Melioidosis

Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. It tends to infect people who have an underlying chronic illness, such as diabetes. The bacteria live in contaminated water and soil and are spread to humans and animals through direct contact with the contaminated source.

Melioidosis can present in a variety of different ways, but it tends to form abscesses (pus pockets). It is similar to the disease glanders found usually in horses, but it is found in different regions and is transmitted through different animals. Melioidosis occurs almost exclusively in tropical climates, especially in Southeast Asia, China and Northern Australia, where it is endemic. In northeastern Thailand, B. pseudomallei is an extremely common pathogen, and at one northern Australian hospital is the most common cause of fatal community-acquired pneumonia.

The disease is often discussed in the media and in medical conferences, because it is a potential agent for biological warfare and terrorism. It can cause devastating disease in populations that have a low natural immunity to it.

Other Names

 * Whitmore's disease
 * Pseudomonas pseudomallei (an older name for the bacterium)

Types
Infection with melioidosis can be acute, subacute or chronic (meaning they can present suddenly; within days to weeks; or over weeks, months and years).

Melioidosis can manifest in a number of ways:


 * Pneumonia/chest infection
 * Skin infection
 * Liver and spleen abscess
 * Joint infection
 * Bone infection (osteomyelitis)
 * Genital infection
 * Brain infection
 * Septicemia (bloodborne infection), particularly in people who are chronically debilitated, such as people with diabetes and chronic renal disease.

Signs and Symptoms
Illness from melioidosis can be divided into four main categories: (1) acute or localized infection, (2) acute pulmonary infection, (3) acute bloodstream infection, and (4) chronic suppurative infection. Inapparent infections are also possible. The incubation period (time between exposure and appearance of clinical symptoms) is not clearly defined, but may range from two days to many years.


 * Acute, localized infection: This form of infection begins when bacteria get into the body through a break in the skin. The germs set up an infection, which causes a skin ulcer, and may cause nearby lymph nodes to swell. The acute form of melioidosis can produce fever and general muscle aches, and may progress rapidly to infect the bloodstream.


 * Pulmonary infection: In this form, the bacteria infect the lungs and bronchi. This form of the disease can range from mild bronchitis to severe pneumonia. The onset of pulmonary melioidosis is typically accompanied by a high fever, headache, anorexia, and general muscle soreness. Chest pain is common, but a nonproductive or productive cough with normal sputum is the hallmark of this form of melioidosis. In addition, abscesses in the lungs and fluid in the pleural sacs surrounding the lungs can form.


 * Acute bloodstream infection: Patients with underlying illness such as HIV, renal failure, and diabetes are affected by this type of the disease, which usually leads to septic shock. The symptoms of the bloodstream infection vary depending on the site of original infection, but generally include respiratory distress, severe headache, fever, diarrhea, development of pus-filled lesions on the skin, muscle tenderness, and disorientation. Abscesses are found throughout the body. This form of the disease has a very high fatality rate; for example, in Singapore, the range is 19%–60%.


 * Chronic suppurative infection: Chronic melioidosis is an infection that involves the organs of the body. These typically include the joints, viscera, lymph nodes, skin, brain, liver, lung, bones, and spleen.

Causes
Melioidosis is caused by the bacterium Burkholderia pseudomallei, which is commonly found in soil in endemic areas.

Diagnosis
Melioidosis is diagnosed by growing Burkholderia pseudomallei from the blood, urine, sputum, or skin lesions. Detecting and measuring antibodies to the bacteria in the blood is another means of diagnosis. Other diagnostic tools that may be useful in melioidosis are radiological tests such as chest x-rays for the diagnosis of pulmonary melioidosis, and computerized tomography (CT) scans used to diagnose abscesses in the liver and spleen.

Treatment
Most cases of melioidosis can be treated with appropriate antibiotics. Burkholderia psuedomallei is usually sensitive to imipenem, penicillin, doxycycline, amoxicillin-clavulanic acid, azlocillin, ceftazidime, ticarcillin-clavulanic acid, ceftriaxone, and aztreonam. Treatment should be started as early as possible, and hospitalization is almost always necessary because the antibiotics are given intravenously. It may take over a week for the fever to subside, even with appropriate treatment. Treatment can take weeks.

