Über unsRats, Bites, Fever – Rat Bite Fever – a Rarely Documented Pathogen is the Focus of a Successful Collaboration
Ein Bericht aus unserem Laboralltag
Dr. Jörg Rau (CVUAS), Dr. Tobias Eisenberg (LHL)
Streptobacillus (S.) moniliformis is one of the causal agents of the so-called rat bite fever. Infections with Streptobacillus have been seldom diagnosed in humans, as is also the case for animals. Now, longstanding cooperation with, and under the leadership of, the State Laboratory of Hesse (LHL) has enabled significant improvement in the analytical tools for laboratory diagnostic detection. Moreover, five new, closely related species of bacteria have been scientifically described.
Streptobacillus (S.) moniliformis is one of the causal agents of the so-called rat bite fever. Infections with Streptobacillus are very seldom diagnosed in humans. In 2015 there were two known cases in the city of Stuttgart, whereby the source of the infections could not be determined [1]. In another case a Bavarian farmer became ill with life-threatening symptoms [2]. The illness is widely acknowledged to be under-diagnosed. This is also due to the special culture conditions required for the cultivation of this oxygen-sensitive pathogen. However, it is assumed that in rats the pathogen occurs at very high detection rates, without causing the animals to become ill.
Rats carry the bacteria in their nasopharyngeal cavity, and are therefore considered to be an important reservoir for S. moniliformis. A rodent bite is not always a precondition for rat bite fever, however – direct or indirect contact with rats or their excretions can also expose humans to the pathogen. The illness is therefore considered a classic so-called zoonosis. In humans the symptoms of fever, muscle and joint pain, and skin rash typically appear after an incubation period of up to three weeks. In addition, joint and throat inflammation, vomiting, and in extreme cases also heart valve inflammation, blood poisoning and abscesses can be observed when adequate medical treatment comes too late. In the past there have been cases of human illnesses stemming from contaminated food. This alimentary form is called Haverhill Fever. Streptobacilli are not only dangerous for humans, however, animals can also suffer from serious illnesses. This was reason enough for the veterinarians at the State Laboratory of Hesse (LHL) in Giessen to have dealt intensively with Streptobacillus moniliformis and its close relatives.
Until recently it was thought that there was only one representative of the genus Streptobacillus – the S. moniliformis. Investigations of bacteria with diverse characteristics as well as the use of new methods quickly showed, however, that the Streptobacillus genus can consist of more than just one species. First, a Chinese research group described the S. hongkongensis, isolated from a sample taken from a diseased human. Then, in quick succession under the leadership of the LHL, the following species were scientifically described:
- S. felis , from a cat (Felis silvestriscatus) with pneumonia [3],
- S. notomytis , from an Australian hopping mouse (Notomys alexis) [4], and
- S. ratti , from a Japanese black rat (Rattus rattus) [5].
Closely related species which, based on their differences, could even be ascribed as new genera within the family (Leptotrichiaceae), were also investigated by the scientists. The bacteria Caviibacter abcessus were able to be isolated from guinea pigs (Cavia porcellus) with lymph node abscesses and Oceanivirga salmonicida were isolated from dying Atlantic salmon (Salmon salar) [6, 7]. Some of the isolates had already been stored for a longer period in strain collections. However, their significance as new species has only recently been recognized by scientists.
Illustration 2: Streptobacillus moniliformis under an electron microscope (Enlargement: 10.000-times; CVUA Stuttgart)
A current review by Eisenberg et al., 2016 summarizes the modern methods used for Streptobacillus including MALDI-TOF-Mass Spectrometry (MALDI-TOF MS) which, in the meantime, has become one of our most important tools in our daily work [8]. Up-to-date MALDI-TOF MS reference spectrums were also now compiled for the newly described family members of the Streptobacillus, which greatly facilitates the definite identification of bacteria in the laboratory. The compiled mass spectra have been put in the "MALDI-UP" user platform catalog and can be requested by other users of this technique for the purpose of scientific exchange [9].
