coli infection in the United States is approximately 8 cases per 100,000 people, with cases peaking between June and September. In some states E. coli O157:H7 is the second or third most frequent cause of diarrhea (more frequent than Shigella and Yersinia). In United States patients with bloody diarrhea, 40% of cases are caused by E. coli O157:H7.
Because E. coli is a prominent normal intestinal bacterium, it is used as an indicator bacterium to monitor fecal contamination in water, food, and dairy products. E. coli, like other coliforms, are present in large number, are more resistant, and are easier and faster to detect than true pathogens. If a certain number of coliforms are found in a water sample, it is deemed unsafe to drink.
An estimated 2,100 people are hospitalized annually in the United States from E. coli O157:H7 infections. The illness is often initially misdiagnosed resulting in more expensive diagnostic procedures and therapies once the disease is properly identified. Patients who develop HUS often require prolonged hospitalization, dialysis, and long-term follow-up care.
E. coli is spread by fecal-oral transmission with some serotypes being species specific, whereas others are not. The organism is excreted in nasal and oral secretions, urine, and feces before clinical signs appear; therefore, animals most likely acquire the bacterium from environmental sources such as manure, manure-contaminated objects, or other objects contaminated by secretions. Bacteria enter the animal's body through the nasal and oropharyngeal mucosa, the intestinal mucosa, or via the umbilicus and umbilical veins. In groups of calves, transmission is by direct nose-to-nose contact, urinary and respiratory aerosols, or as the result of navel-sucking or fecal-oral contact. People tend to acquire E. coli from ingestion of meat that is contaminated during the slaughtering process and is inadequately cooked or from cross-contamination of food during its preparation. The reservoir of this pathogen appears to be mainly cattle and other ruminants and is transmitted to humans primarily through consumption of contaminated foods, such as raw or undercooked ground meat products and raw milk. Fecal contamination of water and cross-contamination during food preparation (contaminated surfaces and kitchen utensils) will also lead to E. coli infection. Foods implicated in outbreaks of E. coli O157:H7 include undercooked hamburgers, dried cured salami, unpasteurized fresh-pressed apple cider, yogurt, cheese and milk, and fruits and vegetables contaminated with feces from domestic or wild animals at some stage during cultivation or handling. Waterborne transmission has been reported, both from contaminated drinking water and from recreational waters. E. coli can survive for months in manure and water-trough sediments. Person-to-person contact (infected people that do not wash their hands after using the toilet or diapering children) is an important mode of transmission through the oral-fecal route and bacteria can be shed for about one week in adults and even longer in children. Farms and other venues where people come into direct contact with farm animals and inappropriate hygiene after contact with these animals is another source of E. coli O157:H7 infection. In a few cases, E. coli O157:H7 is transmitted by direct contact with infected cattle or horses to humans. The infective dose of E. coli O157:H7 in people is 101 to 102 CFU (colony forming units), which indicates high infectivity. Figure 3-33 shows the various transmission routes for E. coli.
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E. coli infection in animals is sometimes known as colibacillosis and is a major cause of bacterial diarrhea in young ruminants especially calves. Two distinct types of diarrheal disease are produced in calves by two different strains of this bacterium.
* Enterotoxigenic E. coli has two virulence factors associated with the production of diarrhea: antigens on fimbria (shorter filaments on the bacterial cell) and production of enterotoxin. Fimbrial antigens enable E. coli to attach to and colonize the villi (microscopic raised portions) of the small intestine resulting in villous atrophy. The loss of mature cells at the tips of the villi results in a decrease in villous height (and subsequent decrease in the surface area for absorption) and in the loss of digestive enzymes produced by these cells (Figure 3-34). Villous atrophy decreases the capacity of the intestinal mucosa to absorb fluids and nutrients and results in malabsorptive diarrhea. Most E. coli strains in calves commonly possess either K99 (F5) or F41 fimbrial antigens or both. Enterotoxigenic E. coli also produce an enterotoxin (Sta) that affects intestinal ion and fluid secretion to produce a non-inflammatory secretory diarrhea. This enterotoxin stimulates hypersecretion by activating enzymes and by producing a net secretion of sodium and chlorine.
* Enteropathogenic E. coli cause diarrhea by adhering to the intestine producing a lesion that results in cellular damage of microvilli at the site of bacterial attachment (these lesions are known as attachment-and-effacement or A/E lesions). These lesions decrease enzyme activity and alter ion transport in the intestine. Some enteropathogenic E. coli produce verotoxin, which may be associated with a more severe hemorrhagic diarrhea. Infections with verotoxin- producing enteropathogenic E. coli result in accumulation of fluid in the large intestine and extensive damage to the large intestinal mucosa (edema, hemorrhage, and erosion and ulceration of the mucosa) which results in blood and mucus in the intestinal lumen. The infection most frequently occurs in the cecum and colon, but the distal small intestine can also be affected. Inflammation is also a major component of the pathology produced by enteropathogenic E. coli. Inflammation leads to vascular and lymphatic damage and to structural damage of the intestinal crypts and villi. Villi
Most human food-poisoning E. coli bacteria do not cause clinical illness in animals (except in young animals). Meat package labels are required to have cooking instructions indicating proper temperatures to kill foodborne bacteria.
