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Chapter 3 Bacterial zoonoses.

LEPROSY

Overview

Leprosy is a disease that derives its name from the Greek word lepros, which means scaly, rough, or mangy. The ancient Greeks described a scaly disease among its people, but this was probably not leprosy as we know it today, but rather psoriasis. Aretaeus the Cappadocian accurately described leprosy in the second century A.D., but he referred to it as leontiasis because of the facial deformity involved with the disease (leonis is Latin for lion, which described the bone abnormalities of people with the disease and is now used to describe the appearance of people with Paget's disease). Leprosy was rampant in Europe from around A.D. 1200 until the Black Death era (bubonic plague) in the fourteenth century, when the loss of human hosts probably halted the spread of the bacterium that caused the disease. Leprosy has been known as Hansen's disease since the 1970s when it was named for Armauer (Gerhard) Hansen, a Norwegian bacteriologist who first diagnosed and described the causative agent (Mycobacterium leprae) of the disease in 1873. Today, about 2 to 3 million people worldwide have leprosy which is usually nonfatal but permanently disfiguring.

Causative Agent

Mycobacterium leprae, like other Mycobacterium organisms, are gram-positive (though weakly staining), acid-fast bacilli that are nonendospore forming, obligate aerobes that have an unusual waxy cell wall that affects many of its properties. My. leprae differs from other Mycobacterium spp. in that it is a strict parasite that has not been grown in artificial media or human tissue culture and it is the slowest growing species of Mycobacterium. My. leprae replicates within host cells in globi (large packets) at an optimal temperature of 30[degrees]C.

Epizootiology and Public Health Significance

Humans are the principle reservoir of leprosy; however, My. leprae is found in nine-banded armadillos, chimpanzees, and mice. These animals can serve as a source of infection for people; however, this is difficult to confirm as a result of the long incubation period of the bacterium in humans and the inability to eliminate a human source of infection in an endemic area. Approximately 12 million people worldwide have leprosy, with the highest prevalence in Asia, Africa, Latin America, and Oceania followed by India, the Philippines, Korea, and some South American countries. The highest burden of leprosy cases is concentrated in six countries: India, Brazil, Myanmar, Madagascar, Nepal, and Mozambique. In the United States, about 2,500 known cases of leprosy exist (found mainly in immigrants); however, naturally-arising cases have been found in Texas, Louisiana, Hawaii, and Puerto Rico. In 1999, 108 new cases of leprosy occurred in the United States. Worldwide, approximately 107,000 new cases are identified annually. An estimated 2 to 3 million people globally are permanently disabled as a result of leprosy. Leprosy tends to be found in areas of low socioeconomic standards. The form of the disease, whether lepromatous leprosy or tuberculoid leprosy, also varies regionally. Asia and North and South America tend to have lepromatous leprosy, whereas Africa tends to have tuberculoid leprosy.
My. lepraemurium can cause disease in
rats, mice, and cats similar to leprosy;
however, this organism is not zoonotic.


Transmission

Leprosy was once believed to be an exclusively human disease; however, research has demonstrated that this infection and disease occur naturally in wild animals. The origin of the animal infection is unknown. Animals may have contracted My. leprae from a human source since these bacilli may remain viable in dried nasal secretions for about 7 days. Since armadillos are in close contact with soil this may be a source of infection if it is contaminated with organisms from nasal secretions. Leprosy in animals can be seen at high levels in certain locations indicating that armadillos may pass the infection to another armadillo either via inhalation of or direct contact with the bacillus. My. leprae has been found in milk, making maternal milk another possible transmission route.
Armadillos harbor a species of
Mycobacterium indistinguishable from
My. leprae making the transmission of
this organism to people possible.


In people, leprosy is believed to be transmitted directly into the skin through contact with a person with leprosy, by mechanical vectors, or by inhalation of respiratory droplets. There have been cases of human leprosy attributed to a person's handling of armadillos and eating their meat and hunting and cleaning armadillos (without known contact with humans with leprosy). About one-third of all leprosy patients in the United States have had contact with armadillos. My. leprae has a very low level of virulence, so most people that come in contact with the organism do not develop clinical disease.

Pathogenesis

Once My. leprae enter the body, they are phagocytosed by macrophages, which destroy the bacilli. In some cases the macrophage response is slow or weak, which allows the bacilli to survive and grow slowly in the lesions. Localized skin and nerve lesions are granulomatous (tumor-like masses, with active fibroblasts and capillaries, containing macrophages surrounded by mononuclear cells), inflammatory processes. The incubation period is typically 2 to 5 years (ranges from 3 months to 40 years). In untreated cases, the bacilli replicate in skin macrophages and Schwann cells of peripheral nerves, causing several different outcomes.
My. leprae can survive for about 7 days
outside the body. This survival time has
supported the belief that armadillos
acquired the disease from people with
lepromatous leprosy whose secretions
came in contact with soil.


Clinical Signs in Animals

Clinical signs of leprosy in animals vary. Skin lesions vary from mild, self-healing lesions to severe, destructive lesions. Dermal nerves can be invaded by these bacilli causing nerve damage. Many organisms can be found in the macrophages of lymph tissue, spleen, and liver. My. leprae prefers cool parts of the body such as the foot pads of mice and bodies of armadillos, which have a body temperature of 30[degrees]C to 35[degrees]C. Armadillos experimentally inoculated with My. leprae had dissemination of the organisms in lymph glands, liver, spleen, lungs, bone marrow, and meninges (Figure 3-40).

[FIGURE 3-40 OMITTED]

Clinical Signs in Humans

Clinical signs of leprosy in humans depend on the form of the disease involved.

* Tuberculoid leprosy is characterized by localized lesions of the skin and nerves that are often asymptomatic. The skin lesi ons are few in number (one to three), asymmetric, and shallow containing few bacilli. If the lesions involve the dermal nerves these nerves may become damaged resulting in local loss of pain perception. This form of leprosy has fewer complications and is more easily treated. Tuberculoid leprosy results in destruction of the organism by cellular immunity (and therefore produce low serum antibody titers).

* Lepromatous leprosy is characterized by many symmetrical skin lesions of varying sizes. Mucosa of the upper respiratory tract, lymph nodes, liver, spleen, and testicles may also be involved. This form of leprosy is responsible for the disfigurations commonly associated with the disease. Because these bacilli prefer the cooler regions of the body such as the nose, ears, eyebrows, and chin the organisms grow there (Figure 3-41). As replication of bacteria continues, the face of the person develops folds and granulomatous thickenings called lepromas. Advanced cases of lepromatous leprosy may cause a loss of sensitivity that results in self-mutilation, secondary infections, and blindness. Lepromatous leprosy activates humoral immunity; therefore, antibody levels are high. Although antibody levels are high, they do not protect the person from developing extensive skin damage as a result of My. leprae.

* Borderline leprosy is intermediate between the above two forms and can progress to either form depending on the patient's treatment and immune status. The borderline leprosy cases can result in early damage to nerves that control the hands and feet as well as sensory nerve damage leading to trauma and loss of fingers and toes.

[FIGURE 3-41 OMITTED]

Diagnosis in Animals

Large numbers of acid-fast bacilli are seen in affected organs such as skin, lymph nodes, spleen, and liver. Smears of skin lesions and nasal secretions may also demonstrate acid-fast bacilli. Bacterial culture for My. leprae is not possible; therefore, diagnosis is based on clinical signs and histopathology. In vivo culture on mouse foot pads can be performed with animal and human samples. ELISA testing of IgM to My. leprae has been used in monitoring armadillos in Texas and Louisiana.

Diagnosis in Humans

Leprosy in humans is diagnosed by clinical symptoms, histopathology, and patient history. A tissue biopsy sample obtained surgically or a tissue smear will show acid-fast bacilli. Tissue biopsies will demonstrate granulomatous, inflammatory lesions. Bacterial culture is unsuccessful. An additional test used in humans is the lepromin test (leprosy skin test). Patients with tuberculoid leprosy mount a cellmediated immune response that will result in a positive lepromin test. Patients not infected with My. leprae or those with compromised immune systems fail to mount a cell-mediated immune response that results in a negative lepromin test.

Treatment in Animals

Treatment of leprosy in animals is not documented.

Treatment in Humans

People with leprosy are treated with the antileprosy drug dapsone (DDS), which is bacteriostatic (often treatment lasts for life). Resistance to dapsone has been reported; therefore, multidrug therapies (MDT) are used to treat human leprosy. Rifampicin is typically used in these combination therapies because it eliminates contagious organisms in 1 to 2 weeks; thereby eliminating the need for isolation of patients in leprosariums. In the United States leprosy patients are treated at the National Hansen's Disease Center in Louisiana (operated by the U.S. Public Health Service).

Management and Control in Animals

Armadillos are being tested in Texas and Louisiana to monitor the level of leprosy in this wildlife source of infection. Other animals do not pose a threat to human health.

Management and Control in Humans

Control of leprosy in humans is based on early detection and antibiotic treatment. The WHO is sponsoring vaccine trials for killed leprosy bacilli. Armadillo-derived killed My. leprae vaccines have been studied since 1984. The use of BCG vaccine (the tuberculosis vaccine) has also been attempted in the control of leprosy and is about 40% to 50% effective. The use of BCG plus killed My. leprae vaccines is being evaluated. Multiple vaccine studies have also been performed in India; however, a widely used vaccine is not available to date. Proper hygiene after handling armadillos or having contact with people with leprosy can also help control the spread of leprosy. The main control strategy is multidrug therapy, which has caused a remarkable decline in leprosy cases. Drugs to treat leprosy are supplied free through some charitable foundations and campaigns to educate people about leprosy through case detection and public awareness are helping control the disease. Continued research is needed to discover more rapid and simplified diagnosis of leprosy, simplified treatment regimens of shorter duration, and prevention of disability in affected patients.

Summary

Leprosy is caused by a slow-growing, acid-fast bacterium called Mycobacterium leprae, which is related to My. tuberculosis and My. bovis. Leprosy is transmitted human to human by respiratory secretions (nasal discharge and respiratory droplets) and direct contact with skin lesions. A natural reservoir of infection is the nine-banded armadillo, which may serve as an important source of infection and research model. Clinical signs of leprosy in animals vary. Skin lesions vary from mild, self-healing lesions to severe, destructive lesions. In humans, lesions from leprosy are not fatal, but disfiguring. Common lesions involve skin and nerve endings leading to skin thickening and folding and loss of sensation. My. leprae does not grow in culture, making diagnosis difficult. In animals, large numbers of acidfast bacilli are seen in affected organs such as skin, lymph nodes, spleen, and liver. Smears of skin lesions and nasal secretions may also demonstrate acid-fast bacilli. Leprosy in humans is diagnosed by clinical symptoms, histopathology, and patient history. Animals are not treated for leprosy. Multidrug treatments and development of vaccines are being used in humans with leprosy.

LEPTOSPIROSIS

Overview

Leptospirosis, also known in people as Weil's disease (named after German physicain Adolph Weil, who first described the disease as infecious jaundice in 1886), is a disease caused by finely coiled spirochetes (leptos is Greek for fine or slender). Leptospirosis is known by a variety of names that typically reflect the sources of infection or species of bacteria that causes the disease. Swineherder's disease (named because people contracted the disease from handling infected animals); rice-field fever, cane-cutter fever, swamp fever, and mud fever (contracted from contaminated water) are names that reflect the source of infection. Icterohemorrhagic fever (caused by serovar L. icterohaemorrhagiae) and Canicola fever (caused by L. canicola) are names that reflect the species of bacteria causing the disease.

