SUMMARY
Signs and Symptoms: Incubation period ranges from 10-14 days after inhalation.
Inhalational exposure produces fever, rigors, sweats, myalgia, headache, pleuritic
chest pain, cervical adenopathy, splenomegaly, and generalized papular/pustular
eruptions. Almost always fatal without treatment.
Diagnosis: Methylene blue stain of exudates may reveal scant small bacilli.
CXR may show miliary lesions, small multiple lung abscesses, or bronchopneumonia.
B. mallei can be cultured from infected secretions using meat nutrients.
Treatment: Few antibiotics have been evaluated in vivo. Sulfadiazine may be
effective in some cases. Ciprofloxacin, doxycycline, and rifampin have in vitro
efficacy. Extrapolating from melioidosis guidelines, a combination of TMP-SMX
+ ceftazidime ± gentamicin might be considered.
Prophylaxis: No human or veterinary vaccine. Post-exposure prophylaxis may be
tried with TMP-SMX.
Isolation and Decontamination: Standard Precautions for healthcare workers.
Person-to-person airborne transmission is unlikely, although secondary cases
may occur through improper handling of infected secretions. Environmental decontamination
using a 0.5% hypochlorite solution is effective.
OVERVIEW
The causative agent of Glanders is Burkholderia (formerly Pseudomonas) mallei,
a gram-negative bacillus primarily noted for producing disease in horses, mules,
and donkeys. In the past man has seldom been infected, despite frequent and
often close contact with infected animals. This may be due to exposure to low
concentrations of organisms from infected sites in sick animals and the fact
that strains virulent for equids are often less virulent for man. There are
four basic forms of disease in horses and man. The acute forms are more common
in mules and donkeys and death typically follows in 3 to 4 weeks. The chronic
form of the disease is more common in horses and causes generalized lymphadenopathy,
multiple skin nodules that ulcerate and drain, and induration, enlargement and
nodularity of regional lymphatics on the extremities and in other areas. The
lymphatic thickening and induration has been called farcy. Human cases have
occurred primarily in veterinarians, horse and donkey caretakers, and abattoir
workers. The organism spreads to man by invading the nasal, oral, and conjunctival
mucous membranes, by inhalation into the lungs, and by invading abraded or lacerated
skin. Aerosols from cultures have been observed to be highly infectious to laboratory
workers. Work with this organism in the laboratory requires biosafety level
3 containment practices. Despite the rarity of contagion to man from infected
horses and donkeys, the attack rates caused by laboratory aerosols have been
as high as 46% and cases have been severe. Since aerosol spread is efficient,
and there is no available vaccine or really dependable therapy, B. mallei has
been viewed as a potential BW agent. The disease in Equidae in its natural form
poses a minimal threat to military personnel.
HISTORY AND SIGNIFICANCE
Despite the efficiency of spread in a laboratory setting, glanders has only
been a sporadic disease in man, and no epidemics of human disease have been
reported. There have been no naturally acquired cases of human glanders in the
United States in over 59 years. Sporadic cases continue to occur in Asia, Africa,
the Middle East and South America. During World War I glanders was believed
to have been spread deliberately by agents of the Central Powers to infect large
numbers of Russian horses and mules on the Eastern Front. This had an effect
on troop and supply convoys as well as on artillery movement which were dependent
on horses and mules. Human cases in Russia increased with the infections during
and after WWI. The Japanese deliberately infected horses, civilians, and prisoners
of war with B. mallei at the Pinfang (China) Institute during World War II.
The United States studied this agent as a possible BW weapon in 1943-44 but
did not weaponize it. The former Soviet Union is believed to have been interested
in B. Mallei as a potential BW agent after World War II. The low transmission
rates of B. mallei to man from infected horses is exemplified by the fact that
in China, during World War II, thirty percent of tested horses were positive
for glanders, but human cases were rare. In Mongolia, 5-25% of tested animals
were reactive to B. mallei, but no human cases were seen. B. mallei exists in
nature only in infected susceptible hosts and is not found in water, soil, or
plants.