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Enterohemorrhagic E. coli causes hemorrhagic colitis in humans. Enterohemorrhagic E. coli have the ability to produce Shiga toxins or verotoxins and the ability to cause attachment-and-effacement lesions. Enterohemorrhagic E. coli is resistant to the acidity of gastric secretions allowing its survival in the stomach and passage into the small intestine where it attaches to the intestinal cells causing structural changes in these cells. Shiga toxins and verotoxins have the ability to cause severe intestinal cell damage and if they enter the bloodstream they can bind to endothelial cells of blood vessels causing platelet aggregation (which can result in a consumptive thrombocytopenia), microinfarcts, red blood cell damage (leading to anemia), and hypertension. The development of HUS is a result of endothelial cell injury that triggers a cascade of events resulting in microvascular lesions and microthrombi that occlude arterioles and capillaries. In HUS microthrombi are confined to the kidney and in thrombocytopenia microthrombi occur throughout the microcirculation including areas of the brain, skin, intestines, skeletal muscle, pancreas, spleen, adrenal glands, and heart.
Clinical Signs in Animals
Animals that develop clinical manifestations of E. coli include:
* Young ruminants. E. coli is commonly found in the feces of healthy young ruminants and whether or not E. coli leads to clinical disease depends on the virulence of strain, the immune status of the animal (especially in relation to the success or failure of passive transfer of colostral antibodies), and environmental factors such as stress and poor diet. Newborn calves, lambs, and kids develop diarrhea from E. coli that can lead to dehydration and death (Figure 3-35). Diarrhea as a result of enterotoxigenic (K99-bearing) E. coli occurs in calves younger than 3 to 5 days of age, is sudden in its onset, and rapid in its clinical course (3 to 8 hours). Profuse amounts of diarrhea are passed, and calves quickly become depressed, dehydrated, and recumbent. Body temperature is usually normal or lower than normal, but may be increased. Hypovolemic shock and death may occur in 12 to 24 hours (mortality can be close to 100%). Disease produced by enteropathogenic E. coli typically occurs in calves from 4 days to 2 months of age producing bloody and/or mucoid diarrhea. The clinical course of enteropathogenic E. coli is short. Septicemia from E. coli may occur during the first week of life (typically between 2 and 5 days of age) in calves and is seen in lambs less than one week of age. Septicemia in young ruminants causes peracute death. Chronic disease can occur for up to 2 weeks of age with localization of infection causing polyarthritis, meningitis, and convulsions. The disease is usually sporadic and is more commonly seen in dairy calves than beef calves.
* Adult ruminants. Healthy adult ruminants may be carriers of E. coli, periodically excreting the organism in feces (Figure 3-36). Stress (such as parturition) may increase the excretion of E. coli making the disease more likely to be seen in ruminants around freshening. Contaminated calving areas and infection of the udder and perineum of the dam can lead to infection in offspring.
* Poultry. In poultry, E. coli causes an acute fatal septicemia or subacute pericarditis and air sacculitis (Figure 3-37). Pathogenic strains most commonly seen in poultry are 01, 02, and 078 serotypes. Poultry facilities contain large numbers of E. coli bacteria through fecal contamination and initial exposure to pathogenic E. coli may occur in the hatchery from infected or contaminated eggs. Systemic infection from E. coli usually requires predisposing environmental factors such as poor air quality or co-infection with other diseases and occurs when large numbers of pathogenic E. coli enter the bloodstream from the respiratory tract or intestine. Bacteremia can lead to septicemia and death, or infection to other organs. Clinical signs in poultry are nonspecific and vary with age, organs involved, and concurrent diseases. Young birds dying of acute septicemia have few lesions other than hepatomegaly and splenomegaly. Birds that survive septicemia may develop air sacculitis, pericarditis, and hepatitis. Air sacculitis is a classic lesion of colibacillosis. Sporadic lesions seen with E. coli infection include pneumonia, arthritis, osteomyelitis, and salpingitis.
* Pigs. Specific serotypes of E. coli can affect healthy, rapidly growing nursery piglets producing a condition called edema disease (also known as bowel edema or gut edema). Edema disease is a peracute toxemia that causes edema of the gastric and intestinal submucosa. Edema disease is caused by four serotypes of enteropathogenic E. coli: O138:K81:NM, O139:K12:H1, O141: K85a,b:H4, and O141:K85a,c:H4. Piglets acquire this infection during nursing from a contaminated sow or after weaning as a result of fecal-oral contact, feed, or short-distance aerosol transmission. Clinical signs range from rapid death to CNS signs such as ataxia and recumbency. Periocular edema, swelling of the facial region, open-mouth breathing, and anorexia are common. Edema disease usually occurs 1 to 2 weeks postweaning and typically involves the healthiest animals in a group. Morbidity levels are approximately 30% to 40% and mortality levels may be 50% to 90%.
