Describing fine spatiotemporal dynamics of rat fleas in an insular ecosystem enlightens abiotic drivers of murine typhus incidence in humans.

Murine typhus is a flea-borne zoonotic disease that has been recently reported on Reunion Island, an oceanic volcanic island located in the Indian Ocean. Five years of survey implemented by the regional public health services have highlighted a strong temporal and spatial structure of the disease in humans, with cases mainly reported during the humid season and restricted to the dry southern and western portions of the island. We explored the environmental component of this zoonosis in an attempt to decipher the drivers of disease transmission. To do so, we used data from a previously published study (599 small mammals and 175 Xenopsylla fleas from 29 sampling sites) in order to model the spatial distribution of rat fleas throughout the island. In addition, we carried out a longitudinal sampling of rats and their ectoparasites over a 12 months period in six study sites (564 rats and 496 Xenopsylla fleas) in order to model the temporal dynamics of flea infestation of rats. Generalized Linear Models and Support Vector Machine classifiers were developed to model the Xenopsylla Genus Flea Index (GFI) from climatic and environmental variables. Results showed that the spatial distribution and the temporal dynamics of fleas, estimated through the GFI variations, are both strongly controlled by abiotic factors: rainfall, temperature and land cover. The models allowed linking flea abundance trends with murine typhus incidence rates. Flea infestation in rats peaked at the end of the dry season, corresponding to hot and dry conditions, before dropping sharply. This peak of maximal flea abundance preceded the annual peak of human murine typhus cases by a few weeks. Altogether, presented data raise novel questions regarding the ecology of rat fleas while developed models contribute to the design of control measures adapted to each micro region of the island with the aim of lowering the incidence of flea-borne diseases.

Murine Typhus Outbreak Presenting as Multisystem Inflammatory Syndrome in Children During SARS-CoV-2 Pandemic.

Multisystem inflammatory syndrome in children is a severe illness associated with the SARS-CoV-2 pandemic that possesses features overlapping with other pediatric diseases causing systemic inflammation. Significant diagnostic and treatment uncertainty remain, and clinicians should maintain a broad differential when evaluating patients for multisystem inflammatory syndrome in children, as antibiotic-susceptible infections such as murine typhus may present similarly.

Laboratory-acquired Scrub Typhus and Murine Typhus Infections: The Argument for a Risk-based Approach to Biosafety Requirements for Orientia tsutsugamushi and Rickettsia typhi Laboratory Activities.

This study examined the literature on laboratory-acquired infections (LAIs) associated with scrub typhus (Orientia tsutsugamushi) and murine typhus (Rickettsia typhi) research to provide an evidence base for biosafety and biocontainment. Scrub typhus LAIs were documented in 25 individuals, from 1931 to 2000 with 8 (32%) deaths during the preantibiotic era. There were 35 murine typhus LAI reports and no deaths. Results indicated that the highest-risk activities were working with infectious laboratory animals involving significant aerosol exposures, accidental self-inoculation, or bite-related infections. A risk-based biosafety approach for in vitro and in vivo culture of O. tsutsugamushi and R. typhi would require that only high-risk activities (animal work or large culture volumes) be performed in high-containment biosafety level (BSL) 3 laboratories. We argue that relatively low-risk activities including inoculation of cell cultures or the early stages of in vitro growth using low volumes/low concentrations of infectious materials can be performed safely in BSL-2 laboratories within a biological safety cabinet.

Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model

BACKGROUND Formation of schistosomal granulomata surrounding the ova can result in schistosomiasis-associated liver fibrosis (SSLF). The current standard of treatment is praziquantel (PZQ), which cannot effectively reverse SSLF. The role of the cannabinoid (CB) receptor family in liver fibrosis has recently been highlighted. OBJECTIVES This study aimed to assess the therapeutic effect of CB1 receptor antagonism in reversing SSLF in a murine model of Schistosoma mansoni infection. METHODS One hundred male Swiss albino mice were divided equally into five groups: healthy uninfected control (group I), infected control (group II), PZQ treated (group III), rimonabant (RIM) (SR141716, a CB1 receptor antagonist)-treated (group IV) and group V was treated with combined PZQ and RIM. Liver sections were obtained for histopathological examination, alpha-1 smooth muscle actin (α-SMA) immunostaining and assessment of CB1 receptor expression using real-time polymerase chain reaction (RT-PCR). FINDINGS The most effective reduction in fibrotic marker levels and granuloma load was achieved by combined treatment with PZQ+RIM (group V): CB1 receptor expression (H = 26.612, p < 0.001), number of α-SMA-positive cells (F = 57.086, p < 0.001), % hepatic portal fibrosis (F = 42.849, p < 0.001) and number of granulomata (F = 69.088, p < 0.001). MAIN CONCLUSIONS Combining PZQ with CB1 receptor antagonists yielded the best results in reversing SSLF. To our knowledge, this is the first study to test this regimen in S. mansoni infection.

