“You want to discuss a patient? Okay, but this telephone line is terrible” replied the Microbiologist, wondering whether the “new” telephone system in the hospital was really an “improvement”.
“Sorry, it’s a bit difficult to hear you” said the ward Doctor, “I wanted to discuss a patient with enlarged glands in the neck.”
“What?!” exclaimed the Microbiologist, “you think your patient has glanders! Why do you think they have glanders?”
“Yes, they have large glands …in their neck.”
“Glanders is extremely rare, and very severe, have you started antibiotics?”
“Yes, we want to start antibiotics.”
The telephone line was still terrible, and the Microbiologist was starting to get really worried. He looked at the number listed on the phone recognising it as the Acute Medical Unit where patients were admitted.
“I’m coming to you, wait for me there” said the Microbiologist putting down the phone.
“Blooming Microbiologist,” muttered the ward Doctor, “he just hung up on me!”
What is glanders?
Glanders is principally an infection of “solipeds” …that’s horses, donkeys and mules to you and me. It is caused by the bacterium Burkholderia mallei, a small, Gram-negative, oxidase positive, bacillus, that only replicates inside its living host being unable to survive in the environment. B. mallei is not to be confused with a similar bacterium I blogged about way, way, back in 2017 called Burkholderia pseudomallei which causes a condition called melliodosis and which is able to survive in the environment!
Nowadays glanders is rare in the developed world but can still occur as a potential zoonotic infection in Veterinary Surgeons, abattoir workers, horse handlers and laboratory workers. Cases are still seen in the Middle East, Asia, Africa, and South and Central America, and sometimes carnivores, e.g. cats, can be a focus if they have eaten infected equine meat.
How is glanders spread?
The main routes of transmission of glanders are inhalation or inoculation of infected material. Infected horses are highly infectious both from respiratory material as well as skin tissue. The incubation can be as little as 1-2 days from inhalation and up to a month with inoculation. However there have also been cases described where people develop infection many years after they became colonised from infected animals, so the “animal exposure” need not be recent.
How does glanders present in horses?
Horses can get two forms of glanders:
- Respiratory – fever with necrotic ulcers and nodules in the trachea with copious thick yellow secretions full of bacteria. Cervical and mediastinal lymphadenopathy occurs with necrotic pneumonia followed by multiorgan dissemination and death.
- Cutaneous – (known as farcy) nodular abscesses containing oily yellow pus containing numerous bacteria, mortality is common but surviving animals can become carriers and infect other animals
How does glanders present in humans?
Like horses, humans can get both respiratory and cutaneous glanders, depending on whether the bacteria are inhaled or inoculated respectively, and the infections are spookily similar to their equine equivalents:
- Respiratory - fever with ulcerative necrosis of the trachea and bronchi along with purulent discharge from the nose, lips, and eyes. Pneumonia with neck and mediastinal lymphadenopathy occurs, followed by multiorgan dissemination. Without treatment, death usually occurs within 10 days. Crikey, that’s quick!
- Cutaneous – purulent nodules and ulcers, with fever and malaise, followed by lymphatic spread to cause lymphangitis and abscesses in regional lymph nodes. Multiorgan dissemination can occur leading to death if untreated.
In the pre-antibiotic era, when most cases of glanders occurred, the mortality in humans was 90-95%!
How is glanders diagnosed?
In order to prove a diagnosis of glanders you need to grow the bacterium B. mallei. This is easier (and safer) said than done! B. mallei is a category 3 pathogen because the organism is really very infectious and the disease is really severe; it has to be handled in a biological safety facility like a TB lab. The lab form therefore needs to indicate the possible diagnosis… lab staff get glanders when lab forms are submitted with insufficient details and poor communication on them!
In terms of growing the bacterium it will grow on most laboratory culture agar under aerobic conditions, and the colonies look a bit like Pseudomonas spp.. In fact, the old commercial identification tests such as the API strips were unable to distinguish B. mallei from Pseudomonas aeruginosa which led to a number of laboratory incidents where BMS staff inadvertently handled the bacterium outside of Category 3 because they were unaware of what it was. The key to recognising that you are dealing with B. mallei and not P. aeruginosa is that B. mallei is sensitive to antibiotics often tested against Gram-negative bacilli but that are not active against P. aeruginosa such as Cefotaxime, Co-trimoxazole and Co-amoxiclav; it is important to recognise these odd patterns of antibiotic sensitivity or resistance so that you stop “playing” with it and don’t get accidentally exposed.
Newer identification methods such as MaldiTOF and 16sRNA PCR are able to identify B. mallei incredibly well so hopefully lab exposures will become less common as more labs have access to this new technology.
How is glanders treated?
There is no specific antibiotic regimen for the treatment of glanders because it is rare in the modern antibiotic era. The problem is that in order to successfully manage the patient you have to treat the initial infection and then eliminate carriage of the organism to prevent relapses.
The last case of glanders that occurred in the USA was treated successfully with a combination of IV Imipenem PLUS IV Doxycycline for 1 month followed by PO Azithromycin PLUS PO Doxycycline for 6 months. This patient had already relapsed after 2 shorter courses of a cephalosporin followed by Clarithromycin.
Current “recommendations”, or maybe its best to say “suggestions”, are that patients with glanders should receive:
(at least 10 days)
OR IV Meropenem
OR IV Ceftazidime
Eradication therapy (acute treatment followed by at least 3 months)
OR PO Doxycycline
OR PO Co-amoxiclav
The Microbiologist arrived on the ward in a rush, breathing hard.
“Where’s the patient with suspected glanders?” he demanded breathlessly.
“They haven’t been to Flanders; I know its Remembrance Sunday but really your hearing is off!” said the ward Doctor
“Not Flanders…glanders… you said they had glanders, I ran here because...it’s so serious!!” gasped the Microbiologist
“I can see…you might need some oxygen” the ward Doctor couldn’t hide his grin… “what’s glanders?” they asked.
“You said you had a patient with glanders” said the Microbiologist.
“No. I have a patient with enlarged glands in their neck and a terrible tonsillitis. They are allergic to first and second line antibiotics and I wasn’t sure what else I could use.”
The Microbiologist stared at the ward Doctor for a moment, sighed with some relief and then chuckled...“Don’t tell me, they also have a 'horse' voice?”
Glanders, an overview of infections in humans. K Van Zandt, M Greer, H Gelhaus. Orphanet J Rare Dis 2013.8;131