Burkholderia mallei (Glanders) and
Burkholderia pseudomallei (Melioidosis) 

(January 6, 2009)

Unless otherwise noted, all information presented in this article is derived from the following two sources:
1) Textbook of Military Medicine: Medical Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General at TMM Publications; 2007. Chapter 6-7. Available at: http://www.bordeninstitute.army.mil//published_volumes/biological_warfare/biological.html.
2) Currie B. Burkholderia pseudomallei and Burkholderia mallei: Melioidosis and Glanders. In: Principles and Practice of Infectious Diseases. Churchill Livingston, 2004. Chapter 218.

Image of Burkholderia pseudomallei grown on sheep blood agar. Source: CDC Public Health Image Library (ID #1928).

Background

Glanders and melioidosis are infectious diseases caused by species of the bacterial genus Burkholderia. Glanders is caused by infection with the bacterium Burkholderia mallei, while melioidosis is caused by Burkholderia pseudomallei. Both have the potential to produce fatal disease and have been identified by the Centers for Disease Control and Prevention (CDC) as Category B biological agents. The Department of Health and Human Services (HHS) has identified these diseases as top priorities for development of medical countermeasures.

Glanders

Glanders, which was described by both Hippocrates and Aristotle, is largely a disease of historical importance, but the disease remains endemic in the Middle East, Asia, Africa, and South America. Horses, mules, and donkeys are animals most often afflicted by glanders, but the disease can spread to other animals. In humans, the main route of transmission has been occupational exposure among workers who handle infected animals; however, infection may also occur if contaminated meat is ingested or respiratory secretions are inhaled.

Glanders as a Biological Weapon

Glanders was one of the first agents to be used for biowarfare in the modern era. During World War I, German agents targeted horses and livestock in the United States, Romania, Spain, Norway, and Argentina for infection with glanders through inoculation and feed contamination. The infamous Japanese Unit 731 utilized glanders in its experiments during World War II, and the Soviet Union has been alleged to have employed glanders in its occupation of Afghanistan in the 1980s. Of note, the organism cannot persist in the environment outside its host (unlike B. pseudomallei—the agent of melioidosis), which potentially limits its usefulness as a bioweapon.

Transmission

Human to human transmission can occur with this agent via highly infectious respiratory and cutaneous secretions.

Infection Control Measures

Airborne and standard contact precautions should be employed in the care of all infected individuals given its potential for transmission. Laboratory workers should utilize BSL-3 lab precautions as laboratory acquired cases have occurred.

Signs and Symptoms

The incubation period for glanders varies depending on the site of infection and transmission characteristics. The incubation period can range from 1 to 14 days, with shorter incubation periods (1 to 2 days) possible with inhalation and longer periods with skin exposure.

Constitutional symptoms—which include malaise, fevers, chills, and fatigue—are common at the onset, and then, depending on the method of infection, more organ system-specific symptomatology may follow.

Inhalational exposure results in a pneumonic presentation with fever, which can progress to ulceration and necrosis of the airways. Lobar or bronchopneumonia, neck and mediastinal lymph node swelling, pustular skin lesions, and spread to internal organs may follow. Without antibiotics, death may occur within 10 days.

After skin exposure, skin nodules may form and become pus-filled; swelling of nearby lymph nodes may occur. This is often accompanied by symptoms such as fatigue, fevers, chills, and malaise. Systemic dissemination at 1 to 4 weeks can result in infection in almost any organ, including the central nervous system.

 

Diagnosis and Countermeasures

Diagnosis is based on culture;  no rapid test is available.

Antibiotics including carbapenems, cephalosporins (ceftazidime and cefepime), macrolides (azithromycin, clarithromycin), doxycycline, TMP/SMX and gentamicin have activity against glanders. An intensive induction regimen of intravenous antibiotics for 10 to 14 days is required, followed by 3 months of oral eradication therapy. Doxycycline post-exposure prophylaxis, as well as potential vaccine candidates, are being studied.

Melioidosis

Melioidosis, like glanders, is a disease that afflicts both humans and animals. It has varied clinical presentations, including asymptomatic infection, localized skin ulcers/abscesses, chronic pneumonia, and fulminant septic shock with abscesses in multiple internal organs. Most cases originate in Southeast Asia—where it is a common cause of pneumonia—and northern Australia. And most cases are the result of percutaneous inoculation following exposure to the bacteria muddy soils or surface water. The disease was first identified in 1912 in morphine addicts in Burma. Unlike B. mallei, B. pseudomallei is found in the environment, where it resides in water and soil.

Melioidosis as a Biological Weapon

Although various countries studied B.pseudomallei for use as a bioweapons, it was never used as such. However melioidosis is considered a potential biological weapon because of the ease with which strains may be obtained from the environment, the ability to engineer multiply antibiotic resistant strains, and the lack of a vaccine.

Transmission

Human to human transmission is rare, but has been documented.

Infection Control Measures

Airborne and standard contact precautions should be employed in the care of patients when severe pneumonia with productive sputum is present. Laboratory workers should utilize BSL-3 lab precautions.

Signs and Symptoms

The inoculating dose, mode of infection, and host risk factors (e.g. presence of diabetes or alcoholism) influence the incubation period of melioidosis, which can range from 1 to 21 days. Clinical presentation can range from localized skin abscesses to disseminated infection with septic shock and pneumonia, which carries a mortality rate of 90%. A chronic form of melioidosis that mimics tuberculosis was once known as the “Vietnamese Time Bomb” due to the potential for reactivation of the infection in U.S. soldiers who had returned home after serving in the Vietnam War.

Diagnosis and Countermeasures

As with glanders, diagnosis is made through culture detection of the organism, and no rapid test is available.

Initial treatment consists of a course of intravenous antibiotics for 14 days followed by eradication therapy for 3 months. Antibiotics including carbapenems, cephalosporins (ceftazidime and cefepime), doxycycline, and TMP/SMX have activity against melioidosis. Notably, macrolides and gentamicin are not active against B. pseudomallei.

Secondary prophylaxis with TMP/SMX, doxycycline, or amoxicillin-clavulanate may be considered, but only in certain scenarios (since the agent is not easily transmitted from person-to person, in the lab, or zoonotically) especially if the exposed person has diabetes or alcoholism.

See Also

Textbook of Military Medicine: Medical Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General at TMM Publications; 2007. Chapters 6-7. Available at: http://www.bordeninstitute.army.mil//published_volumes/biological_warfare/biological.html. Accessed September 30, 2008.

Currie BJ. Burkholderia pseudomallei and Burkholderia mallei: Melioidosis and Glanders Principles and Practice of Infectious Diseases. Churchill Livingston, 2004. Chapter 218.

Glanders General Information. Centers for Disease Control and Prevention. http://www.cdc.gov/nczved/dfbmd/disease_listing/glanders_gi.html.  Accessed January 6, 2009.

Melioidosis General Information. Centers for Disease Control and Prevention. http://www.cdc.gov/nczved/dfbmd/disease_listing/melioidosis_gi.html. Accessed January 6, 2009.