One of the unfading memories of mine from my student years between 1957 and 1963 at the Faculty of Veterinary Medicine, Utrecht State University, Netherlands was a colored picture hanging on the wall of the old surgery theatre. The realistically hand-painted picture showed a skinny, debilitated horse with abscesses, nodules and ulcers covering the entire body, while mucopurulent discharge was streaming out of its nostrils. Malleus and Kwade [Dutch for malignant] Droes were the two titles inscribed beneath the picture, which most probably dated back to the 19th century. (The Imperial veterinary school in Utrecht was established in 1821.)
The picture became for us students, a frightening reminder of the terrible plagues of antiquity; but the truth is that malleus (known as glanders) was still rife during World War I. From August 1914 until the end of that war in 1918, the German Military Veterinary Services condemned 15,776 clinically- or latently-infected animals, mainly contaminated by captured Russian horses. During the same period, 58,843 horses were affected in the French Army, of which 294 died from generalized glanders.
Glanders, which has become history, regained interest in recent years since it is regarded as one of the main eight potential agents of bioterror (together with anthrax, botulism, cholera, plague, Q fever, smallpox and tularemia).
Its first known description was made by Aristotle (384-322 BC), who addressed the disease in donkeys, naming it Melis which became later malleus (Latin for hammer). This name was explained by Roman military historian Vegetius as the force with which the disease strikes horses. In this overview, the French-derived English name, glanders, will be applied.
Glanders was a worldwide problem in equids for centuries, eradicated from most countries by the mid-1900s. Outbreaks are now uncommon and reported from limited geographic areas. In non-endemic regions, cases may be seen in people who work with its causative pathogen, Burkholderia mallei, in secure laboratories. The United States has not seen any naturally occurring cases since the 1940s; an infection was reported in a U.S. researcher in 2000. During 2007, the presence of the disease was officially reported to the OIE from two countries, Iran and Brazil, but this does not implicate its absence from other countries in Africa, Asia, the Middle East, Central America and South America.
Burkholderia mallei, formerly known as Pseudomonas mallei, is a Gram negative rod in the family Burkholderiaceae. It is closely related to and appears to have evolved from the agent of melioidosis, Burkholderia pseudomallei. Although this organism is inactivated by heat and sunlight, its survival is prolonged in wet or humid environments. Some sources suggest that it might be able to survive for more than a year in the environment, under some circumstances.
Glanders primarily affects horses, mules and donkeys, which often become infected when they ingest B. mallei in contaminated food or water. It may occasionally occur in members of the cat family, infected when they eat contaminated meat. Latently-infected as well as clinically-ill animals can spread the disease. Although human disease is uncommon, it is life threatening and painful. The disease is mainly transmitted by contact with skin exudates and respiratory secretions from infected equids. Without antibiotic treatment, the case fatality rate in man can be as high as 95%. The organism can also be spread in aerosols, and by entry through skin abrasions and mucous membranes. B. mallei is readily spread on fomites including harnesses, grooming tools, and food and water troughs.
Aerosols may be the major route of infection in a bioterrorist attack.
Most laboratory-acquired infections have occurred during routine handling of cultures or samples, rather than after injuries or accidents. Rare cases of person-to-person transmission have been reported in family members who nursed sick individuals. Two cases were thought to have been sexually transmitted.
The disease in animals
The incubation period varies from a few days to many months; two to six weeks is typical. Experimental infections can result in clinical signs after three days.
In equids, glanders is traditionally categorized into nasal, pulmonary and cutaneous forms. In the nasal form, deep ulcers and nodules occur inside the nasal passages, resulting in a thick, purulent, yellowish discharge. In the pulmonary form, nodules and abscesses develop in the lungs. Some infections are inapparent; others vary from mild dyspnea to severe respiratory disease. In more severe cases, the clinical signs include coughing, dyspnea, febrile episodes and progressive debilitation.
In the cutaneous form, named Farcy, the skin contains nodules that rupture and ulcerate, discharging an oily, purulent yellow exudate. The regional lymphatics and lymph nodes become chronically enlarged; the lymphatics are filled with a purulent exudate.
Clinical cases are usually a combination of these forms, and can occur as acute, chronic or latent disease.
Affected cats typically have a purulent yellowish nasal discharge that may become bloody. The lymph nodes are swollen, and dyspnea may be seen. Affected cats usually die in one to two weeks.
The disease in humans
The incubation period is a few days to several weeks. It varies with the form of the disease: septicemia or localized disease usually becomes apparent after one to five days, while the pulmonary form typically develops after 10 to 14 days.
The symptoms of glanders vary with the route of exposure. Four forms of the disease septicemia, pulmonary infection, acute localized infection and chronic infection have been described in humans. One form of the disease can progress to another, and combinations of syndromes occur.
Localized infections are characterized by nodules, abscesses and ulcers in the mucous membranes, skin, lymphatic vessels and/or subcutaneous tissues at the site of inoculation. Abscesses often develop in the lymph nodes and may drain. These abscesses are often found in the liver, spleen and lungs, but any tissue including the subcutaneous tissues and muscles can be affected. Disseminated infections often progress to septicemia.
The pulmonary form occurs after inhalation of B. mallei, or by hematogenous spread from other forms. It is characterized by pulmonary abscesses, pleural effusion and pneumonia. The onset is usually acute. Untreated pulmonary disease often develops into septicemia.
The septicemic form develops acutely. Multi-organ failure is common, and death often occurs 24 to 48 hours after the onset of symptoms.
Chronic glanders is characterized by multiple abscesses, nodules and ulcers in a variety of tissues, with periodic recrudescence and milder symptoms than acute disease. A wide variety of organs can be affected including the skin, subcutaneous tissues, liver, spleen, gastrointestinal tract, respiratory tract and skeletal muscles. This form of the disease can last up to 25 years.
Glanders can be diagnosed by culturing B. mallei from lesions or respiratory exudates and identified with biochemical tests. It can also be isolated by inoculation into guinea pigs or hamsters. Polymerase chain reaction (PCR) assays are available in some laboratories. Other specialized genetic techniques may be available mainly in research laboratories.
The mallein test is a sensitive and specific clinical test for hypersensitivity against Burkholderia mallei. Mallein, a water soluble protein fraction of the organism, is injected subcutaneously, intradermo-palpebrally or given by eyedrop. In infected animals, the skin or the eyelid swells markedly within one to two days. Complement fixation test and enzyme-linked immunosorbent assays are the most accurate and reliable serological tests for diagnostic use.
No vaccines are available for glanders. Animals that test positive for glanders are euthanized except in endemic areas. In an outbreak, the premises should be quarantined, thoroughly cleaned and disinfected. Carcasses are burned or buried.
In endemic areas, susceptible animals should be kept away from communal feeding and watering areas, since glanders is more common where animals congregate. Routine testing and euthanasia of positive animals can eradicate the disease.
B. mallei is usually sensitive to tetracyclines, ciprofloxacin, streptomycin, novobiocin, gentamicin, imipenem, ceftrazidime, and the sulfonamides. Resistance to chloramphenicol has been reported.
For more information:
- Arnon Shimshony, DVM, is Associate Professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail Animal Diseases and Zoonoses Moderator. Dr. Shimshony was Chief Veterinary Officer, State of Israel, from 1974 to 1999.