Definition
Glanders is a highly contagious disease of solipeds caused by Pseudomonas
mallei and characterized by nodular lesions of the lungs and other organs as well as
ulcerative lesions of the skin and mucous membranes of the nasal cavity and respiratory
passages. The disease typically has a progressive course and poses a significant human
health risk.
Etiology
Glanders is caused by the bacteria Pseudomonas mallei.
Former names of this pathogen include Loefflerella mallei, Pfeifferella mallei, Malleomyces mallei, Actinobacillus mallei, Corynebacterium mallei, Mycobacterium
mallei, and Bacillus mallei. In experimental infection of guinea pigs Ps.
mallei produces a tenacious capsule that may serve to protect it from phagocytosis
(6). The organism is closely related to Ps. pseudomallei, the cause of melioidosis,
and is serologically indistinguishable in some cases (3,8). Genetic homology between Ps.
mallei and Ps. pseudomallei approaches 70 percent. Because of this many
consider them to be biotypes or isotypes.
The organism is destroyed by direct sunlight and is sensitive to
desiccation. It is readily killed by common disinfectants. It may survive for up to 6
weeks in infected stables (3).
Host Range
Glanders is primarily a disease of solipeds — particularly
horses, donkeys, and mules. Traditionally, donkeys have been regarded as most likely to
experience the acute form of the disease and horses a more chronic form, with mules
intermediate in susceptibility (3,8). Recent reports suggest that chronic and even latent
infections are equally likely in mules (10). Carnivores are susceptible to disease if they
consume glandered meat; felids appear to more susceptible than canids, and outbreaks of
glanders in captive wild felids have been reported (1,3,8). Several laboratory animals are
susceptible to infection including, hamsters and guinea pigs. The susceptibility of the
latter species formed the basis of the Strauss reaction in the diagnosis of the disease.
Humans also are susceptible to infection with glanders, which is an important occupational
disease of veterinarians, farriers, and other animal workers (8). Swine and cattle are
resistant to infection with Ps. mallei, but goats can be infected.
Geographic Distribution
Glanders is currently limited to parts of Asia, Africa, the Middle
East, and Asia (specifically Turkey, Syria, Iraq, Iran, Pakistan, India, Burma, Indonesia,
the Philippines, China, and Mongolia) and possibly the Balkan states, former Soviet
republics, Mexico, and South America (7,8,9,10). Cross-reactions with serological tests
for Ps. pseudomallei may confound estimates of worldwide distribution. Although
glanders was once widespread throughout the world, it has been eradicated from many
countries by diligent test and slaughter programs.
Transmission
The disease is introduced into horse populations by diseased or
latently infected animals. Ingestion of the pathogen, present in secretions from infected
animals, constitutes the major route of infection in glanders. Experimental evidence
suggests that inhalation of the organism is less likely to result in typical cases of the
disease. Although invasion by way of skin lesions is possible, it is regarded as being of
minor importance in the natural spread of the disease. Close proximity alone does not
usually result in transmission of glanders; transmission is facilitated if the animals
share feeding troughs or watering facilities or if they nuzzle each other (3,8,10).
Incubation Period
After artificial infection, a fever, 106o F (41o C), develops in about 3 days and clinical signs within a week. After natural infection,
weeks or months may elapse before manifestations of the disease are apparent. Such latent
infections are a feature of the epidemiology of glanders.
Clincial Signs
Classical descriptions of glanders distinguish between cutaneous,
nasal, and pulmonary forms of the disease, but in most outbreaks these forms are not
clearly distinct and may occur simultaneously in an animal. Chronic infections with slow
progression of an insidious disease are more common than the acute form of glanders. The
acute form (more common in donkeys and mules than in horses) typically progresses to death
within about a week.
The nasal form of glanders is characterized by unilateral or
bilateral nasal discharge. The yellowish-green exudate is highly infectious. The nasal
mucosa has nodules and ulcers. These ulcers may coalesce to form large ulcerated areas, or
they may heal as stellate scars of the mucosa. In some cases the septum may even be
perforated. Nasal lesions are accompanied by enlargement and induration, or sometimes
rupture and suppuration, of regional lymph nodes.
In the cutaneous form of glanders, multiple nodules may develop in
the skin of the legs or other parts of the body (Fig. 56). These nodules may rupture, leaving ulcers that discharge
a yellow exudate to the skin surface and heal slowly. Cutaneous lymphatic vessels in the
region become involved. They become distended and firm by being filled with a tenacious,
purulent exudate (3,8). (These may be referred to as "Farcy pipes.") In the
pulmonary form of glanders, lesions in the lungs develop in concert with nasal and
cutaneous lesions or may be the sole manifestation of the disease (typical of latent
cases). The lung lesions begin as firm nodules or as a diffuse pneumonic process (Fig. 57). The nodules are gray or white
and firm, surrounded by a hemorrhagic zone, and may become caseous or calcified. Clinical
signs in animals with lung lesions may only range from inapparent infection to mild
dyspnea, or severe coughing and obvious lower respiratory tract involvement (3,8).
