Glanders is a contagious, acute or chronic, usually fatal disease of Equidae caused by Burkholderia mallei, a pathoadaptive clone derived from B pseudomallei. It is characterized by serial development of nodules in the upper respiratory tract, lungs, and skin. Felidae and other species are susceptible, and infections are usually fatal. The organism is infectious for people, with a 95% fatality rate in untreated septicemia cases, and is therefore considered a potential bioterrorism agent. Glanders is one of the oldest diseases known and once was prevalent worldwide. It has now been eradicated or effectively controlled in many countries, including the USA. In recent years, the disease has been reported in the Middle East, Pakistan, India, Mongolia, China, South America, Africa, and some European countries, including Russia.
Burkholderia mallei, a clonal gram-negative facultative intracellular obligate pathogen, is present in nasal exudates and discharges from ulcerated skin. Glanders is commonly contracted by:
The organism is susceptible to heat, light, and disinfectants; survival in a contaminated area is limited to 1–2 months. Humid, wet conditions favor survival. A polysaccharide capsule is an important virulence factor and enhances survival in the environment.
After an incubation period of 3 days to 2 weeks, animals acutely affected by glanders usually have:
Death occurs within a few days. The chronic disease is common in horses and is seen as a debilitating condition with nodular or ulcerative lesions of the skin and internal nares. Infected animals may live for years and continue to disseminate the organism. In some, the infection may be latent and persist for long periods. Donkeys and mules are more severely affected than horses.
Nasal, pulmonary, and cutaneous forms of glanders are recognized, and an animal may be affected by more than one form at a time. In the nasal form of glanders, nodules develop in the mucosa of the nasal septum and lower parts of the turbinates. The nodules degenerate into deep ulcers with raised irregular borders. Characteristic star-shaped cicatrices remain after the ulcers heal. In the early stage, the submaxillary lymph nodes are enlarged and edematous and later become adherent to the skin or deeper tissues.
In the pulmonary form of glanders, small, tubercle-like nodules, which have caseous or calcified centers surrounded by inflammatory zones, are found in the lungs. If the disease process is extensive, consolidation of the lung tissue and pneumonia may be present. The nodules tend to break down and may discharge their contents into the bronchioles, resulting in extension of the infection to the upper respiratory tract.
In the cutaneous form of glanders (“farcy”), nodules appear along the course of the lymph vessels, particularly of the extremities. These nodules degenerate and form ulcers that discharge a highly infectious, sticky pus. The liver and spleen also may show typical nodular lesions. Histologically, there may be vasculitis, thrombosis, and infiltration of degenerating inflammatory cells.
The typical nodules, ulcers, scar formation, and debilitated condition may provide sufficient evidence for a clinical diagnosis of glanders. However, because these signs usually do not develop until the disease is well advanced, specific diagnostic tests should be used as early as possible. Culture of B mallei from lesions confirms the diagnosis. A test for delayed hypersensitivity is performed by intrapalpebral inoculation of mallein, a secreted glycoprotein of B mallei found in culture supernatant. Infected hypersensitive horses develop a purulent conjunctivitis within 24 hours and swelling of the eyelid. Complement fixation is also used to screen for infection. Competitive ELISA is more sensitive than complement fixation and may become positive as early as 3 days after infection. PCR based on 16S and 23S rRNA gene sequences may be used for specific identification.
There is no vaccine for glanders. Protective immunity involves T cell responses elicited by live attenuated bacteria. Prevention and control of glanders depend on early detection and elimination of affected animals, as well as complete quarantine and rigorous disinfection of the area involved. Successful control is dependent on efforts to establish awareness among horse and donkey owners in remote areas, in addition to provision of funds to cull affected animals. Treatment of glanders does not reliably produce a bacteriologic cure. Doxycycline, ceftrazidime, gentamicin, streptomycin, and combinations of sulfazine or sulfamonomethoxine with trimethoprim were effective in the prevention and treatment of experimental glanders.