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Glanders

FARCY

Glanders is a term describing a highly contagious and life-threatening infection caused by Burkholderia mallei. Because of its potential use as a biological weapon, vast efforts have been made to limit the possibility of human infection, but rare cases have been described in the past several decades. Many tissues can be infected by glanders, including the mucosal surfaces, the lungs, and the skin, while systemic infections and sepsis might also develop. Clinical findings and microbiological studies are necessary for the diagnosis.


Presentation

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]
  • 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]
  • 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]
  • 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]
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]
  • Development of constitutional symptoms such as fever, rigors, myalgias, fatigue, headache, severe malaise, and pleuritic chest pain [ 22 ]. 2.[doi.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]
  • Development of constitutional symptoms such as fever, rigors, myalgias, fatigue, headache, severe malaise, and pleuritic chest pain [ 22 ]. 2.[doi.org]
Prisoner of War
  • The Japanese deliberately infected horses, civilians, and prisoners of war with B. mallei at the Unit 731 Pingfang (China) Institute and Unit 100 facilities during World War II.[en.wikipedia.org]
  • Cutaneous melioidosis in a man who was taken as a prisoner of war by the Japanese during World War II. J. Clin. Microbiol. 43:970–972. PubMed CrossRef Google Scholar Nierman, W.C., DeShazer, D., Kim, H.S., et al. (2004).[doi.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]
Sore Throat
  • 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]
Pharyngitis
  • Attachment of Burkholderia pseudomallei to pharyngeal epithelial cells: a highly pathogenic bacteria with low attachment ability. Am. J. Trop. Med. Hyg. 60:90–93. PubMed Google Scholar Alibek, K., and Handelman, S. (1999). Biohazard.[doi.org]
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]
  • Mucosal involvement Involvement of the eye and conjunctiva in a B. mallei infection presents with excessive lacrimation and photophobia.[doi.org]
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]
Skin Ulcer
  • 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]
Night Sweats
  • 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, 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]
Cutaneous Manifestation
  • Cutaneous involvement Cutaneous manifestations include papular lesions that may erupt anywhere on the body with a more chronic, indolent course of infection.[doi.org]
Cutaneous Manifestation
  • 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]
Facial Swelling
  • 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]
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]
  • 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]
  • 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]

Workup

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]

Treatment

  • Additionally, we outline current treatment regimens and propose a clinical definition of human pulmonary glanders infection.[ncbi.nlm.nih.gov]
  • All treatment recommendations should be adapted according to the susceptibility reports from any isolates obtained. Post-exposure prophylaxis with trimethoprim-sulfamethoxazole is recommended in case of a biological attack.[ncbi.nlm.nih.gov]
  • Please consult your own licensed physician regarding diagnosis and treatment of any medical condition! Please see also our disclaimer . This site complies with the HONcode standard for health information: verify here . Database updated 2019-02-19.[diseasesdatabase.com]
  • Control is based on the application of general disease control measures and attempts at vaccination and treatment. A study of these procedures enables a comparison of their efficacy and a description of the major steps in their implementation.[ncbi.nlm.nih.gov]

Prognosis

  • 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]

Etiology

  • 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]
  • Abstract Burkholderia pseudomallei and Burkholderia mallei are the etiologic agents of melioidosis and glanders, respectively.[ncbi.nlm.nih.gov]
  • B. mallei, the etiological agent of glanders, is a Gram-negative, non-motile, facultative intracellular pathogen.[doi.org]
  • B. mallei, the etiologic agent of glanders, has come under renewed scientific investigation as a result of recent concerns about its past and potential future use as a biological weapon.[ncbi.nlm.nih.gov]

Epidemiology

  • 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]
  • Genomic and epidemiological studies have shown that B. mallei is a recently emerged, host restricted clone of B. pseudomallei.[ncbi.nlm.nih.gov]
  • 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 Like 0 This item has no PDF Download A C Cheng 1,2 , D A B Dance 3[eurosurveillance.org]
  • This contrasts starkly with our lack of understanding of many aspects of their ecology, epidemiology, and the clinical diseases that they cause.[doi.org]
  • 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]
Sex distribution
Age distribution

Pathophysiology

  • 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]

Prevention

  • 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]
  • 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]
  • As an immediate preventive measure, the government has ordered blood samples of all horses in the district to be taken for examination, as also of one per cent of horses from other parts of the state.[indianexpress.com]
  • […] 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[symptoma.com]

References

Article

  1. Van Zandt KE, Greer MT, Gelhaus HC. Glanders: an overview of infection in humans. Orphanet J Rare Dis. 2013;8:131.
  2. Neubauer H. et al. Serodiagnosis of Burkholderia mallei infections in horses: state-of-the-art and perspectives. J Vet Med B Infect Dis Vet Public Health. 2005;52(5):201–205.
  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.
  5. Srinivasan A. et al. Glanders in a military research microbiologist. N Engl J Med. 2001;345(4):256–258.
  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.

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Last updated: 2019-07-11 22:45