glanders

Pictures

Picture	Title	Caption	Copyright
Title External symptoms Caption A granulomatous lesion in the lip of a donkey. Copyright ©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)	External symptoms	A granulomatous lesion in the lip of a donkey.	©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)
Title Pathology Caption An extensive pyogenic granulomatous pneumonia in a donkey. Copyright ©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)	Pathology	An extensive pyogenic granulomatous pneumonia in a donkey.	©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)

Identity

Preferred Scientific Name

• glanders

International Common Names

• English: farcy

Pathogen/s

Overview

Glanders is a highly infectious zoonotic disease of equids (horses, donkeys, mules), caused by the bacterium Burkholderia mallei (Cárdenas et al., 2019). It is on the list of diseases notifiable to the World Organisation for Animal Health (OIE). Glanders is characterized by chronic suppurative lesions of skin and mucous membrane, pneumonia, and septicaemia. The disease has been eradicated in most European and North American countries, but outbreaks still occur in South America, parts of Africa, the Middle East and Southern Asia (OIE, 2020). The acute form of glanders is usually observed in donkeys and mules with high fever, respiratory symptoms, and death occurring within a few days. The disease is mainly chronic in horses and latently-infected animals pose a high risk of reintroduction of the infection into glanders-free countries (Khan et al., 2013). Quarantine testing before and after the international transport of horses is very important to prevent the spread of glanders (Kinoshita et al., 2019). As a highly infectious agent that can be transmitted by aerosol, causing fatal disease in humans, B. mallei is considered to be a biothreat agent (Scholz et al., 2014).

Host Animals

Hosts/Species Affected

The natural hosts for B. mallei are horses, donkeys and mules (Khan et al., 2013). Donkeys are most susceptible, mules somewhat less and horses demonstrate some resistance, developing chronic forms of the disease (OIE, 2020).

Susceptibility to glanders has been reported for bears, wolves, jackals, hyenas, dogs, cats and other felids (Spickler, 2018). Carnivores may become infected by eating infected meat (OIE, 2020). Small ruminants and dromedary camels may also be infected if kept in close contact with glanderous horses (Wittig et al., 2006; Wernery et al., 2011). Many other mammals can be infected experimentally, but pigs and cattle are reported to be resistant. Birds are highly resistant (OIE, 2020). Glanders is a zoonotic disease (Khan et al., 2013).

Distribution

The prevalence of glanders has been significantly reduced worldwide by national control programmes. The disease has been eradicated in North America, Australia and Europe through testing and then eliminating any positive animal, together with import control measures (OIE, 2020). However, glanders continues to be reported in South Asia (Ghori et al., 2017; Harisankar Singha et al., 2017), parts of Africa (Getachew et al., 2014), the Middle East (Elschner et al., 2016; Kianfar et al., 2019) and South America (Machado et al., 2013; Fonseca-Rodríguez et al., 2019). In April 2010, Bahrain notified the first occurrence of the disease (Scholz et al., 2014). In Brazil, the disease reappeared in 2009 and remains a serious problem (Fonseca-Rodríguez et al., 2019; OIE, 2020). Germany notified the occurrence of the disease in a limited area in 2014/2015 (OIE, 2020). Following the re-emergence of glanders in northern states of India during 2006, the disease has spread to several states of India (Praveen Malik et al., 2015).

For the most recent, detailed information on the occurrence of this disease worldwide, see the OIE World Animal Health Information Database (WAHIS) interface

Distribution Table

The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.

Pathology

In equids, findings include nodules, granulomas and/or ulcers in various tissues. The upper respiratory tract is often affected, with ulcers, nodules and/or stellate scars in the nasal passages, larynx and other tissues. Internally, nodules are most likely to be found in the lungs. Nodules and other lesions may be detected in other visceral organs, particularly the liver and spleen. Swollen lymphatics, with chains of nodules and ulcerated nodules, may be found in the skin, while the lymph nodes may be enlarged, congested and/or fibrotic, and can contain abscesses (Spickler, 2018).