* Rabbits. Colibacillosis in rabbits is caused by enteropathogenic strains of E. coli. Normal healthy rabbits do not have E. coli of any strain associated with their gastrointestinal tract; however, rises of intestinal pH can cause E. coli to colonize the gut causing attachment-and-effacement lesions. Intestinal lesions lead to diarrhea and possibly death. Two types of colibacillosis are seen in different ages of rabbits: in 1- to 2-week old rabbits a severe yellowish diarrhea develops that results in high mortality and in 4- to 6-week old weaned rabbits diarrhea develops in which the intestines are fluid-filled causing death in 5 to 14 days or leaving rabbits stunted and unthrifty.
* Dogs and cats. The role of E. coli as a primary intestinal pathogen in small animals is unclear. Several studies have suggested that the incidence of enterotoxigenic E. coli diarrhea is extremely low in dogs (less than 1% to 2% of diarrhea cases). There is some evidence that enteropathogenic E. coli plays a role in diarrhea in cats.
Acute E. coli septicemia in neonatal calves, sometimes called colisepticemia and septicemic colibacillosis, may be rapidly fatal.
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Clinical Signs in Humans
E. coli produces three types of infections in humans depending upon the virulence of the bacterium: intestinal diseases (gastroenteritis), urinary tract infections (UTI), and neonatal meningitis. UTIs and neonatal meningitis are nonzoonotic.
* Five types of E. coli cause diarrheal diseases in humans: enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), and enteroaggregative E. coli (EAggEC).
** ETEC are an important cause of diarrhea in infants and travelers in underdeveloped countries or regions of poor sanitation. Clinical signs vary from minor discomfort to severe diarrhea without fever.
** EIEC cause a dysentery-like diarrhea with fever.
** EPEC produce watery diarrhea and are an important cause of traveler's diarrhea in Mexico and North Africa.
** EAggEC are associated with persistent nonbloody diarrhea in young children.
** EHEC are typically represented by a single strain O157:H7 (although it is believed there are more EHEC strains that cause disease), which causes a diarrheal syndrome producing large amounts of bloody discharge and no fever. Diarrhea caused by this strain can be fatal especially in children developing acute kidney failure as a result of HUS. HUS develops when E. coli O157:H7 enters the bloodstream through the intestinal wall and begins to release shiga-like toxin (SLT) causing kidney failure and the hemolysis of red blood cells. Red blood cell hemolysis leads to brain hemorrhaging, uncontrolled bleeding, and the formation of clots in the bloodstream.
* E. coli cause 90% of the urinary tract infections (UTI) in anatomically normal, unobstructed urinary tracts of humans. E. coli colonize the feces or perineal region and ascend the urinary tract to the urinary bladder.
* E. coli strains invade the blood stream of human infants from the nasopharynx or gastrointestinal tract and are carried to the meninges causing neonatal meningitis. Neonatal meningitis affects 1 out of every 2,000 to 4,000 infants in the United States.
Diagnosis in Animals
Tissue samples obtained from biopsy or surgical excision containing E. coli bacteria can be Gram stained and cultured for diagnostic identification. Several samples should be taken in the early stages of diarrhea from untreated animals to obtain the best culture results. E. coli grows well on blood agar, chocolate agar, and MacConkey agar. On MacConkey agar E. coli produces flat, dry, pink colonies (pink colonies are produced as a result of its ability to ferment lactose). E. coli also grows on selective agars such as Hektoen enteric (HE) agar, xylose-lysinedeoxycholate (XLD) agar, and Salmonella-Shigella (SS) agar. Slow fermentation of sorbitol on sorbitol MacConkey (SMAC) agar is the basis of microbiologic identification of E. coli O157: H7 (colonies grow colorless on SMAC plates, whereas other E. coli bacteria grow pink on SMAC plates). Latex agglutination tests using O157-specific serum are also available.
Blood results may show a moderate leukocytosis and neutrophilia early in the disease with a marked leukopenia seen in the later stages of disease. Joint fluid may show an increase in protein and inflammatory cells with bacteria evident on microscopic examination. A deficiency of circulating IgG may be seen in calves using zinc sulfate or total protein estimation. Demonstration of the bacteria in blood or tissue can be seen using Gram-stain techniques.
The best clinical diagnostic test for E. coli in animals is necropsy of untreated, acutely affected animals. Examination of intestinal mucosa for diagnostic lesions and for the presence of bacteria is the optimal way to diagnose disease associated with the attachment-and-effacement strains of E. coli. The diagnostic value of a necropsy diminishes quickly with time after death as a result of autolysis of lesions. Edema in the gastric submucosa, fibrin strands in the peritoneal cavity, and serous fluid in the pleural and peritoneal cavity help diagnose E. coli infection in necropsied swine. Birds will show respiratory lesions consistent with pneumonia and air sacculitis. In rabbits the intestine will be fluid-filled with petechial hemorrhages on the serosal surface.
