Streptobacillus moniliformis and IgM and IgG Immune Response in Patient with Endocarditis1.

We describe a case of endocarditis caused by Streptobacillus moniliformis bacteria, a known cause of rat-bite fever, in a 32-year-old woman with pet rats in Germany. The patient had a strong serologic response, with high IgM and IgG titers. Serologic analysis is a promising tool to identify S. moniliformis bacterial infection.

What a Rat Race: A Case Study of Rat Bite Fever in an Emergency Department.

Rat bite fever is an acute illness caused by bacteria from rodents. In the United States, rat bite fever is considered rare; however, actual incidence is unknown because of lack of mandatory disease reporting requirements. Risk of development of rat bite fever after being bitten by a rat is approximately 10%. Early treatment is imperative as death is a potential complication. The following case study demonstrates the gravity of the syndrome.

Development and validation of a triplex real-time qPCR for sensitive detection and quantification of major rat bite fever pathogen Streptobacillus moniliformis.

Streptobacillus (S.) moniliformis is the most important pathogen causing rat bite fever (RBF) worldwide. This zoonotic pathogen is understudied mainly due to difficulties in culturing S. moniliformis as a fastidious microorganism. Therefore, advances in molecular detection techniques are highly needed, especially with regard to the widespread availability of real-time quantitative (q) PCR in laboratories. In this study, we aimed to develop a qPCR for the identification of Streptobacillus species and quantification of S. moniliformis in clinical samples, especially those derived from tissue samples of animal origin. We optimized a previously described PCR protocol in order to develop a qPCR, which can detect different Streptobacillus species with high specificity and is simultaneously able to quantitate S. moniliformis in different clinical matrices. The qPCR exhibited a limit of detection (LOD) of 21 copies/reaction representing ~4-5 streptobacilli, while the limit of quantification (LOQ) was 2.1 × 103 copies/reaction. It was also more sensitive than conventional PCR by two orders of magnitude and proved to have a substantial agreement (Kappa 0.74) compared to it with a superior detection rate in 374 samples from wild rats, laboratory rats and animals from holdings of wild-trapped rats. To conclude, the qPCR described in this study is an important molecular tool that is able to quantify S. moniliformis in tissue samples of animal origin. It represents a suitable tool for future establishment and evaluation of other molecular assays that are highly needed for a better understanding of epidemiology and pathophysiology of RBF. In experimental studies, it will also be useful for titration purposes since the quantification of the organism using classical plate counting technique is problematic and inaccurate.

Streptobacillus notomytis Bacteremia after Exposure to Rat Feces.

To determine the source of Streptobacillus notomytis bacteremia in a woman in Japan with signs of rat-bite fever, we examined rat feces from her home. After culture and PCR failed to identify the causative organism in the feces, next-generation sequencing detected Streptobacillus spp., illustrating this procedure's value for identifying causative environmental organisms.

Rat bite fever: a case report review.

CONTEXT: Rat bite fever is a rare disease with a challenging differential diagnosis. The zoonosis has a potentially lethal course in a vulnerable population (children and low socioeconomic class) and a commonly available standard therapy (penicillin). This case report review outlines common epidemiological and clinical factors to improve clinical awareness and timely response to therapeutic actions. METHODS: A systematic literature review was conducted in the PubMed database looking for English language European case reports of rat bite fever from 2000 to 2021. RESULTS: In 17 out of 20 selected cases, the condition of the index patient was identified as an infectious syndrome. Thanks to the almost omnisensitive susceptibility pattern of Streptobacillus moniliformis, timely antibiotic administration prevented an unfavorable outcome in all these cases. However, in the three remaining cases, the initial diagnoses were arthritis (on autoimmune basis and gout) and viral syndrome. Due to delayed antibiotic administration, one case suffered persistent harm, while the other two cases encountered prolonged illness. CONCLUSION AND RECOMMENDATIONS: Rat bite fever is a diagnosis that can be easily missed from both a clinical and a microbiological point of view. As such, rat bite fever becomes part of the differential diagnosis whenever a patient presents with a fever syndrome after being in contact with rodents. In the case of persistent fever, blood culture sampling should be performed even in the absence of a systemic inflammatory response. A bacterial 16S ribosomal RNA PCR on blood or joint aspiration (cultures) is an even more sensitive diagnostic test. Since most transmissions occurred in a domestic setting, keeping rats as pets cannot be recommended.

