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Glanders and Melioidosis

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Last Update: August 14, 2023.

Continuing Education Activity

Glanders and melioidosis are infectious diseases caused by Burkholderia mallei and Burkholderia pseudomallei, respectively. Glanders has been eliminated from the United States but is still present in Africa, Asia, the Middle East, Central America, and South America. Melioidosis is endemic to southeast Asia and northern Australia but has also occurred in South America, Central America, Africa, and the Middle East. In humans, the first symptom of glanders is usually fever, followed by pneumonia, pustules, and abscesses. The acute form of the disease usually is fatal within 7 to 10 days of onset, though chronic glanders does occur. The incubation period of melioidosis can be highly variable, ranging from 2 days to several years. Symptoms of acute melioidosis include fever, cough, pleurisy, arthralgia, myalgia, headache, anorexia, and night sweats. However, melioidosis can occur acutely or chronically, and presentation is highly variable, ranging from localized infections to abscesses of the liver, spleen, prostate, or parotid glands to sepsis. This activity reviews the evaluation and management of glanders and melioidosis infections and highlights the role of the interprofessional team in the recognition and management of these conditions.

Objectives:

  • Describe the epidemiology of glanders and melioidosis infections.
  • Outline the presentation of patients with glanders and melioidosis infections.
  • Explain the management of patients with glanders and melioidosis infections.
  • Review the importance of improving care coordination amongst the interprofessional team to enhance the delivery of care and improve outcomes for patients with glanders or melioidosis infections.
Access free multiple choice questions on this topic.

Introduction

Glanders is an infectious disease caused by Burkholderia mallei, a gram-negative aerobic nonmotile bacterium. Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a gram-negative aerobic, motile bacterium. The two bacteria are closely related, and both can cause disease in animals and humans. Historically, glanders was a common disease of horses, donkeys, and mules. Melioidosis was first described as a case series of 38 patients in Rangoon, Burma, by pathologist Alfred Whitmore in 1912.[1][2]

Etiology

Glanders is rare in humans, but those in close contact with infected solipeds such as horses, mules, and donkeys may become infected. The bacteria enter through the eyes, nose, mouth, or wounds in the skin. Burkholderia mallei is an obligate mammalian pathogen and must cause the disease to be transmitted between hosts. Melioidosis may present in an acute form with an incubation period of one day to three weeks. However, latent melioidosis may not present for decades. Melioidosis often infects those with underlying risk factors such as diabetes, kidney disease, alcohol abuse, and thalassemia, although healthy patients may also contract the disease. Burkholderia pseudomallei live in soil and water, and patients almost always report exposure to mud or pools of water.

Epidemiology

Glanders has been eliminated from the United States but is still present in Africa, Asia, the Middle East, Central America, and South America. Melioidosis is endemic to southeast Asia and northern Australia but has also occurred in South America, Central America, Africa, and the Middle East. In 2016, a statistical model estimated that there would be 165,000 new cases of melioidosis worldwide and suggested that the disease is significantly underreported. Because it resides in soil and water, weather events such as flooding and typhoons have been implicated in outbreaks of melioidosis. No vaccine is available for either disease. Humans may contract glanders from contact with infected animals; animals without clinical symptoms can still be infectious to humans. Glanders can be transmitted by contact with mucous membranes, inhalation, and contact with breaks in the skin. Person-to-person transmission is rare for both glanders and melioidosis but can occur.[3][4][5][6][7][8][9][10]

Pathophysiology

Burkholderia mallei and Burkholderia pseudomallei can enter cells and spread from cell to cell by polymerizing actin; this can lead to the fusion of cells and the formation of multinucleated giant cells. Both are resistant to a large number of antibiotics because of their ability to pump them out of the cell, and both possess type VI secretion systems. Burkholderia mallei cause damage to and death of endothelial cells lining blood vessels, which increases the likelihood of thrombi formation. Numerous virulence factors of Burkholderia pseudomallei have been described.[11][12][13][14]

Toxicokinetics

Burkholderia pseudomallei can produce both endotoxins and exotoxins. In addition, Burkholderia lethal toxin 1 has been shown to act on eukaryotic initiation factor 4A (eIF4A), halting its helicase activity on double-stranded RNA and thus inhibiting translation.