Diagnosis in Humans
Routine stool cultures will allow growth of E. coli, but because E. coli are normal fecal flora, laboratories must be advised to check for pathogenic E coli when a sample is submitted. Most 0157:H7 isolates do not ferment sorbitol; therefore, cultivation of specimens on sorbitol MacConkey (SMAC) medium is warranted (and is required by the CDC in all cases of bloody diarrhea submitted to human laboratories). SMAC uses sorbitol instead of lactose as the primary carbohydrate, which E. coli O157:H7 does not ferment (it grows as colorless colonies on SMAC plates). Confirmation requires identification of presumptive isolates with specific antiserum. Rapid enzyme immunoassays (EIA) for E. coli 0157:H7 have been developed but are not yet widely used clinically. All infants with suspected sepsis should have specimens of blood, urine, and cerebrospinal fluid sent for culture and Gram stain prior to initiating antimicrobial therapy to detect possible E. coli infections.
Treatment in Animals
Treatment of E. coli infection in animals varies with the affected species and the severity of clinical signs. In calves, fluid and electrolyte replacement are essential to counteract severe dehydration seen in young animals. Antibiotic therapy is initiated using an antibiotic with efficacy against gram-negative bacteria because culture and sensitivity testing takes too long to wait for these results. Despite aggressive treatment mortality in calves is high. In poultry treatment involves antibiotic treatment along with controlling predisposing infections and environmental factors. In swine antibiotics administered via the drinking water prior to disease outbreak in a herd may be helpful in controlling the spread of E. coli. Management techniques such as altering feeding practices and adding high levels of fiber to the diet have also been utilized in E. coli infections in swine. In rabbits antibiotics may be helpful in mild cases of E. coli infections. In severe cases, affected rabbits are culled and the facility is disinfected.
Treatment in Humans
Symptoms associated with E. coli O157:H7 infections are typically self-limiting within 5 to 10 days. In more severe cases, fluid and electrolyte therapy is the main treatment for diarrhea caused by E. coli because it helps correct any dehydration that may have developed as well as contributes to kidney perfusion which may help prevent HUS development. Antibiotic therapy rarely is indicated and should not be instituted in cases of enterohemorrhagic E. coli as a result of the potential risks of developing HUS. Antidiarrheal agents should not be given to patients with E. coli O157:H7 infections because they may prolong the clinical and bacteriologic course of disease. Cases of HUS are treated with kidney dialysis.
Management and Control in Animals
There are many causes of diarrhea in young animals and total prevention in large facilities may not be obtainable; however, limiting exposure to the infectious agent and ensuring adequate immune status in young animals is critical. Principles that apply to newborns and young animals in all herds/flocks include isolating diseased animals from healthy ones, practicing good general hygiene, providing good nutrition to dams and young animals, assuring that newborns receive colostrum within a few hours after birth, and by vaccinating dams or newborns if available for that species. Vaccination of pregnant dams with E. coli vaccine can control enterotoxigenic colibacillosis in calves. Monoclonal K99 E. coli antibody is commercially available for oral administration to calves immediately after birth serving as an effective substitute for the K99-specific antibody in the colostrum of vaccinated cows and as a supplement to calves who receive adequate levels of colostrum. Clinical trials began in 2002 for a cattle vaccine against E. coli 0157:H7. In poultry, commercial bacterins are available for breeder hens and chicks providing some protection against specific E. coli serotypes. Vaccines are not currently available for swine and rabbits.
Management and Control in Humans
Most human cases of E. coli are caused by fecal contamination of food, making proper hygiene critical in preventing these infections. To kill E. coli O157:H7, the contaminated material must be cooked at 165[degrees]F or higher. Annually in the United States, approximately 73,000 people are infected with E. coli O157:H7 toxicity and 61 people die. The prevention of infection requires control measures at all stages of the food chain, from agricultural production on the farm to processing, manufacturing, and preparation of foods in both commercial establishments and the environment. At the national level the number of cases of E. coli contamination may be reduced by implementing strategies for ground beef (i.e., preslaughter screening of animals to reduce large numbers of pathogens in the slaughtering environment, proper sanitation of the facility, adequate hygiene measures, irradiation of the product) (Figure 3-38). Prevention of contaminated raw milk includes the education of farm workers in principles of good hygienic practices and pasteurization or irradiation of milk. Water areas and drinking sources also need to be protected from animal wastes to prevent their contamination.