Diagnosis

Identification

Bacterial isolation and identification of B. mallei from cutaneous lesions and nasal exudates are considered to be the gold standard for diagnosis of glanders. Bacteria grow aerobically and prefer media that contain glycerol (OIE, 2020). B. mallei usually grows slowly on most culture media, and this property makes it difficult to isolate from clinical specimens. B. mallei is easily overgrown by other bacteria, especially in animal specimens collected from non-sterile sites. Kinoshita et al. (2019) developed a new selective medium (Burkholderia mallei agar: BM agar) for laboratory diagnosis of glanders. The authors say that BM agar can be used to efficiently isolate B. mallei from mixed samples such as those typically collected from horses and other contaminated environments.

Once isolated, B. mallei is usually identified with biochemical tests. B. mallei is not motile and this distinguishes it from other Burkholderia spp., including B. pseudomallei. Due to the risks of human infection, isolates suspected to be B. mallei are typically sent to a reference laboratory for identification. Genetic techniques available in specialized laboratories (e.g., PCR–restriction fragment length polymorphism, pulse-field gel electrophoresis, 16S rRNA sequencing) can distinguish B. mallei from its close relative B. pseudomallei (Spickler, 2018).

Serological tests

Serological tests include complement fixation, ELISA, immunoblot assays and Rose Bengal plate agglutination test (RBT) (OIE, 2020).

Serodiagnosis can be challenging because of false-positive and false-negative test results. The World Organisation for Animal Health (OIE) recommends the complement fixation test (CFT) for international trade, but this test has been shown to have varying sensitivities and specificities depending on the antigen and methodology used. False positives are problematic for the horse-owner and veterinary authority, whereas false negatives may allow the reintroduction of B. mallei into B. mallei-free areas (Kettle and Werney, 2016). The accuracy of the CFT, five ELISAs and a Western blot (WB) were compared by Elschner et al. (2019). Four of the ELISA tests are based on recombinant antigens (TssA, TssB, BimA and Hcp1), the IDVet ELISA is based on a semi-purified fraction of B. mallei and WB makes use of a purified LPS-containing B. mallei-antigen. Given their comparable sensitivities and specificities, the authors concluded that the CFT (98.0%, 96.4%), the WB (96.8%, 99.4%), the Hcp1-ELISA (95.3%, 99.6%) and the IDVet-ELISA (92.5%, 99.5%) should be further developed to meet OIE requirements.

Mallein test

A hypersensitivity reaction called the mallein test was used in glanders eradication programmes, and is still used to detect infected equids in some remote endemic areas, where sample transport or proper cooling is not possible (Spickler, 2018; OIE 2020). However, the test is not generally recommended because of animal welfare concerns (OIE, 2020). Mallein, a water-soluble protein fraction of the organism, is injected intradermo-palpebrally (into the eyelid). In infected animals, the eyelid swells markedly within 1-2 days (Spickler, 2018).

Disease Course

The incubation period in equids is reported to range from a few days to many months, but many cases become apparent in 2-6 weeks (Spickler, 2018). There are three clinical forms of the disease in equids: nasal, pulmonary and cutaneous (farcy) glanders. Clinical cases are often a combination of the three forms, and may be acute (or subacute), chronic or latent. Nasal and pulmonary forms tend to be more acute in nature, while the cutaneous form of the disease is a chronic process (OIE, 2020).

Acute cases are typically fatal in a few days. Animals show signs of respiratory disease, cough and fever and the release of an infectious nasal discharge, followed by septicaemia and death within days. In the chronic form, nasal and subcutaneous nodules develop, eventually ulcerating (Marsella, 2019). A latent form of glanders has also been described but may provoke few signs, e.g. nasal discharge and dyspnoea. Donkeys and mules often develop acute glanders after exposure, although mules appear to be somewhat more resistant and the course of the illness may be slower. Horses usually develop chronic glanders (OIE, 2020).

Epidemiology

The transmission of B. mallei occurs by direct contact (Cárdenas et al., 2019). Glanders can spread widely when large numbers of animals are in close contact. A common source of infection appears to be ingestion of food or water contaminated via discharges from the respiratory tract or ulcerated skin lesions from carrier animals. Subclinical carriers are often more important in transmission of disease than clinical cases: Chronically or subclinically infected equids can shed B. mallei intermittently or constantly into food and water troughs. There are reports of venereal transmission from stallions to mares, and vertical transmission from the mare. B. mallei is readily spread with fomites (OIE, 2020). This disease is reported to be more common in animals that are undernourished or otherwise in poor condition (Spickler, 2018).