History and Physical

The incubation period of glanders is usually 1 to 21 days but can be months or years. In humans, the first symptom of glanders is usually fever, followed by pneumonia, pustules, and abscesses. The acute form of the disease usually is fatal within 7 to 10 days of onset. Chronic glanders does occur, which can cause death within months; survivors remain carriers of disease. The incubation period of melioidosis also can be highly variable; it may range from as little as 2 days to as long as several years. Symptoms of acute melioidosis include fever, cough, pleurisy, arthralgia, myalgia, headache, anorexia, and night sweats. Melioidosis may present in many ways, ranging from acute or chronic localized infections to sepsis. Abscesses of the liver, spleen, prostate, and parotid glands have been documented. Intra-abdominal infections may be present without focal abdominal pain. These abscesses often appear loculated on CT scans and have been described as having a “honeycomb” appearance. Chronic melioidosis is defined as a duration of symptoms longer than 2 months and occurs in 10% of patients.[15][16][17][18][19][20][21]

Evaluation

Both glanders and melioidosis can be cultured in a lab. Burkholderia pseudomallei can be diagnosed by blood culture, sputum culture, urine culture, and a throat swab; however, blood cultures are rarely positive in cases of Burkholderia mallei. Cultures of these diseases must be performed under BSL-3 precautions. Indirect hemagglutination, latex agglutination, and direct immunofluorescence tests are available in some countries. Diagnosis of melioidosis cannot be made by imaging; however, CT or ultrasound of the abdomen is recommended to assess for abscesses of the liver, spleen, or prostate that may not be clinically apparent. Chest X-ray is also routinely performed and may show consolidations, cavitary lesions, effusions, empyemas, and multiple lung abscesses.[22][23][24]

Treatment / Management

Patients with significant pulmonary involvement may progress to respiratory failure, requiring mechanical ventilation. Sepsis and coagulopathy also may occur. Treatment of glanders with imipenem and doxycycline for 2 weeks, followed by azithromycin and doxycycline for six months, was successful in a laboratory worker that became infected with the disease. A CT scan after this therapy showed improvement of splenic and hepatic abscesses. 

Glanders is fatal in 95% of cases without treatment, and death occurs within 7 to 10 days of onset. Mortality is 50% with appropriate antibiotic treatment. Mortality of the septicemic form of melioidosis exceeds 90%, but mortality may decrease to as low as 10% in uncomplicated cases managed with appropriate antibiotic therapy. 

Surgical management of prostatic abscesses and septic arthritis caused by melioidosis is indicated; however, surgical intervention often is not indicated for hepatic and splenic abscesses. The treatment of choice for acute melioidosis is intravenous ceftazidime. Meropenem and imipenem also have been shown to be effective. In the acute phase of the disease, patients are treated with intravenous antibiotics for at least 2 weeks. Following the conclusion of intravenous antibiotic administration, patients are treated with doxycycline and trimethoprim/sulfamethoxazole for up to 20 weeks to eradicate the disease. Abscesses in most organ systems of patients with melioidosis often resolve after antibiotic therapy; however, prostatic abscesses usually require surgical debridement.[25][26][27][28][29] Treatment with meropenem and granulocyte colony-stimulating factor has been shown to significantly decrease mortality in critically ill patients with melioidosis in Australia. Recurrence of melioidosis may occur in up to 20% of patients; however, this can be reduced to as little as 4% with trimethoprim/sulfamethoxazole eradication therapy. Because of the risk of relapse, lifelong follow-up is recommended.[30][31][32][33] No vaccines are currently available for glanders or melioidosis. There are no approved antibiotic prophylaxis regimens for glanders or melioidosis, but one study demonstrated that mice receiving trimethoprim/sulfamethoxazole as pre-exposure prophylaxis or as post-exposure prophylaxis within 24 hours following exposure to Burkholderia pseudomallei had a 100% survival rate.[34][35][36][37][38]

Differential Diagnosis

  • Anthrax
  • Bacterial pneumonia
  • CBRNE-plague
  • CBRNE-smallpox
  • Malaria
  • Mycoplasmal pneumonia
  • Typhoid fever
  • Viral pneumonia

Prognosis

The mortality rate in the cutaneous form of systemic and untreated glanders is 90% to 95% but 50% if properly treated.

