Glanders has been long known as a highly contagious and frequently fatal infection of solipeds - horses, donkeys, and mules [1] [2]. Since its initial description, it has been discovered that the causative agent is Burkholderia mallei, a nonmotile gram-negative bacterial microorganism [1]. The majority of infections occurred after direct contact with infected animals, either through abrasions and breaks in the skin, inoculation onto mucosal surfaces (conjunctiva or the oral cavity), or by inhalation, and its highly contagious properties resulted in its classification as a biological weapon (category B) by the Center for Disease Control and Prevention (CDC) [1] [3]. Glanders is now very rarely diagnosed in the Western world because of large efforts to eradicate this bacterial pathogen through euthanizing infected animal hosts [1] [4], and only a few cases were reported in the past century, including a laboratory-acquired case in the United States [5]. However, cases have been reported from other continents, and a number of clinical manifestations are documented [1] [5] [6]. After a highly variable incubation period (several days to a few months), the first clinical symptoms start to appear [1]. Cough, chest pain, tachypnea, and dyspnea, often accompanied by high fever, chills, night sweats, headaches, vomiting, nausea, tachycardia, and fatigue in the case of pulmonary infections, are considered as the most severe form [1]. A papular erosion arising at the site of B. mallei entry with local inflammation and swelling is the main feature of cutaneous glanders, whereas photophobia, excessive lacrimation, nasal discharge, facial swelling, lymphadenopathy and progression to a pulmonary infection are hallmarks of a conjunctival or ocular infection [1]. Finally, disseminated infections and septicemia may develop [1].

• Fever

  Chest pain, cough, fever, headache, loss of appetite, and muscle pain are common. The lung infection can become chronic and may be mistaken for tuberculosis. [dermnetnz.org]

  Inhalational exposure results in a pneumonic presentation with fever, which can progress to ulceration and necrosis of the airways. [web.archive.org]

  The acute disease is characterized by papule at the site of inoculation, followed by bacteremia with severe prostration, fever, vomiting, and generalized pain. [histopathology-india.net]

  Viral Hemorrhagic Fevers Viral hemorrhagic fevers are caused by four families of viruses. [emedicinehealth.com]

• Chills

  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. [web.archive.org]

  Weapon Range: 9 Requires Level 66, 212 Str 15% reduced Enemy Stun Threshold Adds (5-10) to (15-23) Physical Damage (150-200)% increased Physical Damage (15-25)% reduced Enemy Stun Threshold with this Weapon Cannot Knock Enemies Back All Attack Damage Chills [pathofexile.gamepedia.com]

  Cough, chest pain, tachypnea, and dyspnea, often accompanied by high fever, chills, night sweats, headaches, vomiting, nausea, tachycardia, and fatigue in the case of pulmonary infections, are considered as the most severe form. [symptoma.com]

• Veterinarian

  TODAY, GLANDERS is a disease rarely heard of in Western Europe, Britain, and North America; but a hundred years ago the annual total of cases of glanders in the horse, published by the Board of Agriculture, exceeded 2,000,1 and British veterinarians were [pdfs.semanticscholar.org]

  Veterinarians diagnose glanders using serology (blood) or Mallein tests. [thehorse.com]

  Chapman Hopkins who had been involved in a similar case of an Irish racehorse last Christmas to help get U.S. government veterinarians to conduct the different tests that found the horse negative for glanders. [dressage-news.com]

  Glanders is a recognized occupational risk for veterinarians, equine butchers, stable hands and laboratory workers. [histopathology-india.net]

• Rigor

  Prevention and control depend on early detection and elimination of affected animals, as well as complete quarantine and rigorous disinfection of the area involved. [msdvetmanual.com]

  Dani Inkpen, Yvan Prkachin, Avi Kelman and Carol De Rose have proven to be especially generous and rigorous readers. I am indebted to Lucas Mueller and Jolien de Vuyst for discussions about the nuances of German and Dutch. [doi.org]

  Constitutional symptoms often accompany the infection, with fever, rigors, and malaise predominating. If the infection is left untreated, abscesses in the lymph nodes will generally form, then break down and drain. [nejm.org]

  However, rigorous examination regarding the rarity of transmission has not been conducted. [ojrd.biomedcentral.com]

• Malaise

  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. [web.archive.org]

  Constitutional symptoms-which include malaise, fever, chills, and fatigue-are common at the onset, and then, depending on the method of infection, more specific symptoms may follow. [centerforhealthsecurity.org]