Lesions may also occur in the liver or spleen and, in male
animals, glanderous orchitis is a common lesion (5,8).
Gross Lesions
Nodular lesions of glanders are most consistently found beneath
the pleura of the lung. In some acute cases, however, a more diffuse form of lobular
pneumonia may be present. The nodular lesions, typically about 1 cm in diameter, consist
of a gray or white core of necrotic material that may become calcified and are surrounded
by a zone of hyperemia and edema. Similar lesions may be found in other viscera.
Glanderous orchitis may be seen in intact males.
Nasal lesions consist of submucosal nodules surrounded by a small
zone of hyperemia. These nodules may rupture, leaving exudative ulcers. As new lesions
develop it is not unusual to find small nodules, ulcers, and scars side by side.
Lymphadenitis of associated lymph nodes is a consistent finding. In some cases laryngeal
lesions similar to the nasal lesions may be found.
Cutaneous lesions consist of cord-like thickening of subcutaneous
lymphatics along which are distributed chains of nodules, some of which are ulcerated.
Morbidity and Mortality
When horses, donkeys, and mules are concentrated, the morbidity
can be high.
Diagnosis
Field Diagnosis
Typical nodules, ulcers, scars, and a debilitated condition can be
sufficient to diagnose glanders. Unfortunately, many cases of glanders are latent and
clinically inapparent. Therefore, systematic testing is essential to identify all infected
animals in an outbreak (3,5,8,9). The mallein test has been the mainstay of field
diagnosis. Mallein is a lysate of Ps. mallei containing both endotoxins and
exotoxins elaborated by the organism. Infected animals are allergic to mallein and exhibit
local and systemic hypersensitivity after mallein inoculation similar to that exhibited in
tuberculin testing. Inoculation with mallein may trigger a humoral serologic reaction to
the complement fixation test. This seroconversion is thought to be transient but may be
permanent if the animal undergoes repeated mallein testing. This is extremely important to
consider if animals are destined for export to countries that depend on the complement
fixation test.
The preferred method of application of mallein is intrapalpebral.
The mallein (0.1 ml) is injected into the dermis of the lower eyelid. In positive cases
marked edema of the eyelid, purulent conjunctivitis, photophobia, pain, and depression may
be observed within 12 to 72 hours. The test is usually read 48 hours after injection.
The ophthalmic mallein test consists of the instillation of
mallein into the conjunctival sac. A positive reaction is characterized by development of
severe purulent conjunctivitis within 6 to 12 hours. A larger volume of dilute mallein
(2.5 MI) may be injected subcutaneously, causing fever, local swelling, and pain in
positive animals.
Specimens for Laboratory
A whole or section of a lesion and a serum sample should be
collected aseptically. The samples should be kept cool and shipped on wet ice as soon as
possible. Sections of lesions in 10 percent buffered formalin and air-dried smears of
exudate on glass slides should be submitted for microscopic examination.
Laboratory Diagnosis
The causative organism may be cultured from fresh lesions or lymph
nodes. It may also be demonstrated micoscopically in films made from this material.
The Strauss reaction is observed when infectious material from
glanders patients is injected intraperitoneally into male guinea pigs. In positive cases,
the guinea pig develops localized peritonitis involving the scrotal sac. Glanderous
orchitis follows with painful enlargement of the testes. The testis becomes enlarged and
painful and ultimately necrotic and is discharged through the scrotal skin.
A variety of serologic tests for glanders have been developed.
They are superior to mallein testing in sensitivity and specificity. The complement
fixation test is widely used and is reported to have an overall accuracy of 95 pecent. A
counter-immunoelectrophoresis test has been described (4). Recently a dot enzyme-linked
immunosorbent assay has been developed and found to be superior to all previously
described tests in its sensitivity. This test is inexpensive, rapid, and easy to perform
and is not influenced by anticomplement activity (11). Cross-reactions with Ps.
pseudomallei, the cause of melioidosis, are features of all of the serological tests
for glanders. Therefore, these tests will result in false positive reactions in animals
from areas where melioidosis is endemic.
Differential Diagnosis
Signs of glanders must be distinguished from strangles, epizootic
lymphangitis, ulcerative lymphangitis, melioidosis, and other forms of pneumonia. Purulent
sinusitis, guttural pouch empyema, and other causes of nasal catarrh should also be
considered. Skin lesions may be similar to those of dermatophilosis or dermatomycoses such
as sporotrichosis. Knowledge of the progressive debilitating nature of glanders and
application of serological or mallein tests will serve to distinguish glanders from other
similar diseases.
Strangles is caused by Streptococcus equi. It is
characterized by fever, anorexia, and depression with swollen submandibular lymph nodes
and mucopurulent nasal discharge. The nasal discharge is usually bilateral, whereas it is
most often unilateral in cases of glanders. Skin nodules and typical lung lesions are
absent. Animals with strangles will not react to mallein testing or serological tests for
glanders. S. equi is readily demonstrable. Strangles does not develop into a
chronic, debilitating condition, and most infected horses recover within a few weeks.