Complications

  • Septic shock
  • Abscesses of the liver, spleen, and prostate
  • Death

Pearls and Other Issues

Burkholderia mallei was used by the Germans in World War I to infect livestock being shipped to Allied countries. It has been alleged that the Soviet Union employed it as a biological weapon in Afghanistan between 1982 and 1984. Burkholderia pseudomallei was investigated as a possible biological warfare agent by both the United States and the Soviet Union, however, it has never been successfully weaponized.[39][40] 

Enhancing Healthcare Team Outcomes

Glanders is an uncommon zoonotic disease that is transmitted to humans from solipeds such as horses, mules, and donkeys. It has been eradicated in many parts of the world. Transmission is uncommon even in the setting of frequent close contact with infected animals. However, occupational exposure is a key risk factor. Melioidosis is endemic in Southeast Asia, China, and northern Australia. There have also been cases in India as well as the Middle East, Africa, and Central and South America. It is found in soil and water, and it is known to cause disease in animals such as cats, goats, sheep, and horses. A history of contact with soil and surface water is almost always present in humans with melioidosis. Contaminated groundwater, flooding, and typhoons have been implicated in outbreaks of melioidosis. Epidemiological surveillance is vital to detect any outbreak or local emergence in humans or animals. Expert evidence indicates that glanders and melioidosis are best managed by an interprofessional team of health care workers that includes an epidemiologist, an infectious disease consultant, internists, a pharmacist, and a nurse. (Level V)

Since glanders and melioidosis can present with the involvement of almost any organ system, high suspicion should be maintained in those with identified risk factors. The medical laboratory is essential to help make the diagnosis of the disease. In the setting of a large outbreak in people without risk factors, a biological attack should be considered, and public health and law enforcement officials should be notified. Once the infection is treated, the pharmacist should ensure that the patient remains compliant with drug therapy. In addition, if there is any evidence of recurrence, the patient should be referred to an internist for evaluation; rates of recurrence of melioidosis may be as high as 20% but can be reduced with appropriate therapy. (Level V)