Leptospirosis has historically been found in miners, farmers, fish handlers, and sewer workers exposed to bacteria from infected animals or contaminated water. During World War I, soldiers living in trenches came down with leptospirosis, most likely from contamination of the environment with animal urine, especially rat urine. In 1942 soldiers training at Fort Bragg, North Carolina came down with a disease producing high fever, headache, and rash, which was later traced to swimming in ponds and streams contaminated by livestock urine. The largest recorded outbreak of leptospirosis in the United States was in Illinois in 1998 during a triathlon event that sickened 110 participants. Leptospira bacteria are ubiquitous, making leptospirosis one of the world's most widespread zoonotic diseases. It is most common where the climate is warm and humid, soils are alkaline, and there is abundant surface water.

Causative Agent

Leptospira bacteria are gram-negative, aerobic spirochetes (tight coils) with hooked ends (Figure 3-42). Leptospira spp. are motile by means of axial filaments and do not have external flagella. The nomenclature system used to classify leptospires has been revised; the traditional system divided the genus into two species: the pathogenic L. interrogans and the nonpathogenic L. biflexa. These species were divided further into serogroups, serovars, and strains (based on shared antigens), which gave the species L. interrogans more than 250 serovars. Prior to DNA-DNA hybridization, the classification system divided Leptospira biflexa into five species and recognized the variability within the classic L. interrogans species, dividing it into seven named and five unnamed species as follows:

* L. interrogans

* L. weilii

* L. santarosai

* L. noguchi

* L. borgpetersenii

* L. inadai

* L. kirschner

* Leptospira species 1, 2, 3, 4, and 5.

Leptospira bacteria are now divided into 17 genomospecies based on DNADNA hybridization which added L. alexander to the list of pathogenic Leptospira organisms.

[FIGURE 3-42 OMITTED]

Leptospira spp. infect many types of mammals including rats, mice, dogs, cats, cattle, pigs, squirrels, raccoons, bats, deer, foxes, rabbits, goats, birds, frogs, snakes, fish, and mongooses. Animals are critical to the maintenance of Leptospira in a particular location. The reservoir host animals of the different Leptospira species and serogroups vary from region to region, do not typically cause disease in these hosts, and individual animals may carry multiple serovars. L. interrogans has multiple serovars found in animals including L. interrogans serovar canicola in dogs; L. interrogans serovar icterohaemorrhagiae in rats; L. interrogans serovar hardjo in cattle, L. interrogans serovar grippotyphosa in voles, raccoons and other small mammals; and L. interrogans serovar bratislava in pigs, rats, and other small mammals. The pathogenic serovars of Leptospira do not replicate outside of an animal host. Leptospira bacteria can persist and evade the immune system in the renal tubules of these animals without causing clinical signs of disease, and they can be excreted in the urine for prolonged periods of time. Rats are the most common source of infection for humans worldwide; in the United States the most significant sources of infection for humans are dogs, followed by livestock, followed by rodents, followed by wild mammals.
Animals exposed to Leptospira bacteria
will develop immunity (even if they do
not show signs of the disease) but only
to the particular serotype to which they
have been exposed.


Epizootiology and Public Health Significance

Leptospirosis is endemic worldwide and is an occupational hazard for people who work outdoors or with animals (farmers, sewer workers, veterinarians, fish workers, dairy farmers, or military personnel) and is a recreational hazard (campers or those who participate in outdoor sports in contaminated lakes and rivers). In humans, the disease is seen more frequently during summer and fall.
Leptospirosis most commonly occurs
in temperate or tropical climates. One
hundred to 200 cases of leptospirosis
occur in the United States annually,
mainly in the Southeast and Hawaii,
where water temperatures are optimal
for the bacterium's reproduction.


The incidence of leptospirosis is highest in tropical areas, especially following heavy rainfall, which increases risks for waterborne infection and drives rodents into urban dwellings. In 2000, there was a massive outbreak associated with flooding in Thailand in which over 5,000 people were infected and over 180 people died. In 1998, 9 workers at the University of Missouri swine facility developed leptospirosis from handling infected swine and drinking or smoking while working with the animals. In the United States, leptospirosis is most likely underdiagnosed and underreported. The reported annual incidence ranged from 0.02 to 0.04 cases per 100,000 persons from 1985 to 1994, prompting recommendations to remove leptospirosis from the list of notifiable diseases. Internationally high-risk areas include the Caribbean islands, Central and South America, Southeast Asia, and the Pacific islands. Reporting of leptospirosis in these areas is flawed and frequently the disease gains public attention when outbreaks occur in association with natural disasters, such as flooding. Leptospirosis can reach a mortality rate of 10%. Leptospirosis is diagnosed most commonly in adult males as a result of occupational and recreational exposures.

In animals, outbreaks of mastitis and a significant decrease in milk production can be seen in dairy herds infected with Leptospira. In both dairy and beef herds, decreased calving percentage as a result of abortions and high death rate in calves may constitute considerable economic loss. The cost of leptospirosis vaccination is an affordable way to prevent disease.

Leptospirosis continues to re-emerge as a notable source of morbidity and mortality in the Western Hemisphere. The largest recorded outbreak in the continental United States (110 cases in a group of 775 people who participated in triathlons, which included swimming in a lake) occurred in June and July 1998 in Illinois. Significant increases in incidence were also reported from Peru and Ecuador (following heavy rainfall and flooding) in 1998, and Thailand has also reported a rapid increase in incidence of leptospirosis between 1995 and 2000.

Transmission

The bacterium infects a variety of wild and domestic animals that excrete the organism in their urine or in the fluids excreted during parturition. Humans are exposed to the organism when they come in contact with water or soil contaminated by infected animals. Leptospira bacteria multiply in fresh water, damp soil, vegetation, and mud. Flooding following heavy rainfall helps spread the organism because, as the flood water saturates the environment, Leptospira present in the soil pass directly into surface waters. Leptospira bacteria can enter the body either through nonintact skin and mucous membranes (including the conjunctiva) or ingestion of contaminated water. Humans are susceptible to infection with a variety of serovars.
Veterinary personnel (veterinarians,
veterinary technicians, veterinary
assistants, and kennel workers) should
handle urine specimens and urine
contamination as if they contained
Leptospira bacteria by wearing gloves
and a face shield.


Leptospira spp. localize in the kidneys and are shed in the urine for long periods of time. In both animals and humans, Leptospira bacteria are transmitted via contaminated urine (direct contact with urine or through contact with contaminated water and soil) followed by invasion of the organisms across mucosal surfaces or nonintact skin. Under favorable conditions, Leptospira spp. can survive in fresh water for as long as 16 days and in soil for as long as 24 days. Human-to-human transmission is rare.

Pathogenesis

Leptospirosis occurs in two phases: the leptospiremic phase and the immune phase.

* Leptospiremic, acute, or early phase. During this phase the bacterium enters the animal or human via mucous membranes or breaks in the skin. Once the organism, which is highly motile, penetrates the mucous membranes or damaged skin, it enters the bloodstream and distributes throughout the body. Bacteria that reach the kidneys multiply there and are excreted in the urine. During this phase bacteria can also enter the cerebrospinal fluid. Clinical signs at this stage of the disease include high fever, weakness, anorexia, and vomiting.

* Immune, subacute, or second phase. During this phase the blood infection resolves and the fever lessens as a result of circulating IgM antibodies. Clinical signs during this phase include milder fever, labored breathing, increased thirst, icterus, reluctance to rise, and signs of lumbar or abdominal pain (in animals) and milder fever, headache secondary to meningitis, and kidney and liver involvement resulting in jaundice and anemia (in humans).
Transmission of leptospirosis can
occur following bites by mice, rats, or
hamsters, when these animals void
urine at the time of the bite.


Research suggests that Leptospira spp. produce an endotoxin (hemolysin) and lipase as possible causes of its pathogenicity. The true mechanism of host tissue injury, however, remains unclear and likely involves a complex set of interactions. The most common pathologic finding in cases of leptospirosis is vasculitis of capillaries in every affected organ system resulting in loss of red blood cells and fluid through enlarged capillary spaces. This leads to secondary tissue injury and most likely accounts for many of the clinical signs associated with leptospirosis.

Clinical Signs in Animals

Leptospirosis is a contagious disease that may occur without clinical signs or may result in a variety of disease conditions.

* Leptospirosis in dogs is also known as canine typhus, Stuttgart disease, and infectious jaundice and is caused by L. interrogans serovar canicola or L. interrogans serovar icterohaemorrhagiae (although atypical canine infection with L. interrogans serovar grippotyphosa, L. interrogans serovar bratislava, and/or L. interrogans serovar pomona is seen in dogs). Dogs of any age can contract leptospirosis; however, it is most common in young males. The incubation period is 5 to 15 days and many canine cases of Leptospira infections are subclinical. When clinical signs are observed the classical presentation includes fever, anorexia, vomiting, and hepatic disease and oral hemorrhages (petechiae and ecchymoses) (Figure 3-43). This acute form of hepatic and hemorrhagic disease is most often associated with infection with L. interrogans serovar icterohaemorrhagiae. Within days, the temperature will drop, breathing becomes labored, thirst increases, and reluctance to stand from a sitting position may be noted. Salivary secretions may thicken and become blood tinged and swallowing becomes difficult. Bloody vomit and feces may be seen if hemorrhagic gastroenteritis develops. Once signs of acute renal failure are observed (oliguria or anuria), the prognosis for recovery worsens. Fatality rates are about 10% and in fatal cases death usually occurs 5 to 10 days after disease onset.

* Leptospirosis in cattle is also known as redwater of calves and is caused primarily by L. interrogans serovar hardjo, L. interrogans serovar pomona, and L. interrogans serovar grippotyphosa. In 50% of young calves infected with leptospirosis, hemolytic icterus and hemoglobinuria (producing clear-red or port-wine colored urine) occurs and mortality rates range from 5% to 15%. calves, additional clinical signs include fever, anorexia, dyspnea, and anemia. A common manifestation of Leptospira infection in adult cattle is abortion with retention of the placenta occurring most often in the third trimester, and the fetuses are generally autolyzed and icteric. Approximately 30% of cows will reabort during the next pregnancy. Stillbirths, birth of weak calves, rapid drops in milk production, and atypical mastitis can also occur with Leptospira infections. Cows will occasionally show evidence of systemic disease with fever, icterus, and hemoglobinuria.

* Leptospirosis in sheep and goats occurs less frequently than in cattle and is caused primarily by L. interrogans serovar pomona and L. interrogans serovar hardjo. Clinical signs in sheep and goats are similar to those described in mature cattle and calves.

* Leptospirosis in swine is primarily caused by L. interrogans serovar pomona (they may also be infected with L. interrogans serovar grippotyphosa, L. interrogans serovar canicola, and L. interrogans serovar icterohaemorrhagiae serovars) and typically presents as either inapparent disease, febrile reactions lasting 3 to 4 days, or reproductive disease (later term abortions or birth of weak neonates). Occasionally, typical signs of systemic leptospirosis such as fever, icterus, hemorrhages, and death will develop in young pigs. L. interrogans serovar pomona can also be introduced to cattle herds following the animals' exposure to infected pigs onto the property.

