Serological Survey of Humans Exposed to Burkholderia mallei-Infected Equids: A Public Health Approach.

Glanders is a fatal bacterial infection of equids caused by Burkholderia mallei. The infection can be transmitted to humans through prolonged direct contact with glanderous equids. Recently, reemergence of equine glanders has been reported in many countries. To investigate zoonotic transmission of B mallei infection, sera were collected from 538 humans including equine handlers and veterinary professionals exposed to glanderous equids. Samples were tested by ELISA (enzyme-linked immunosorbent assay) and complement fixation test and found negative for B mallei-specific antibodies. Even though there was no incidence of human glanders during this survey period, occupational exposure will continue to remain a serious concern and a key risk factor. Therefore, we emphasize the need for intersectoral collaboration and coordination among veterinary, human, and public health authorities for continuous surveillance and monitoring of human glanders under one health concept.

Burkholderia mallei: The dynamics of networks and disease transmission.

Glanders is a highly infectious zoonotic disease caused by Burkholderia mallei. The transmission of B. mallei occurs mainly by direct contact, and horses are the natural reservoir. Therefore, the identification of infection sources within horse populations and animal movements is critical to enhance disease control. Here, we analysed the dynamics of horse movements from 2014 to 2016 using network analysis in order to understand the flow of animals in two hierarchical levels, municipalities and farms. The municipality-level network was used to investigate both community clustering and the balance between the municipality's trades and the farm-level network associations between B. mallei outbreaks and the network centrality measurements, analysed by spatio-temporal generalized additive model (GAM). Causal paths were established for the dispersion of B. mallei outbreaks through the network. Our approach captured and established a direct relationship between movement of infected equines and predicted B. mallei outbreaks. The GAM model revealed that the parameters in degree and closeness centrality out were positively associated with B. mallei. In addition, we also detected 10 communities with high commerce among municipalities. The role of each municipality within the network was detailed, and significant changes in the structures of the network were detected over the course of 3 years. The results suggested the necessity to focus on structural changes of the networks over time to better control glanders disease. The identification of farms with a putative risk of B. mallei infection using the horse movement network provided a direct opportunity for disease control through active surveillance, thus minimizing economic losses and risks for human cases of B. mallei.

Glanders and the risk for its introduction through the international movement of horses.

Glanders is the contagious zoonotic disease caused by infection with Burkholderia mallei. It affects primarily horses, donkeys and mules. The disease was eradicated from large areas of the Western world in the early 20th century, but, over the last 10-20 years, has emerged and re-emerged in areas in which it was previously unknown or had been eradicated. Although glanders was previously thought to manifest in only acute or chronic presentations, it now appears that B. mallei can produce latent infections similar to those caused by Burkholderia pseudomallei. These latent infections may or may not be detectable by current diagnostic tests. The diagnostic test currently recommended by the World Organisation for Animal Health (Office International des Epizooties [OIE]) for international trade in equids is the complement fixation test (CFT). 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. These gaps in knowledge of the epidemiology of glanders, and weaknesses in its diagnosis, coupled with the increased movement of equids, indicate that infection with B. mallei remains a major risk in the context of international movement of equids.

The Autotransporter BpaB Contributes to the Virulence of Burkholderia mallei in an Aerosol Model of Infection.

Burkholderia mallei is a highly pathogenic bacterium that causes the zoonosis glanders. Previous studies indicated that the genome of the organism contains eight genes specifying autotransporter proteins, which are important virulence factors of Gram-negative bacteria. In the present study, we report the characterization of one of these autotransporters, BpaB. Database searches identified the bpaB gene in ten B. mallei isolates and the predicted proteins were 99-100% identical. Comparative sequence analyses indicate that the gene product is a trimeric autotransporter of 1,090 amino acids with a predicted molecular weight of 105-kDa. Consistent with this finding, we discovered that recombinant bacteria expressing bpaB produce a protein of ≥ 300-kDa on their surface that is reactive with a BpaB-specific monoclonal antibody. Analysis of sera from mice infected with B. mallei indicated that animals produce antibodies against BpaB during the course of disease, thus establishing production of the autotransporter in vivo. To gain insight on its role in virulence, we inactivated the bpaB gene of B. mallei strain ATCC 23344 and determined the median lethal dose of the mutant in a mouse model of aerosol infection. These experiments revealed that the bpaB mutation attenuates virulence 8-14 fold. Using a crystal violet-based assay, we also discovered that constitutive production of BpaB on the surface of B. mallei promotes biofilm formation. To our knowledge, this is the first report of a biofilm factor for this organism.

