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Glanders is a contagious
zoonotic A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
infectious disease An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
that occurs primarily in
horse The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million y ...
s, mules, and
donkey The domestic donkey is a hoofed mammal in the family Equidae, the same family as the horse. It derives from the African wild ass, ''Equus africanus'', and may be classified either as a subspecies thereof, ''Equus africanus asinus'', or as a ...
s. It can be contracted by other animals, such as dogs, cats, pigs, goats, and humans. It is caused by infection with the
bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
''
Burkholderia mallei ''Burkholderia mallei'' is a Gram-negative, bipolar, aerobic bacterium, a human and animal pathogen of genus ''Burkholderia'' causing glanders; the Latin name of this disease (''malleus'') gave its name to the species causing it. It is closely re ...
''. Glanders is endemic in Africa, Asia, the Middle East, and Central and South America. It has been eradicated from North America, Australia, and most of Europe through surveillance and destruction of affected animals, and import restrictions. Glanders has not been reported in the United States since 1945, except in 2000, when an American lab researcher had an accidental exposure in the lab. It is a
notifiable disease A notifiable disease is any disease that is required by law to be reported to government authorities. The collation of information allows the authorities to monitor the disease, and provides early warning of possible outbreaks. In the case of live ...
in the UK, although it has not been reported there since 1928. The term is from
Middle English Middle English (abbreviated to ME) is a form of the English language that was spoken after the Norman conquest of 1066, until the late 15th century. The English language underwent distinct variations and developments following the Old English p ...
' or
Old French Old French (, , ; Modern French: ) was the language spoken in most of the northern half of France from approximately the 8th to the 14th centuries. Rather than a unified language, Old French was a linkage of Romance dialects, mutually intelligib ...
', both meaning glands. Other terms include la, malleus, es, muermo, german: Rotz and no, snive.


Presentation

Signs of glanders include the formation of nodular
lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...
s in the lungs and
ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
ation of the
mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
s in the
upper respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to th ...
. The acute form results in coughing, fever, and the release of an infectious nasal discharge, followed by
septicaemia Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
and death within days. In the chronic form, nasal and subcutaneous nodules develop, eventually ulcerating; death can occur within months, while survivors act as carriers.


Cause and transmission

Glanders is caused by infection with the ''Burkholderia mallei'', usually by ingestion of
contaminated Contamination is the presence of a constituent, impurity, or some other undesirable element that spoils, corrupts, infects, makes unfit, or makes inferior a material, physical body, natural environment, workplace, etc. Types of contamination ...
feed or water. ''B. mallei'' is able to infect humans, so it is classed as a
zoonotic A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
agent. Transmission occurs by direct contact with infected animal's body fluid and tissues and entry is through skin abrasions, nasal and oral mucosal surfaces, or inhalation.


Diagnosis

The
mallein test The mallein test is a sensitive and specific clinical test for glanders, a common bacterial disease of equids (horses, donkeys, mules). This test is an allergic hypersensitivity test used as a diagnosis for glanders. It is caused by a bacterium c ...
is a sensitive and specific clinical test for glanders. Mallein (
ATCvet The Anatomical Therapeutic Chemical (ATC) Classification System is a drug classification system that classifies the active ingredients of drugs according to the organ or system on which they act and their therapeutic, pharmacological and chemical ...
code: ), a protein fraction of the glanders organism (''B. mallei''), is injected intradermopalpebrally or given by eye drop. In infected animals, the eyelid swells markedly in 1 to 2 days.