* Leptospira infection in horses is characterized by fever, dullness, anorexia, and icterus. Abortion may occur several weeks after the fever and chronic uveitis months later. The etiologic agent of recurrent uveitis (moon blindness) is L. interrogans serovar pomona, which has been isolated from the eyes of afflicted horses and may progress to blindness. Uveitis typically develops 12 or more months after infection and is an immune-mediated disorder. It has been suggested that the basis for this immune reaction is antigenic crossreactivity between a Leptospira protein and a protein in the equine cornea. L. interrogans serovar pomona is a major cause of abortion in horses and can cause liver disease in the equine fetus.

* Leptospira infection and disease is rare in cats and if present resembles the disease seen in dogs.
The source of Leptospira infection in
farm animals is through pastures,
drinking water, or feed, when
contaminated by infected urine.
Infection may also occur as a result of
contact with infected uterine discharges
and aborted fetuses.

Leptospirosis in cattle, pigs, sheep,
and goats is characterized by fever,
depression, anemia, and abortion; in
horses the disease produces an ocular
infection; in dogs the disease causes a
severe kidney infection.


[FIGURE 3-43 OMITTED]

Clinical Signs in Humans

People with leptospirosis may present without any symptoms of disease or may present with a wide range of symptoms such as high fever, headache, chills, muscle aches, vomiting, jaundice (10% of cases), abdominal pain, diarrhea, or a rash. The incubation period is 2 days to 4 weeks (average is about 10 days). Following the incubation period, leptospirosis begins abruptly typically producing fever as the first symptom. Leptospirosis may be biphasic: the first phase produces fever, chills, headache, muscle aches, vomiting, or diarrhea and the second phase produces more severe systemic disease. Direct tissue injury from invasion of Leptospira bacteria and their toxins characterize the acute phase. Symptoms resolve when systemic proliferation of bacteria ends. The patient may recover from the first phase but become ill again. If the second phase occurs, it is more severe and the person may develop kidney or liver failure or meningitis. This phase is also called Weil's disease and is most often a result of infection with the serovar L. interrogans serovar icterohaemorrhagiae. The second phase is characterized by increasing antibody titers and inflammation of affected organ systems. Aseptic meningitis and renal dysfunction are commonly seen in the second phase. Symptoms may persist for 6 days to more than 4 weeks. Without treatment, recovery may take several months and kidney damage, meningitis, liver failure, and respiratory distress as a result of pulmonary hemorrhage may occur. Mortality rates are 10%.

Diagnosis in Animals

Biopsies of tissues infected with Leptospira spp. present in a variety of different ways. Membranes such as oral mucosa, pleura, and peritoneum will have petechial hemorrhages. Grossly the liver appears swollen and yellowish with petechiae. Hepatocytes will shrink and the microscopic architecture of the liver will lose its organization. In all affected species, the kidney may have areas of petechiae and renal tubules are severely altered (they become swollen, granular, and vacuolated). In time the kidneys may contain grayish to white lesions that may be scattered in the cortex (bovine) or concentrated at the corticomedullary junction (canines). The spleen and lymph nodes are grossly enlarged and may contain areas of edema and hemorrhage. Other organs, such as the heart, urinary bladder, pancreas, and lung, may also show areas of hemorrhage and edema. In pigs, abortion and birth of stillborn pigs may be seen. In horses, ocular tissue is affected and bacteria are not present in the urine. Microscopic lesions of the equine eye include alterations to the anterior uvea with congestion of the iris and ciliary body including lymphocyte infiltration. Corneal vascularization is also seen in horses.
Vaccine-induced titers in dogs rarely
exceed 1:400 and generally decrease to
approximately 1:100 by 2 to 3 months
after vaccination.


Leptospirosis in animals is diagnosed using multiple testing methods. Darkfield microscopic examination of urine may show the spirochete; however, absence of the organism does not rule-out Leptospira infection. Bacterial culture of the Leptospira organisms in blood (early in the course of disease) or urine (later in the course of disease) should be performed. Heparinized blood is inoculated into semisolid media tubes enriched with rabbit serum or bovine serum albumin. Urine should be inoculated as soon as possible because the acidity of the urine may harm the spirochetes. All cultures are incubated at room temperature and kept in the dark for up to 6 weeks. Microscopic agglutination (MA) testing is the standard serologic test used to identify Leptospira bacteria. MA uses live cells and pools of bacterial antigens that contain many different serotypes for identification of agglutination. If antibody is present in the sample it will agglutinate with its specific antigen providing a positive result. The presence of agglutination is examined under darkfield microscopy. Other serologic tests include FA or antigen-capture ELISA identification. PCR tests are also available.

Diagnosis in Humans

Laboratory diagnosis of leptospirosis requires culture of the organism (using blood, CSF, or urine) or demonstration of serologic conversion by the microagglutination (MA) test. Bacterial culture is relatively insensitive and requires specialized media (such as Fletcher, Stuart, Ellinghausen combined with neomycin to control growth of other bacteria). The MA test is difficult to perform making the use of reference laboratories important. Serodiagnosis of leptospirosis requires a fourfold or greater rise in titer between the acute and convalescent sample using the MA test. More recently, several rapid, simple serologic tests such as the indirect hemagglutination assay (IHA) have been developed that are reliable and commercially available. Histopathology using silver staining techniques for identification of the organism in tissues can be done on tissue biopsies.

Treatment in Animals

Dogs require aggressive antibiotic therapy as well as supportive therapy such as fluid administration for renal failure. Penicillin is given IV initially to eliminate the leptospiremia, followed by 3 weeks of oral doxycycline to eliminate the leptospiruria. Other treatments include tetracycline, streptomycin, and dihydrostreptomycin. Cattle, small ruminants, horses, and swine may be treated with similar antibiotics and treatment is successful if initiated early in the disease course.

Treatment in Humans

In humans leptospirosis is treated with antibiotics, such as doxycycline or penicillin, which are effective if given early in the course of the disease. Intravenous antibiotics may be required for people with more severe symptoms. Supportive treatment including fluid therapy and renal dialysis is also helpful in treating leptospirosis.

Management and Control in Animals

The prevalence of leptospirosis in dogs in the United States and Canada has increased since 1983. Dogs at greatest risk are male herding and other working dogs and hounds; however, leptospirosis has also been documented in house pets (with German shepherd dogs having the highest rate of reporting). Vaccination using multivalent (including multiple serovars) vaccines is used. In dogs, two vaccine forms are available: the original vaccine, which contained only the L. interrogans serovar canicola and L. interrogans serovar icterohaemorrhagiae serovars; more recent vaccines are also affective against L. interrogans serovar grippotyphosa and L. interrogans serovar pomona.

Cattle should receive annual vaccination. Management methods used to control exposure to Leptospira bacteria include rodent control, fencing of cattle from contaminated water, separation of cattle from swine and wildlife, and selection of replacement stock for leptospirosis-negative herds.

Early in a swine outbreak, swine abortions can be prevented by early treatment and vaccination of all sows in the herd and by separation of age groups.

Management and Control in Humans

Currently, no vaccine is available to prevent leptospirosis in humans. Travelers are advised to consider preventive measures such as wearing protective clothing and footwear and minimizing contact with potentially contaminated water. Antibiotic prophylaxis with doxycycline may be warranted when traveling to some areas.
Vaccinated dogs and livestock are
protected from clinical disease, but they
can still persistently shed Leptospira
organisms in their urine serving as a
source of infection for humans.


Summary

Leptospirosis is a zoonotic disease caused by a spirochete that is common worldwide, especially in tropical countries with heavy rainfall. Infected rodents and other wild and domestic animals pass Leptospira bacteria in their urine, which can directly infect a person or can contaminate an environmental source that can transmit the organism. Leptospira bacteria can live for a long time in fresh water, damp soil, vegetation, and mud. Flooding after heavy rainfall helps spread the bacteria in the environment. Leptospira bacteria can enter the body through broken skin and mucous membranes or by ingestion of contaminated food or water, including water swallowed during water sports. Once in the bloodstream, bacteria can reach all parts of the body and cause signs and symptoms of illness. Signs of disease vary with animal species and include fever, muscle aches, acute renal failure, abortion, and liver disease. Leptospirosis in people may be biphasic: the first phase produces fever, chills, headache, muscle aches, vomiting, or diarrhea and the second phase produces more severe systemic disease. Leptospirosis is common in tropical countries where people have regular contact with fresh water and animals. The disease is probably underdiagnosed in the United States (about 50 to 150 cases are reported annually). Leptospirosis in animals and humans is diagnosed using multiple testing methods including darkfield microscopic examination of urine, bacterial culture of the Leptospira organisms in blood (early in the course of disease) or urine (later in the course of disease), microscopic agglutination (MA) testing, and serologic tests including FA, or antigen-capture ELISA identification. PCR tests are also available. Leptospirosis is treatable with antibiotics and supportive care. Vaccines are available for dogs, cattle, and swine, but not for humans.
Preventative measures for controlling
leptospirosis include vaccination of
livestock and dogs, rodent control
measures, and preventing recreational
exposures (such as avoiding swimming
in freshwater ponds).

Leptospirosis is a not a nationally
reportable disease in the United
States; however, many states require
notification of leptospirosis.


LISTERIOSIS

Overview

Listeriosis, also known as circling disease, listeriasis, and listerellosis, is caused by the gram-positive motile bacteria in the Listeria genus. The genus Listeria contains the two pathogenic species: Listeria monocytogenes and Li. ivanovii (Li. ivanovii subspecies ivanovii and subspecies londoniensis are rare agents of human disease) and the four apparently apathogenic or rarely pathogenic species Li. innocua, Li. seeligeri, Li. welshimeri, and Li. grayi. Listeriosis is most commonly caused in animals and humans by Listeria monocytogenes (there are 13 serovars); however, Li. ivanovii is also associated with animal disease. Listeria bacteria were first cultured by Murray, Webb, and Swann in 1926 from Guinea pigs and rabbits with hepatic necrosis. Listeria is named for Joseph Lister, the English surgeon who pioneered antiseptic surgery and the species monocytogenes is used for this bacterium's effect on monocytes. Li. monocytogenes has been recognized as a human pathogen for approximately 60 years, but its role as a foodborne pathogen was not known until relatively recently. Listeriosis produces flu-like symptoms (headache, fever, and diarrhea) and meningitis/encephalitis in humans and encephalitis, abortions, and septicemia in animals. Listeriosis occurs primarily in newborn infants, elderly patients, and immunocompromised people. Li. monocytogenes may be present in the intestinal tract of 1% to 10% of humans and has been found in at least 37 mammalian species and at least 17 species of birds and some species of fish, shellfish, and insects.

Causative Agent

Li. monocytogenes organisms are gram-positive, nonendospore-forming, motile, pleomorphic bacilli that are sometimes arranged in short chains (Figure 3-44). Li. monocytogenes are considered foodborne pathogens because the majority of these infections are associated with the consumption of contaminated food (mainly unpasteurized dairy products and meat); however, a woman can pass Li. monocytogenes to her baby during pregnancy and farmers/veterinarians/butchers can develop Listeria skin infections by touching infected calves or poultry. Li. monocytogenes is relatively resistant to drying, freezing, and heat. It will grow at a wide range of temperatures (1[degrees]C to 45[degrees]C) and can multiply at refrigeration temperatures on contaminated foods. It can survive at pH range 3.6 to 9.5 and a pH greater than five favors its growth. In susceptible humans, an infective dose of Li. monocytogenes is less than 1,000 organisms.

