“So, what can you tell me about deer fly fever?” he asked.
The trainees all looked at the floor, the ceiling, each other, in fact anything to avoid making eye contact with their overzealous teacher.
“Come on, come on” encourage the Microbiologist, “it’s a possible FRCPath exam question.”
“Okay, what about if I said the patient had recently returned from a summer holiday in Martha’s Vineyard, a 96-square-mile island shaped like a shark’s tooth off the coast of Massachusetts, with a high fever and severe pneumonia?”
The silence was deafening…
Then the Registrar piped up “isn’t that where the 2010 film Ghost Writer was set? Yeah, Martha’s Vineyard, yep, I’m sure it was! Some big cast names in it too”.
“Errrrr, lab worker with a painful ulcer and lymphadenopathy”, the Clinical Scientist said sheepishly.
“Rabbit skinner with sore eyes, or maybe a deer hunter with possible typhoid?” the Registrar piped up excitedly.
The Microbiologist rolled his eyes, took a deep breath! It was getting too uncomfortable…they really had “no-eyed deer”
The Microbiologist tried to make it as easy as possible, “has anyone heard of tularaemia?”
The pin dropping in the corner of the room made everyone jump violently!
What is tularaemia?
Tularaemia is a rare zoonotic infection caused by the bacterium Francisella tularensis. The “tularensis” part of the name comes from the place in the USA where the bacterium was first isolated, Tulare County in California; “Franciscella” comes from Dr Edward Francis who proved the link between the bacterium and the infection known as tularaemia between 1919-1928.
Francis referred to the infection as “deer fly fever” because of its association with bites from these flies, but it had also been associated with hares and rabbits in Japan and ground squirrels in the US as well as cases occurring in Russia. The most disturbing reference I can find to the history of tularaemia is that of a Japanese Doctor called Ohara, in 1926, who was studying the rabbit association of the infection; he deliberately infected his wife by rubbing rabbit hearts, taken from infected animals, on her hand and then isolating the causative bacterium from her inflamed lymph glands! What the heck?! Why did he think this was a good idea? And why did she let him???!
“Must have been LOVE” said the Registrar.
Ignoring the Registrar, the Microbiologist continued…
F. tularensis is a small, pleomorphic, aerobic Gram-negative coccobacillus. It is a hazard group 3 pathogen because it is so infectious and the infection can be severe, which means it has to be handled in a Category 3 biological safety facility in the same way as TB.
There are two subtypes of F. tularensis, known as A and B. Type A is the more pathogenic and causes more severe infections, and is predominantly found in North America; Type B has been found in North America, Europe, Asia and Australia. The increasing incidence in Europe is thought to be due to climate change expanding the range of its host species further North. The incidence of tularaemia in North America is now as low as 1 in a million population per year but it is still a notifiable infection in most countries because of its potential use as a bioterrorist weapon!
How does tularaemia spread?
Tularaemia is normally acquired from infected bites from flies or ticks infected with F. tularensis or by contact with infected animal tissue. Traditionally at-risk occupations have included hunters, farmers and veterinary surgeons, although more recently the risk has expanded to include laboratory workers and landscape gardeners. Hundreds of vertebrates and invertebrates have been found to harbour F. tularensis, and animal species shown to be able to be colonised or infected include rabbits, hares, voles, hamsters, mice, squirrels, muskrats, beavers, skunks, raccoons, deer and even domestic cats and dogs! Remember, the colonised animals will show no outward signs of infection but could still be infectious.
The landscape gardener one is a bit odd; it came about following the investigation of an outbreak of tularaemia in 2000 on Martha’s Vineyard, a summer holiday island destination off Cape Cod, Massachusetts (and the setting of that dreadful film!). In 2000 there were 15 cases of tularaemia on Marth’s Vineyard occurring in those involved in grass and brush cutting; most of the cases were landscape gardeners who were thought to be exposed through the aerosolization of infected material during cutting. That’s a lot of bug splatter!
How does tularaemia present?