Historical cases and potential use in war

Glanders has been known since antiquity, with a description by Hippocrates around 425 BCE. However, historian Lise Wilkinson has described the incredible difficulty of studying outbreaks of glanders in history. From the Middle Ages to the 1900s, glanders was a significant threat to armies. Before the
Battle of Blenheim The Battle of Blenheim (german: Zweite Schlacht bei Höchstädt, link=no; french: Bataille de Höchstädt, link=no; nl, Slag bij Blenheim, link=no) fought on , was a major battle of the War of the Spanish Succession. The overwhelming Allied v ...
in 1704, glanders may have afflicted and greatly diminished the horses of Marshal Tallard's cavalry, helping the Duke of Marlborough win the battle. Glanders was a significant problem for civilian use of horses, as well. In the 18th-century veterinary hospital at the
École Nationale Vétérinaire d'Alfort The National veterinary school of Alfort ( or ''ENVA'') is a French public institution of scientific research and higher education in veterinary medicine, located in Maisons-Alfort, Val-de-Marne, close to Paris. It is operated under the superv ...
, glanders was the most common disease among their equine patients and the one most likely to cause death. Due to the high mortality rate in humans and the small number of organisms required to establish infection, ''B. mallei'' is regarded as a potential
biological warfare Biological warfare, also known as germ warfare, is the use of biological toxins or infectious agents such as bacteria, viruses, insects, and fungi with the intent to kill, harm or incapacitate humans, animals or plants as an act of war. Bio ...
or
bioterrorism Bioterrorism is terrorism involving the intentional release or dissemination of biological agents. These agents are bacteria, viruses, insects, fungi, and/or toxins, and may be in a naturally occurring or a human-modified form, in much the same ...
agent, as is the closely related organism, ''B. pseudomallei'', the causative agent of
melioidosis Melioidosis is an infectious disease caused by a gram-negative bacterium called ''Burkholderia pseudomallei''. Most people exposed to ''B. pseudomallei'' experience no symptoms; however, those who do experience symptoms have signs and symptoms t ...
. During
World War I World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, the United States, and the Ottoman Empire, with fightin ...
, glanders was believed to have been spread deliberately by
German German(s) may refer to: * Germany (of or related to) ** Germania (historical use) * Germans, citizens of Germany, people of German ancestry, or native speakers of the German language ** For citizens of Germany, see also German nationality law **Ge ...
agents to infect large numbers of
Russian Russian(s) refers to anything related to Russia, including: *Russians (, ''russkiye''), an ethnic group of the East Slavic peoples, primarily living in Russia and neighboring countries *Rossiyane (), Russian language term for all citizens and peo ...
horses and mules on the Eastern Front. Other agents attempted to introduce the disease in the United States and Argentina. 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
Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
ese deliberately infected horses, civilians, and prisoners of war with ''B. mallei'' at the
Unit 731 , short for Manshu Detachment 731 and also known as the Kamo Detachment and Ishii Unit, was a covert Biological warfare, biological and chemical warfare research and development unit of the Imperial Japanese Army that engaged in unethical h ...
Pingfang Pingfang District () is one of nine districts of the prefecture-level city of Harbin, the capital of Heilongjiang Province, Northeast China, forming part of the city's urban core. The least spacious of Harbin's county-level divisions, it borde ...
(China) Institute and
Unit 100 was an Imperial Japanese Army facility called the Kwantung Army Warhorse Disease Prevention Shop that focused on the development of biological weapons during World War II. It was operated by the Kempeitai, the Japanese military police. Its hea ...
facilities during
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...
. The U.S. studied this agent as a possible biological weapon in 1943–44, but did not weaponize it. U.S. interest in glanders (agent LA) continued through the 1950s, except it had an inexplicable tendency to lose virulence in the lab, making it difficult to weaponize. Between 1982 and 1984, the
Soviet Union The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, it was nominally a federal union of fifteen national ...
allegedly used weaponized ''B. mallei'' during the
Soviet–Afghan War The Soviet–Afghan War was a protracted armed conflict fought in the Democratic Republic of Afghanistan from 1979 to 1989. It saw extensive fighting between the Soviet Union and the Afghan mujahideen (alongside smaller groups of anti-Soviet ...
.


Vaccine research

No vaccine is licensed for use in the U.S. Infection with these bacteria results in nonspecific symptoms and can be either acute or chronic, impeding rapid diagnosis. The lack of a vaccine for either bacterium also makes them potential candidates for bioweaponization. Together, with their high rate of infectivity by aerosols and resistance to many common antibiotics, both bacteria have been classified as category B priority pathogens by the US NIH and US CDC, which has spurred a dramatic increase in interest in these microorganisms. Attempts have been made to develop vaccines for these infections, which would not only benefit military personnel, a group most likely to be targeted in an intentional release, but also individuals who may come in contact with glanders-infected animals or live in areas where melioidosis is endemic.


References


External links


CDC list of articles on glanders

Current status of Glanders worldwide
at OIE. WAHID Interface - OIE World Animal Health Information Database
Disease card





Burkholderia mallei
genomes and related information a
PATRIC
a Bioinformatics Resource Center funded b
NIAID

Notes On Glander Disease in Horse
{{Authority control Bacterium-related cutaneous conditions Biological anti-agriculture weapons Biological weapons Horse diseases Zoonotic bacterial diseases