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“Oh Rats! This Sudoku is hard…”

9/3/2018

 
​“I think my patient has plague!” exclaimed the over excited junior doctor.
 
Knowing that plague had not been seen in the UK for 100 years this year the Microbiologist sighed, “Why do you think your patient has plague?” he asked.
 
“Because they have a rash and have been bitten by a rat” explained the junior doctor.
 
“Have they got a fever, headache and any swollen joints? Is the rash maculopapular?” asked the Microbiologist starting to take more of an interest, but not because they thought this might be plague.
 
“Yes!” said the junior doctor getting even more excited.
 
“This sounds like rat bite fever” said the Microbiologist “let’s get a joint fluid sample and then we can discuss treatment.”
 
“Oh, so you don’t think it’s plague then….” muttered the junior doctor.
Picture
Rat bite fever is a bacterial infection caused by either Streptobacillus moniliformis or Spirillum minus. Both of these bacteria are part of the normal upper respiratory and oral flora of rats, although very occasionally other animals can be colonised including squirrels, mice, gerbils, weasels, ferrets, and even cats and dogs (although I wonder if the cats and dogs become colonised by attacking or eating the other rodents!).
 
Transmission usually occurs from a bite from a colonised animal but infection has also been described from contact with secretions or urine from a colonised animal. Direct contact with the animal isn’t always necessary. Outbreaks have occurred from contact with rat-infested buildings and in fact the first description of rat bite fever caused by S. moniliformis occurred at Haverhill in Massachusetts, USA, when 86 people developed a fever after ingesting milk contaminated by rats. The other name for rat bite fever is therefore Haverhill Fever. The other name for rat bite fever caused by S. minus is Sodoku (as in the number puzzle, Sudoku, so popular in newspapers!) for which the translation is “the numbers must remain single” but I don’t know why this name is used, maybe because there is only one cause? Do any of you know why the name is Sodoku?
Picture
This has been described as evil level, I guess that means it's difficult!
How does rat bite fever present?
Rat bite fever is not common, but it can be found throughout the World; S. moniliformis is more common in North and South America and Europe whereas S. minus is more common in Asia.
 
There is almost always a history of exposure to rats or other rodents; and usually a history of a rat bite. Those most at risk include people who keep rodents as pets, Veterinarians and Veterinary nurses, sewerage workers and those who work in derelict buildings.
 
The incubation period for S. moniliformis is 3-10 days whereas S. minus is from 2 days to 3 weeks. Infection with S. moniliformis usually settles within 2 weeks but relapses are common. The most common presentations for S. moniliformis are:
  • Fever
  • Headache
  • Vomiting
  • Myalgia
  • Maculopapular rash, 2-4 days after onset of fever
  • Polyarthritis, usually non-suppurative, in 50% of cases
  • Complications include infective endocarditis, pericarditis, parotitis, tenosynovitis and abscesses.

​Infection with S. minus is similar to S. moniliformis but arthritis is less common, the rash is normally patches of red or purple skin and the presence of an indurated area of skin at the site of the original bite.
 
The mortality for rat bite fever irrespective of the causative bacterium is up to 10%.
 
How is rat bite fever diagnosed?
Rat bite fever is diagnosed by detecting the bacteria in normally sterile sites. Samples should be sent to the microbiology laboratory with good clinical details suggesting exposure to rats or other animals otherwise the laboratory will not routinely look for these bacteria.
 
Both S. moniliformis and S. minus are Gram-negative bacilli which are facultative anaerobes. They are fastidious and slow growing and very hard to isolate using routine culture methods. Culture for S. moniliformis should be performed using enriched media such as heart infusion agar with 5% rabbit blood supplemented with additional rabbit or horse serum spread on top of the agar and allowed to dry before inoculating the plate! What a palaver and another good reason why it’s not a routine culture then. And on top of that S. minus cannot be cultured!
 
Nowadays most diagnoses are made using PCR, especially 16sRNA PCR which detects the presence of bacteria even though they are not easy to grow or may be dead. This can be done on a normally sterile sample such as joint fluid, lymph nodes or pus.
 
There are also serology tests for rat bite fever but these are prone to false negatives and are rarely used anymore.
 
How is rat bite fever treated?
The first line treatment for rat bite fever is penicillin, usually IV Benzylpenicillin 1.2g 4 hourly for at least 1 week followed by oral Penicillin V to finish a total of 2 weeks treatment. Alternatives in penicillin allergic patients are IV Ceftriaxone 1g OD and IV Doxycycline 100mg BD. For septic arthritis and endocarditis treatment should be continued for 4 weeks.
 
So our patient had a synovial fluid taken from their swollen elbow, above the site where they had been bitten by their new pet rat a week earlier. Treatment was stated with IV Ceftriaxone to cover for rat bite fever as well as the more common staphylococcal and streptococcal causes of joint infections. The sample was sent to the Reference Laboratory for 16sRNA testing as well as having routine culture. The routine culture was negative. The patient improved quickly and their temperature settled in a couple of days.

​A few days later the Microbiologist got a call from the Ref Lab to be told excitedly that S. moniliformis had been found in the synovial fluid and did the Microbiologist know that the patient had rat bite fever? The Microbiologist chuckled and said “yes”, he was relieved that he didn’t need to tell the junior doctor that his patient did indeed have the first detected plague in the UK for 100 years… but thought with more pet rat owners this type of call might become more common, before returning to finish his Sudoku puzzle!
Robert A. Thompson link
12/3/2018 06:15:12 pm

This has been an interesting read. I wonder if you might have time to bring up more such illnesses? The Rat Fever has caught my attention because Plague has always interested me since I follow by the CDC website and WHO any incidents of Plague. Thanks for a very interesting piece!

David
10/4/2018 09:56:31 am

Hi Robert, thanks for the feedback, glad you enjoyed it. I agree plague is fascinating, and for me historical medicine is a bit of a hobby. There is lots of good stuff mixed in Roy Porter's book Greatest Benefit to Mankind... it's a long read but worth it.
David

shawn acosta
12/3/2018 10:08:20 pm

What properties of the rabbit and horse enhanced agar samples made them the ideal media? Or is it just a random discovery?

David
10/4/2018 09:59:39 am

Hi Shawn
Good question. I suspect this was a random or lucky discovery as you say... most of medicine is a bit like this... think penicillin! Some blood is just better at showing certain properties than others. There may well be something in these species that make them more effective. In a similar way you get different decrees of beta-haemolysis on blood agar when it contains horse, sheep or even human blood. There will be a reason and if you find out please let me know...
Thanks

David

Makayla P Messer
25/3/2018 06:10:31 am

What could be done about the prevention of rat bite fever even though it is very uncommon?

David
10/4/2018 10:01:20 am

Hi Makayla
I suspect the only way to really prevent rat bite fever is to avoid exposure. The obvious one is to not get bitten, but also using rat proof bins to store food etc. or protecting water and milk supplies. Pest control would also be important as well as sanitary disposal of waste. There is no way I know of to specifically target the bacteria though.
Hope that answers your question
David


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    Blog Author:

    David Garner
    Consultant Microbiologist
    Surrey, UK

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