Glanders results from infection by Burkholderia mallei, a Gram negative, aerobic, nonmotile rod (family Pseudomonadaceae). This organism was formerly known as Pseudomonas mallei and is closely related to the agent of melioidosis, Burkholderia pseudomallei.
Glanders is seen in some Middle Eastern countries, the Indian subcontinent, Southeast Asia, parts of China and Mongolia, and Africa. Sporadic cases are also seen in South America. Cross-reactions with B. pseudomallei may interfere with serologic estimates of the prevalence and distribution of B. mallei.
Infectious organisms are found in skin exudates and respiratory secretions. Latently infected horses can also spread the disease. Transmission is usually by ingestion in horses and related species; the infection can also be spread by inhalation or through skin abrasions and the conjunctiva. Carnivores can become infected after eating contaminated meat. B. mallei is spread on fomites, including harnesses, grooming tools, food and water troughs. This organism can survive in room temperature water for as long as 30 days and may be able to survive for a few months in other favorable environments. It is susceptible to heat, light, drying and a variety of chemicals.
Humans can become infected after contact with sick animals or infectious materials. Transmission is typically through small wounds and abrasions in the skin; ingestion or inhalation, with invasion through the mucous membranes, is also possible. Cases are usually seen in people who handle laboratory samples or have frequent close contact with horses, mules and donkeys. Natural human infections are rare even when infection rates in horses are 5-30%. Weaponization of B. mallei has been attempted by some countries.
Burkholderia mallei is susceptible to numerous disinfectants including benzalkonium chloride, iodine, mercuric chloride in alcohol, potassium permanganate, 1% sodium hypochlorite, 70% ethanol and 2% glutaraldehyde. It is less susceptible to phenolic disinfectants. This organism can also be destroyed by heating to 55°C for 10 min or by ultraviolet irradiation.
In natural infections, the incubation period is 1 to 14 days. Infections from aerosolized forms in biological weapons are expected to have an incubation period of 10-14 days.
Humans can develop four forms of disease: septicemia, pulmonary infection, acute localized infection or chronic infection. Combinations of syndromes can occur.
In the septicemic form, fever, chills, myalgia, and pleuritic chest pain develop acutely. Other symptoms may include generalized erythroderma, jaundice, photophobia, lacrimation, diarrhea and granulomatous or necrotizing lesions. Tachycardia, cervical adenopathy and mild hepatomegaly or splenomegaly may also be seen. Death usually occurs in 7 to 10 days.
The pulmonary form is characterized by symptoms of pneumonia, pulmonary abscesses and pleural infusions. A cough, fever, dyspnea and mucopurulent discharge may be seen. Skin abscesses sometimes develop after several months.
Localized infections are characterized by nodules, abscesses and ulcers in the mucous membranes, skin, lymphatic vessels and/or subcutaneous tissues. A mucopurulent, blood-tinged discharge may be seen from the mucous membranes. The lymph nodes may be swollen. Mucosal or skin infections can disseminate; symptoms of disseminated infections include a papular or pustular rash, abscesses in the internal organs (particularly the liver and spleen) and pulmonary lesions. Disseminated infections are associated with septic shock and high mortality.
In the chronic form, multiple abscesses, nodules or ulcers can be seen in the skin, liver, spleen or muscles.
Person to person transmission has been reported, but appears to be uncommon. Human epidemics have not been seen.
Glanders can be diagnosed by isolation and identification of Burkholderia mallei. In the septicemic form, blood cultures may be negative until just before death. B. mallei is a nonmotile Gram negative rod; organisms from young cultures and clinical samples are rods with bipolar staining, while bacteria from older cultures can be pleomorphic. Few bacteria may be found in clinical samples. On blood agar or Loeffler’s serum agar, colonies are approximately 1 mm, white, semitranslucent and viscid. Older colonies turn yellow. On glycerin-potato media, a clear honey-like layer is seen by day 3; this eventually darkens to reddish-brown or brown. B. mallei can also be isolated by inoculation into guinea pigs. A polymerase chain reaction can differentiate B. mallei DNA from B. pseudomallei.
Serology is sometimes helpful; serologic tests include agglutination tests and complement fixation. High background titers can be found in normal serum and cross-reactions may occur with Burkholderia mallei, the causative agent of glanders. Positive reactions in agglutination tests develop only after 7 to 10 days.
Treatment and Vaccination
B. mallei is variably susceptible to antibiotics. Long-term treatment or multiple drugs may be necessary. Treatment may be ineffective, particularly in cases of septicemia; the bacteria produce toxins. No vaccine is available.