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Guidelines are established to educate food handlers in the handling of food for public consumption. Food handlers should follow the Recommended International Code of Practice, General Principles of Food Hygiene contained in the Joint FAO/ WHO Food Standards Programme (updated in 2001). Important recommendations in this document include cooking meat thoroughly so that at least the center of the food reaches 165[degrees]F. Outbreaks of E. coli involving fresh fruits and vegetables in recent years have resulted in guidelines for growing and harvesting fruits and vegetables in a document called Codex Code of Hygienic Practice for Fresh Fruits and Vegetables (adopted in 1969). It is believed that some vegetables, especially sprouts, are contaminated as seeds in the field or during harvesting, storage, or transportation. During the germination process, low levels of pathogens present on seeds may quickly reach levels high enough to cause disease. By following procedures outlined in this document the risk of developing disease from fruit and vegetable consumption is lowered. The recommendations in this code include the sanitary use of irrigation water, the sanitary disposal of human and animal wastes, sanitary harvesting of crops, and proper processing techniques (using equipment and product containers that do not pose a health threat and adopting processing techniques that remove unfit product and do not contain microbe, insect, or chemical contamination). Preventing cross-contamination of food is covered in the salmonellosis section.
E. coli O157:H7 infection is nationally reportable and is reportable in most U.S. states. HUS is also reportable in most states. A nationally notifiable disease is one for which regular, frequent, timely information on individual cases is necessary to prevent and control the disease. Each year the list is agreed upon and maintained by the Counsel of State and Territorial Epidemiologists (CSTE) and the CDC. Diseases that are nationally notifiable may or may not be designated by a given state as notifiable (reportable) by legislation or regulation at the local or state level (as a result of cost/benefit factors such as incidence versus cost to maintain state records in addition to using the national notifiable list). The CDC currently has six surveillance systems for obtaining information about E. coli O157:H7 that serve different purposes and provide information on various features of the organism's epidemiology including:
* Public Health Laboratory Information System (PHLIS) is a laboratory-based surveillance system that collects data about many infections, including E. coli O157:H7. Cases confirmed by culture and verified at the state public health laboratory are reported to the PHLIS and information about the infection is reported to the CDC by the state.
* National Electronic Telecommunications System for Surveillance (NETSS) is a physician-based surveillance system that records both laboratory-confirmed and clinically suspected cases of all nationally notifiable diseases, including E. coli O157:H7. E. coli O157:H7 infections and other surveillance data collected by NETSS are published weekly in the CDC Morbidity and Mortality Report (MMWR).
* The Foodborne Diseases Active Surveillance Network (FoodNet) is a surveillance system for identifying culture-confirmed foodborne infections including E. coli O157:H7. In addition to monitoring the number of E. coli O157:H7 infections, investigators monitor laboratory techniques for isolation of bacteria, determine foods associated with illness, and administer questionnaires to people to better understand trends in the eating habits of Americans.
* National Molecular Subtyping Network for Foodborne Diseases Surveillance (PulseNet) is a national network of public health laboratories that perform pulsed-field gel electrophoresis (PFGE) on certain foodborne bacteria, including E. coli O157:H7. PFGE, a type of DNA fingerprinting, provide patterns that are submitted to CDC and can be compared with others in a large database to help determine if individual infections are related or if an outbreak is occurring.
* National Antimicrobial Resistance Monitoring System (NARMS) is a surveillance system that monitors antimicrobial resistance of E. coli O157:H7 and selected other bacteria that cause human illness.
* Foodborne Outbreak Detection Unit of the CDC monitors outbreaks of foodborne disease. Each year epidemiologists report the results of outbreak investigations to the CDC.
E. coli are gram-negative bacteria that normally reside in the intestines of animals and humans. Most strains are harmless and part of the intestinal normal flora; however, several strains produce toxins that can cause diarrhea. The strain of E.coli of most concern is E. coli O157:H7 that is acquired by eating contaminated food. E. coli O157:H7 bacteria live in the intestines of some healthy cattle and meat can become contaminated with feces containing this microbe during the slaughtering process. Careless food handling, drinking contaminated water, swimming in contaminated lakes, exposure to infected farm animals, and inappropriate personal hygiene after using the toilet or diapering children are other ways of spreading this bacterium. E. coli infections in animals, sometimes called colibacillosis, tend to produce severe diarrheal disease in young animals. In infected people, signs range from mild diarrhea to bloody, severe diarrhea with abdominal cramps. Culturing of bacteria and specialized laboratory techniques are used to identify E. coli bacteria and to identify them by type. Colibacillosis in animals is treated with antibiotics and fluid therapy; in people enterohemorrhagic E. coli generally resolves in 5 to 10 days without treatment and the use of antibiotics and antidiarrheal drugs is contraindicated. The spread of E. coli infection can be limited by isolating diseased animals from healthy ones, practicing good general hygiene, providing good nutrition to dams and young animals, assuring that newborns receive colostrum within a few hours after birth, and by vaccinating dams or newborns if a vaccine is available for that species. E. coli infections in people can be prevented by through cooking of meat, proper food handling procedures, and adequate hygiene practices. Infection with E. coli O157:H7 is a reportable disease in most states and a variety of agencies monitor outbreaks caused by this bacteria.