Use of the common marmoset to study Burkholderia mallei infection.

Burkholderia mallei is a host-adapted bacterium that does not persist outside of its equine reservoir. The organism causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by B. mallei typically occurs via the respiratory or percutaneous route, and the most common manifestations are life-threatening pneumonia and bacteremia. Glanders is difficult to diagnose and requires prolonged antibiotic therapy with low success rates. There is no vaccine to protect against B. mallei and there is concern regarding its use as a biothreat agent. Thus, experiments were performed to establish a non-human primate model of intranasal infection to study the organism and develop countermeasures. Groups of marmosets (Callithrix jacchus) were inoculated intranasally with B. mallei strain ATCC 23344 and monitored for clinical signs of illness for up to 13 days. We discovered that 83% of marmosets inoculated with doses of 2.5 X 10(4) to 2.5 X 10(5) bacteria developed acute lethal infection within 3-4 days. Signs of disease were severe and included lethargy, inappetence, conjunctivitis, mucopurulent and hemorrhagic nasal discharges, and increased respiratory effort with abdominal lifts. Burkholderia mallei was cultured from the lungs, spleen and liver of these animals, and pathologic examination of tissues revealed lesions characteristic of glanders. Challenge experiments also revealed that 91% of animals infected with doses ranging from 25 to 2.5 X 10(3) bacteria exhibited mild non-specific signs of illness and were culture negative. One marmoset inoculated with 2.5 X 10(3) organisms developed moderate signs of disease and reached humane end-points 8 days post-infection. The liver and spleen of this animal were colonized with the agent and pathological analysis of tissues showed nasal, splenic and hepatic lesions. Taken together, these data indicate that the marmoset is a suitable model to study respiratory infection by B. mallei.

Natural Burkholderia mallei infection in Dromedary, Bahrain.

We confirm a natural infection of dromedaries with glanders. Multilocus variable number tandem repeat analysis of a Burkholderia mallei strain isolated from a diseased dromedary in Bahrain revealed close genetic proximity to strain Dubai 7, which caused an outbreak of glanders in horses in the United Arab Emirates in 2004.

Molecular epidemiology of glanders, Pakistan.

We collected epidemiologic and molecular data from Burkholderia mallei isolates from equines in Punjab, Pakistan from 1999 through 2007. We show that recent outbreaks are genetically distinct from available whole genome sequences and that these genotypes are persistent and ubiquitous in Punjab, probably due to human-mediated movement of equines.

Pathogenesis of Burkholderia pseudomallei and Burkholderia mallei.

Burkholderia pseudomallei and mallei are biological agents of military significance. There has been significant research in recent years to develop medical countermeasures for these organisms. This review summarizes work which details aspects of the pathogenesis of B. pseudomallei and mallei and discusses key scientific questions and directions for future research.

[Glanders--a comprehensive review]. / Ein Ubersichtsreferat zur Rotzerkrankung.