The Chemical and Veterinary Investigations Office (CVUA) of Stuttgart supported all of this work through a variety of contributions (PCR, MALDI-TOF MS, infrared spectroscopy and electron microscopy) with an interdisciplinary team from biology, veterinary medicine and food chemistry. In addition to the above-mentioned scientific articles, the results of this long-term, successful cross-state collaboration have also been presented in various lectures and now also in April on a poster for the audience of experts at the Medical Biodefense Conference in Munich: Rau J, Eisenberg T 2016. Prepare for the rare – fast exchange of database entries for strengthening MALDI-TOF MS diagnostics on the example of Streptobacillus. Poster, 26.-29.04.2016, 15. Medical Biodefense Conference, Munich.
Photo credits:
Illustration 1: J. Rau; Illustration 2: V. Akimkin (CVUA Stuttgart)
Sources:
[1] Regnath T, Kurb N, Wolf M, Ignatius R.
Rat-bite fever – two cases of infection with Streptobacillus moniliformis within two months [in German].
Dtsch Med Wochenschr 2015; 140:741–743.
[2] Kondruweit M, Weyand M, Mahmoud FO, Geissdörfer W, Schoerner C, Ropers D, Achenbach S, Strecker T.
Fulminant endocarditis caused by Streptobacillus moniliformis in a young man. J Thorac Cardiovasc Surg. 2007; 134:1,579–1,580.
Erratum in: J Thorac Cardiovasc Surg. 2008: 135:770.
[3] Eisenberg T, Glaeser S, Nicklas W, Mauder N, Contzen M, Aledelbi K, Kämpfer P.
Streptobacillus felis sp. nov. isolated from a cat with pneumonia.
Int J Syst Evol Microbiol 2015; 65:2,172–8.
[4] Eisenberg T, Glaeser SP, Ewers C, T Semmler, Nicklas W, Rau J, Mauder N, Hofmann N, Imaoka K, Kimura M, Kämpfer P.
Streptobacillus notomytis sp. nov. isolated from an Australian spinifex hopping mouse (Notomys alexis) THOMAS, 1922 and emended description of Streptobacillus Levaditi et al. 1925, Eisenberg et al. 2015 emend.
Int J Syst Evolut Microbiol, accepted 2 Oct., 2015
[5] Eisenberg T, Imaoka K, Kimura M, Glaeser SP, Ewers C, T Semmler, Rau J, Nicklas W, Tanikawa T; Kämpfer P.
Streptobacillus ratti sp. nov. isolated from a black rat (Rattus rattus)
Int J Syst Evolut Microbiol, accepted 21 Dec., 2015
[6] Eisenberg T, Glaeser SP, Ewers C, Semmler T, Drescher B, Kämpfer P.
Caviibacter abscessus gen. nov. sp. nov., a novel member from the Leptotrichiaceae isolated from guinea pigs (Cavia porcellus)
Int J Syst Evolut Microbiol 2016; in press.
[7] Eisenberg T, Kämpfer P, Ewers C, Semmler T, Glaeser SP, Collins E, Ruttledge M, Palmer R.
Oceanivirga salmonicida gen. nov. sp. nov., a novel member from the Leptotrichiaceae isolated from Atlantic salmon (Salmo salar)
Int J Syst Evolut Microbiol 2016; in press.
[8] Eisenberg T, Ewers C, Rau J, Akimkin V, Nicklas W.
Approved and novel strategies in diagnostics of rat bite fever and other Streptobacillus infrections in humans and animals.
Virulence (2016), Review 18 April, 2016: accepted manuscript online
[9] Rau J, Eisenberg T, Männig A, Wind C, Lasch P, Sting R.
MALDI-UP – An Internet Platform for the Exchange of MALDI-TOF Mass Spectra, User guide for http://maldi-up.ua-bw.de/
Aspects of food control and animal health 01 2016