Review Questions

References

1.
Dance D. A glanders-like disease in Rangoon: Whitmore A. J Hyg 1913; 13: 1-34. Epidemiol Infect. 2005 Oct;133 Suppl 1:S9-S10. [PubMed: 24965251]
2.
Whitmore A. An Account of a Glanders-like Disease occurring in Rangoon. J Hyg (Lond). 1913 Apr;13(1):1-34.1. [PMC free article: PMC2167219] [PubMed: 20474526]
3.
Jilani MS, Robayet JA, Mohiuddin M, Hasan MR, Ahsan CR, Haq JA. Burkholderia pseudomallei: Its Detection in Soil and Seroprevalence in Bangladesh. PLoS Negl Trop Dis. 2016 Jan;10(1):e0004301. [PMC free article: PMC4714902] [PubMed: 26771511]
4.
Wilkinson L. Glanders: medicine and veterinary medicine in common pursuit of a contagious disease. Med Hist. 1981 Oct;25(4):363-84. [PMC free article: PMC1139069] [PubMed: 7038356]
5.
Chewapreecha C, Holden MT, Vehkala M, Välimäki N, Yang Z, Harris SR, Mather AE, Tuanyok A, De Smet B, Le Hello S, Bizet C, Mayo M, Wuthiekanun V, Limmathurotsakul D, Phetsouvanh R, Spratt BG, Corander J, Keim P, Dougan G, Dance DA, Currie BJ, Parkhill J, Peacock SJ. Global and regional dissemination and evolution of Burkholderia pseudomallei. Nat Microbiol. 2017 Jan 23;2:16263. [PMC free article: PMC5300093] [PubMed: 28112723]
6.
Limmathurotsakul D, Golding N, Dance DA, Messina JP, Pigott DM, Moyes CL, Rolim DB, Bertherat E, Day NP, Peacock SJ, Hay SI. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol. 2016 Jan 01;1(1) [PubMed: 26877885]
7.
Ko WC, Cheung BM, Tang HJ, Shih HI, Lau YJ, Wang LR, Chuang YC. Melioidosis outbreak after typhoon, southern Taiwan. Emerg Infect Dis. 2007 Jun;13(6):896-8. [PMC free article: PMC2792857] [PubMed: 17553230]
8.
Prakash A, Thavaselvam D, Kumar A, Kumar A, Arora S, Tiwari S, Barua A, Sathyaseelan K. Isolation, identification and characterization of Burkholderia pseudomallei from soil of coastal region of India. Springerplus. 2014;3:438. [PMC free article: PMC4152474] [PubMed: 25187882]
9.
Brilhante RS, Bandeira TJ, Cordeiro RA, Grangeiro TB, Lima RA, Ribeiro JF, Castelo-Branco DS, Rodrigues JL, Coelho IC, Magalhães FG, Rocha MF, Sidrim JJ. Clinical-epidemiological features of 13 cases of melioidosis in Brazil. J Clin Microbiol. 2012 Oct;50(10):3349-52. [PMC free article: PMC3457459] [PubMed: 22814457]
10.
Katangwe T, Purcell J, Bar-Zeev N, Denis B, Montgomery J, Alaerts M, Heyderman RS, Dance DA, Kennedy N, Feasey N, Moxon CA. Human melioidosis, Malawi, 2011. Emerg Infect Dis. 2013 Jun;19(6):981-4. [PMC free article: PMC3713813] [PubMed: 23735189]
11.
Bernhards RC, Cote CK, Amemiya K, Waag DM, Klimko CP, Worsham PL, Welkos SL. Characterization of in vitro phenotypes of Burkholderia pseudomallei and Burkholderia mallei strains potentially associated with persistent infection in mice. Arch Microbiol. 2017 Mar;199(2):277-301. [PMC free article: PMC5306356] [PubMed: 27738703]
12.
Varga JJ, Vigil A, DeShazer D, Waag DM, Felgner P, Goldberg JB. Distinct human antibody response to the biological warfare agent Burkholderia mallei. Virulence. 2012 Oct 01;3(6):510-4. [PMC free article: PMC3524150] [PubMed: 23076276]
13.
Waag DM, England MJ, DeShazer D. Humoral immune responses in a human case of glanders. Clin Vaccine Immunol. 2012 May;19(5):814-6. [PMC free article: PMC3346324] [PubMed: 22398248]
14.
Currie BJ. Melioidosis: evolving concepts in epidemiology, pathogenesis, and treatment. Semin Respir Crit Care Med. 2015 Feb;36(1):111-25. [PubMed: 25643275]
15.
Andersen EW, Mackay MT, Ryan MM. Neurologic Melioidosis: Case Report of a Rare Cause of Acute Flaccid Paralysis. J Pediatr. 2016 Mar;170:319-21. [PubMed: 26778096]
16.
Dan M, Taran D. Melioidosis of the Skin in an Israeli Traveler Returning from Thailand. Isr Med Assoc J. 2015 Nov;17(11):724-5. [PubMed: 26757575]
17.
Saravu K, Kadavigere R, Shastry AB, Pai R, Mukhopadhyay C. Neurologic melioidosis presented as encephalomyelitis and subdural collection in two male labourers in India. J Infect Dev Ctries. 2015 Nov 30;9(11):1289-93. [PubMed: 26623640]
18.
Guo RF, Wong FL, Perez ML. Splenic abscesses in a returning traveler. Infect Dis Rep. 2015 Feb 24;7(1):5791. [PMC free article: PMC4387372] [PubMed: 25874071]
19.
Leth S, Wang M, Deutch S. [Melioidosis in a Danish tourist returning from North-eastern Thailand]. Ugeskr Laeger. 2014 Jun 09;176(12) [PubMed: 25096943]
20.
Wijekoon S, Prasath T, Corea EM, Elwitigala JP. Melioidosis presenting as lymphadenitis: a case report. BMC Res Notes. 2014 Jun 14;7:364. [PMC free article: PMC4062509] [PubMed: 24927768]
21.
Stephens DP, Thomas JH, Ward LM, Currie BJ. Melioidosis Causing Critical Illness: A Review of 24 Years of Experience From the Royal Darwin Hospital ICU. Crit Care Med. 2016 Aug;44(8):1500-5. [PubMed: 26963328]
22.
Lau SK, Sridhar S, Ho CC, Chow WN, Lee KC, Lam CW, Yuen KY, Woo PC. Laboratory diagnosis of melioidosis: past, present and future. Exp Biol Med (Maywood). 2015 Jun;240(6):742-51. [PMC free article: PMC4935216] [PubMed: 25908634]
