Rat-Bite Fever: Streptobacillus moniliformis and Spirillum minus

Bacteriology

S. moniliformis is a pleomorphic, nonmotile, nonsporulating, nonencapsulated gram-negative bacillus in the family Leptotrichiaceae, measuring 0.3 to 0.7 µm wide by 1 to 5 µm long. Filaments and beadlike chains up to 150 µm long may contain 1- to 3-µm-wide fusiform swellings ( Fig. 231.1 ). The organism is microaerophilic and capnophilic, requiring a partial pressure of carbon dioxide between 8% and 10% for primary isolation at 37°C. Trypticase soy agar or broth must be supplemented with 10% to 20% rabbit, sheep, or horse serum; defibrinated blood; or ascites to support optimal growth. A shell vial cell culture technique that used human endothelial cells rescued viable S. moniliformis after conventional culture methods failed. Sodium polyanethol sulfonate, a substance sometimes added to aerobic blood culture bottles as an anticoagulant or to trypticase soy or thioglycollate broth to inhibit the antibacterial activity of human blood, impedes the growth of S. moniliformis in concentrations of at least 0.0125%. Thus if rat bite fever is suspected, the laboratory should be informed and serum-supplemented broth or agar medium without sodium polyanethol sulfonate should be used.

On blood agar plates, nonhemolytic cotton-like colonies, 1 to 2.5 mm in diameter, appear after approximately 3 days of incubation. In broth media, characteristic flocculent “puffballs” are seen at the bottom of the broth after 2 to 10 days ( Fig. 231.2 ). Penicillin-resistant L-phase variants may form spontaneously or in the presence of penicillin both in vivo and in vitro. Low muramic acid content in cell envelopes may contribute to the propensity of S. moniliformis to produce L forms, which impart a turbid appearance to broth media and a “fried egg” colony morphology on solid agar. Sugar fermentation is variable but often includes galactose, glucose, maltose, and salicin. Fatty acid analysis by gas-liquid chromatography is useful for the rapid identification of S. moniliformis isolates. In addition, sodium dodecyl sulfate–polyacrylamide gel electrophoresis patterns of cellular proteins may be useful for epidemiologic studies of the epidemic (Haverhill fever) form of the infection. Guanine plus cytosine content is 24 to 26 mol%, and the complete genome sequence has been reported.

Epidemiology

In the United States, where 50% to 100% of rats are colonized with S. moniliformis, persons who are at risk for percutaneous inoculation with S. moniliformis include animal laboratory personnel and individuals (especially children) inhabiting crowded urban dwellings or rural areas infested with wild rats. Although rat bite fever is not reportable, based on an estimated 20,000 rat bites annually and a 10% bite infection rate, an incidence of more than 1000 cases per year is estimated. The infection is typically transmitted by the bite or scratch of rats, mice, guinea pigs, squirrels, or carnivores that prey on those rodents, including cats, dogs, pigs, ferrets, weasels, and snakes. One reported case followed the bite of a gerbil, another the scratches of a rooster. The infection may also be acquired by handling rats, without any apparent breach of intact skin or with a portal of entry, such as varicella lesions. Wild rats as well as laboratory and pet rats harbor S. moniliformis in their nasopharyngeal microbiota, and they may develop otitis media. In contrast, healthy laboratory mice are generally not colonized with S. moniliformis but are susceptible to epizootic infections characterized by polyarthritis, septicemia, pneumonia, otitis media, and high rates of abortion. S. moniliformis has also been reported to cause pleuritis in a koala, cervical abscesses and pneumonia in guinea pigs, arthritis in turkeys and a monkey, and endocarditis in a macaque.

Pathophysiology

The clinical disease is probably the consequence of failed local cutaneous defenses and bacterial dissemination. The few available published pathology reports described interstitial pneumonia, lymph node hyperplasia, erythrophagocytosis, vasculitis, and intravascular thrombi.

Oral ingestion of organisms has caused several epidemics of Haverhill fever (erythema arthriticum epidemicum), an illness clinically resembling rat-bite fever. Potential sources of such outbreaks include foods such as turkey, or milk or water contaminated with rat excrement. Presumably, once ingested, S. moniliformis organisms gain access to the peripheral circulation by penetrating the gastrointestinal mucosa.