Characterization of the L-form switch in the Gram-negative pathogen Streptobacillus moniliformis.

Almost all major classes of bacteria are surrounded by a peptidoglycan cell wall, which is a crucial target for antibiotics. It is now understood that many bacteria can tolerate loss of the cell wall provided that they are in an isotonic environment. Furthermore, in some cases the cells can continue to proliferate in a state known as the L-form. L-form proliferation occurs by an unusual blebbing or tubulation mechanism that is completely independent of the normally essential division machine or cell wall synthetic enzymes, and is resistant to cell wall-active antibiotics. However, the growth is limited by reactive oxygen species generated by the respiratory chain pathway. In this work, we examined the walled to L-form transition in a pathogenic Gram-negative bacterium, Streptobacillus moniliformis, which naturally lacks the respiratory chain pathway, under aerobic conditions. L-form-like cells often emerged spontaneously, but proliferation was not observed unless the cells were treated with cell wall-active antibiotics. Time-lapse imaging revealed that cell division of S. moniliformis L-forms involves unusual membrane dynamics with an apparent imbalance between outer membrane and cytoplasmic volume growth. The results suggest that outer membrane expansion may be an important general factor for L-form proliferation of diderm bacteria.

Septic Polyarthritis Caused by Streptobacillus moniliformis.

Streptobacillus moniliformis is a pleomorphic, fastidious gram-negative bacillus that colonizes rodent respiratory tracts and causes rat-bite fever in humans. Rat-bite fever is associated with septic arthritis, usually monoarticular or pauciarticular. We report a rare case of polyarticular septic arthritis caused by S. moniliformis; the disease was initially misdiagnosed as inflammatory arthritis.

Rat bite fever due to Streptobacillus notomytis complicated by meningitis and spondylodiscitis: a case report.

BACKGROUND: Only three other cases of rat bite fever caused by Streptobacillus notomytis in humans have been reported since this species was identified in 2015. Data specific to the differences in clinical features and geographic distribution between S. notomytis infection and S. moniliformis infection are scarce. All previous cases of human S. notomytis infection were reported from Japan. This is the first case of S. notomytis infection reported from outside of Japan. CASE PRESENTATION: A 72-year-old Thai woman was admitted to Siriraj Hospital (Bangkok, Thailand)-Thailand's largest university-based national tertiary referral center-in August 2020 with fever, myalgia, and polyarthralgia for 3 days, and gradually decreased consciousness for the past 1 day. Physical examination and laboratory investigations revealed septic arthritis of both knee joints, meningitis, and hepatitis. She was initially misdiagnosed as rheumatoid arthritis in the elderly since the initial investigations were unable to detect a causative pathogen. However, S. notomytis infection was later confirmed by polymerase chain reaction amplification of a part of the 16S rRNA gene and sequencing from synovial fluid. Her clinical course was also complicated by spondylodiscitis and epidural abscess caused by S. notomytis, which was detected from tissue biopsy. Therefore, rat bite fever in this patient manifested as meningitis, septic polyarthritis, hepatitis, and spondylodiscitis. The patient was treated with intravenous ceftriaxone then switched to oral amoxicillin with complete recovery. CONCLUSIONS: The clinical manifestations of S. notomytis infection are similar to those demonstrated in S. moniliformis infection. This case also showed that arthritis caused by S. notomytis mimics rheumatoid arthritis, and that meningitis and spondylodiscitis are potential coexisting complications that can be found in S. notomytis infection.

Prevalence and Diversity of the Streptobacillus Rat-bite Fever Agent, in Three Invasive, Commensal Rattus Species from South Africa.

