Glanders and Melioidosis – coming soon to a crowded shopping centre near you?
Glanders is an infectious disease which occurs mainly in horses, mules, and donkeys, but can also be contracted by other animals such as dogs, cats and goats. It is caused by infection with the bacterium Burkholderia mallei, usually by ingestion of contaminated food or water. Melioidosis [mel-ee-oi-doh-sis] affects humans as well as animals such as goats, sheep, horses and cattle, and is caused by Burkholderia pseudomallei. Burkholderia species are Gram-negative, non-spore-forming bacteria quite commonly found in soil and water, especially in tropical climates.
Symptoms of glanders in animals include the formation of lesions in the lungs and ulceration of mucous membranes in the upper respiratory tract. The acute form of the disease results in coughing, fever and the release of an infectious nasal discharge, followed by septicaemia and death within days. In the chronic form, nasal and skin nodules develop, eventually forming ulcers. Death can occur within months, while survivors act as carriers. Glanders rarely affects humans and I’ll explain the reason for this shortly.
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In contrast to glanders, melioidosis often affects humans. The mode of infection is through a break in the skin, or through the inhalation of aerosolized B. pseudomallei cells. There is an association with increased rainfall, with the number of cases increasing following heavy rains. The mean incubation period for acute melioidosis is 9 days (range 1-21 days), but patients with latent melioidosis may remain symptom free for decades. The longest known period between presumed exposure and clinical symptoms is 62 years. Melioidosis has a wide spectrum of severity. Patients usually have a fever, but other symptoms such as a cough or chest pains can indicate pneumonia, and bone or joint pains may indicate bone infections or septic arthritis, etc. The treatment of melioidosis is divided into two stages, an intravenous high intensity stage followed by an oral maintenance stage to prevent recurrence. Surgical drainage is usually required for abscesses. Without access to appropriate antibiotics, melioidosis has a mortality rate which exceeds 90%. With appropriate treatment, the mortality rate is about 10% for uncomplicated cases but up to 80% for cases with bacteraemia or severe sepsis.
The unusual genome of Burkholderia pseudomallei has two large chromosomes (most bacteria have only one) and the two chromosomes have different roles (Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei PNAS USA 2004 101: 14240-5). The larger 4.07 megabase pair chromosome contains “standard issue” genes for most of the housekeeping work of the cell, whereas the smaller 3.17 megabase pair chromosome contains genes which allow B. pseudomallei to adapt and survive in a range of environments. A further striking feature of the genome is the presence of 16 genomic islands which together made up 6% of the genome. These are present in clinical and in soil isolates but entirely absent from B. mallei and so may be related to the greater pathologic potential of B. pseudomallei over its close relative.
The infectious dose of B. pseudomallei for humans is not known, but probably varies. Most infections with B. pseudomallei in previously healthy individuals have followed major contamination (e.g. near-drowning episodes, contaminated war wounds, inoculation with contaminated medications or laboratory accidents). However, other cases are thought to have occurred following relatively minor exposure (e.g. inhalation of aerosols by helicopter crews in Vietnam). In some susceptible animals, the lethal dose by inoculation is less than 10 organisms. However, there are only few unusual cases documented for direct person-to-person transmission. In endemic areas, at-risk people (e.g. rice-paddy farmers) are warned to avoid contact with soil, mud and surface water where possible.
Due to the high mortality rate in humans and the small number of organisms required to establish infection, Burkholderia species have been investigated as a potential biological warfare or bioterrorism agents. During World War I, glanders was believed to have been spread deliberately by German agents to infect Russian horses and mules on the Eastern Front. This had an effect on troop and supply convoys as well as on artillery movements, which were then dependent on horses and mules. Both the USA and the Soviet Union are believed to have studied these agents as possible biological warfare weapons during and after World War II, but so far as is known they were never weaponized (i.e. manipulated to form more deadly strains). The features of these bacteria which make them candidates for deliberate release include:
- Ability to cause severe, rapidly fatal invasive infections
- Ability to initiate infections via aerosols, inoculation and possibly ingestion
- Intrinsic resistance to many antibiotics
- Ability to infect a wide range of animals as well as humans
- Long term persistence in the environment under suitable conditions (there were many human cases of glanders in Russia in the years after World War II)
So far, so bad. But it gets worse. Currently, there is no vaccine available for either B. mallei or B. pseudomallei in humans or animals. Because the presence of antibodies does not appear to be protective, a vaccine must also stimulate the cellular immune response. Burkholderia are intracellular pathogens, and the presence of antibodies does not appear to be protective against disease, so any vaccine must also stimulate cellular immune responses. As a biological weapon, B. pseudomallei lacks some of the immediate terror of anthrax or smallpox, but infections can be very difficult to diagnose (it has been called “the Great Mimicker”), and may occur many decades after exposure to the bacterium. No-one knows how the bacteria survive in the body for so long, but in many late-onset cases, a chronic illness such as diabetes or kidney disease is the spark which ignites the latent infection. And unlike growing smallpox virus, it would be relatively easy for a terrorist group with limited microbiological knowledge to brew up cultures of Burkholderia pseudomallei….
Links:
- Glanders: off to the races with Burkholderia mallei. FEMS Microbiology Letters 26 Oct 2007
- Racing to Defuse a Bacterial Time Bomb. Science 2007 317: 1022-1024
- UK HPA: Glanders and Melioidosis (includes Guidelines for Action in the Event of a Deliberate Release of Glanders and Melioidosis)
Tags: Agriculture, Antibiotics, Bacteria, Biology, Bioterrorism, Health, Medicine, Microbiology, Podcast, Science