Epizootic lymphangitis (caused by Histoplasma farciminosum)
is characterized by cutaneous nodules originating from superficial lymph vessels. In
epizootic lymphangitis, conjunctivitis is a common lesion. Demonstration of the infectious
agent and application of the mallein test and serological testing will help distinguish
between these diseases.
Ulcerative lymphangitis (caused by Corynebacterium
pseudotuberculosis) is characterized by dermatitis and abscess formation predominantly
in the pectoral and ventral abdominal regions. Standard diagnostic tests are again
valuable in distinguishing this disease from glanders.
Melioidosis (caused by Ps. pseudomallei) is characterized
by multiple abscesses in a variety of tissues and organs. Unlike glanders, it is not
specifically a disease of equids and occurs most often in sheep, goats, and swine. It is
characterized by dyspnea and lameness, but a wide array of clinical signs may be elicited.
Diagnosis is confirmed by isolation of the causative organism. Serological cross-reactions
occur with Ps. mallei.
Treatment
Ps. mallei is sensitive to many antimicrobials (2,5), but
the risk of spreading infection to other equids or to people dictates that infected
animals be destroyed. This policy has successfully eradicated glanders from most parts of
the world. Sulfonamides have traditionally been used for the treatment of human infection
(8).
Vaccination
Protective vaccines have not been developed.
Control and Eradication
In endemic areas, routine testing and destruction of positive
animals have proven successful in the eradication of the disease. Particular care is
required where animals are congregated — most often for military purposes. In endemic
areas, communal feeding and watering sites should be avoided.
Ps. mallei is quite sensitive to heat, desiccation, and
common disinfectants. In warm, moist environments, however, it may remain viable for
several months. In outbreaks it is important to bury or burn all contaminated bedding and
foodstuffs to prevent infection of susceptible animals. Stalls and harness equipment
should be thoroughly disinfected. Removal of susceptible species from contaminated
premises for a period of months is advisable.
Public Health
People are susceptible to glanders. The human form of the disease
is painful and frequently fatal. Laboratory workers and animal attendants are most at
risk. Symptoms of glanders in people include nodular eruption on the face, legs, and arms;
involvement of the nasal mucosa; and later pyemia and metastatic pneumonia. Human glanders
may be confused with a variety of other diseases, including typhoid fever, tuberculosis,
syphilis, erysipelas, lymphangitis, pyemia, yaws, and melioidosis. The diagnosis can be
confirmed by serology and by isolation of the causative organism.
GUIDE TO THE LITERATURE
1. ALIBASOGLU, M., YESILDERS, T., CALISLAR, T., INAL, T., and
CALSIKAN, U. 1986. Malleus-Ausbruch bei Lowen im Zoologischen Garten Istanbul. Berl.
Munch. Tierarztl. Wochenschr., 99:57-63
2. AL-LZZI, S.A., and AL-BASSAN, L.S. 1990. In vitro
susceptibility of Pseudomonas mallei to antimicrobial agents. Comp. Immunol. Microbiol.
lnfect. Dis., 13:5-8.
3. HENNING, M.W. 1956. Animal Diseases in South Africa.
Johannesburg, South Africa: Central News Agency, pp.159-181.
4. JANA, A.M., GUPTA, A.K., PANDYA, G., VERMA, R.D., and RAO, K.M.
1982. Rapid diagnosis of glanders in equines by counter-immunoelectrophoresis. Indian Vet.
J., 59:5-9.
5. MOHAMMAD, T.J., SAWA, M.I., and YOUSIF, Y.A. 1989. Orchitis in
Arab stallion due to Pseudomonas mallei. Indian J. Vet. Med., 9:1517.
6. POPOV, S.F., MEL'NIKOV, B.I. LAGUTIN, M.P., and KURILOV, V.I.
1991. Izuchenie kapsuloobrazovaniia u vobuditelia sapa. Mikrobiol. Zh., 53:90-92.
7. RAY, D.K. 1984. Incidence of glanders in the horses of mounted
platoon of 4th A.P. Bn. Kahilipara, Gauhati-19 - - a case history. Indian Vet. J., 61
:264.
8. STELLE, J.H. 1979. Glanders, in CRC Handbook Series in
Zoonoses. Steele, J.H., ed. Boca Raton, FL:CRC Press, pp.339-362.
9. VAID, M.Y., MUNEER, M.A. and NAEEM, M. 1981. Studies on the
incidence of glanders at Lahore. Pakistan Vet. J., 1:75.
10. VERMA, R.D. 1981. Glanders in India with special reference to
incidence and epidemiology. Indian Vet. J., 58:177-183.
11. VERMA, R.D., SHARMA, J.K., VENKATESWARAN K.S., and BATRA, H.V.
1990. Development of an avidin—biotin dot enzyme-linked immunosorbent assay and its
comparison with other serological tests for diagnosis of glanders in equines. Vet.
Microbiol., 25:77-85.
R.O. Gilbert, B.V.Sc., M.Med.Vet., College of Veterinary Medicine,
Cornell University, Ithaca, NY 14853-6401
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