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].

• Axillary Lymphadenopathy

  The clinical manifestation of unilateral axillary lymphadenopathy in this patient was consistent with percutaneous infection. [doi.org]

• Fever

  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]

  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]

  Symptoms of lung infection include cough, fever, shortness of breath, or lung abscesses. 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. [vdh.virginia.gov]

• 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]

  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]

  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]

• Constitutional Symptom

  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]

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

• Vietnamese

  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. [web.archive.org]

  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. [centerforhealthsecurity.org]

  The name melioidosis (also known as Whitmore disease, Rangoon beggar’s disease, Vietnamese time bomb) is a combination of Greek words “melis” meaning distemper of assess and “eidos” meaning resembles glanders. [antimicrobe.org]

• Pleural Effusion

  • May result in pneumonia, pulmonary abscesses, and pleural effusions. Septicemic • Systemic infection in the bloodstream. • Following sudden onset of symptoms, death occurs within 7-10 days. [web.archive.org]

  Pneumonia, pulmonary abscesses, and pleural effusions can occur. The incubation period is 10-14 days. With inhalational melioidosis, cutaneous abscesses may develop and take months to appear. [emedicine.com]

  effusions Cutaneous abscesses may develop and take months to appear Septicemic Systemic infection in the bloodstream Death occurs within 7 to 10 days of onset of symptoms Chronic Asymptomatic Flare-ups and remissions occur over the course of years The [centerforhealthsecurity.org]

• Tachypnea

  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]

  Nonspecific signs and symptoms such as fatigue, fever (often exceeding 102 F), chills, headache, myalgias, lymphangitis, sore throat, pleuritic chest pain, cough, tachypnea, dyspnea, discharge, and gastrointestinal signs often accompany respiratory infections [doi.org]

• Sputum Production

  Infection may also extend lower in the respiratory tract, resulting in bronchitis which can be accompanied by cough and mucopurulent sputum production. [doi.org]

• Back Pain

  Different species of the organism can cause different symptoms from skin sores to low back pain to liver disease. [emedicinehealth.com]

• 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]

• Eye Swelling

  A small dose (0.1ml) of antigen is injected in the tissue below the eye. Swelling at the injection site, often with a high temperature, often indicates a potential carrier state, and can be an aid to field diagnosis. [web.archive.org]

• Swelling of Eyelid

  Positive reaction is marked oedematous swelling on eyelid with blepharospasm and severe purulent conjunctivitis • The ophthalmic test: Less reliable in comparison to intradermo-palpebral test. [scialert.net]

• Skin Ulcer

  Signs : acute respiratory disease especially in donkeys and mules, or chronic skin ulcerations/nodules particularly in horses; some animals may be asymptomatic carriers. Diagnosis : Mallein test and bacterial culture of pus from nodules. [vetstream.com]

  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]

  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]

• Subcutaneous Nodule

  In the chronic form, nasal and subcutaneous nodules develop, eventually ulcerating. Death can occur within months, while survivors act as carriers. Glanders is endemic in Africa, Asia, the Middle East, and Central and South America. [en.wikipedia.org]

  In skin form, there is subcutaneous nodules (1-2 cm in diameter) which ulcerate and discharge pus like dark honey. Thickened fistulous lymphatics radiate from the lesions and connect one to the other. [scialert.net]

• Chronic Abscess

  abscesses in stellate (starlike) or honeycomb patterns; and Multiple small abscesses in the lung and/or abscesses in the liver or spleen. [thehorse.com]

• 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]

  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]

  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]

  Incubation period before symptoms 1-14 days Symptoms General symptoms: fever and headaches muscle aches, muscle tightness, chest pain Other symptoms vary according to how the organism enters the body—through the skin, eyes, nose, or respiratory tract—but [pbs.org]

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].

• Cavitary Lesion

  May also exhibit cavitary lesions or abscesses not only in the lungs but virtually any remote sites such as spleen, liver, subcutaneous tissue and muscle. 3. [doi.org]

• Pleural Effusion

  • May result in pneumonia, pulmonary abscesses, and pleural effusions. Septicemic • Systemic infection in the bloodstream. • Following sudden onset of symptoms, death occurs within 7-10 days. [web.archive.org]

  Pneumonia, pulmonary abscesses, and pleural effusions can occur. The incubation period is 10-14 days. With inhalational melioidosis, cutaneous abscesses may develop and take months to appear. [emedicine.com]

  effusions Cutaneous abscesses may develop and take months to appear Septicemic Systemic infection in the bloodstream Death occurs within 7 to 10 days of onset of symptoms Chronic Asymptomatic Flare-ups and remissions occur over the course of years The [centerforhealthsecurity.org]

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

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]

The adenopathy and fever persisted despite treatment for 10 days with a first-generation cephalosporin. An evaluation after this treatment, which included chest radiography as well as cultures of blood and urine, was unrevealing. [nejm.org]

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

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]

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]

Genomic and epidemiological studies have shown that B. mallei is a recently emerged, host restricted clone of B. pseudomallei. [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]

Epidemiological studies – ie. the ‘how’ of the infection – are continuing by unnamed German authorities, and if the FLI have any leads on these, their PR machine is keeping mum. [horsemagazine.com]

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]

Centers for Disease Control and Prevention. . Accessed January 6, 2009. Melioidosis General Information. Centers for Disease Control and Prevention. . Accessed January 6, 2009. [web.archive.org]

The potential malicious use of these organisms has accelerated the investigation of new ways to prevent and to treat the diseases. [ncbi.nlm.nih.gov]

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

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3. Waag DM, England MJ, DeShazer D. Humoral Immune Responses in a Human Case of Glanders. Clin Vaccine Immunol. 2012;19(5):814-816.
4. Derbyshire B. The eradication of glanders in Canada. Can Vet J. 2002;43(9):722-726.
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6. Whitlock GC, Estes DM, Torres AG. Glanders: off to the races with Burkholderia mallei. FEMS Microbiol Lett. 2007;277(2):115–122.
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.