Analysis of Health-Care Charges in Murine Typhus: Need for Improved Clinical Recognition and Diagnostics for Acute Disease.

Murine typhus, caused by Rickettsia typhi, is an undifferentiated febrile illness with no available rapid and sensitive diagnostic assay for use during early disease. We aimed to compare the health-care charges in those diagnosed with murine typhus to those with influenza, a febrile illness with an available rapid diagnostic test. A comparison of health-care-associated charges at the University of Texas Medical Branch at Galveston demonstrated a median of $817 for influenza versus $16,760 for murine typhus (P < 0.0001). Median laboratory ($184 versus $3,254 [P < 0.0001]) and imaging charges ($0 versus $514 [P < 0.0001]) were also higher in those with murine typhus. Those receiving at least one imaging study during their illness were greater in the murine typhus group (91.3% versus 20.3%) (P < 0.0001). The median time needed to establish a confirmed or presumptive diagnosis was 2 days for influenza compared with 9 days for murine typhus (P < 0.0001). The median number of health-care encounters was greater for those with murine typhus (2 versus 1) (P < 0.0001). Eleven patients (15.9%) with influenza were hospitalized as a result of their illness compared with 16 (69.6%) with murine typhus (P < 0.0001). The estimated mortality based on disease severity at presentation by Acute Physiology and Chronic Health Evaluation II scoring was similar in the two groups-both had a median 4% mortality risk (P = 0.0893). These results highlight the need for improved clinical recognition and diagnostics for acute rickettsioses such as murine typhus.

Newly Recognized Pediatric Cases of Typhus Group Rickettsiosis, Houston, Texas, USA.

An increase in typhus group rickettsiosis and an expanding geographic range occurred in Texas, USA, over a decade. Because this illness commonly affects children, we retrospectively examined medical records from 2008-2016 at a large Houston-area pediatric hospital and identified 36 cases. The earliest known cases were diagnosed in 2011.

Molecular evidence of Rickettsia typhi infection in dogs from a rural community in Yucatán, México.

INTRODUCTION: Rickettsia typhi causes murine or endemic typhus, which is transmitted to humans primarily through flea bites contaminated with feces. Synanthropic and domestic animals also contribute to the infection cycle of R. typhi. Cases of murine typhus in humans were reported in the rural community of Bolmay, Yucatán, México, between 2007 and 2010.  OBJECTIVE: To identify the presence of R. typhi and estimate the frequency of infection in dogs from Bolmay, México, a locality with previous reports of murine typhus in humans.  MATERIALS AND METHODS: Whole blood samples were taken from 128 dogs. Total DNA was extracted for use in the polymerase chain reaction (PCR) to amplify fragments of the 17 kDa and omp B genes and confirms the presence of Rickettsia spp. The reaction products were sequenced, and alignment analysis was performed using the BLAST tool.  RESULTS: The frequency of R. typhi infection in dogs was 5.5 % (7/128). The alignment identified 99% and 100% homology to the R. typhi 17 kDa and omp B genes, respectively.  CONCLUSION: We confirmed the presence of R. typhi in dogs in the studied community but at a low frequency. However, there is potential risk of transmission to humans.

Spotted Fever Group Rickettsioses and Murine Typhus in a Malaysian Teaching Hospital.

Limited information is available on the etiological agents of rickettsioses in southeast Asia. Herein, we report the molecular investigation of rickettsioses in four patients attending a teaching hospital in Malaysia. DNA of Rickettsia sp. RF2125, Rickettsia typhi, and a rickettsia closely related to Rickettsia raoultii was detected in the blood samples of the patients. Spotted fever group rickettsioses and murine typhus should be considered in the diagnosis of patients with nonspecific febrile illness in this region.