[FIGURE 3-44 OMITTED]

Virulence and resistance factors associated with Li. monocytogenes include:

* The ability to grow at low temperatures. Listeria can grow and remain viable in certain foods at freezing and refrigeration temperatures. Li. monocytogenes is usually killed by cooking or pasteurization.

* Resistance to drying. Li. monocytogenes can survive for months in food, bedding (straw and shavings), and soil.

* Motility. Listeria bacteria have flagella at room temperature, but do not produce flagella at human body temperature (37[degrees]C). This allows for bacterial existence and spread outside of the host environment.

* Adherence and invasion. Listeria organisms produce chemical substances to aid in their adhesion, invasion, and survival in host cells.

** A membrane protein called internalin mediates invasion of the host cell by Listeria bacteria.

** Act A, a gene product, promotes the lengthening of actin (part of the host cell cytoskeleton) on the bacterial cell surface. Actin sheets function to move bacteria across the cytoplasm to the cell surface where pseudopods form.

** Listeriolysin O (LLO) is a hemolytic and cytotoxic substance that helps Listeria bacteria survive within host cells.

** Other hemolysins such as phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphatidylcholine-specific phospholipase C (PC-PLC) disrupt membrane lipids.

Epizootiology and Public Health Significance

Li. monocytogenes is found worldwide and is widely distributed in the environment. Li. monocytogenes can be found in the feces of farm animals, domestic animals, wild animals, birds, and insects and it has been found in fecal-contaminated soil, water, sewage, and animal feed. Five out of every 100 people carry Li. monocytogenes asymptomatically in their intestinal tract. Human infections peak in July and August, whereas animal infections peak between February and April.

In the United States, the estimated annual incidence of listeriosis is approximately 7.4 cases per million people (approximately 2,500 cases are reported each year since 1997, with 500 of them being fatal). Internationally the estimated annual incidence of listeriosis is approximately 4 cases per million people in Canada with lower incidences reported in Australia, England, and Denmark. In susceptible groups, the overall mortality rate is 20% to 30% reaching as high as 70% in untreated cases. The overall death rate for listeriosis is 26%.

Transmission

The main reservoirs of Li. monocytogenes are soil and the intestinal tract of animals. Animals can carry the bacterium without appearing ill and can contaminate foods of animal origin such as meats and dairy products via feces, milk, and uterine discharges. The bacterium has been found in a variety of raw foods, such as uncooked meats and vegetables, as well as in processed foods that become contaminated after processing, such as soft cheeses and cold cuts. Vegetables become contaminated from the soil or from manure used as fertilizer. Listeria is killed by pasteurization and cooking; however, in certain ready-to-eat foods such as hot dogs and deli meats, contamination may occur after cooking but before packaging (Figure 3-45). Listeria is mainly spread through ingestion, but can also be spread by inhalation or direct contact. Venereal transmission might also be possible. In ruminants, consumption of contaminated silage or other feed is the typical route of transmission, whereas in humans, ingestion of contaminated raw meat and fish, unpasteurized dairy products, and undercooked vegetables are the main routes of transmission.
The seasonal use of silage as livestock
feed is frequently followed by an
increased incidence of listeriosis in
animals.


[FIGURE 3-45 OMITTED]

Vertical transmission is the main route of infection for newborn human infants and ruminants. Vertical transmission is either transplacentally or from an infected birth canal. Humans can also be infected after handling infected animals during calving, lambing, or necropsies.

Pathogenesis

Li. monocytogenes is typically ingested with raw, contaminated food (humans) or contaminated silage (ruminants). Li. monocytogenes bacteria are facultative intracellular parasites that bind to epithelial cells of the gastrointestinal tract or macrophages. This binding of Listeria bacteria triggers phagocytosis. After engulfment the bacteria produce a pore-forming protein called listeriolysin O that forms a hole in the host cell's cytoplasm before the bacterium is destroyed by a lysosome. Listeria bacteria can then survive and replicate in the host cell's cytoplasm avoiding identification by the host's immune system. Listeria bacteria then transfer themselves to nearby cells without having to leave the originally-infected host cell through a mechanism of movement through pseudopods. Li. monocytogenes activates the host cell's actin molecules to stiffen and lengthen, which pushes the bacterium to the host cell's surface, forming a pseudopod (false foot or extension). A nearby macrophage or epithelial cell phagocytizes the pseudopod and Listeria bacteria tunnel out of the cell that engulfed it and continue to survive as an intracellular parasite in the new host cell. Once inside a host cell, this bacterium can enter the blood stream and can then be transported to a variety of body systems (most commonly the central nervous system (brain and spinal cord) and placenta). Figure 3-46 illustrates how Listeria bacteria avoid the host's immune system.
Direct zoonotic transmission of
Li. monocytogenes between infected
animals and humans is relatively
uncommon.


[FIGURE 3-46 OMITTED]

Clinical Signs in Animals

A wide variety of animal species, such as domestic and wild mammals, birds, fish, and crustaceans, carry Li. monocytogenes as commensals in the gastrointestinal tract. Clinical disease is mainly seen in ruminants, but may also be seen in rabbits, pigs, dogs, cats, poultry, and pet birds.

* Ruminants. In ruminants the incubation period for Li. monocytogenes is 10 to 21 days and can cause encephalitis, abortions, and septicemia in cattle, sheep, and goats. Li. monocytogenes can affect all ages of ruminants and may appear as an epizootic disease in feedlot cattle or sheep.

** In cases of encephalitis, infected animals become solitary and anorexic followed by neurologic signs including leaning against stationary objects, circling in one direction, facial paralysis with profuse salivation, torticollis, strabismus, incoordination, and head pressing (Figure 3-47). Neurologic signs are usually unilateral. The disease course is short in small ruminants (1 to 4 days in sheep and goats with death in 1 to 2 days) and more chronic in cattle (4 to 14 days). Encephalitis is usually not seen in ruminants before the rumen becomes functional and is most commonly seen in 1- to 3-year-old animals. The mortality rate in the neurologic form of the disease is 70% in sheep and 50% in cattle.

** The reproductive form of the disease produces placental infection, abortions and stillbirths that occur late in gestation in animals displaying no other clinical signs except fever and anorexia. Retained placentas and metritis may develop in some animals. Herd morbidity rates are typically about 30% with the abortion rate as high as 20% in sheep and cattle.

** The septicemic form of the disease is usually seen in newborns and young ruminants with typical signs being fever, anorexia, and death.

** Rabbits. Li. monocytogenes in rabbits typically causes abortion during late pregnancy, encephalitis (rare), and sudden death. Animals will display nonspecific clinical signs such as anorexia, being obtunded (severe depression or unresponsiveness), and weight loss.

** Pigs. Li. monocytogenes infection is rare in pigs, but may occur as the septicemic form in young piglets, with death occurring within 3 to 4 days.

** Dogs and cats. Li. monocytogenes is rare in dogs and cats. Clinical signs include being obtunded, anorexia, vomiting, and diarrhea. In dogs septicemia and neurologic signs may mimic rabies. In cats encephalitis and septicemia may occur.

** Birds. Li. monocytogenes infection is rare in birds, but may occur in young animals. Affected birds usually have the septicemic form with clinical signs of being obtunded, lethargy, diarrhea, and emaciation. Death can occur without clinical signs. In some birds (geese) encephalitis may also be seen. The incubation period for Li. monocytogenes in turkeys is 16 hours to 52 days.
Once inside host cells, Listeria bacteria can
hide from immune responses and become
inaccessible to certain antibiotics.


[FIGURE 3-47 OMITTED]

Clinical Signs in Humans

Humans become infected with Li. monocytogenes following the consumption of contaminated food (contaminated milk, raw meat, cold cuts, vegetables, seafood, etc.) with symptoms of infection appearing anywhere from 3 to 70 days (the median incubation period is about 21 days). Newborns infected during the birthing process can develop symptoms a few days to a few weeks after birth. Most healthy people do not develop noticeable disease symptoms when infected with Li. monocytogenes but may develop gastrointestinal symptoms such as fever, headache, nausea and vomiting, lethargy, and diarrhea. The incubation period for gastroenteritis caused by Li. monocytogenes is 1 to 2 days.

Listeriosis is a serious problem in pregnant, newborn, elderly, and immunocompromised people. Pregnant women experience mild, flu-like symptoms such as fever, muscle aches, upset stomach and intestinal problems or may be asymptomatic. These women recover from the disease, but the infection can cause miscarriage, premature labor, septicemia in the newborn, and stillbirth. Abortions typically occur during the third trimester.

Newborns can contract listeriosis in utero (transplacental) or during vaginal delivery from bacteria in the vagina (vertical transmission). There are two types of disease processes in newborns: early-onset disease (a serious septicemia present at birth that usually causes the baby to be born prematurely) and late-onset disease (a disease of full-term babies that become infected during childbirth resulting in meningitis about 2 weeks after birth). Babies infected during the pregnancy that become septic may develop systemic infection called granulomatosis infantisepticum. Babies with late-onset disease have a better chance of surviving the infection. Approximately half of the newborns infected with Li. monocytogenes die from the illness.

Immunocompromised adults are at risk of developing meningitis or less frequently septicemia from Listeria infections. Symptoms of listerial meningitis occur about four days after the flu-like symptoms and include fever, personality change, incoordination, tremors, muscle contractions, seizures, and loss of consciousness. Other conditions that have been reported in people are endocarditis, brain abscesses, ocular infections, hepatitis, peritonitis, arthritis, and rarely pneumonia.

Diagnosis in Animals

Listeria bacteria cause minimal if any lesions in animals with the encephalitic form of listeriosis. The CSF may be turbid and congestion of meningeal vessels and softening of the medulla oblongata may be seen at necropsy. The septicemic form of listeriosis may show necrotic foci in internal organs such as the liver. In the placental form aborted fetuses may be autolyzed with focal necrosis of the liver, lung, or spleen. The placental cotyledons may also be necrotic. In birds, myocardial necrosis and pericarditis may be seen with petechial hemorrhage in the proventriculus (gizzard) and heart.

Listeriosis can be diagnosed by culture of the bacterium from affected organs (placenta, fetus, uterine discharge, CSF, or blood depending upon the form of disease present). Necropsy samples may include the liver, kidney, spleen, or brain tissue (pons or medulla). Milk and feces can also be cultured; however, Li. monocytogenes can be found in clinically normal animals. Samples are typically plated on blood agar and incubated at normal conditions and with a cold enrichment technique (incubating in cooler temperatures prior to normal incubation conditions). Cold enrichment techniques may require up to 3 months for growth. Li. monocytogenes grow as small, white, smooth, transparent, beta-hemolytic colonies on blood agar. Biochemical tests such as the CAMP test and hippurate test are also used to identify Li. monocytogenes. Commercial rapid identification techniques such as ELISA, immunofluorescence, immunochromatography, and PCR are available. Serology is not routinely used for diagnosis as a result of cross-reactions with enterococci and Staphylococcus aureus. Antibodies against listeriolysin O can be used, but the methods have not been standardized.

Diagnosis in Humans

In human newborns, lesions associated with early-onset listeriosis are typical of sepsis (microabscesses or granulomas) or meningitis. Late-onset listeriosis frequently presents with purulent meningitis. A rash with small, pale nodules is histologically characteristic of granulomatosis infantisepticum. Other people with Listeria infections usually have an underlying immunodeficiency or are immunocompromised and lesions vary depending on the degree of immune suppression and the organs affected.