  Constitutional symptoms often accompany the infection, with fever, rigors, and malaise predominating. If the infection is left untreated, abscesses in the lymph nodes will generally form, then break down and drain. [nejm.org]

  Clinical signs of chronic glanders in horses include: Coughing; Malaise; Weight loss; Intermittent fever; Possible thick nasal discharge, usually out of one nostril; Ulcers and nodules on the nasal mucosa; Enlarged submaxillary lymph nodes; Chronic enlargement [thehorse.com]

• Diarrhea

  They develop respiratory distress, headaches, fever, diarrhea, pus-filled lesions on the skin, and abscesses throughout the body. Septicemia may be overwhelming, with a 90% fatality rate and death occurring within 24-48 hours. [emedicine.com]

  When the bacteria get into the blood, symptoms include fever, chills, muscle aches, chest pain, skin rash, diarrhea or enlargement of the liver and/or spleen. Some people have symptoms that come and go over a long period of time. [vdh.virginia.gov]

• Nausea

  Cough, chest pain, tachypnea, and dyspnea, often accompanied by high fever, chills, night sweats, headaches, vomiting, nausea, tachycardia, and fatigue in the case of pulmonary infections, are considered as the most severe form. [symptoma.com]

  At low doses, injection exposures produce flulike symptoms, body aches, nausea, vomiting, and localized pain and swelling at the injection site. [emedicinehealth.com]

  Nonspecific signs, such as dizziness, rigors, myalgia, nausea, night sweats, severe headache, tachycardia, weight loss, and mucosal eruptions are also usually present and may indicate a disseminated infection[ 9 ]. [doi.org]

• Myalgia

  Development of constitutional symptoms such as fever, rigors, myalgias, fatigue, headache, severe malaise, and pleuritic chest pain [ 22 ]. 2. [doi.org]

  Symptoms Symptoms include: Fever Rigors Night sweats Myalgia Anorexia Headache Depending upon the route of infection there may also be: Chest pain Cough Photophobia Lacrimation Diarrhoea Signs Examination may show: Fever Cervical lymphadenopathy Papular [patient.info]

  Symptoms in humans include low-grade fever and chills, malaise, fatigue, myalgias, backache, headache, rigors, chest pain and lymphadenopathy. [scialert.net]

  Patients with typhoidal disease can have fever, chills, anorexia, abdominal pain, diarrhea, headache, myalgias, sore throat, and cough. Patients with pneumonic tularemia have mostly pulmonary findings. [emedicinehealth.com]

• Photophobia

  A papular erosion arising at the site of B. mallei entry with local inflammation and swelling is the main feature of cutaneous glanders, whereas photophobia, excessive lacrimation, nasal discharge, facial swelling, lymphadenopathy and progression to a [symptoma.com]

  Symptoms Symptoms include: Fever Rigors Night sweats Myalgia Anorexia Headache Depending upon the route of infection there may also be: Chest pain Cough Photophobia Lacrimation Diarrhoea Signs Examination may show: Fever Cervical lymphadenopathy Papular [patient.info]

  Mucosal involvement Involvement of the eye and conjunctiva in a B. mallei infection presents with excessive lacrimation and photophobia. [doi.org]

  Others may be excessive lacrimation, photophobia, inflammation/swelling of the nose, copious nasal discharge, facial swelling and pneumonic signs of bronchitis with cough and mucopurulent sputum, dyspnea. [scialert.net]

• Lacrimation

  A papular erosion arising at the site of B. mallei entry with local inflammation and swelling is the main feature of cutaneous glanders, whereas photophobia, excessive lacrimation, nasal discharge, facial swelling, lymphadenopathy and progression to a [symptoma.com]

  Symptoms Symptoms include: Fever Rigors Night sweats Myalgia Anorexia Headache Depending upon the route of infection there may also be: Chest pain Cough Photophobia Lacrimation Diarrhoea Signs Examination may show: Fever Cervical lymphadenopathy Papular [patient.info]

  Mucosal involvement Involvement of the eye and conjunctiva in a B. mallei infection presents with excessive lacrimation and photophobia. [doi.org]

  Others may be excessive lacrimation, photophobia, inflammation/swelling of the nose, copious nasal discharge, facial swelling and pneumonic signs of bronchitis with cough and mucopurulent sputum, dyspnea. [scialert.net]

• Ulcer

  Post-mortem The skin may show ulcers if farcy has been present. There may be ulceration of the throat and air passages. The most constant changes are, however, found in the lungs. [web.archive.org]