Impact: Economic

Throughout the western world, glanders has been eradicated through large scale culling of infected animals. In developing countries, however, economic and cultural circumstances may hinder culling of asymptomatic animals and enable the persistence of glanders (Scholz et al., 2014). The disease is considered endemic in many developing countries of Asia, Africa and South America (Ghori et al., 2018).

In Brazil, glanders remains a serious problem, with the obligatory sacrifice of disease-positive animals without compensation. Each year, glanders cases are reported in several regions of the country, causing severe economic losses and trade restrictions (Fonseca-Rodríguez et al., 2019).

Due to weaknesses in the diagnosis of glanders, coupled with the increased movement of horses, infection with B. mallei remains a major risk in the context of international movement of equids (Kettle and Wernery, 2016).

Zoonoses and Food Safety

Humans may acquire the infection through direct contact with the organism and prolonged contact with diseased animals. Veterinarians, horse caretakers and laboratory workers handling this organism are considered as the professional risk groups. The most common manifestations are life-threatening pneumonia and bacteraemia. Although, early and aggressive treatment with combinations of systemic antibiotics can be curative (Srinivasan et al., 2001), an extremely high rate of mortality can occur in untreated humans (Praveen Malik et al., 2015). There is no vaccine to protect against B. mallei and there is concern regarding its potential use as a biothreat agent (Jelesijevic et al., 2015).

Disease Treatment

Antibiotic treatments have been used in endemic zones, but this may lead to subclinical carrier animals that can infect humans and other animals (OIE, 2020). It is believed that partially treated equines with chronic or subclinical infection may be responsible for frequent and continuous outbreaks of glanders in India (Praveen Malik et al., 2015).

Designing effective treatments for glanders is complicated by differences in antibiotic susceptibility patterns between B. mallei isolates, and the inability of some drugs to penetrate into the host cells where this organism replicates (Spickler, 2018).

Muhammad Saqib et al. (2012) note that certain situations e.g. wild life conservation, highly valuable breeding stock, could benefit from effective treatment schemes and post-exposure prophylaxis. They describe a treatment protocol of 12 weeks duration based on the parenteral administration of enrofloxacin and trimethoprim + sulfadiazine, followed by the oral administration of doxycycline during a confined glanders outbreak in horses in Lahore, Pakistan. Although the treatment was successful, they conclude that more studies are needed to test the effectiveness of this treatment regime on B. mallei strains from different endemic regions. Furthermore, due to its cost and duration, this treatment can only be an option in certain situations and should not replace the current “testing and culling” policy, in conjunction with adequate compensation to prevent spreading of disease.

Prevention and Control

Prevention and control of glanders requires a programme for early detection, testing of suspect clinical cases, screening of apparently healthy equids, and humane culling of reactors (OIE, 2020). Latently-infected animals pose a high risk of reintroduction of the infection into glanders-free countries (Kettle and Wernery, 2016). Therefore, trade restrictions with animals and products from endemic regions or outbreak areas are mandatory. There is no vaccine.

References

Arjun Srinivasan, Kraus, C. N., DeShazer, D., Becker, P. M., Dick, J. D., Spacek, L., Bartlett, J. G., Byrne, W. R., Thomas, D. L., 2001. Glanders in a military research microbiologist. New England Journal of Medicine, 345(4), 256-258. doi: 10.1056/NEJM200107263450404

Aschenbroich, S. A., Lafontaine, E. R., Hogan, R. J., 2016. Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches. Expert Review of Vaccines, 15(9), 1163-1181. http://www.tandfonline.com/loi/ierv20

Cárdenas, N. C., Galvis, J. O. A., Farinati, A. A., Grisi Filho, J. H. H., Diehl, G. N., Machado, G., 2019. Burkholderia mallei: the dynamics of networks and disease transmission. Transboundary and Emerging Diseases, 66(2), 715-728. doi: 10.1111/tbed.13071

Elschner, M. C., Laroucau, K., Harisankar Singha, Tripathi, B. N., Muhammad Saqib, Gardner, I., Sheetal Saini, Subodh Kumar, El-Adawy, H., Melzer, F., Iahtasham Khan, Praveen Malik, Sauter-Louis, C., Neubauer, H., 2019. Evaluation of the comparative accuracy of the complement fixation test, Western blot and five enzyme-linked immunosorbent assays for serodiagnosis of glanders. PLoS ONE, 14(4), e0214963. doi: 10.1371/journal.pone.0214963