After the patient has shown signs of improvement, additional antibiotics are given by mouth to suppress the remnant of the infection. A combination of chloramphenicol plus trimethoprim-sulfamethoxazole plus doxycycline, or amoxicillin-clavulanic acid for children and pregnant women, are the suppressive treatments of choice. Depending on the severity of the infection being treated, this suppressive therapy is continued for between 12 and 20 weeks, and sometimes as long as one year. Even with 20 weeks' antibiotic treatment, 10% of patients relapse. Resistance to trimethoprim-sulfamethoxazole is increasing.

Prevention
There is no vaccine for melioidosis. Prevention of the infection in endemic-disease areas can be difficult since contact with contaminated soil is so common. Persons with diabetes and skin lesions should avoid contact with soil and standing water in these areas. Wearing boots during agricultural work can prevent infection through the feet and lower legs. In health care settings, using common blood and body fluid precautions can prevent transmission.

Chances of Developing Melioidosis
Melioidosis is endemic in Southeast Asia, with the greatest concentration of cases reported in Vietnam, Cambodia, Laos, Thailand, Malaysia, Myanmar (Burma), and northern Australia. It is also seen in the South Pacific, Africa, India, and the Middle East. In many of these countries, Burkholderia pseudomallei is so prevalent that it is a common contaminant in microbiology labs. Moreover, it has been a common pathogen isolated from troops of all nationalities serving in endemic areas. A few isolated cases of melioidosis have occurred in the Western Hemisphere in Mexico, Panama, Ecuador, Haiti, Brazil, Peru, and Guyana, and in the states of Hawaii and Georgia. In the United States, confirmed cases range from none to five each year and occur among travelers and immigrants.

How Melioidosis is Spread
Besides humans, many animal species are susceptible to melioidosis. These include sheep, goats, horses, swine, cattle, dogs, and cats. Transmission occurs by direct contact with contaminated soil and surface waters. In Southeast Asia, the organism has been repeatedly isolated from agricultural fields, with infection occurring primarily during the rainy season. Humans and animals are believed to acquire the infection by inhalation of dust, ingestion of contaminated water, and contact with contaminated soil especially through skin abrasions, and for military troops, by contamination of war wounds.

Melioidosis can spread from person to person by contact with the blood and body fluids of an infected person. Male-to-female sexual transmission of melioidosis has occurred, involving males with chronic prostatic infection due to melioidosis.

Complications
Melioidosis can present in a variety of ways. Some of the more unusual types of infections it can cause include:
 * Pericarditis (infection of the sac surrounding the heart)
 * Septic arthritis (joint infection)
 * Necrotizing fasciitis (connective-tissue infection)
 * Osteomyelitis (bone infection)

Clinical Trials
For a list of American government-sponsored studies of melioidosis, click here.

Expected Outcome
Although bloodstream infection with melioidosis can be fatal, the other types of the disease usually are not. The type of infection and the course of treatment can predict any long-term consequences.

History
In 1911, Alfred Whitmore and C S Krishnaswami identified a bacterium from sick and dying patients in Rangoon, Burma. The bacterium bore a certain resemblance to the bacteria that was known to cause glanders, Bacillus mallei, so Whitmore and Krishnaswami named it Bacillus pseudomallei. (The genus name changed over the years from Pseudomonas to Burkholderia.)

It wasn't until the 1930s that the disease melioidosis was described and named by Stanton and Fletcher, and the symptoms matched to the bacterium that Whitmore and Krishnaswami had already isolated.

During the Vietnam War, many soldiers contracted chronic cases of melioidosis, and the disease was sometimes referred to as the “Vietnam time-bomb.”

In the 1970s, melioidosis killed many large mammals at the Paris zoo owing to a case imported with a panda that was donated from Mao Zedong to Georges Pompidou.

Etymology
The word "melioidosis" comes from the Greek roots melis, a distemper of asses; and eidos, resemblance.