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.

Rat bite fever caused by Streptobacillus moniliformis infection in a Chinese patient.

BACKGROUND: Rat bite fever (RBF), a severe infectious disease, can result from transmission of the pathogen Streptobacillus moniliformis (S. moniliformis) by rat bite. RBF diagnosis can be overlooked. CASE PRESENTATION: We present a case of RBF in a Chinese patient who was infected with S. moniliformis in mainland China. Meta-next generation sequencing (mNGS) was used to identify potential pathogens and detected S. moniliformis genome sequences in the pustular sample in less than 72 h. Then the diagnosis was validated by polymerase chain reaction analysis. Despite having severe RBF with complications, this 54-year-old male patient was successfully cured with penicillin as a result of timely pathogen-based diagnosis. CONCLUSIONS: Physicians should inquire about recent rat exposure and consider the possibility of RBF when a patient develops unexplained fever and rashes. mNGS is a new diagnostic technology and may identify RBF pathogens even when blood culture results are negative.

Oh rats! Fever, rash and arthritis in a young woman.

A 17-year-old girl presented with worsening right-sided hip and low back pain for 2 days. She had also experienced intermittent fevers and a recurring maculopapular rash over the past 2 weeks. Social history revealed the presence of three domestic rats living in the girl's home. Blood cultures returned positive for Streptobacillus moniliformis, the causative agent of rat-bite fever. Rat-bite fever often goes undiagnosed, as the clinical presentation is non-specific. Untreated, the infection can result in death due to sepsis or endocarditis. The bacterium is generally susceptible to penicillin antibiotics with full clinical recovery when treated in a timely and appropriate manner. After 4 weeks of intravenous antibiotics, our patient fully recovered without long-term sequelae.

[Clinical and epidemiological analysis of rat bites in Buenos Aires]. / Análisis clínico y epidemiológico de mordeduras de rata en Buenos Aires.

We report 62 cases of rat bites that occurred between 2002 and 2008. Forty of these happened in Buenos Aires city, unrelated to social class or urban conditions. The bites occurring in daylight were related to invasion of the animal habitat by man, and to rat activity during the night. In 79% of the cases the rat bite was in the limbs and in 16% in the face. Five patients developed clinical manifestations of rat bite fever. We discuss the value of post exposition prophylaxis with antibiotics.

Análisis clínico y epidemiológico de mordeduras de rata en Buenos Aires / Clinical and epidemiological analysis of rat bite in Buenos Aires

Analizamos 62 casos de mordedura de rata asistidos entre los años 2002 y 2008. cuarenta de ellos ocurrieron en la ciudad de Buenos Aires, sin clara relación con las condiciones urbanas o socioeconómicas de los afectados. Las mordeduras producidas durante el día ocurrieron por invasión del hombre al hábitat de los roedores, situación inversa a las sucedidas durante la noche. En el 79% de los casos fueron afectados los miembros y en un 16% la cara. Cinco pacientes desarrollaron manifestaciones clínicas de enfermedad por mordedura de rata. Se discute el valor de la profilaxis post exposición con antibióticos.

We report 62 cases of rat bites that occurred between 2002 and 2008. Forty of these happened in Buenos Aires city, unrelated to social class or urban conditions. The bites occurring in daylight were related to invasion of the animal habitat by man, and to rat activity during the night. In 79% of the cases the rat bite was in the limbs and in 16% in the face. Five patients developed clinical manifestations of rat bite fever. We discuss the value of post exposition prophylaxis with antibiotics.

Fiebre aguda por mordedura de rata / Acute fever due to rats

La mordedura de rata puede transmitir diversos microorganismos, no obstante el desarrollo de medidas sanitarias y las mejores condiciones de habitabilidad de las viviendas han permitido que las enfermedades infecciosas transmitidas por agresiones de estos animales sean infrecuentes en los países industrializados. En circunstancias ocasionales este tipo de agresiones aún puede producirse, especialmente en zonas desfavorecidas de la periferia de grandes ciudades y en locales no habitados, siendo recomendable tener presente esta posibilidad. Se presenta un caso de fiebre por mordedura de rata en un paciente agredido mientras realizaba la limpieza de un local industrial. La evolución del cuadro fue típica, aislándose Streptobacillus moniliformis como agente causal, y el cuadro se controló sin presentar complicaciones con doxiciclina (AU)

Streptobacillus moniliformis: case report and review of the literature.

Streptobacillus moniliformis is one of the causes of rat bite fever. The clinical and microbiological diagnosis of this rare infectious disease is often quite problematic. Penicillin, in sufficiently high dosis, is the treatment of choice and leads to a prompt resolution of the infection, whereas lack of treatment leads to a 13% mortality rate. As far as we know, this paper reports the first human isolate in Belgium.

Gatos y ratas: rasguños y mordeduras / Cats and rats: scratches and bites

Numerosas afecciones son transmitidas al hombre por diferentes vectores, sean éstos insectos, pájaros o mamíferos. Entre las transmitidas por estos últimos, en la presente revisión se abordaron: la enfermedad por mordedura de rata que es básicamente un cuadro febril agudo, intenso, de comienzo brusco y de evolución recurrente y la enfermedad por rasguño de gato que se manifiesta por adenopatías sin signos inflamatorios locales, de lenta evolución regresiva y con escasa repercusión sobre el estado general. Ambas afecciones son más comunes en nuestro medio de lo que habitualmente se piensa y responden favorablemente a diversos antibióticos pero inicialmente plantean, con frecuencia, problemas de diagnóstico diferencial con enfermedades de pronóstico más grave

[Rat-bite--an infant bitten by a rat]. / Rottebid--spaedbarn bidt af rotte.

Three days after a rat-bite a two-month-old girl developed clinical symptoms of Streptobacillus moniliformis infection, called rat-bite fever. She became seriously ill, but responded well to treatment with benzylpencillin. In the light of our case and previous publications, we recommend prophylactic penicillin to be given to infants after rat-bites.

Rat bite fever without the bite.

The case is reported of a patient who developed an acute arthropathy, which was initially diagnosed as acute septic arthritis. The true diagnosis of rat bite fever due to Streptobacillus moniliformis was delayed because of difficulty in growing the organism, which has fastidious growth requirements. The patient had no history of rat bite, which is the usual form of transmission of this disease.

Rat-bite fever in a gerbil breeder.

A case of rat-bite fever caused by Streptobacillus moniliformis in a gerbil-breeder is described. Such a case has not been previously recorded.