Glanders, also known as malleus (named for its devastating effect on horses), farcy (Latin for sausage which describes the cutaneous lesions associated with this form of the disease), and droes, is an acute to chronic infectious disease caused by the bacterium Burkholderia mallei (formerly known as Pseudomonas mallei and Actinobacillus mallei) and one of the oldest known diseases (it was first described by Hippocrates in 425 B.C.). Glandulus is Latin for little nut, which describes the subcutaneous nodules that form, ulcerate, and discharge pus with this disease. Glanders is primarily a fatal skin and respiratory disease affecting horses, donkeys, and mules, but it can also be naturally contracted by goats, dogs, and cats (glanders is technically the respiratory form of the disease and farcy is the cutaneous form of the disease). Human infection is characterized by pustular skin lesions, multiple abscesses, respiratory tract necrosis, pneumonia, and sepsis. Other than one case in a laboratory worker in 2000, glanders has not been seen in the United States since 1945. Glanders occurs rarely and sporadically among laboratory workers and those in direct and prolonged contact with infected, domestic animals; however, there have never been reports of any epidemics of human disease. Sporadic cases continue to occur in Asia, Africa, South and Central America, and the Middle East.
Glanders is believed to have been deliberately spread by the Central Powers in World War I to infect Russian horses and mules in Eastern Europe resulting in the slowing of troop, supply, and artillery convoys. During and after World War I human cases of glanders increased in Russia. The Japanese infected horses, civilians, and war prisoners with Bu. mallei at the Pinfang China Institute during World War II. In 1943-1944, the United States studied Bu. mallei as a potential biological weapon, but as a result of the low transmission rates to humans from infected horses its use as an infectious weapon was abandoned.
Bu. mallei bacteria are small, gram-negative, nonmotile, aerobic bacilli (some sources say coccobacilli) that grow in 48 hours on blood agar (growth is accelerated with the addition of 1% to 5% glucose and/or 5% glycerol). On blood agar the colonies appear white, semitranslucent, and viscid (older colonies appear yellow). Bu. mallei also grows on MacConkey agar. Its oxidase status is variable.
In nature, Bu. mallei is only found in infected hosts; it is not found in water, soil, or plants.
Epizootiology and Public Health Significance
Glanders is rarely seen in the United States, but is endemic in Africa, Asia, the Middle East, and Central and South America. Globally, naturally-acquired cases of glanders are rare and if they occur are sporadic. People who are at greater risk of contracting this disease are people who work with clinical samples or have close contact with horses. The fatality rate in humans with the septicemic form of glanders is about 95% in untreated cases and greater than 50% in treated cases. The fatality rate in humans with localized disease is 40% in untreated cases and 20% in treated cases. There have not been reported human epidemics of glanders.
Bu. mallei is found in nasal and skin exudates of infected animals. The bacterium is commonly spread among animals by ingestion of contaminated food or water, but can also be spread by inhalation, discharges of actively infected animals and subclinical carriers, or through skin abrasions and the conjunctiva. Carnivores can be infected after consumption of contaminated meat. After ingestion, bacteria invade the intestinal wall and localize in the lungs, skin, nasal mucosa, and other viscera. Bu. mallei is also spread on fomites such as harnesses, grooming equipment, and water troughs. Bu. mallei can survive for up to 30 days at room temperature.
Bu. mallei is transmitted to humans by direct contact with infected animals which enables bacteria to enter the body through the skin and mucosal surfaces of the eyes and nose. Ingestion and inhalation are also possible routes of transmission. Cases of human-to-human transmission have been reported (two suggested cases of sexual transmission and several cases in family members who cared for infected patients). Bu. mallei is inactivated by heat, light, drying, and a variety of chemicals.
Once in the host, Bu. mallei produce toxins such as pyocyanin (blue-green pigment that interferes with energy production via the electron transfer system), lecithinase (causes cell lysis by degrading lecithin of cell membranes), collagenase, lipase, and hemolysin. These toxins interfere with cellular functions causing cell death in affected areas.
Clinical Signs in Animals
In animals there are several forms of glanders including:
* Acute form. Signs of the acute form of glanders in horses, mules, and donkeys include high fever, cough, dyspnea, thick nasal discharge, and deep ulcers on the nasal mucosa (Figure 3-39). Ulcers that heal appear star-shaped. Submaxillary lymph node enlargement and pain as well as thickening of facial lymphatic vessels are seen with acute glanders. Secondary skin infections may occur. Affected animals typically die in 1 to 2 weeks.
* Chronic form. The chronic form of glanders produces more vague signs of coughing, unthriftiness, weight loss, an intermittent fever, and purulent nasal discharge (usually from one nostril). Ulcers and nodules on the nasal mucosa, enlarged submaxillary lymph nodes, joint swelling, and edema of the legs are also seen. The chronic form slowly progresses and may be fatal.
* Latent form. The latent form of glanders shows few signs other than nasal discharge and labored breathing. Lesions may be found in the lung.