The incubation period of tularaemia ranges from 1-21 days, but is usually 3-5 days. Some patients are completely asymptomatic however when symptoms do occur there are said to be 6 main forms but with a lot of overlap. All start with fevers, headaches, malaise and fatigue.
- Ulceroglandular – the most common form, with a tender ulcer developing at the site of an insect bite and associated localised lymphadenopathy, untreated ulcers can take weeks to heal and cause permanent scarring
- Glandular –similar to ulceroglandular but without the ulcer at the site of the insect bite
- Oculoglandular – occurs when the bacterium is inoculated from contaminated hands through the conjunctiva causing conjunctivitis, bruising, photophobia and corneal ulceration; visual loss is rare but can occur
- Pharyngeal – occurs after ingesting contaminated food or water and is similar to ulceroglandular but the site of the ulceration is the pharynx, and the lymphadenopathy is primarily cervical
- Typhoidal – can occur with any mode of acquisition, usually in patients with other underlying health problems, who present with sepsis, nausea, vomiting, abdominal pain and cough, which can progress rapidly to death
- Pneumonic – occurs due to direct inhalation or secondary spread in typhoidal tularaemia and is clinically indistinguishable from any other cause of severe community acquired pneumonia
There is no human-to-human spread of tularaemia and so multiple cases of pulmonary tularaemia should raise a concern about the possibility of a deliberate bioterrorist release of the bacterium whilst a common environmental source is being investigated.
Mortality ranges from 2-24% depending on the presentation, the subspecies of F. tularensis and the speed in which treatment is initiated.
How is tularaemia diagnosed?
It is important to consider tularaemia in anyone who has been in an endemic country who presents with one of the classical illnesses above as all specimens sent to the microbiology laboratory should be labelled HIGH RISK and dealt with in a Category 3 biological safety facility to prevent the BMSs from getting tularaemia themselves from handling the bacterium.
Older methods of bacterial identification, such as API strips, can misidentify F. tularensis as Haemophilus influenzae or Aggregatibacter spp. which can result in laboratory staff being put at risk of tularaemia as they believe the bacterium is safe to handle under basic laboratory conditions. Fortunately newer MaldiTOF and PCR methods of identification can easily identify the bacterium correctly.
There are serology tests for tularaemia, detecting both IgM and IgG, but these are of limited value in endemic countries as they can remain positive (even the IgM) for decades after infection. They have a use in travellers returning to non-endemic countries as these travellers would not be expected to have a positive test at all, and so the positive result means they have the infection.
How is tularaemia treated?
The main treatment for tularaemia are the aminoglycosides such as Gentamicin or Streptomycin. Doxycycline and Ciprofloxacin can also be used. Treatment duration is usually 7-10 days depending on how quickly the patient responds and how sick they were in the first place.
I’m not sure I would be comfortable just using an aminoglycoside to treat pneumonic or disseminated typhoidal tularaemia as the aminoglycosides don’t get into the chest well and won’t cross the blood brain barrier to treat CNS spread. In these cases, I would combine the aminoglycoside with Ciprofloxacin to ensure my antibiotics got into all of the body sites the bacterium might be hiding in.
The tutorial ended and the trainees turned back to the outstanding list of blood cultures and authorisation that still needed doing.
The trainee tasked with phoning out the new blood cultures starting flicking through the list, prioritising what was urgent and what could wait for further results. Suddenly something caught their eye. A blood culture where the clinical details said fever in a returned traveller, recently returned from Martha’s Vineyard …no, it couldn’t be … no way could the Consultant have guessed that …could they? It must be a contaminant or something else in the blood culture, surely?!
The trainee scrolled down to look at the Gram film result and read “aerobic bottle positive, pleomorphic Gram-negative bacillus seen”.
Turning back to face the Consultant the trainee started to speak, “errrr boss, you know that whole Martha’s Vineyard thing you just talked about? Well, you might want to have a look at this…. Oh and it wasn’t labelled HIGH RISK!!!”