The only way to diagnose listeriosis in people is to isolate Li. monocytogenes from blood, CSF, or reproductive tissue (stool samples are not valid because up to 10% of the human population can be carriers of Li. monocytogenes). Identification methods are the same for humans as described for animals; identification of Li. monocytogenes in the food source strengthens the diagnosis.

Treatment in Animals

Listeriosis can be treated using a variety of antibiotics (tetracyclines, sulfonamides, and penicillin), but must be given at high doses and early in the disease. Supportive therapy may also be needed. Animals with neurologic signs usually die despite treatment.

Treatment in Humans

Listeriosis in people is treated with antibiotics (ampicillin or trimethoprim-sulfamethoxazole). Because the bacteria live intracellularly, treatment may be difficult and the treatment periods prolonged. The cure rate can be low as a result of the infection occurring in the young, elderly, and immunocompromised. Human patients are often hospitalized for treatment and monitoring. Other drugs may be given to the patient to relieve pain and fever.

Management and Control in Animals

The risk of ruminants developing listeriosis can be reduced by feeding good quality, low pH silage. Corn silage ensiled before it is too mature is likely to have a low pH, which discourages the replication of Li. monocytogenes. Spoiled or moldy silage should be discarded. Rodent control can also decrease the spread of Li. monocytogenes. Quarantine of new animals and clinically affected animals is important in containing and preventing infection as are removal of the placenta and fetus following abortion. There is currently no vaccine commercially available for listeriosis.

Management and Control in Humans

Prevention of human listeriosis revolves around food safety. High-risk people (young, elderly, and immunocompromised) should thoroughly cook all food from animal sources, wash raw vegetables, and avoid drinking or eating unpasteurized dairy products. Avoiding cross-contamination during food preparation by frequent hand washing and washing of food-preparation equipment is also important. Immunocompromised people should avoid eating hot dogs, luncheon meats, or deli meats, unless they are reheated until steaming hot. Li. monocytogenes can be shed up to 10% to 30% of subclinically infected people, so proper hygiene is important in prevent disease transmission.
In 2006, the FDA approved
bacteriophage treatment of
processed meat in an effort to control
Li. monocytogenes contamination of
these products.


In the 1980s, the U.S. government began testing processed meats and dairy products for Li. monocytogenes. The FDA and the Food Safety and Inspection Service (FSIS) can legally prevent food shipment or order food recalls if any Listeria bacteria are detected in food. In 1996, the CDC began a nationwide foodborne disease surveillance program called FoodNet, which determined that the hospitalization rate for listeriosis (94%) was higher than for any other foodborne illness and that Listeria bacteria reached the blood and CSF in 89% of cases, a higher percentage than in any other foodborne illness. The National Center for Infectious Diseases (NCID) studies listeriosis in several states to help measure the impact of prevention activities, recognize trends in disease occurrence, and assist local health departments in investigating outbreaks.

Summary

Listeriosis is a disease caused by infection with Li. monocytogenes and Li. ivanovii with the latter being a rare cause of zoonotic disease. Li. monocytogenes organisms are gram-positive, nonendospore-forming, motile, pleomorphic bacilli that are sometimes arranged in short chains. Li. monocytogenes are considered foodborne pathogens but can be passed from mother to fetus during pregnancy and farmers/veterinarians/ butchers can develop Listeria skin infections by touching infected calves or poultry. Virulence and resistance factors associated with Li. monocytogenes include the ability to grow at low temperatures and resistance to drying. Li. monocytogenes is found worldwide and is widely distributed in the environment. The main reservoirs of Li. monocytogenes are soil and the intestinal tract of animals. Clinical disease is mainly seen in ruminants, but may also be seen in rabbits, pigs, dogs, cats, poultry, and pet birds. Clinical signs in animals range from encephalitis, abortions, and septicemia in cattle, sheep, and goats; abortion during late pregnancy, encephalitis (rare), and sudden death in rabbits; septicemia in young piglets; anorexia, vomiting, and diarrhea in dogs and cats; and lethargy, diarrhea, and emaciation in birds. Most healthy people do not develop noticeable disease symptoms when infected with Li. monocytogenes but may develop gastrointestinal symptoms such as fever, headache, nausea and vomiting, lethargy, and diarrhea. Listeriosis is a serious problem in pregnant, newborn, elderly, and immunocompromised people. Pregnant women experience mild, flu-like symptoms such as fever, muscle aches, upset stomach, and intestinal problems or may be asymptomatic. These women recover from the disease, but the infection can cause miscarriage, premature labor, septicemia in the newborn, and stillbirth. Babies infected during the pregnancy develop sepsis may develop systemic infection called granulomatosis infantisepticum; babies with late-onset disease have a better chance of surviving the infection. In immunocompromised adults meningitis or less frequently septicemia are the main forms of disease.

Listeriosis can be diagnosed by culture of the bacteria from affected organs. Biochemical tests and commercial rapid identification techniques (ELISA, immunofluorescence, immunochromatography, and PCR) are available. Treatment of listerosis involves the use of antibiotics that need to be administered early in the disease and at high doses. Prevention of listeriosis revolves around feeding/ consumption of uncontaminated food products.

MELIOIDOSIS

Overview

Melioidosis, also called Whitmore's disease and pseudoglanders, is a collective term for infection caused by the soil bacterium Burkholderia pseudomallei (formerly known as Pseudomonas pseudomallei and Malleomyces pseudomallei). Whitmore first described and isolated the causative organism of melioidosis in 1912 from a drug addict in Rangoon, Burma. The causative agent of melioidosis was classified for many years within the Pseudomonas genus; however, in 1992, it was reclassified along with P. mallei and four other species, to a new genus named after the U.S. microbiologist Walter Burkholder. Melioidosis is clinically similar to glanders disease, but the ecology and epidemiology of melioidosis are different from glanders. Melioidosis is predominately found in contaminated water and soil in tropical regions; especially in Southeast Asia (it is endemic in this region). Melioidosis also affects birds and mammals such as sheep, goats, horses, pigs, and cattle. Both humans and animals acquire the disease from the soil and surface water; zoonotic transmission to humans from contact with infected animal fluid is extremely rare.

Causative Agent

Bu. pseudomallei bacteria are aerobic, straight, slender, gram-negative, bipolar-staining, motile rods and are isolated from wet soils, agricultural soils, streams, pools, stagnant water, and rice paddy fields. Burkholderia bacteria grow well on routine culture media such as blood, chocolate, and MacConkey agar. Bu. pseudomallei have been shown to form an extracellular polysaccharide capsule in response to low pH.
In many countries, Bu. pseudomallei
bacteria are so prevalent that it is a
common contaminant found when
culturing bacteria in laboratory settings.


Epizootiology and Public Health Significance

Melioidosis is endemic in Southeast Asia and Oceania (the region between the Tropic of Cancer and the Tropic of Capricorn) occurring mainly in Vietnam, Laos, Cambodia, Burma, Thailand, Malaysia, and northern Australia. It has a seasonal peak during the rainy season. Within the tropics, there are two areas where melioidosis is in extremely high numbers: the Northern Territory in Australia and some northeastern provinces of Thailand. Almost all cases of melioidosis have been diagnosed in temperate climates, with the exception of an outbreak in France in the mid-1970s. The average annual incidence of melioidosis in the Northern Territory of Australia between 1989 and 1998 was 16.5 per 100,000 people. Melioidosis has become an important cause of morbidity and mortality in foreign troops fighting in Southeast Asia. Melioidosis is rare in the United States and tends to be found more frequently in IV drug users.

Transmission

Transmission occurs by direct contact with contaminated soil and water. Humans and animals acquire the infection by inhalation of dust, ingestion of contaminated water, consumption of food (meat, milk, cheese) from infected animals, and contact with contaminated soil especially through skin abrasions (cuts and burns), and contamination of war wounds. Person-to-person transmission has occurred, but it is rare. Animals are rarely the direct source of infection.

Pathogenesis

Bu. pseudomallei is a facultative, intracellular pathogen that can survive within phagocytic cells and macrophages. The presence of a capsule in some forms of Bu. pseudomallei may permit prolonged survival within phagocytes. Once in the host, Bu. pseudomallei produce toxins such as pyocyanin (blue-green pigment that interferes with energy production), lecithinase (causes cell lysis), collagenase, lipase, and hemolysin. The exact roles these toxins play are unknown.

Acute infection typically exhibits localized necrosis and often presents as a painful nodule at the site of inoculation. Regional lymphadenitis is also seen with some lymph nodes producing yellow odorless pus. As bacteria enter the blood, the localized forms may progress to hematogenous melioidosis involving many organs (most frequently the lungs, liver, and spleen). Acute pulmonary suppurative disease may follow inhalation of the bacterium, but is more frequently from hematogenous spread.

[FIGURE 3-48 OMITTED]

Clinical Signs in Animals

Many animal species are susceptible to melioidosis including sheep, goats, horses, swine, cattle, dogs, cats, birds, tropical fish, and a variety of wild animals. Laboratory animals, such as Guinea pigs, hamsters, and rabbits, are highly susceptible. Clinical signs vary with the site of the lesion and may mimic many other diseases. In sheep and goats, lung abscess and pneumonia-like signs are common (Figure 3-48). In horses, nervous disorders, respiratory signs, and gastrointestinal signs (colic and diarrhea) are common. In pigs, splenic abscesses are common.

Clinical Signs in Humans

The incubation period for melioidosis is not clearly defined and can range from 2 to 3 days to many years because the organism can remain quiescent for long periods of time. Melioidosis in people is classified as acute, subacute, and chronic. Because most people exposed to Bu. pseudomallei do not become ill, there is also a recognized subclinical infection classification.

* Acute infection occurs in the monsoonal wet seasons of the various endemic regions and presents with symptoms that have been present for less than 2 months. Acute melioidosis occurs in three forms: localized skin infection that may spread to regional lymph nodes; lung infection with high fever, headache, chest pain, and coughing; and a septicemic form that is characterized by disorientation, dyspnea, severe headache, and skin eruptions on the head or trunk. The septicemic form may be rapidly fatal.

* Subacute infection is characterized by suppurative lesions most frequently found in the lungs as abscesses. The liver may also be involved and will demonstrate solitary or multiple abscesses.

* Chronic infection involves a variety of organs (typically joints, viscera, lymph nodes, skin, brain, liver, lung, bones, and spleen). Chronic melioidosis is often characterized by osteomyelitis and pus-filled abscesses in the skin, lungs, and other organs.

[FIGURE 3-49 OMITTED]

Diagnosis in Animals

Melioidosis can be identified via routine staining, culture, and agglutination tests using specific antisera. Bu. pseudomallei is a gram-negative rod with bipolar staining. This bacterium grows well on blood (smooth and mucoid to dry and wrinkled colonies), chocolate, and MacConkey agar (colorless colonies because it does not ferment lactose) (Figure 3-49). Biochemical tests can also help in the identification of Bu. pseudomallei. Complement fixation and indirect hemagglutination assays on serum are also available.