[FIGURE 3-39 OMITTED]
Clinical Signs in Humans
Bu. mallei is usually associated with infections in laboratory workers or those with close and frequent contact with infected animals, such as veterinarians, animal caretakers, slaughterhouse workers, and laboratory personnel. The symptoms of glanders vary with the route of infection. There are several different forms of glanders in humans including:
* Localized form. Bu. mallei enter nonintact skin through a laceration or abrasion producing local infection that leads to nodules, abscesses, and ulcers in mucous membranes, skin, and lymph nodes. A mucopurulent, blood-tinged discharge may be seen from the mucous membranes. The incubation period is 1 to 5 days. If the infection spreads, a pustular rash, abscesses in internal organs, and pulmonary lesions may be seen.
* Pulmonary form. Aerosolized Bu. mallei that enter the respiratory tract via inhalation may cause pulmonary infections such as pneumonia, pulmonary abscesses, and pleural effusions. A cough, fever, dyspnea, and mucopurulent discharge may be seen. The incubation period is 10 to 14 days.
* Septicemia. When Bu. mallei are disseminated in the bloodstream the disease is usually fatal within 7 to 10 days. Septicemia affects many organs of the body such as skin, liver, and spleen. Signs include fever, chills, muscle pain, and chest pain that develop rapidly.
* Chronic infection. In chronic forms of glanders, multiple abscesses, nodules, or ulcers can be observed in the skin, liver, and spleen. The chronic form of glanders in humans is known as farcy.
Bu. mallei can survive for up to 6 weeks in infected stables.
Diagnosis in Animals
Pathologic findings for glanders vary with the form of disease. Bloody, purulent discharge is usually present in the nasal cavity and paranasal sinuses (this discharge is highly infectious). In equine, there may be ulcers, nodules, and stellate (star-shaped) scars in the nasal cavity, trachea, pharynx, larynx, and skin. In all forms of the disease, pathologic findings are characterized by poorly encapsulated pyogranulomas that may spread locally or disseminate along lymphatics. In the pulmonary form there may be signs of bronchopneumonia with enlarged bronchial lymph nodes and variable numbers of pyogranulomatous lesions scattered throughout the lung tissue. In the septicemic form the lungs, liver, spleen, and kidneys may have firm, round, gray nodules. In the nasal form, nodular lesions that ulcerate the nasal septum mucosa are seen. In the cutaneous form, multiple, pyogranulomatous nodules occur along lymphatics. These pus-filled lesions become enlarged and are known as farcy pipes. These lesions may rupture releasing tenacious exudate and bacteria.
Glanders can be identified via culture, animal inoculation, the mullein test, or serology in animals. Bu. mallei may be cultured from a lesion or blood sample. Bu. mallei is a gram-negative rod that grows as small, white, semitranslucent, viscous colonies on blood agar. PCR testing is available to identify this bacterium to the species level.
Animal inoculation into guinea pigs is known as the Straus reaction. Guinea pigs are injected intraperitoneally with infectious material from affected animals. In positive cases, Guinea pigs develop peritontitis involving the scrotal sac. The testes will become enlarged, painful, and necrotic in Guinea pigs injected with material from affected animals.
The intracutaneous mallein test is the standard test for identifying Bu. mallei. Mallein is a product formed from the lysis of Bu. mallei that contains both endotoxins and exotoxins. Animals that are infected with Bu. mallei are allergic to mullein and following inoculation with mullein will exhibit local and systemic hypersensitivity reactions similar to tuberculin tests. Mallein (0.1 mL) is usually injected intrapalpebrally into the dermis of the lower eyelid. Positive cases will show edema of the eyelids, conjunctivitis, photophobia, and pain within 12 to 72 hours. The test is typically read 48 hours after injection. Other mullein tests include an ophthalmic test with injection of mullein into the conjunctival sac and a subcutaneous test. It should be noted that animals inoculated with mullein may produce a humoral serologic reaction that may be permanent if the animals undergoes repeated mullein testing.
A variety of serologic tests are available for identification of Bu. mallei, including complement fixation, ELISA, indirect hemagglutination, immunoelectrophoresis, and immunofluorescence. In horses, the most accurate and reliable tests are complement fixation (not valid when used in donkeys or mules) and ELISA.
Diagnosis in Humans
Glanders in people is diagnosed in the laboratory by isolating Bu. mallei from blood, sputum, urine, or skin lesions. Gram stain may reveal small, gram-negative bacilli, which stain irregularly with methylene blue or Wright stain, and may demonstrate a safety pin, bipolar appearance. Organisms can be grown on blood agar as described above. Animal inoculation in Guinea pigs and serology tests such as agglutination and complement fixation tests are also available. Agglutination tests may be positive after 7 to 10 days, but a high background titer and cross-reactivity makes interpretation difficult. Complement fixation tests are more specific and are considered positive for glanders if the titer is equal to or greater than 1:20.
Treatment in Animals
A variety of antibiotics are effective against Bu. mallei; however, treatment is typically not recommended as a result of the potential spread to humans and the development of asymptomatic carriers.
Treatment in Humans
Bu. mallei is usually sensitive to a variety of antibiotics including tetracyclines, ciprofloxacin, streptomycin, novobiocin, gentamicin, imipenem, ceftrazidime, and the sulfonamides. Resistance to chloramphenicol has been reported. Treatment may be ineffective especially in cases of septicemia.