23.
Pal V, Saxena A, Singh S, Goel AK, Kumar JS, Parida MM, Rai GP. Development of a real-time loop-mediated isothermal amplification assay for detection of Burkholderia mallei. Transbound Emerg Dis. 2018 Feb;65(1):e32-e39. [PubMed: 28649808]
24.
Zakharova I, Teteryatnikova N, Toporkov A, Viktorov D. Development of a multiplex PCR assay for the detection and differentiation of Burkholderia pseudomallei, Burkholderia mallei, Burkholderia thailandensis, and Burkholderia cepacia complex. Acta Trop. 2017 Oct;174:1-8. [PubMed: 28634144]
25.
Limmathurotsakul D, Funnell SG, Torres AG, Morici LA, Brett PJ, Dunachie S, Atkins T, Altmann DM, Bancroft G, Peacock SJ., Steering Group on Melioidosis Vaccine Development. Consensus on the development of vaccines against naturally acquired melioidosis. Emerg Infect Dis. 2015 Jun;21(6) [PMC free article: PMC4451926] [PubMed: 25992835]
26.
Hatcher CL, Muruato LA, Torres AG. Recent Advances in Burkholderia mallei and B. pseudomallei Research. Curr Trop Med Rep. 2015 Jun;2(2):62-69. [PMC free article: PMC4410361] [PubMed: 25932379]
27.
Podnecky NL, Rhodes KA, Schweizer HP. Efflux pump-mediated drug resistance in Burkholderia. Front Microbiol. 2015;6:305. [PMC free article: PMC4396416] [PubMed: 25926825]
28.
Cheng AC, Currie BJ, Dance DAB, Funnell SGP, Limmathurotsakul D, Simpson AJH, Peacock SJ. Clinical definitions of melioidosis. Am J Trop Med Hyg. 2013 Mar;88(3):411-413. [PMC free article: PMC3592517] [PubMed: 23468355]
29.
Georgiades C, Fishman EK. Clinical image. Glanders disease of the liver and spleen: CT evaluation. J Comput Assist Tomogr. 2001 Jan-Feb;25(1):91-3. [PubMed: 11176300]
30.
Russell P, Eley SM, Ellis J, Green M, Bell DL, Kenny DJ, Titball RW. Comparison of efficacy of ciprofloxacin and doxycycline against experimental melioidosis and glanders. J Antimicrob Chemother. 2000 Jun;45(6):813-8. [PubMed: 10837435]
31.
Kenny DJ, Russell P, Rogers D, Eley SM, Titball RW. In vitro susceptibilities of Burkholderia mallei in comparison to those of other pathogenic Burkholderia spp. Antimicrob Agents Chemother. 1999 Nov;43(11):2773-5. [PMC free article: PMC89557] [PubMed: 10543761]
32.
Waag DM. Efficacy of postexposure therapy against glanders in mice. Antimicrob Agents Chemother. 2015 Apr;59(4):2236-41. [PMC free article: PMC4356808] [PubMed: 25645854]
33.
Heine HS, England MJ, Waag DM, Byrne WR. In vitro antibiotic susceptibilities of Burkholderia mallei (causative agent of glanders) determined by broth microdilution and E-test. Antimicrob Agents Chemother. 2001 Jul;45(7):2119-21. [PMC free article: PMC90610] [PubMed: 11408233]
34.
McLeod C, Morris PS, Bauert PA, Kilburn CJ, Ward LM, Baird RW, Currie BJ. Clinical presentation and medical management of melioidosis in children: a 24-year prospective study in the Northern Territory of Australia and review of the literature. Clin Infect Dis. 2015 Jan 01;60(1):21-6. [PubMed: 25228703]
35.
Sivalingam SP, Sim SH, Jasper LC, Wang D, Liu Y, Ooi EE. Pre- and post-exposure prophylaxis of experimental Burkholderia pseudomallei infection with doxycycline, amoxicillin/clavulanic acid and co-trimoxazole. J Antimicrob Chemother. 2008 Mar;61(3):674-8. [PubMed: 18192684]
36.
Sarovich DS, Ward L, Price EP, Mayo M, Pitman MC, Baird RW, Currie BJ. Recurrent melioidosis in the Darwin Prospective Melioidosis Study: improving therapies mean that relapse cases are now rare. J Clin Microbiol. 2014 Feb;52(2):650-3. [PMC free article: PMC3911345] [PubMed: 24478504]
37.
Chetchotisakd P, Chierakul W, Chaowagul W, Anunnatsiri S, Phimda K, Mootsikapun P, Chaisuksant S, Pilaikul J, Thinkhamrop B, Phiphitaporn S, Susaengrat W, Toondee C, Wongrattanacheewin S, Wuthiekanun V, Chantratita N, Thaipadungpanit J, Day NP, Limmathurotsakul D, Peacock SJ. Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial. Lancet. 2014 Mar 01;383(9919):807-14. [PMC free article: PMC3939931] [PubMed: 24284287]
38.
Cheng AC, Currie BJ. Melioidosis: epidemiology, pathophysiology, and management. Clin Microbiol Rev. 2005 Apr;18(2):383-416. [PMC free article: PMC1082802] [PubMed: 15831829]
39.
Wolfe DN, Florence W, Bryant P. Current biodefense vaccine programs and challenges. Hum Vaccin Immunother. 2013 Jul;9(7):1591-7. [PubMed: 23428906]
40.
Wheelis M. First shots fired in biological warfare. Nature. 1998 Sep 17;395(6699):213. [PubMed: 9751039]

Disclosure: HoanVu Nguyen declares no relevant financial relationships with ineligible companies.

Disclosure: Matthew Smith declares no relevant financial relationships with ineligible companies.

Disclosure: Michael Hayoun declares no relevant financial relationships with ineligible companies.

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