  The nodules degenerate into deep ulcers with raised irregular borders. Characteristic star-shaped cicatrices remain after the ulcers heal. [msdvetmanual.com]

  The disease is characterised by the formation of nodular lesions in the lung and other internal organs and ulcerations of the mucous membrane at the upper respiratory tract. [daera-ni.gov.uk]

• Sweating

  Cough, chest pain, tachypnea, and dyspnea, often accompanied by high fever, chills, night sweats, headaches, vomiting, nausea, tachycardia, and fatigue in the case of pulmonary infections, are considered as the most severe form. [symptoma.com]

  Common symptoms of glanders include fever with chills and sweating, muscle aches, chest pain, muscle tightness, and headache. Additional symptoms may include excessive tearing of the eyes, light sensitivity, ulcers, and diarrhea (loose stool/poop). [health.ny.gov]

  Symptoms Symptoms include: Fever Rigors Night sweats Myalgia Anorexia Headache Depending upon the route of infection there may also be: Chest pain Cough Photophobia Lacrimation Diarrhoea Signs Examination may show: Fever Cervical lymphadenopathy Papular [patient.info]

  During the next few weeks, the patient had increasing fatigue, night sweats, malaise, rigors, and weight loss. Figure 1. Figure 1. Pretreatment (Panel A) and Post-Treatment (Panel B) Abdominal Computed Tomographic Scans from a Patient with Glanders. [nejm.org]

  Abortion in pregnant mares Rapid dehydration Droopy ears and half closed eyes Dyspnea at terminal stages Subacute form An acute onset of disease and subsequent recovery Swollen icteric conjunctivae Exertion may cause an increase in temperature and pulse, sweating [fao.org]

• Skin Ulcer

  Skin infections : Usually within a few days, skin ulcers and abscesses (large collections or pockets of pus under the skin or in deeper tissues) may form at the site where bacteria entered the skin. Swollen lymph glands may also occur. [www1.nyc.gov]

  Transmitted on fomites or by direct contact with infected animals → ingested or inhaled organisms or contamination of skin abrasions → localizes in skin, lung, nasal mucosa, other organs → acute, usually fatal, bronchopneumonia or chronic cutaneous ulcerations [vetstream.com]

  It has varied clinical presentations, including asymptomatic infection, localized skin ulcers/ abscesses, chronic pneumonia, and fulminant septic shock with abscesses in multiple internal organs. [web.archive.org]

  It has varied clinical presentations, including asymptomatic infection, localized skin ulcers/abscesses, chronic pneumonia, and fulminant septic shock with abscesses in multiple internal organs. [centerforhealthsecurity.org]

• Cutaneous Manifestation

  Consider also: Anthrax Plague Other causes of pneumonia Recognition of cutaneous manifestations may be very important, especially in identifying biological attack. [ 8 ] Investigations [ 3 ] The diagnosis is inevitably a challenge: FBC shows a mild leukocytosis [patient.info]

  Cutaneous involvement Cutaneous manifestations include papular lesions that may erupt anywhere on the body with a more chronic, indolent course of infection. [doi.org]

• Headache

  Chest pain, cough, fever, headache, loss of appetite, and muscle pain are common. The lung infection can become chronic and may be mistaken for tuberculosis. [dermnetnz.org]

  Fever, chills, headache, tiredness and muscle aches are common. Infections can be spread to the eyes by rubbing them with contaminated fingers. Pulmonary (lung) infections : Lung infections cause fever, muscle aches, headache, chest pain and cough. [www1.nyc.gov]

  They develop respiratory distress, headaches, fever, diarrhea, pus-filled lesions on the skin, and abscesses throughout the body. Septicemia may be overwhelming, with a 90% fatality rate and death occurring within 24-48 hours. [emedicine.com]

  Cough, chest pain, tachypnea, and dyspnea, often accompanied by high fever, chills, night sweats, headaches, vomiting, nausea, tachycardia, and fatigue in the case of pulmonary infections, are considered as the most severe form. [symptoma.com]

The diagnosis of glanders might be quite difficult due to the nonspecific clinical presentation and rarity of the condition in clinical practice. For this reason, the physician should obtain a meticulous patient history during which recent contact with animal hosts (horses, donkeys, and mules) can provide crucial information. The physical examination, although essential for the assessment of the patient's general condition and observation of symptoms that may point to the tissue affected by the infection, will rarely reveal findings that are specific for glanders. Radiographic studies that have been performed in patients who suffered from this infection - ultrasonography and computed tomography (CT), discovered multiple abscesses in different organs (spleen, liver, lungs), but in order to make a definite diagnosis, microbiological identification is necessary [1] [5]. Specific tests for B. mallei are yet to be designed, which is why serological studies (complement fixation tests and indirect hemagglutination assays) are described as somewhat useful in recognizing glanders [1] [7]. Some studies, however, advocate the use of polymerase chain reaction (PCR) as a superior method for detection of B. mallei, although only animal subjects have been evaluated through this method so far [1] [2] [8].