Management and Control in Animals
In glanders-endemic areas, routine testing and euthanasia of positive animals have been successful in eradication of this disease from some areas. In endemic areas, congregation of animals, communal feeding, and communal watering sites should be avoided. Bu. mallei is sensitive to heat, drying, and common disinfectants; however, it can survive for long periods in warm, moist environments. When outbreaks occur, bedding, feed, stalls, and harness equipment need to be disinfected and susceptible species removed from the environment and isolated. There is no animal vaccine for glanders.
Management and Control in Humans
In endemic countries, prevention of glanders in humans involves identification and elimination of the infection in the animal population. Transmission of Bu. mallei in the health-care setting can be prevented by using routine blood and body fluid precautions. There is no human vaccine for glanders.
Glanders is an acute to chronic infectious disease caused by the bacterium Bu. mallei (formerly known as Pseudomonas mallei and Actinobacillus mallei). Bu. mallei bacteria are small, gram-negative, nonmotile, aerobic bacilli that are only found in infected hosts and not in water, soil, or plants. Bu. mallei is found in nasal and skin exudates of infected animals. The bacterium is commonly spread among animals by ingestion of contaminated food or water, but can also be spread by inhalation, discharges of actively infected animals and subclinical carriers, or through skin abrasions and the conjunctiva. After ingestion, bacteria invade the intestinal wall and localize in the lungs, skin, nasal mucosa, and other viscera. Bu. mallei is transmitted to humans by direct contact with infected animals, which enables bacteria to enter the body through the skin and mucosal surfaces of the eyes and nose. In animals there are several forms of glanders including the acute form, chronic form, and latent form. Bu. mallei in people is usually associated with infections in laboratory workers or those with close and frequent contact with infected animals, such as veterinarians, animal caretakers, slaughter house workers, and laboratory personnel. There are several different presentations of glanders in humans including the localized form, pulmonary form, septicemia, and chronic infection. Glanders can be identified via culture, animal inoculation, the mullein test, or serology in animals and culture, animal inoculation, or serology in humans. Treatment of glanders in animals is usually not recommended as a result of the zoonotic nature of the disease. Antibiotic treatment in humans may or may not be successful.
Glanders is a reportable disease. Table 3-5 Selected Species of Clostridium and Their Properties Clostridium Disease Spore Species Location Cl. perfringens Gas gangrene in humans; food Subterminal poisoning in humans; enteric disease in animals Cl. novyi Type A: gas gangrene in humans, Subterminal cattle, and sheep; big head in rams Type B: black disease in sheep (occasionally cattle) Type C: osteomyelitis in water buffalo Cl. septicum Gas gangrene in humans Subterminal Malignant edema in cattle, sheep, horses, pigs, and other animals Cl. tetani Tetanus in humans and animals Terminal Cl. botulinum Botulism in humans and animals; Subterminal termed limberneck in birds Cl. difficile Colitis (antibiotic associated in Subterminal people; Cl. difficile associated diarrhea in horses) Pseudomembranous colitis in humans; ileocecitis in laboratory animals Cl. bifermentans Gas gangrene in humans and animals Subterminal Cl. sporogenes Gas gangrene in humans and animals; Subterminal enterotoxemia in rabbits Cl. histolyticum Gas gangrene in humans and animals; Subterminal (formerly known bacillary hemoglobinuria or red as Cl. novyi water disease in sheep and cattle type D) Table 3-6 The Different Types of E. coli and Their Properties Type of E. coli Human Disease Animal Disease * Enterohemorrhagic Hemorrhagic colitis, Hemorrhagic colitis (EHEC) hemolytic uremic syndrome, thrombotic thrombocytopenic purpura * Enteropathogenic Enteritis in infants Enteritis (EPEC) (infantile diarrhea) Enterotoxigenic Choleriform enteritis, Enteritis in newborn (ETEC) traveler's diarrhea, and young diarrhea Enteroinvasive Dysentery-like colitis ? (EIEC) Enteroaggregative Chronic enteritis ? (EAggEC) Type of E. coli Description of Diarrhea Virulence Factors * Enterohemorrhagic Bloody or nonbloody Adherence causing (EHEC) A/E lesions, enterotoxin production that may enter the bloodstream and bind to endothelial cells * Enteropathogenic Watery Adherence causing A/E (EPEC) lesions Enterotoxigenic Watery, may be bloody Adherence, enterotoxin (ETEC) animals production that stimulates infant hypersecretion Enteroinvasive Bloody or nonbloody Adherence, mucosal (EIEC) invasion Enteroaggregative Watery Adherence, enterotoxin (EAggEC) production * zoonotic
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|Title Annotation:||Part 2: CAT-SCRATCH DISEASE-GLANDERS|
|Author:||Romich, Janet Amundson|
|Publication:||Understanding Zoonotic Diseases|
|Article Type:||Disease/Disorder overview|
|Date:||Jan 1, 2008|
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