Rickettsia typhi in rodents and R. felis in fleas in Yucatán as a possible causal agent of undefined febrile cases.

Rickettsia typhi is the causal agent of murine typhus; a worldwide zoonotic and vector-borne infectious disease, commonly associated with the presence of domestic and wild rodents. Human cases of murine typhus in the state of Yucatán are frequent. However, there is no evidence of the presence of Rickettsia typhi in mammals or vectors in Yucatán. The presence of Rickettsia in rodents and their ectoparasites was evaluated in a small municipality of Yucatán using the conventional polymerase chain reaction technique and sequencing. The study only identified the presence of Rickettsia typhi in blood samples obtained from Rattus rattus and it reported, for the first time, the presence of R. felis in the flea Polygenis odiosus collected from Ototylomys phyllotis rodent. Additionally, Rickettsia felis was detected in the ectoparasite Ctenocephalides felis fleas parasitizing the wild rodent Peromyscus yucatanicus. This study's results contributed to a better knowledge of Rickettsia epidemiology in Yucatán.

Rickettsia typhi IN RODENTS AND R. felis IN FLEAS IN YUCATÁN AS A POSSIBLE CAUSAL AGENT OF UNDEFINED FEBRILE CASES / Rickettsia typhi y R. felis en roedores y sus pulgas en Yucatán como posible agente causal de casos febriles indefinidos

Rickettsia typhi is the causal agent of murine typhus; a worldwide zoonotic and vector-borne infectious disease, commonly associated with the presence of domestic and wild rodents. Human cases of murine typhus in the state of Yucatán are frequent. However, there is no evidence of the presence of Rickettsia typhi in mammals or vectors in Yucatán. The presence of Rickettsia in rodents and their ectoparasites was evaluated in a small municipality of Yucatán using the conventional polymerase chain reaction technique and sequencing. The study only identified the presence of Rickettsia typhi in blood samples obtained from Rattus rattus and it reported, for the first time, the presence of R. felis in the flea Polygenis odiosus collected from Ototylomys phyllotis rodent. Additionally, Rickettsia felis was detected in the ectoparasite Ctenocephalides felis fleas parasitizing the wild rodent Peromyscus yucatanicus. This study’s results contributed to a better knowledge of Rickettsia epidemiology in Yucatán.

Rickettsia typhi es el agente causal del tifo murino; una enfermedad zoonótica transmitida por vector mundialmente distribuida, comúnmente asociada con la presencia de roedores domésticos y silvestres. Los casos humanos de tifo murino en el Estado de Yucatán son frecuentes. Sin embargo, no existe evidencia de la presencia de Rickettsia typhi en mamíferos o vectores en Yucatán. En la búsqueda de vectores y reservorios de Rickettsia typhi, evaluamos la presencia de bacterias del género Rickettsia en roedores y sus ectoparásitos de un pequeño municipio del estado de Yucatán por medio de técnicas de PCR convencional y secuenciación de ADN. Se identificó la presencia de Rickettsia typhi en muestras de sangre obtenidas de Rattus rattus y reportamos por primera vez la presencia de Rickettsia felis en la pulga Polygenis odiosus colectado de Ototylomys phyllotis. Complementariamente, Rickettsia felis fue detectado en la pulga Ctenocephalides felis parasitando al roedor Peromyscus yucatanicus. No se identificó especie de Rickettsia en las muestras de sangre de O. phyllotis y P. yucatanicus analizados. Nuestros resultados contribuyen también en el conocimiento de ciclo de vida biológico del género Rickettsia.

Reemergence of murine typhus in Galveston, Texas, USA, 2013.

Twelve patients with murine typhus were identified in Galveston, Texas, USA, in 2013. An isolate from 1 patient was confirmed to be Rickettsia typhi. Reemergence of murine typhus in Galveston emphasizes the importance of vector control and awareness of this disease by physicians and public health officials.

Of mice and men.

A case study of a patient returning from sub-Saharan Africa with a febrile illness and symptoms reminiscent of a previous malarial infection is discussed. The patient had a relative bradycardia with respect to febrile episodes, a transient macular rash and thrombocytopenia. The illness was conservatively managed for 1 month before positive Rickettsia serology and PCR results were reported. The patient was then treated with doxycycline with a complete resolution of symptoms.

Liver function test abnormalities in murine typhus in Greece: a retrospective study of 165 cases.