Oral Treatment There are very few reported studies of oral treatment in non-severe melioidosis. Much of the current knowledge stems from studies of oral maintenance therapy (See Maintenance Treatment section below). [antimicrobe.org]

Glanders is a very painful disease and can lead to death without treatment. [vahorsevet.com]

Additionally, we outline current treatment regimens and propose a clinical definition of human pulmonary glanders infection. [ncbi.nlm.nih.gov]

The psychiatrist who diagnosed Morva considered his prognosis for successful treatment to be “very promising,” in part because Morva’s older brother was successfully treated for a psychotic disorder when he was around Morva's current age. [deathpenaltyinfo.org]

Prognosis [ 1 ] Untreated, the death rate for melioidosis with septicaemia approaches 100%. [patient.info]

Abstract Burkholderia mallei, the etiologic agent of the disease known as glanders, is primarily a disease affecting horses and is transmitted to humans by direct contact with infected animals. [ncbi.nlm.nih.gov]

Pathogenesis Etiology Non spore-forming gram-negative bacillus bacteria Burkholderia mallei Burkholderia mallei. Must be differentiated from Burkholderia pseudomallei infection (melioidosis) on culture as clinical signs are similar. [vetstream.com]

B. mallei, the etiological agent of glanders, is a Gram-negative, non-motile, facultative intracellular pathogen. [doi.org]

Here, we present a literature review of human glanders in which we discuss the clinical epidemiology and risk factors, potential routes of exposure, symptoms, the incubation period, and specific diagnostics. [ncbi.nlm.nih.gov]

Due to its rareness, little is known about outbreak dynamics of the disease and its epidemiology. [journals.plos.org]

Munich, Germany 3 Institute for Veterinary Pathology, University of Munich, Veterinaerstrasse 13, D-80539 Munich, Germany Institute for Veterinary Pathology, University of Munich, Veterinaerstrasse 13, D-80539 Munich, Germany Abstract In the course of an epidemiological [veterinaryrecord.bmj.com]

Europe's journal on infectious disease surveillance, epidemiology, prevention and control Home Eurosurveillance Volume 10, Issue 3, 01/Mar/2005 Article Letter to the Editor Open Access http://instance.metastore.ingenta.com/content/10.2807/esm.10.03.00528 [eurosurveillance.org]

Pathophysiology Contagious disease caused by gram-negative bacillus Burkholderia mallei Pseudomonas spp. [vetstream.com]

Melioidosis: Epidemiology, Pathophysiology, and Management. Clin Micro Rev 2005;18(2):383-416. DOI: 10.1128/CMR.18.2.383-416.2005. PubMed. PMC Central. Journal. [dermnetnz.org]

Melioidosis: Epidemiology, pathophysiology and management. Clin Microbiol Rev 2005; 18: 383-416. [PubMed] 1 9. [antimicrobe.org]

What can be done to prevent the spread of glanders? There is no vaccine available for glanders. [health.ny.gov]

NIH-funded research has greatly increased knowledge of asthma and led to better treatment and prevention options. Director, Dr. Anthony S. Fauci NIAID Offices, Divisions & Centers [niaid.nih.gov]

How can glanders be prevented? There is no vaccine for glanders. In countries where glanders is common in animals, prevention of the disease in humans involves identifying and eliminating the infection in animals. [vdh.virginia.gov]

Centers for Disease Control and Prevention. http://www.cdc.gov/nczved/dfbmd/disease_listing/melioidosis_gi.html. Accessed January 6, 2009. [web.archive.org]

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7. Tiyawisutsri R. et al. Antibodies from patients with melioidosis recognize Burkholderia mallei but not Burkholderia thailandensis antigens in the indirect hemagglutination assay. J Clin Microbiol. 2005;43(9):4872–4874.
8. Tomaso H. et al. Development of a 5′-nuclease real-time PCR assay targeting fliP for the rapid identification of Burkholderia mallei in clinical samples. Clin Chem. 2006;52(2):307–310.