Xishan Biology

Introduction to Pathogens

Streptobacillus moniliformis

Introduction to Pathogenology

 

Streptobacillus moniliformis is a Gram-negative, pleomorphic, filamentous bacterium that lacks motility. It is the pathogen responsible for causing rat-bite fever and Haverhill fever (also known as epidemic erythematous polyarthritis) in humans. This bacterium primarily colonizes the nasopharynx, pharynx, middle ear, and upper trachea of wild rodents, pet rats, and even healthy laboratory rats—animals that serve as its main reservoirs. Notably, it exhibits high pathogenicity toward humans, laboratory mice, and non-human primates. With the expansion of urban areas and the increasing diversity of pets, many rare pathogens—including Streptobacillus moniliformis—have emerged as potential threats to human health. Countries such as the United States and Canada have already classified this bacterium as a deadly zoonotic disease, placing it among the newly emerging infectious diseases. In recent years, clinical cases have been reported in China, and outbreaks have even occurred in laboratory mice, underscoring the ongoing threat posed by Streptobacillus moniliformis within the country. As life science research continues to advance, incidents of infection resulting from bites by bacteria-carrying rats during animal experiments have become increasingly common. Consequently, this bacterium is now recognized as an occupational hazard for researchers working with laboratory animals.

Epidemiology

 

Since rodents are the natural hosts of *Arcanobacterium canis*, this bacterium has been isolated from wild mice, pet rats, and laboratory rats. Overseas reports indicate that the carriage rate in wild and laboratory rats can range from 50% to 100%, making rodents the primary source of transmission for this bacteria.

The primary transmission routes to humans are broadly categorized into two types: one is through rodent bites, where the infection spreads via saliva; the other occurs when people ingest contaminated food or water, potentially triggering localized outbreaks in the region. Additionally, reports indicate that approximately 39% of patients were exposed to the pathogen through unknown means, such as scratching or biting wounds, or even through close contact like kissing. In animals, infection with this bacterium can occur via aerosols or contaminated bedding materials, among other transmission pathways.

Directly triggering outbreaks of disease or infection.

All warm-blooded animals, including humans, are susceptible to this pathogen, which can cause severe illness in all species except laboratory and wild rats. As for mice, Kunming and C57BL/6J strains exhibit significantly higher susceptibility to the bacterium compared to other strains.

Clinical symptoms

 

Rats show no symptoms after infection, with occasional cases of lung infection and abscesses.

In mice, susceptibility varies significantly depending on the strain. For instance, C57BL/6 and Swiss inbred mice are highly sensitive, while DBA/2 mice exhibit moderate sensitivity, and BALB/C and C3H/HE mice demonstrate resistance. After infection, mice often experience sudden death due to septicemia, or they may develop prolonged symptoms of sepsis. Typical clinical signs include cervical lymphadenitis, diarrhea, conjunctivitis, cyanosis, hemoglobinuria, and weight loss. In surviving animals that recover from acute infection, pyogenic polyarthritis, osteomyelitis, and abscesses may be observed. Post-mortem examination reveals extensive necrotic lesions and inflammation in the liver and spleen, along with petechial hemorrhages or ecchymoses on serous surfaces. Furthermore, secondary kidney damage often occurs following sepsis, characterized by interstitial nephritis and the presence of bacterial colonies.

 

Human infection with Streptobacillus moniliformis primarily causes two types of diseases: one is rat-bite fever, which results from infection after being bitten by a carrier rodent, with main symptoms including localized lymphadenitis, bacteremia, sepsis, endocarditis, pericarditis, and erythematous papules; the other is Haverhill fever, contracted either through bites or by consuming water or milk contaminated with rodent excreta. This form mainly manifests as multi-organ abscesses, polyarthritis—sometimes accompanied by rare cases of suppurative arthritis—and can lead to complications such as endocarditis and pericarditis.

Human infection with Corynebacterium ulcerans can be fatal; therefore, bites from wild or pet rats should be reported to a doctor immediately and treated without delay.

Diagnosis

 

The nasopharyngeal secretions or tracheal swabs collected from rats or mice infected with or carrying *Corynebacterium ulcerans* can be cultured on blood agar at 36±1°C for 48 hours, yielding round, grayish-white, non-hemolytic colonies approximately 1 mm in size—colonies that are difficult to emulsify when examined under a smear. Gram staining reveals Gram-negative, slender bacilli that exhibit pleomorphism and typically appear scattered or arranged in clusters. Confirmation of the diagnosis is then achieved through manual biochemical tests, the VITEK 2 Compact automated microbial analysis system, or mass spectrometry. Alternatively, serological assays or PCR-based methods may also be employed for diagnostic purposes.

The Impact on Research

 

Streptococcus viridans is a harmless commensal bacterium in the upper respiratory tract of rats but can cause disease in mouse populations. Moreover, since this bacterium is zoonotic, rats carrying Streptococcus viridans are unsuitable for research purposes.

Prevention and Control

 

Since *Streptobacillus moniliformis* infection is primarily transmitted through direct contact with infected animals, preventing the entry of carrier animals into facilities is key to effective prevention. Laboratory animal housing areas must be strictly guarded against unauthorized non-experimental animals, and robust rodent-control measures should be implemented. Newly acquired animals must undergo rigorous quarantine and pathogen testing before being introduced. Additionally, all personnel entering or leaving the laboratory animal housing area should follow strict protective protocols to avoid contaminating the environment.

Since Corynebacterium diphtheriae does not produce spores, it has relatively weak resistance to the environment. Common environmental disinfectants can effectively eliminate Corynebacterium diphtheriae from the environment.

References

 

Baker DG. Natural Pathogens of Laboratory Animals: Their Effects on Research. Washington, D.C.: ASM Press; 2003. 385 pp.

Fox JG, Anderson LC, Lowe FM, Quimby FW, editors. Laboratory Animal Medicine. 2nd ed. San Diego: Academic Press; 2002. 1325 pp.

Fox J, Barthold S, Davisson M, Newcomer C, Quimby F, and Smith A, editors. The Mouse in Biomedical Research: Diseases. 2nd ed. New York: Academic Press; 2007. 756 pp.

Percy DH, Barthold SW. Pathology of Laboratory Rodents and Rabbits. Ames: Iowa State University Press; 2007. 325 pp.

Li Hong, Xu Hufeng, Chen Weilan, and others. Observation on the Susceptibility of Different Mouse Strains to Experimental Infection with Corynebacterium glutamicum [J]. Chinese Journal of Laboratory Animal Science, 1997(01):12-17.

Liu Xing, Li Hong. Current Status of Research on Streptobacillus moniliformis [J]. Chinese Journal of Laboratory Animal Science, 2007(06):474-476.

Wang Chunling, Guan Weihong, Cai Jinxia, et al. Diagnosis of Mixed Infection with Corynebacterium diphtheriae-like Organism and Mousepox Virus in Laboratory Mice[J]. Laboratory Animal Science and Management, 1999(02):5-7.

 

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