Overview of Melioidosis
(Pseudoglanders, Whitmore disease)
Melioidosis is a bacterial infection of animals and people. It is often associated with suppurative or caseous lesions, comprising a mixed purulent and granulomatous response that can occupy any body organ.
The etiologic agent is Burkholderia pseudomallei, an oval, motile, gram-negative, facultative anaerobic bacillus with bipolar staining. The organism is ubiquitous throughout southeast Asia, northern Australia, and the South Pacific. Its distribution is predominantly tropical and subtropical with “hyperendemicity” in the top end of the Northern Territory of Australia and northeast Thailand. The true boundaries of its endemicity are ambiguous because of movement of the organism and its ability to travel to and exist in temperate regions (eg, southwest Australia, France), where it may cause sporadic disease and outbreaks. B pseudomallei has been introduced to new environments with the export of animals, and shipments of contaminated soil and water could potentially produce the same results. Reports of possible autochthonous melioidosis have also come from India, Pacific islands, Central and South America, the Caribbean, Africa, and the Middle East.
B pseudomallei is a widespread saprophyte and has been isolated from various soil types and surface water of varying depths. Melioidosis outbreaks have coincided with heavy rainfall and flooding associated with high humidity or temperature. Major excavations and disturbances in plumbing resulting in contamination of water supplies have also resulted in outbreaks.
Melioidosis is most commonly seen in sheep, goats, and pigs; other affected species include cattle, buffalo, horses, mules, deer, camels, alpacas, dogs, cats, dolphins, wallabies, koala, primates, birds, tropical fish, reptiles, and people. Laboratory animals affected by melioidosis include hamsters, guinea pigs, rabbits, mice, and rats. Host susceptibility and disease manifestations vary between species. The introduction of naive livestock to endemic regions may predispose them to disease, as seen with sheep, goats, pigs, and camelids. Other species (eg, dogs and cats) may succumb to infection due to immunocompromising conditions.
Infection is thought to be opportunistic and primarily a result of transmission from the environment (eg, contaminated soil and surface waters) rather than from animal to animal. The most common routes of infection are via percutaneous inoculation, contamination of wounds, ingestion of soil or contaminated carcasses, or inhalation. Transplacental infection resulting in abortion has been reported in goats. Transmission during breeding and other means of host-to-host transmission may occur. Laboratory-acquired infection and iatrogenic infection via contaminated antiseptics, injections, or other hospital or surgical equipment have been reported.
The virulence of B pseudomallei appears to vary among isolates, but these virulence factors are not well understood. Molecular-typed clonal outbreaks have produced a range of different clinical presentations, which indicate that host factors and infecting dose may be just as important in determining the severity of disease. The incubation period ranges from a few days to months or even years. B pseudomallei is a facultative intracellular pathogen that can remain dormant for many years before emerging as an active infection.
Signs can vary widely within a species, depending on the site of infection, and range from acute to chronic. Fever, anorexia, or swollen glands may be noted. Subclinical infection is common. Infection may be associated with single or multiple suppurative or caseous nodules/abscesses, which can be located in any organ tissue with variable effects. Disease most likely due to percutaneous inoculation often develops at distant sites without evidence of active infection at the inoculation site. The organs most commonly affected include the lungs, spleen, liver, and associated lymph nodes.
Goats often develop mastitis, and aortic aneurysms have been reported. The respiratory system is involved preferentially in sheep; signs can include fever, severe coughing, respiratory distress, and mucopurulent nasal and ocular discharge. CNS disease, with signs that include circling, incoordination, blindness, nystagmus, and spasms, has been seen in cattle, horses, sheep, and goats. Pigs often have asymptomatic lesions on the spleen that are incidental findings at slaughter. Lameness due to septic arthritis and osteomyelitis can occur. Fatalities often occur in association with acute fulminating infections or when vital organs are affected. Various forms of melioidosis have been reported in horses; signs may include weakness, edema and lymphangitis of the limbs, mild colic, diarrhea, coughing, or nasal discharge. Skin infections may resemble fungal eczema initially, progressing to become papular. In dogs, disease may be acute, subacute, or chronic. In acute cases, septicemia with fever, severe diarrhea, and fulminant pneumonia are common. Subacute cases may present as a skin lesion with lymphangitis and lymphadenitis; untreated cases may progress to septicemia. Chronic disease can occur in any organ with clinical signs that include anorexia, myalgia, edema of the limbs, and skin abscesses.
Multiple abscesses that contain thick, caseous greenish yellow to off-white material are noted at necropsy. The organs most commonly involved are the lungs, spleen, lymph nodes, liver, and subcutaneous tissues. Exudative bronchopneumonia, consolidation, and abscesses may be found in the lungs of animals with respiratory disease. Nodules and ulcers may be found on the nasal mucosa and septum and on the turbinates; these may coalesce into irregular plaques. Meningoencephalitis, severe enteritis, suppurative polyarthritis, and other syndromes also have been reported.
The clinical signs of melioidosis are not diagnostic because of the protean nature of the disease. For a definitive diagnosis, isolation and identification of the organism are required. The organism can be isolated from lesions and discharges. It is possible to culture the organism on routine diagnostic media; however, Ashdown’s media is preferred because of a consistently distinctive colony morphology and odor. Gram-stained smears of exudate or pus can sometimes identify bipolar “safety pin”–shaped, gram-negative rods. Serologic tests such as complement fixation and indirect hemagglutination are effective herd surveillance tools. More recently, DNA probes and PCR tests have been developed.
Treatment with the appropriate antibiotics should be based on culture and sensitivity results. Treatment may be expensive, prolonged, and possibly unsuccessful, with the risk of recrudescence once treatment is discontinued. The possibility of underlying immunosuppressive conditions should be investigated in less susceptible species. With severe disease, treatment regimens can follow guidelines for human melioidosis with initial intensive therapy using the newer β-lactams (ceftazidime and the carbepenems), possibly in combination with cotrimoxazole for up to 2 mo. This should be followed by subsequent eradication therapy for a minimum of 3 mo with high-dose cotrimoxazole or conventional combination therapy using chloramphenicol, cotrimoxazole, and doxycycline or amoxicillin/clavulanate. Preventive measures are more practical and economical in intensive farming environments and involve raising the animals off the soil, especially avoiding exposing animals to muddy or water-inundated regions and providing clean drinking water via chlorination and filtration. Minimization of environmental contamination by diseased animals is also an important control measure. There is no effective vaccine.
Melioidosis has zoonotic potential. Infected animals can shed the organism in wound exudates and, depending on the site of infection, from other sources, including nasal secretions, milk, feces, and urine. Mastitis in goats is a common manifestation, and B pseudomallei has been isolated from milk, resulting in the requirement for pasteurization of commercial goats’ milk in the tropics. Infected animal carcasses are condemned at the abattoir.