Elschner, M. C., Thomas, P., Melzer, F., 2016. Complete genome sequence of a Burkholderia mallei isolate originating from a glanderous horse from the Kingdom of Bahrain. Genome Announcements, 4(6), e01296-16. http://genomea.asm.org/content/4/6/e01296-16.full

Fonseca-Rodríguez, O., Pinheiro Júnior, J. W., Mota, R. A., 2019. Spatiotemporal analysis of glanders in Brazil. Journal of Equine Veterinary Science, 78, 14-19. doi: 10.1016/j.jevs.2019.03.216

Getachew, M., Alemayehu, F., Chala, C., Amare, B., Kassa, D., Burden, F., Wernery, R., Wernery, U., 2014. A cross-sectional sero-survey of some infectious diseases of working equids in Central Ethiopia. Journal of Veterinary Medicine and Animal Health, 6(9), 231-238. http://www.academicjournals.org/article/article1408030860_Getachew%20et%20al.pdf

Ghori, M. T., Khan, M. S., Khan, J. A., Masood Rabbani, Shabbir, M. Z., Chaudhry, H. R., Ali, M. A., Javed Muhammad, Elschner, M. C., Jayarao, B. M., 2017. Seroprevalence and risk factors of glanders in working equines - findings of a cross-sectional study in Punjab province of Pakistan. Acta Tropica, 176, 134-139. doi: 10.1016/j.actatropica.2017.07.031

Ghori, M. T., Khan, M. S., Khan, J. A., Rabbani, M., Chaudhary, M. H., Shabbir, M. Z., Ahmed, R., Chaudhry, H. R., Muhammad, J., 2018. Molecular detection of Burkholderia mallei in nasal swabs from draught horses with signs of respiratory tract infection. JAPS, Journal of Animal and Plant Sciences, 28(6), 1717-1724. http://www.thejaps.org.pk/docs/v-28-06/24.pdf

Harisankar Singha, Praveen Malik, Sheetal Saini, Khurana, S. K., Elschner, M. C., Mertens, K., Barth, S. A., Tripathi, B. N., Singh, R. K., 2017. Draft genome sequences of two clinical isolates of Burkholderia mallei obtained from nasal swabs of glanderous equines in India. Genome Announcements, 5(14), e00063-17. doi: 10.1128/genomea.00063-17

Jelesijevic, T., Zimmerman, S. M., Harvey, S. B., Mead, D. G., Shaffer, T. L., Estes, D. M., Michel, F., Quinn, F. D., Hogan, R. J., Lafontaine, E. R., 2015. Use of the common marmoset to study Burkholderia mallei infection. PLoS ONE, 10(4), e0124181. doi: 10.1371/journal.pone.0124181

Kettle, A. N. B., Wernery, U., 2016. Glanders and the risk for its introduction through the international movement of horses. Equine Veterinary Journal, 48(5), 654-658. doi: 10.1111/evj.12599

Khan, I., Wieler, L. H., Melzer, F., Elschner, M. C., Muhammad, G., Ali, S., Sprague, L. D., Neubauer, H., Saqib, M., 2013. Glanders in animals: a review on epidemiology, clinical presentation, diagnosis and countermeasures. Transboundary and Emerging Diseases, 60(3), 204-221. doi: 10.1111/j.1865-1682.2012.01342.x

Kianfar, N., Ghasemian, A., Al-Marzoqi, A. H., Eslami, M., Vardanjani, H. R., Mirforughi, S. A., Vardanjani, H. R., 2019. The reemergence of glanders as a zoonotic and occupational infection in Iran and neighboring countries. Reviews in Medical Microbiology, 30(3), 191-196. doi: 10.1097/MRM.0000000000000165

Kinoshita, Y., Cloutier, A. K., Rozak, D. A., Khan, M. S. R., Niwa, H., Uchida-Fujii, E., Katayama, Y., Tuanyok, A., 2019. A novel selective medium for the isolation of Burkholderia mallei from equine specimens. BMC Veterinary Research, 15(133), (7 May 2019). https://link.springer.com/article/10.1186/s12917-019-1874-0