CLINICAL FEATURES
Glanders may occur in an acute localized form, as a septicemic rapidly fatal
illness, or as an acute pulmonary infection. Combinations of these syndromes
commonly occur in human cases. A chronic cutaneous form with lymphangitis and
regional adenopathy is also frequent.
Aerosol infection produced by a BW weapon containing B. mallei could produce
any of these syndromes. The incubation period ranges from 10- 14 days, depending
on the inhaled dose and agent virulence. The septicemic form begins suddenly
with fever, rigors, sweats, myalgia, pleuritic chest pain, photophobia, lacrimation,
and diarrhea. Physical examination may reveal fever, tachycardia, cervical adenopathy
and mild splenomegaly. Blood cultures are usually negative until the patient
is moribund. Mild leukocytosis with a shift to the left or leukopenia may occur.
The pulmonary form may follow inhalation or arise by hematogenous spread. Systemic
symptoms as described for the septicemic form occur. Chest radiographs may show
miliary nodules (0.5-1.0 cm) and/or a bilateral bronchopneumonia, segmental,
or lobar pneumonia and necrotizing nodular lesions.
Acute infection of the oral, nasal and/ or conjunctival mucosa can cause mucopurulent,
blood streaked discharge from the nose, associated with septal and turbinate
nodules and ulcerations. If systemic invasion occurs from mucosal or cutaneous
lesions then a papular and/ or pustular rash may occur that can be mistaken
for smallpox (another possible BW agent).
The chronic form is unlikely to be present within 14 days after a BW aerosol
attack. It is characterized by cutaneous and intramuscular abscesses on the
legs and arms. These lesions are associated with enlargement and induration
of the regional lymph channels and nodes. Rare cases develop osteomyelitis,
brain abscess, and meningitis. Recovery from chronic glanders may occur or the
disease may erupt into an acute septicemic illness. Nasal discharge and ulceration
are present in 50% of chronic cases.
Diagnosis
Gram stain of lesion exudates reveals small gram negative bacteria. These stain
irregularly with methylene blue. B. mallei grows slowly on ordinary nutrient
agar, but growth is accelerated with addition of 1-5% glucose and or 5% glycerol.
Primary isolation requires 48 hours at 37.5 ºC. Growth is also rapid on
most meat infusion nutrient media. Agglutination tests are not positive for
7-10 days, and a high background titer in normal sera (1:320 to 1:640) makes
interpretation difficult. Complement fixation tests are more specific and are
considered positive if the titer is equal to, or exceeds 1:20. Cultures of autopsy
nodules in septicemic cases will usually establish the presence of B. mallei.
Occurrence in the absence of animal contact and/ or in a human epidemic form
is presumptive evidence of a BW attack. Mortality will be high despite antibiotic
use. In the hamster 1 to 10 organisms administered by aerosol is lethal. "Resistant
species" such as albino mouse can be infected with higher inhalation doses.
MEDICAL MANAGEMENT
Standard Precautions should be used to prevent person-to-person transmission
in proven or suspected cases. Sulfadiazine 100 mg/kg per day in divided doses
for 3 weeks has been found to be effective in experimental animals and in humans.
Other antibiotics that have been effective in experimental infection in hamsters
include doxycycline, rifampin, trimethoprim-sulfamethoxazole, and ciprofloxacin.
The limited number of infections in humans has precluded therapeutic evaluation
of most of the antibiotic agents, therefore, most antibiotic sensitivities are
based on animal in vitro studies. Various isolates have markedly different antibiotic
sensitivities, so that each isolate should be tested for its own individual
resistance pattern.
PROPHYLAXIS
Vaccine: There is no vaccine available for human use.
Antibiotics: Post-exposure chemoprophylaxis may be tried with TMP-SMX.
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