Diagnosis in Humans

Melioidosis should be suspected based on the patient's history, especially travel, occupational exposure to infected animals, or a history of intravenous drug use. Diagnosis is confirmed by staining, culture, biochemical tests, and serology. Bu. pseudomallei can be cultured from the person's sputum, blood, or tissue fluid from abscesses. When stained with methylene blue, Bu. pseudomallei displays a characteristic bipolar or "safety pin" configuration. Isolation is achieved by using routine culture media such as blood, chocolate, and MacConkey agars. Selective media, such as modified Ashdown's broth, are usually required for culturing respiratory tract specimens to ensure reliable isolation. Bu. pseudomallei may require 48 to 72 hours of incubation and may be easily overgrown in mixed cultures on nonselective media. The colonies are typically wrinkled, purplish, and emit a musty odor. Biochemical tests include oxidase (positive) and production of gas from nitrate. Blood tests, including complement fixation (CF) tests and hemagglutination tests, help confirm the diagnosis. Serologic testing in endemic areas is limited by the high numbers of latent seropositivity rates. Several PCR tests have also been developed, but are not used clinically at this point.

Treatment in Animals

Some antibiotics (such as tetracycline, sulfonamides, and kanamycin) are effective against Bu. pseudomallei; however, once treatment is discontinued many animals relapse.

Treatment in Humans

Bu. pseudomallei is resistant to many antibiotics; however, it is sensitive to ceftazidime, penicillin, and amoxicillin-clavulanate. High doses of antibiotics for 6 to 12 months are recommended. Surgery to remove abscesses may be needed in some cases. Approximately 5% of all cases recur following antibiotic therapy.

Management and Control in Animals

There is no animal vaccine for melioidosis. Since animals are rarely the source of direct infection, controlling their role in disease transmission is limited.

Management and Control in Humans

There is no human vaccine for melioidosis. Preventing infection in endemic areas is difficult because contact with contaminated soil is so common. People with immune compromising diseases (such as diabetes mellitus) and skin lesions should avoid contact with soil and standing water. Wearing boots while doing agricultural work can prevent infection through the feet and distal legs. In health care settings, using universal precautions can prevent transmission. Prompt cleansing of scrapes, burns, or other open wounds in people who live in endemic areas is important. Avoiding needle sharing among drug addicts can also prevent the spread of melioidosis.

Summary

Melioidosis, caused by the gram-negative rod-shaped bacterium Bu. pseudomallei, is an important disease in Southeast Asia and northern Australia. Bu. pseudomallei is found in the environment predominantly in wet soils. The disease can be found in a variety of animals including sheep, goats, horses, swine, cattle, dogs, cats, birds, tropical fish, and a variety of wild animals. Laboratory animals, such as Guinea pigs, hamsters, and rabbits, are highly susceptible. Clinical signs in animals vary with the site of the lesion and may mimic many other diseases. In people it typically infects adults with an underlying predisposing condition, mainly diabetes mellitus. Melioidosis in people presents as an acute, subacute, or chronic form. Acute melioidosis occurs in three forms: localized skin infection that may spread to regional lymph nodes; lung infection with high fever, headache, chest pain, and coughing; and a septicemic form that is characterized by disorientation, dyspnea, severe headache, and skin eruptions on the head or trunk. Subacute infection is characterized by suppurative lesions most frequently found in the lungs as abscesses. Chronic infection involves a variety of organs (typically joints, viscera, lymph nodes, skin, brain, liver, lung, bones, and spleen). Melioidosis can be identified via routine staining, culture, biochemical tests, and serology. Melioidosis should be suspected based on the patient's history, especially travel, occupational exposure to infected animals, or a history of intravenous drug use. Treatment in animals and people includes the use of antibiotics; however, once antibiotics are discontinued there is a risk of relapse. There are currently no vaccines for melioidosis. Preventing exposure is difficult because the bacterium is commonly found in endemic environments.

ORNITHOSIS

Overview

Ornithosis, also known as parrot fever, chlamydiosis, and psittacosis, is a bacterial disease of people caused by Chlamydophila psittaci (formerly known as Chlamydia psittaci). The term psittacosis comes from the Greek psittakos, which means parrot and the term ornithosis comes from the Greek word ornis, which means bird. Outbreaks of "ornithosis" have occurred in birds other than psittacines (parrots and parrot-like birds such as budgerigars and cockatiels); therefore, the term ornithosis is more accurate than psittacosis. In birds, Ch. psittaci infections are referred to as avian chlamydiosis (AC). Ornithosis is a worldwide zoonosis that is carried latently in wild and domesticated birds becoming active under stressful conditions such as overcrowding. Documented cases of ornithosis have been known for more than one hundred years (it was identified for the first time in 1879), but the clinical aspects of the disease were not known during the pandemic of 1929 to 1930 when it was believed that only psittacines could transmit the disease. This pandemic occurred as an atypical and often severe pneumonia in humans and because of its believed origin was termed psittacosis. This pandemic resulted from the shipment of large numbers of amazon parrots from Argentina to a variety of locations around the world. As a result of this pandemic, the United States and other countries banned the importation of birds (this ban was partially lifted in the United States in 1967 and completely removed in 1973). These outbreaks stimulated research of this organism, which included identification of minute basophilic particles in blood and tissue from infected birds. The relationship of these particles with ornithosis was concluded by Bedson, who also described these organisms as obligate intracellular parasites with bacterial affinity (a concept that was not accepted for another 30 years). This bacterium was known at one time as Bedsonia; the term Chlamydia (chlamus is Greek for cloak) did not appear in the literature until 1945. In 1965 it became evident that chlamydiae are not viruses and for many years was the only bacterial order that had just one family and one genus. In the 1990s new diagnostic techniques have resulted in identification of over 40 chlamydial strains and the splitting of the Chlamydiaceae family into two genera, Chlamydia and Chlamydophila. The name Chlamydophila was given to the group of bacteria that were "like chlamydia" by Hans Truper and Johannes Storz after the order Chlamydiales was established in 1999.

Since the 1929-1930 pandemic Ch. psittaci has been found in over 100 species of birds including pet psittacine birds, pigeons, doves, poultry, birds of prey, and shore birds. Ornithosis in people typically causes influenza-like symptoms that can lead to severe pneumonia. Prior to the development of tetracycline antibiotics, ornithosis was a serious human disease with an estimated mortality of 20%. Clinical signs of AC are typically inapparent and shedding of the organism is common. The disease is widespread in birds.

Causative Agent

Ornithosis is caused by a group of closely related, gram-negative, aerobic, nonmotile, coccoid bacteria that are obligate intracellular bacteria. Chlamydial cells are unable to carry out energy metabolism and are dependent on eukaryotic host cells to supply them with ATP (cellular energy). Originally, they were categorized into their own order (Chlamydiales) with one family (Chlamydiaceae) with one genus (Chlamydia) with four species (C. trachomatis, C. psittaci, C. pneumoniae, and C. pecorum). In 1999, Everett recommended that the genus Chlamydia be divided into two genera (Chlamydia and Chlamydophila) containing nine species. The genera of Chlamydia and Chlamydophilla are summarized in Table 3-7.
Chlamydial infections are endemic in
avian and mammalian populations.


The life cycle of Chlamydophila has a biphasic cycle with two distinct forms (intracellular and extracellular). The large and fragile intracellular form, also known as the initial body or reticulate body, is the reproductive stage. The metabolically inert extracellular form, also known as the elementary body, is the infectious, nonreplicating form. Infectious elementary bodies start the cycle by attaching to host cell membranes and gain access into the host cell via endocytosis. Once inside the cell, the bacterium remains within an enlarging intracellular vacuole in order to avoid damage by lysosomes. Elementary bodies will differentiate into metabolically active reticulate bodies during the first few hours. Reticulate bodies will multiply using the host cell's energy and nutrients. After multiple sets of divisions, reticulate bodies will transform back to elementary bodies. The infectious elementary bodies are released into the cytoplasm by exocytosis or host cell lysis and can initiate new cycles in new host cells. This cycle typically takes 48 to 72 hours. When an infected animal defecates, sneezes, or coughs it releases these infective elementary bodies into the environment. The intracellular and extracellular phases of Chlamydophila are illustrated in Figure 3-50.

[FIGURE 3-50 OMITTED]

All strains of Chlamydiaceae share an identical genus-specific antigen in the lipopolysaccharide of their cell wall but differ in the composition of other cell-wall antigens, which accounts for the different serotypes. There are three bacteria mainly responsible for human disease (C. trachomatis, C. pneumoniae, and Ch. psittaci), which differ in respect to their antigens, host cell preference, antibiotic susceptibility, and morphology. Ch. psittaci is the most important zoonotic bacterium in this group and will be the focus of this section.

Epizootiology and Public Health Significance

Avian chlamydiosis is a subclinical, acute, subacute, or chronic disease of wild and domestic birds worldwide and is characterized by respiratory, digestive, or systemic infection. Inapparent infections are common and a high percentage of avian populations are positive. Birds are the natural hosts of Ch. psittaci and this bacterium has been detected in over 130 bird species (57 psittacine species). AC is mainly a disease of nestlings and young birds, particularly in colonial nesting species, domestic poultry (turkeys, pigeons, and ducks), caged birds (primarily psittacines), and raptors. The incidence of disease is high following capture as a result of the stresses of poor nutrition, overcrowding, and physiologic stress. This disease is most often diagnosed in birds owned for less than six months. Different strains of Ch. psittaci are also found in other animal species such as Guinea pigs, mice, sheep, goats, cattle, and horses. AC occurs worldwide as a result of its presence in the worldwide bird population. From 1988 through 2003, the CDC received 935 reported cases of avian chlamydiosis, which is probably an under-representation of the disease.
The elementary body is the infectious
form of the bacterium, which grows
into the reticulate body (the vegetative
phase).


Since 1996, fewer than 50 confirmed human cases of ornithosis have been reported annually in the United States. According to the CDC, about 70% of infected people had contact with infected pet birds. People at greatest risk of contracting ornithosis include bird owners, pet shop employees, veterinarians, and people with compromised immune systems (no person-to-person cases have ever been reported).

Transmission

Ch. psittaci is excreted in the feces and respiratory secretions of infected birds where it can remain infectious in the environment for months (elementary bodies are resistant to drying and are the form found in the environment). Apparently healthy birds can shed the organism intermittently and shedding can be activated by stress. Spread of Ch. psittaci occurs via inhalation or ingestion of air- or dust-borne organisms. Humans become infected when exposed to infected birds (when processed at dressing plants, working with birds, or handling a single pet bird). Infection in people usually occurs after inhalation of bacteria that have been aerosolized from dried feces or respiratory secretions of infected birds. Other infection routes for humans include mouth-to-beak contact and handling infected birds' plumage and tissues. Strains of Ch. psittaci found in other species causing infection of the reproductive tract can be spread to humans and animals via exposure to reproductive fluids and placentas of infected animals.
Ch. psittaci can survive in the
environment for several months.


Pathogenesis

After Ch. psittaci are inhaled, they are deposited in the alveoli. Some bacteria are engulfed by alveolar macrophages and carried to regional lymph nodes. From the lymph nodes they are disseminated through the body and grow within cells of the reticuloendothelial system (macrophages of the liver, spleen, and bone marrow; tissue macrophages, and circulating monocytes). Ch. psittaci initiate infection when elementary bodies attach to the microvilli on the host's mucosal epithelial cells and are engulfed by endocytosis. Elementary bodies within endosomes of the host cell's cytoplasm differentiate into metabolically active, noninfectious reticulate bodies that replicate and form many infectious, metabolically inactive elementary bodies. Newly formed elementary bodies are released from the host cell via cell lysis or exocytosis and the cycle begins again.