Machado, M. B., Silveira, P. P. M. da, Bandeira, J. de T., Morais, R. S. M. M. de, Santos, F. L. dos, Barçante, T. A., 2013. Glanders prevalence in the State of Pernambuco, Brazil, from 2006 to 2011. (Prevalência de mormo no estado de Pernambuco no período de 2006 a 2011). Ciência Veterinária nos Trópicos, 16(1), 37-44. http://www.rcvt.org.br/volume16/rcvt_16_1-2-3.pdf

Marsella, R., 2019. Clinical approach to nodular diseases. In: Manual of equine dermatology, [ed. by Marsella, R.]. Wallingford, UK: CABI. 82-95. doi: 10.1079/9781786395085.0082

Muhammad Saqib, Ghulam Muhammad, Abeera Naureen, Hussain, M. H., Asi, M. N., Mansoor, M. K., Mehdi Toufeer, Iahtasham Khan, Neubauer, H., Sprague, L. D., 2012. Effectiveness of an antimicrobial treatment scheme in a confined glanders outbreak. BMC Veterinary Research, 8(214), (7 November 2012). http://www.biomedcentral.com/content/pdf/1746-6148-8-214.pdf

OIE Handistatus, 2002. World Animal Health Publication and Handistatus II (dataset for 2001). Paris, France: Office International des Epizooties

OIE Handistatus, 2003. World Animal Health Publication and Handistatus II (dataset for 2002). Paris, France: Office International des Epizooties

OIE Handistatus, 2004. World Animal Health Publication and Handistatus II (data set for 2003). Paris, France: Office International des Epizooties

OIE Handistatus, 2005. World Animal Health Publication and Handistatus II (data set for 2004). Paris, France: Office International des Epizooties

OIE, 2009. World Animal Health Information Database - Version: 1.4. World Animal Health Information Database. Paris, France: World Organisation for Animal Health. http://www.oie.int

OIE, 2020. Glanders (updated January 2020). In: OIE Technical disease cards Paris, France: World Organisation for Animal Health .https://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/Disease_cards/GLANDERS.pdf

Praveen Malik, Harisankar Singha, Goyal, S. K., Khurana, S. K., Tripathi, B. N., Abha Dutt, Dabal Singh, Neeraj Sharma, Sanjay Jain, 2015. Incidence of Burkholderia mallei infection among indigenous equines in India. Veterinary Record Open, 2(2), e000129. http://vetrecordopen.bmj.com/content/2/2/e000129.abstract

Scholz, H. C., Pearson, T., Hornstra, H., Projahn, M., Terzioglu, R., Wernery, R., Georgi, E., Riehm, J. M., Wagner, D. M., Keim, P. S., Joseph, M., Johnson, B., Kinne, J., Jose, S., Hepp, C. M., Witte, A., Wernery, U., 2014. Genotyping of Burkholderia mallei from an outbreak of glanders in Bahrain suggests multiple introduction events. PLoS Neglected Tropical Diseases, 8(9), e3195. doi: 10.1371/journal.pntd.0003195

Spickler, A. R., 2018. Glanders. Iowa, USA: Center for Food Security and Public Health (CFSPH), Iowa State University.http://www.cfsph.iastate.edu/DiseaseInfo/factsheets.php

Wernery, U., Wernery, R., Joseph, M., Al-Salloom, F., Johnson, B., Kinne, J., Jose, S., Jose, S., Tappendorf, B., Hornstra, H., Scholz, H. C., 2011. Natural Burkholderia mallei infection in dromedary, Bahrain. Emerging Infectious Diseases, 17(7), 1277-1279. doi: 10.3201/eid1707.110222

Wittig, M. B., Wohlsein, P., Hagen, R. M., Al-Dahouk, S., Tomaso, H., Scholz, H. C., Nikolaou, K., Wernery, R., Wernery, U., Kinne, J., Elschner, M., Neubauer, H., 2006. Glanders - a comprehensive review. (Ein Übersichtsreferat zur Rotzerkrankung). Deutsche Tierärztliche Wochenschrift, 113(9), 323-330. http://www.schaper-verlag.de

Distribution References

OIE Handistatus, 2005. World Animal Health Publication and Handistatus II (dataset for 2004)., Paris, France: Office International des Epizooties.

OIE, 2009. World Animal Health Information Database - Version: 1.4., Paris, France: World Organisation for Animal Health. https://www.oie.int/

Distribution Maps