Rat-bite fever is an over-looked, global zoonotic disease that has a mortality rate of up to 13%, if untreated. Historically, this rat-borne disease has been attributed to one of two causative agents, Streptobacillus moniliformis or Spirillum minus. Given the confirmed presence of multiple invasive Rattus host species, high rat densities in urban, informal human settlements and increasing reports of rat bites in South Africa, we undertook a retrospective assessment of Streptobacillus in rats sampled from 16 urban sites, in Gauteng, the smallest but most populous Province in South Africa. Using a multi-gene PCR-sequencing approach, we confirmed Streptobacillus presence in 50.9% of oral swabs from three rat species and the presence of two Streptobacillus species, viz.S. moniliformis and S. notomytis. The two members of the cryptic Rattus rattus species complex (R. rattus and R. tanezumi), which are morphologically indistinguishable from each other, had markedly different colonization rates. Whereas 48.6% of rats from this species complex were Streptobacillus-positive, only 32.3% of Rattus tanezumi were positive compared to 61.5% R. rattus. Rattus norvegicus had an intermediate prevalence of 55.6%. Phylogenetic analysis of four gene regions (16S rRNA, gyrB, groEL, recA) identified two discrete lineages; S. moniliformis occurred exclusively in R.norvegicus, and S. notomytis was restricted to the two members of the R. rattus species complex; this represents the first report of Streptobacillus in R. tanezumi. These results highlight a largely overlooked zoonotic threat posed by invasive rats and confirm the presence of two discrete and potentially host-specific Streptobacillus lineages in South Africa.

Rat Bite Fever: Variability in Clinical Presentation and Management in Children.

Rat bite fever is a systemic illness most commonly caused by Streptobacillus moniliformis that is classically characterized by fever, rash and migratory polyarthritis. Here, we highlight the highly variable clinical presentations of rat bite fever in children and the importance of maintaining a high degree of suspicion so appropriate treatment can be promptly initiated.

Rat bite fever, a diagnostic challenge: case report and review of 29 cases.

Rats can transmit Streptobacillus moniliformis, which may cause rat-bite fever (RBF), a rare and potentially lethal zoonosis. Fastidious in vitro growth and unspecific symptoms, including fever, arthralgia, and polymorphous skin lesions, complicate the diagnosis. Rat-bite fever follows exposure to contaminated bodily fluids of infected rodents; however, reports on Streptobacillus moniliformis-related infections are few so far. A female patient presented with painful hemorrhagic pustules and purpuric lesions on hands and feet. She developed fever and migratory polyarthralgia. Blood culture yielded growth with Streptobacillus moniliformis. The patient owned rats and handled contaminated rat feces and urine, making this the most likely etiology of infection. We report a case of RBF due to Streptobacillus moniliformis in a rat handling-patient. Difficulties in clinical and microbiological diagnosis highlight the need for a thorough and complete history-taking and a greater understanding of this rare infectious disease.

Rat bite fever with osteomyelitis and discitis: case report and literature review.

BACKGROUND: Rat bite fever (RBF) is a rare systemic febrile illness transmitted by rats. Streptobacillus moniliformis is a pleomorphic Gram-negative bacillus which is the usual etiologic organism for rat bite fever in the United States. CASE PRESENTATION: Here we present a case of rat bite fever complicated by vertebral osteomyelitis and discitis. The patient revealed an exposure history of being bitten by pet rats. The patient's symptoms dramatically improved with a six-week course of cephalexin therapy. CONCLUSIONS: It is important to obtain a thorough zoonotic exposure history and maintain rat bite fever in the differential when considering potential causes of discitis and osteomyelitis.

Using the BDFX40 Automated Continuous Blood Culture System to Isolate and Recover Streptobacillus moniliformis in the Presence of 0.05% SPS: A 55-Year, 56-Strain Retrospective Study.