Clinical Signs in Animals

Ch. psittaci has been isolated from a variety of animals and the clinical presentation varies with the animal species. Affected species include:

* Birds. The duration between exposure to Ch. psittaci and onset of disease ranges from 3 days to several weeks. Active disease can appear without identifiable exposure making incubation periods difficult to assess. Birds may pre sent with acute disease with such signs as weight loss, air sacculitis, transient anorexia, yellow to green urates, nasal and ocular discharges, conjunctivitis, sinusitis, inactivity, ruffled feathers, weakness, and loose feces. Many birds are emaciated when presented for examination. Some birds may simply appear unthrifty (chronic disease) or may not show any signs (chronic carrier).

* Livestock. Ch. psittaci has been isolated from fecal samples of clinically normal cattle, goats, sheep, and pigs making the gastrointestinal tract an important reservoir and source for disease transmission. Some strains may cause abortions, whereas others cause pneumonia, polyarthritis, encephalomyelitis, or conjunctivitis. Enteritis caused by Ch. psittaci has been documented in newborn calves.

* Cats. Feline pneumonitis caused by Ch. psittaci is a less frequent cause of respiratory disease in cats. Ch. psittaci infections characteristically produce low-grade conjunctivitis and infected cats sneeze and have a fever occasionally. Convalescent cats may go through several disease relapses.
Birds with avian chlamydiosis either
present with acute disease (upper
respiratory signs, anorexia, lethargy,
and green feces), chronic disease (sick,
unthrifty bird with poor feather coat),
or as an asymptomatic chronic carrier
(appear normal with no signs of disease).


Clinical Signs in Humans

Ornithosis presents itself in humans in a variety of ways depending on host and microbial factors, route of transmission, and intensity of exposure. Onset of clinical signs typically follows a 5- to 14-day incubation period. Clinical signs vary from inapparent illness to systemic illness with severe pneumonia. Symptomatic infection usually has an abrupt onset of fever, chills, headache, lethargy, and muscle pain. A nonproductive cough may be accompanied by dyspnea. Splenomegaly and a nonspecific rash may also be seen. If the bacterium affects organ systems other than the respiratory system, it tends to produce endocarditis, myocarditis, hepatitis, arthritis, conjunctivitis, and encephalitis.
Inapparent chlamydial infection is the
most frequently seen form in mammals
and birds.


Diagnosis in Animals

Birds with AC may have hepatomegaly, splenomegaly, air-sac changes (opacification, thickening, caseation), and fibrous pericarditis on necropsy. The liver may have necrotic areas with inflammatory cell infiltrates (Figure 3-51). The air sacs may be thickened by fibrinous exudates and the lungs may be congested and edematous. Enlargement and discoloration of the spleen or liver are seen with chronic infections. Lesions are usually absent in latently infected birds, even though the bacterium is often being shed.

[FIGURE 3-51 OMITTED]

Due to the variety of clinical presentations and presence of latently infected carriers, there is not a single diagnostic test that can reliably determine infection with Ch. psittaci. History and clinical signs are very important factors in diagnosing AC. In acute disease, there are greater numbers of infective organisms and the diagnosis is easier. The organism can often be identified in impression smears of affected tissues stained by Giemsa or Gimenez stains. Confirmation requires cell culture isolation and identification of Ch. psittaci via submission of cloacal, choanal, and conjunctival swabs from live birds, and tissues (liver, spleen, and serosal membranes) from dead birds. Only laboratories with Biosafety level 3 biohazard containment facilities can culture this bacterium.

Serology is almost always used to confirm Ch. psittaci. Antibodies may or may not be detectable depending on the stage of infection, whether the bird has been treated, and the test used. Interpretation of single serum titers is difficult making paired or sequential samples or samples from several birds in a population beneficial. Multiple samples collected for 3 to 5 days are recommended for detection of intermittent shedding. Available antigen-antibody test methods include complement fixation, latex agglutination, ELISA, and immunofluorescence (Figure 3-52). PCK tests are also available. Microimmunofluorescence (MIF) using chick yolk sacs is a more recent test developed for identification of Ch. psittaci.

Live birds being screened for Ch. psittaci might not shed bacteria daily; therefore, serial species should be collected for 3 to 5 consecutive days and pooled before being cultured (to reduce costs).
Freezing, improper handling, and
certain transport media can affect the
viability of Ch. psittaci; refrigeration,
placing specimens in sealed plastic bags
or other containers, and prompt delivery
are preferred methods of shipment.


Diagnosis in Humans

Laboratory diagnosis of Ch. psittaci in humans involves the use of MIF and PCR. Cultivation methods are restricted to state public health laboratories.

[FIGURE 3-52 OMITTED]

Treatment in Animals

Tetracyclines are the antibiotics of choice for treating Ch. psittaci. This group of antibiotics is effective against actively multiplying Ch. psittaci organisms and in acutely affected birds it rapidly controls shedding. Birds used to be treated by using chlortetracycline (CTC) in the feed of all imported psittacines during the 30-day quarantine (formerly required by law in the United States). Currently approved therapy for bird flocks includes CTC premix in food for 45 days (large psittacines), CTC-containing pelleted feeds, or hulled millet impregnated with CTC. Doxycycline is effective but also requires 45 days of treatment. Prolonged treatments using high levels of antibiotic may not completely eliminate latent infection and shedding may recur. Tetracycline antibiotics are the treatment of choice for livestock infected with Ch. psittaci and cats with respiratory disease caused by Ch. psittaci.

Treatment in Humans

Tetracycline antibiotics are the treatment of choice for Ch. psittaci in people. Relapses are common and treatment should continue for at least 10 to 14 days after the fever is controlled. Macrolide antibiotics such as erythromycin may be used in children and pregnant women.

Management and Control in Animals

There is not a vaccine approved in the United States for Ch. psittaci in birds or livestock. In cats some of the upper respiratory vaccine combinations contain either chick-embryo- or cell-line-origin Ch. psittaci. A single parenteral dose is recommended for cats older than 12 weeks of age, whereas younger kittens that were vaccinated younger than 12 weeks of age should be revaccinated when they reach 16 weeks. All cats should be revaccinated annually.

Controlling the introduction and spread of Ch. psittaci in an avian population is critical. Specific control standards include quarantine and examination of all new birds (these records should be kept for at least one year to help identify sources of infected birds and potentially exposed people); isolation of newly acquired, ill, or exposed birds to minimize cross-contamination; isolation and treatment of affected and contact birds (including stress reduction and maintaining proper nutrition); testing birds before they are boarded or sold; thorough cleaning and disinfection of premises; and practicing preventative husbandry (such as positioning cages to prevent the transfer of fecal material, feathers, and food from one cage to another). Ch. psittaci is susceptible to most disinfectants such as 1:10 bleach solution and 70% alcohol. Applying a detergent antiseptic to wet the feathers of dead birds can also reduce exposure to this bacterium.

Ch. psittaci is relatively rare in poultry. Quarantine practices for pet birds do not mandate treatment of Ch. psittaci; however, treatment is common. AC is not considered an exotic disease because it is found in wild and captive bird populations in North America. AC is a reportable disease in the United States and specific quarantine and treatment regimens must be carried out for active cases.

Management and Control in Humans

Ornithosis is an important occupational hazard in the poultry and pet bird industries. Avoiding exposure to affected birds (wearing face masks and protective clothing, proper sanitation and hygiene, etc.), treatment of infected birds, and/or quarantine of imported birds can prevent this disease.

Summary

Ornithosis, also known as parrot fever, chlamydiosis, and psittacosis, is a bacterial disease mainly of birds and people caused by Ch. psittaci (the disease in birds is called avian chlamydiosis) Ch. psittaci are gram-negative, aerobic, nonmotile, coccoid bacteria that are obligate intracellular bacteria. The life cycle of Chlamydophila has a biphasic cycle with two distinct forms (the reproductive, intracellular stage and the infectious, nonreproductive, extracellular stage). Ch. psittaci is excreted in the feces and respiratory secretions of infected birds where it can remain infectious in the environment for months. Apparently healthy birds can shed the organism intermittently and shedding can be activated by stress. Spread of Ch. psittaci occurs via inhalation or ingestion of air- or dustborne organisms. After Ch. psittaci are inhaled, they are deposited in the alveoli and are disseminated from the lymph nodes through the body and grow within cells of the reticuloendothelial system.
Large-scale commercial importation of
psittacine birds from foreign countries
ended in 1993 with the implementation
of the Wild Bird Conservation Act.


Ch. psittaci has been isolated from a variety of animals and the clinical presentation varies with the animal species. In birds the acute disease may present with signs such as weight loss, air sacculitis, yellow to green urates, conjunctivitis, sinusitis, and ruffled feathers. Some birds may simply appear unthrifty (chronic disease) or may not show any signs (chronic carrier). Ch. psittaci has been isolated from fecal samples of clinically normal cattle, goats, sheep, and pigs, making the gastrointestinal tract an important reservoir and source for disease transmission. Ornithosis presents itself in humans in a variety of ways and can vary from inapparent illness to systemic illness with severe pneumonia. This organism can often be identified in stained impression smears of affected tissues, cell culture, and serology. Antigen-antibody test methods and PCR methods are available. Treatment of Ch. psittaci typically consists of tetracycline antibiotics in both animals and humans. Controlling the introduction and spread of Ch. psittaci in an avian population is critical in managing this disease. Ornithosis continues to be an important occupational hazard in the poultry and pet bird industries.

PASTEURELLOSIS

Overview

Pasteurellosis, a bacterial disease of various animals caused by Pasteurella multocida, can cause local or systemic human disease, mainly after people are bitten or scratched by infected animals. P. multocida also causes a variety of diseases in animals and is named after Louis Pasteur, the French chemist who made numerous contributions to microbiology including the discovery of anaerobes, vaccines, and methods for controlling the spread of infectious organisms. Pasteurellosis in cattle was first described in 1878 by Bollinger in Germany. The causative agent of pasteurellosis was isolated by Kitt in 1885 during a period in history that also saw the discovery of the microorganisms causing fowl cholera (Pasteur 1880) and swine plague (Loeffler 1886). Ruappe, a German pathologist, noted similarities in the diseases pasteurellosis, fowl cholera, and swine plague thereby proposing that they share the collective name Bacillus septipaemiae haemorrhagicae. In 1896, Kmae shortened the name to Bacillus bovispotlous and in 1900 Ligniers described the whole group by the name Pasteurella. The species name multocidum was given to this bacterium by Lehown and Neumann and did not appear in the literature until 1899. In 1937, Rosenbusch and Merchant's named the organism P. multocida. Multocida comes from the Latin multi meaning many and cidere meaning to kill. There are many species of Pasteurella and as bacterial identification techniques have improved, some bacteria formerly classified as Pasteurella organisms have been renamed. In 1999, the organism P. hemolytica was renamed Mannheimia hemolytica. This name change was based on taxonomic differences of this organism from other closely related organisms, in particular P. multocida. These differences were identified and described by Dr. Mannheim in 1974.