Morbidity and Mortality
In most parts of the world, naturally acquired cases of glanders are rare and sporadic. Infections are typically seen in people who work with clinical samples or have frequent, close contact with horses. Human epidemics have not been seen.
The septicemic form of glanders has a high mortality rate in humans: the case fatality rate is 95% in untreated cases and more than 50% when the infection is treated. The mortality rate for localized disease is 20% when treated. The overall mortality rate is 40%.
The major hosts are horses, mules and donkeys. Infections can also occur in dogs, cats, goats and camels; cats may be particularly susceptible. Hamsters and guinea pigs can be infected in the laboratory.
In natural infections, the incubation period varies from 6 days to many months; 2 to 6 weeks is typical. Experimental infections can result in clinical signs after 3 days.
Acute, chronic and latent forms of glanders are seen in horses, mules and donkeys.
The clinical signs in the acute form may include a high fever, cough, inspiratory dyspnea, a thick nasal discharge, and deep, rapidly spreading ulcers on the nasal mucosa. Healed ulcers become star-shaped scars. The submaxillary lymph nodes are usually swollen and painful, and the lymphatic vessels on the face may be thickened. Secondary skin infections, with nodules, ulcers and abscesses may be seen. Affected animals usually die within 1 to 2 weeks.
The chronic form develops insidiously. The symptoms may include coughing, malaise, unthriftiness, weight loss and an intermittent fever. A chronic purulent nasal discharge may be seen, often only from one nostril. Other symptoms may include ulcers and nodules on the nasal mucosa, enlarged submaxillary lymph nodes, chronic enlargement and induration of lymphatics and lymph nodes, swelling of the joints and painful edema of the legs. The skin may contain nodules, particularly on the legs, that rupture and ulcerate. This form is slowly progressive and may be fatal.
In the latent form, there may be few symptoms other than a nasal discharge and occasional labored breathing. Lesions may be found only in the lungs.
Yes. Horses, donkeys and mules can transmit the disease to other animals and humans; nasal discharges and wound exudates are infectious. Laboratory samples are highly infectious to humans.
Natural transmission from infected animals to humans appears to be inefficient; despite infection rates of 30% in horses in China during World War II and 5-25% in Mongolia, few or no human cases occurred.
Glanders can be diagnosed by bacteriologic isolation of B. mallei, animal inoculation into guinea pigs, the mallein test or serology.
In live animals, B. mallei is isolated from skin lesions or blood samples. Organisms are much easier to find in fresh than in old lesions, where they may be scant. At necropsy, bacteria can also be isolated from exudates in the nasal passages and the upper respiratory tract. B. mallei is a nonmotile Gram negative rod; bacteria from young cultures and clinical samples are rods with bipolar staining while organisms from older cultures may be pleomorphic. On blood agar or Loeffler’s serum agar, colonies are approximately 1 mm, white, semitranslucent and viscid. Older colonies turn yellow. On glycerin-potato media, a clear honey-like layer is seen by day 3; this eventually darkens to reddish-brown or brown. A polymerase chain reaction can differentiate B. mallei DNA from B. pseudomallei.
In the mallein test, a positive reaction is indicated by eyelid swelling 1 to 2 days after intrapalpebral injection of a protein fraction of B. mallei, or by conjunctivitis after administration in eyedrops.
A variety of serologic tests are available, including complement fixation, enzyme-linked immunosorbent assay (ELISA), indirect hemagglutination, counter- immunoelectrophoresis and immunofluorescence. The most accurate and reliable tests in horses are complement fixation and ELISA. Agglutination and precipitin tests are unreliable for horses with chronic glanders and animals in poor condition. Complement fixation tests cannot be used with donkey or mule serum.
Treatment and Vaccination
Antibiotics may be effective; however, treatment is not generally recommended, as infections can be spread to humans and other animals, and treated animals may become asymptomatic carriers. Vaccines are not available.
Morbidity and Mortality
Glanders can spread widely when large numbers of animals are in close contact; in China, 30% of horses were infected when large numbers of animals were gathered together in World War II. Acute infections are usually fatal within 1 to 2 weeks. Animals with the chronic form can sometimes survive for years.
At necropsy, there may be ulcers, nodules and stellate scars in the nasal cavity, trachea, pharynx, larynx, skin and subcutaneous tissues. Catarrhal bronchopneumonia with enlarged bronchial lymph nodes may be evident. The lungs, liver, spleen and kidneys may contain firm, rounded, encapsulated miliary gray nodules similar to tubercles. The lymphatic vessels may be swollen; the lymph nodes are typically enlarged and fibrotic and contain focal abscesses. In addition, necrosis may be noted in the internal organs and testes.
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