Rat bite fever and Haverhill fever are often difficult to diagnose in a clinical setting. This difficulty results in part from clinicians and laboratory professionals not being able to reliably recover the causative agent Streptobacillus moniliformis using culture-based methods. After utilizing an automated continuous-monitoring blood culture bottle system, we showed that the organism can be reliably cultured when a blood volume inoculum of 10 mL is used. Further, we showed that when the above recommendation is followed, sodium polyanethole sulfonate (up to a concentration of 0.05% w/v) in commercially purchased blood culture bottle formulations seems to be inactivated, allowing for the growth and detection of S. moniliformis. Herein, we offer data and methods used to overcome these clinical limitations. This is a comprehensive study of the historical collection of S. moniliformis isolates maintained by our facility and believed to be the largest of its kind to date.

A real-time multiplex PCR assay for detection of the causative agents of rat bite fever, Streptobacillus moniliformis and zoonoticStreptobacillus species.

Rat bite fever (RBF) caused by Streptobacillus moniliformis has been described as a diagnostic challenge. While it has a favorable prognosis with treatment, timely diagnosis is hindered by the lack of culture-free identification methods. Here we present a multiplex real-time PCR assay that detects the zoonotic Streptobacillus spp. as well as differentiate the primary causative agent of RBF, Streptobacillus moniliformis. The performance of this assay was evaluated using mock clinical specimens for blood, serum, and urine. Analytical sensitivity was determined to be 3-4 genome equivalents (GE)/µl for the zoonotic Streptobacillus spp. target, and 1-2 GE/µl for the S. moniliformis specific target. The assay correctly detected only the intended targets with no cross-reactivity identified. The pathogen was detected in all spiked matrices and not detected in the negative non-spiked specimens. This rapid diagnostic assay may permit quicker diagnosis of RBF patients.

Infection in a Young Immunocompetent Male Caused by Streptobacillus felis, a Putative Zoonotic Microorganism Transmitted by Cats.

Rat bite fever (RBF) is predominantly caused by Streptobacillus moniliformis. We report a human infection with Streptobacillus felis. Clinical presentation was consistent with RBF, but serologic testing was negative for S moniliformis. Eventually, S felis-specific sequences were detected in skin lesions of the patient and in the oropharynx of local cats.

Revealing oral microbiota composition and functionality associated with heavy cigarette smoking.

BACKGROUND: Heavy tobacco smoking, a hallmark feature of lung cancer, is drastically predominant in Middle Eastern populations. The precise links between nicotine dependence and the functional contribution of the oral microbiota remain unknown in these populations. METHODS: We evaluated the composition and functional capabilities of oral microbiota with relation to cigarette smoking in 105 adults through shotgun metagenomics using buccal swabs. RESULTS: The oral microbiota composition in our study subjects was dominated by the phyla Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes, in addition to the genera Prevotella and Veillonella, similar to previously described westernized cohorts. Furthermore, the smoker's oral microbiota represented a significant abundance of Veillonella dispar, Leptotrichia spp. and Prevotella pleuritidis when compared to non-smokers. Within the smoking groups, differential relative abundance testing unveiled relative abundance of Streptobacillus hongkongensis, Fusobacterium massiliense, Prevotella bivia in high nicotine dependent compared to low nicotine dependent profiles based on Fagerström Test for Nicotine Dependence. Functional profiling showed marked differences between smokers and non-smokers. Smokers exhibited an enrichment of Tricarballylate utilization and Lactate racemization when compared to the non-smokers. According to their nicotine dependence, enrichment of Xanthosine utilization, p-Aminobenzoyl-Glutamate utilization, and multidrug efflux pump in Campylobacter jejuni biosynthesis modules were detected in the high nicotine dependent group. CONCLUSIONS: These compositional and functional differences may provide critical insight on how variations in the oral microbiota could predispose to respiratory illnesses and smoke cessation relapse in cigarette smokers. In particular, the observed enrichment of Fusobacterium and Prevotella in the oral microbiota possibly suggests an intriguing linkage to gut and lung cancers.