Causative Agent

P. multocida is a small, facultatively anaerobic, oxidase-positive, gram-negative, nonendospore forming rod that exhibits bipolar staining. Pasteurella bacteria are part of the normal oral, respiratory, genital, and gastrointestinal flora in a variety of wild and domestic animals. P. multocida has a strongly hydrophilic capsule that protects it from dehydration and makes it more resistant to phagocytosis. P. multocida grow well on blood agar as convex, smooth, gray, nonhemolytic colonies that may be rough or mucoid in appearance. There are three subspecies of P. multocida:

* P. multocida subspecies multocida is the most common strain that causes disease in domestic animals.

* P. multocida subspecies septica has been recovered most frequently from cats and dogs, and infrequently humans.

* P. multocida subspecies gallicida is most frequently isolated from birds and occasionally pigs.

Epizootiology and Public Health Significance

Pasteurellosis occurs worldwide in wild and domestic animals as a normal inhabitant of the pharynx of birds and many mammals. Sources of human infection include pets (cats, dogs, birds, rabbits, and Guinea pigs), livestock (cattle, pigs, and sheep), and wild and zoo animals (buffalo, deer, and lions). Other species of Pasteurella can cause human disease such as P. dagmatis, P. canis, P. stomatis, P. cabali, and P. hemolytica (now known as Mannheimia hemolytica); however, P. multocida is the most common.
P. dagmatis is a commensal of the
pharynx of dogs and cats and has been
isolated from animal bite wounds in
humans.


Because pasteurellosis is typically acquired by bite and scratch wounds, the risk of contracting pasteurellosis is good especially since there are more than 100 million dogs and cats in the United States (half of all Americans will be bitten in their lifetime). Approximately 5% of dog bites and 30% of cat bites become infected. Refer to the chapter on animal bite wounds for more statistics on animal bites.

Transmission

P. multocida causes opportunistic disease in animals. Stress is an important factor in the breakdown of respiratory defense mechanisms allowing P. multocida to invade lung tissue causing pneumonia. Transmission among animals can occur via bite and scratch wounds from infected animals, ingestion, and inhalation.

Transmission of P. multocida to humans occurs primarily by bite and scratch wounds of infected animals. Respiratory droplets and consumption of infected meat are rare routes of transmission.

Pathogenesis

P. multocida bacteria are introduced in humans and animals via a bite or scratch wound producing local inflammation and swelling of regional lymph nodes. From the lymph nodes infection spreads to the joints, bones, and other lymph nodes. Complications include cellulitis, abscesses, and osteomyelitis. Cat bites are particularly bad as a result of the small, sharp, penetrative characteristics of cat teeth.

[FIGURE 3-53 OMITTED]

In addition to bite wound injuries, P. multocida in animals causes a variety of clinical disease such as hemorrhagic septicemia and shipping fever of cattle, fowl cholera, swine plague, snuffles in rabbits, and pneumonia in sheep. Many times P. multocida is a secondary invader following stress or immune system weakening by another infectious agent. Viruses are believed to alter alveolar macrophage function resulting in decreased clearance of inhaled bacteria. The host response of sending increased numbers of neutrophils to the area of infection causes enzyme release when these neutrophils are lyzed contributing to lung tissue damage. This damage also allows P. multocida bacteria to gain a foothold and multiply.

Clinical Signs in Animals

Many animal species are susceptible to Pasteurella infection including sheep, goats, swine, cattle, and rabbits. The diseases in these animals include:

* Bronchopneumonia in all ages of sheep and goats especially lambs and kids. Bronchopneumonia of the cranioventral lung lobes is caused by both P. multocida and Mannheimia hemolytica (formerly known as P. hemolytica and the more common cause). Edematous bright red lungs and pericardial effusion are seen on necropsy.

* Shipping fever in cattle, a severe respiratory disease associated with Pasteurella bacteria generally occurring in younger animals following shipping.

* Snuffles (rhinitis) and pneumonia in rabbits (Figure 3-53).

* Torticollis, commonly known as wry neck, in rabbits as a result of middle or inner ear infections (Figure 3-54).

* Abscesses in a variety of animals especially rabbits.

* Fowl cholera in birds that produces clinical signs such as rapid death, fever, anorexia, mucus discharge, ruffled feathers, diarrhea, tachypnea, and localized swelling of wattles, joints, and footpads. In the peracute form, fowl cholera is one of the most virulent and infectious diseases of poultry.

* Abortion in cattle, sheep, and goats.

* Respiratory disease in dogs and cats.

* Atrophic rhinitis (along with other bacteria) and bronchopneumonia in swine.

* Meningitis in dogs.

[FIGURE 3-54 OMITTED]

Clinical Signs in Humans

The incubation period for pasteurellosis varies from 2 to 14 days depending on the route of entry. Wound infections show redness, swelling, and pain. Cellulitis and abscess formation in the skin and subcutaneous tissue may follow. Other disease complications include respiratory infections (mainly upper respiratory infections like sinusitis rather than lower respiratory tract infections), endocarditis, and rarely meningitis. Septicemia is uncommon and usually indicates an underlying medical condition in affected people.

Diagnosis in Animals

Pasteurellosis can be identified via routine staining such as Gram stain (bipolar staining gram-negative rods) and culture methods of samples obtained via swabs or washes. Bipolar staining bacteria can be demonstrated in Wright-stained blood smears of animals with septicemia. P. multocida grow well on blood agar as convex, smooth, gray, nonhemolytic colonies that may be rough or mucoid. Biochemical testing can also be used to identify P. multocida. It is indole positive, urea negative, catalase positive, and ferments mannitol, sucrose, and maltose. Indirect fluorescent antibody tests and ELISA tests are also available. Serologic tests are rarely used for diagnosis of fowl cholera.

Diagnosis in Humans

Pasteurellosis in people is diagnosed via Gram stain, special stain (such as Wright stain), culture, and biochemical tests as described in animals.

Treatment in Animals

Antibiotic treatment should be initiated as soon as possible to be effective against P. multocida. The best basis for antibiotic choice is culture and sensitivity results; however, ceftiofur, oxytetracycline, and tylosin have been effective. Removal of environmental stressors is also important in the treatment of pasteurellosis.

Treatment in Humans

P. multocida infections in humans are typically treated with beta-lactam antibiotics (such as amoxicillin or amoxicillin-clavulanic acid). Resistance to macrolides has been documented. Any bite wound should be thoroughly cleansed and irrigated. Debridement of nonviable tissue can reduce the risk of infection. Rabies and tetanus status should be determined in patients with animal bite wounds.
The risk of multiple bacteria in a bite
wound must be considered in cases of
animal bite injuries.


Management and Control in Animals

There is an animal vaccine for pasteurellosis in cattle (both P. multocida and Mannheimia hemolytica; however, there are many strains of these bacteria that may or may not be covered in all vaccines) and in birds (either bacterins containing aluminum hydroxide or oil as adjuvant prepared from multiple serotypes or live vaccine). Correcting poor ventilation, overcrowding, poor nutrition, failure of passive transfer, commingling of animals from various farms, avoiding animal-to-animal bites and scratches, and minimizing transportation are all ways to control pasteurellosis. Vaccinating cattle for other respiratory diseases that may predispose them to contracting Pasteurella bacteria is also helpful in reducing cases of pasteurellosis.

Management and Control in Humans

There is no human vaccine for pasteurellosis. Proper hygiene after handling animals and avoiding animal bites and scratches is indicated.

Summary

Pasteurellosis, caused by P. multocida, is a disease found worldwide and people are typically infected through animal bites. Pasteurella bacteria are part of the normal oral, respiratory, genital, and gastrointestinal flora in a variety of wild and domestic animals. P. multocida is a small, facultatively anaerobic, oxidase-positive, gramnegative, nonendospore forming rod that exhibits bipolar staining. P. multocida causes opportunistic disease in animals with stress being a predisposing factor. Transmission among animals can occur via bite and scratch wounds from infected animals, ingestion, and inhalation. Transmission of P. multocida to humans occurs primarily by bite and scratch wounds of infected animals. Pasteurellosis in animals presents as bronchopneumonia in all ages of sheep and goats; shipping fever in cattle; snuffles, pneumonia, and wry neck in rabbits; abscesses in a variety of animals especially rabbits; fowl cholera in birds; abortion in ruminants; respiratory disease in dogs and cats; atrophic rhinitis and bronchopneumonia in swine; and meningitis in dogs. In humans wound infections are red, swollen, and painful. Disease complications include cellulitis, abscesses, respiratory infections, endocarditis, and rarely meningitis. Pasteurellosis can be identified in animals and people via routine staining and culture methods of samples obtained via swabs or washes. Biochemical testing can also be used to identify P. multocida. Indirect fluorescent antibody tests and ELISA tests are also available. Antibiotic treatment should be initiated as soon as possible to be effective against P. multocida. Removal of environmental stressors and thoroughly cleansing and irrigation of wounds are also important in treating pasteurellosis. There is an animal vaccine for pasteurellosis in cattle and birds. Correcting poor environmental and management practices, preventing commingling of animals from various farms, and minimizing transportation are all ways to control pasteurellosis. There is no human vaccine for pasteurellosis. Proper hygiene after handling animals and avoiding animal bites is indicated.
Table 3-7 Divisions in the Family Chlamydiaceae

Genus Chlamydia
Species                 Host                    Properties

Chlamydia trachomatis   Humans                  * Most common
                                                  sexually
                                                  transmitted
                                                  bacterial pathogen
                                                  in United States
                                                * Causes ocular and
                                                  venereal infections
                                                  in people

Chlamydia suis          Swine                   * Pneumonia,
                                                  conjunctivitis, and
                                                  polyarthritis in
                                                  pigs
                                                * Most likely is
                                                  endemic in pigs

Chlamydia muridarum     Mouse, hamsters         * Genital infection
                                                  in murine species
                                                * Closely related to
                                                  Chlamydia
                                                  trachomatis

Genus Chlamydophila

Chlamydophila           Humans, birds (six      * Flu-like disease
psittaci                avian serovars and        in people
                        two mammalian           * Respiratory
                        serovars)                 disease, diarrhea,
                                                  and polyuria
                                                  in birds

Chlamydophila           Hamsters, horses,       * Pneumonia,
pneumoniae              humans, other mammals     bronchitis, and
                                                  sinusitis in
                                                  animals
                                                * Pneumonia and
                                                  possibly
                                                  atherosclerosis
                                                  in people

Chlamydophila pecorum   Mammals                 * Encephalomyelitis
                                                  and endometritis
                                                  in cattle
                                                * Pneumonia and
                                                  conjunctivitis
                                                  in sheep
                                                * Polyarthritis
                                                  in ruminants
                                                * Urogenital disease
                                                  in koalas

Chlamydophila felis     Cats                    * Conjunctivitis
                                                  in cats
                                                * Atypical pneumonia
                                                  in humans

Chlamydophila caviae    Guinea pigs             * Conjunctivitis in
                                                  Guinea pigs
                                                * Highly specific
                                                  for Guinea pigs

Chlamydophila abortus   Ruminants               * Abortion and
                                                  stillbirths as a
                                                  result of
                                                  colonization of
                                                  the placenta
                                                * Probably endemic
                                                  in ruminants
                                                * Reports of abortion
                                                  and respiratory
                                                  disease in humans
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Title Annotation:Part 3: LEPROSY-PASTEURELLOSIS
Author:Romich, Janet Amundson
Publication:Understanding Zoonotic Diseases
Article Type:Disease/Disorder overview
Geographic Code:1USA
Date:Jan 1, 2008
Words:15550
Previous Article:Chapter 3 Bacterial zoonoses.
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