Since 1990 the number of glanders outbreaks in race, military and pleasure horses in Asia and South America is steadily increasing. Glanders, which is eradicated in Western Europe, Australia and Northern America, is currently considered a re-emerging disease. Consequently, the disease may be introduced into glanders-free regions by subclinical carriers at any time. The causative agent of glanders, Burkholderia (B.) mallei, is highly contagious and leads to chronic disease in horses whereas in donkeys and mules the disease is acute and often fatal. Occurrence of the disease leads to international trading restrictions and infected animals immediately have to be culled and safely disposed off. In humans B. mallei infection results in a severe clinical course, and is fatal without appropriate therapy. Its pathogenicity makes B. mallei a potential biological agent that may be used in bioterroristic attacks. Due to the eradication of glanders in the second half of the last century, veterinarians in western European countries are no longer familiar with its clinical presentation in solipeds. Having these facts in mind, this review describes the epidemiology, clinical signs, pathology and the current eradication strategy of this interesting zoonosis. Pictures of imported endurance horses infected with glanders taken during an eradication campaign in Dubai, United Arab Emirates, in 2004 illustrate most typical clinical findings.

[Glanders, melioidosis and biowarfare]. / Morve, mélioïdose et bioterrorisme.

MANY COMMON FACTORS: Glanders and melioidosis are infectious diseases that are caused by the bacteria of the Burkholderia species. These infections are endemic in tropical regions and can lead to la broad spectrum of common clinical manifestations. TWO PRINCIPLE CLINICAL FORMS: The most frequent clinical presentation is the pulmonary form, which can mimic pulmonary tuberculosis. The septicemic form is the most severe form, and lethal in nearly 50% of cases. WEAPONS FOR BIOTERRORISM AND WAR: Very few organisms are required to cause disease by aerosolisation, which could be the main route of contamination for humans after a deliberate release. This property has permitted yet the use of these bacteria as biological warfare weapon during the past century. We have to consider these agents as possible biological warfare agents. Europeans guidelines for treatment and post-exposure prophylaxis are detailed.

[Glanders--a potential disease for biological warfare in humans and animals].

Infection with Burkholderia mallei (formerly Pseudomonas mallei) can cause a subcutaneous infection known as "farcy" or can disseminate to condition known as Glanders. It is primarily a disease affecting horses, donkeys and mules. In humans, Glanders can produce four types of disease: localized form, pulmonary form, septicemia, and chronic form. Necrosis of the tracheobronchial tree and pustular skin lesions characterize acute infection with B. mallei. Other symptoms include febrile pneumonia, if the organism was inhaled, or signs of sepsis and multiple abscesses, if the skin was the port of entry. Glanders is endemic in Africa, Asia, the Middle East, and Central and South America. Glanders has low contiguous potential, but because of the efficacy of aerosolized dissemination and the lethal nature of the disease, B. mallei was considered a candidate for biological warfare. During World War I, Glanders was believed to have been spread to infect large numbers of Russian horses and mules on the Eastern front. The Japanese infected horses, civilians and prisoners of war during World War II. The USA and the Soviet Union have shown interest in B. mallei in their biological warfare program. The treatment is empiric and includes mono or poly-therapy with Ceftazidime, Sulfadiazine, Trimethoprim + Sulfamethoxazol, Gentamicin, Imipenem etc. Aggressive control measures essentially eliminated Glanders from the west. However, with the resurgent concern about biological warfare, B. mallei is now being studied in a few laboratories worldwide. This review provides an overview of the disease and presents the only case reported in the western world since 1949.

[Glanders--an eradicable disease--or a threat?]. / Vozhrivka--eradikovaná nemoc--nebo hrozba?

Glanders (malleus), attacking equids and transmissible to humans, does not occur in our geographical area any more, but world-wide eradication has not yet been achieved. Cases of glanders have been reported from India, Iraq, Mongolia and China and in 2001 also from South America. The disease is caused by Burkholderia mallei (earlied known as Bacillus, Pfeiferella, Loefflerella, Malleomyces, Actinobacillus, or Pseudomonas mallei). The continual interest of microbiologists in the causative agents indicates that glanders cannot be regarded as a closed historic episode. Occupational infections of laboratory personnel occurred during World War II and the years thereafter and the last accident was reported in May 2000. Topical problems of glanders include the development of a vaccine and antibiotic therapy tested in experimentally infected subjects.