The aim of this study was to analyse data relating to the liver function profile during acute infection from murine typhus in the city of Chania in the island of Crete (Greece). A retrospective study of the files of all the cases with a diagnosis of murine typhus admitted to the Saint George General Hospital of Chania over a 15-year period (1993-2008) was performed. Variations in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels were recorded from three consecutive examined serum samples. A total of 165 patients were diagnosed with murine typhus during the above time period. Serum aminotransferase and lactate dehydrogenase were abnormal in most of the first examined samples. Remarkably on admission, serum levels of AST, ALT, and LDH recorded an increase above the cut-off point in 142 (86%), 114 (69%) and 136 (82.4%) patients respectively. More than two out of every ten patients presented hepatomegaly. In conclusion, liver dysfunction occurs frequently in patients with murine typhus. A high level of physicians' awareness is required for the liver biochemical abnormalities caused by this worldwide zoonotic disease, especially in endemic areas such as Greece.

Murine typhus in returned travelers: a report of thirty-two cases.

Murine typhus, caused by Rickettsia typhi and transmitted mainly by the rat fleas, Xenopsylla cheopis, has emerged in the field of travel medicine. We analyzed retrospectively the epidemiological, clinical, and biological characteristics of the 32 murine typhus cases that were diagnosed during the past 3 years at the World Health Organization Collaborative Center for Rickettsial diseases, Marseille, France. All of the cases occurred in travelers and most of them had returned from Africa (N = 13 of 32) and South-east Asia (N = 12 of 32). Exposure to rats was reported only in a few (N = 2 of 32) patients. Almost half of the cases were diagnosed in August and September. Only four patients presented the classic triad: fever, rash, and headache. Moreover, we report the first known cases of a hemophagocytic syndrome associated with this disease. Murine typhus must be considered as an etiologic agent of febrile illness in returning travelers, particularly in those with unspecific symptoms.

Transmission of flea-borne zoonotic agents.

Flea-borne zoonoses such as plague (Yersinia pestis) and murine typhus (Rickettsia typhi) caused significant numbers of human cases in the past and remain a public health concern. Other flea-borne human pathogens have emerged recently (e.g., Bartonella henselae, Rickettsia felis), and their mechanisms of transmission and impact on human health are not fully understood. Our review focuses on the ecology and epidemiology of the flea-borne bacterial zoonoses mentioned above with an emphasis on recent advancements in our understanding of how these organisms are transmitted by fleas, maintained in zoonotic cycles, and transmitted to humans. Emphasis is given to plague because of the considerable number of studies generated during the first decade of the twenty-first century that arose, in part, because of renewed interest in potential agents of bioterrorism, including Y. pestis.

Murine typhus in the homeless.

Homeless populations are particularly exposed to many vector-borne diseases because of their poor living conditions. We tested sera from 299 homeless people recruited in 2010 and 2011 in Marseilles, France for antibodies to Rickettsia typhi by microimmunofluorescence using a titer of 1:25 as a cut-off titer, and we confirmed the results by Western blot and cross-adsorption studies. Sixty-three persons (22%) had antibodies against R. typhi. The murine typhus seroprevalence rates have significantly increased in homeless populations between the 2000-2003 and 2010-2011 periods. These findings indicate that the homeless are increasingly exposed to flea-borne murine typhus in Marseilles. One might suggest that multiple strikes of sanitation workers resulting in the increase of waste and construction sites combined with the poor living conditions of the homeless expose this population to rodents and their fleas. Further annual studies are necessary to follow rodent-associated diseases among homeless people in Marseille.

Detection of arbitrarily-shaped clusters using a neighbor-expanding approach: a case study on murine typhus in south Texas.

BACKGROUND: Kulldorff's spatial scan statistic has been one of the most widely used statistical methods for automatic detection of clusters in spatial data. One limitation of this method lies in the fact that it has to rely on scan windows with predefined shapes in the search process, and therefore it cannot detect cluster with arbitrary shapes. We employ a new neighbor-expanding approach and introduce two new algorithms to detect cluster with arbitrary shapes in spatial data. These two algorithms are called the maximum-likelihood-first (MLF) algorithm and non-greedy growth (NGG) algorithm. We then compare the performance of these two new algorithms with the spatial scan statistic (SaTScan), Tango's flexibly shaped spatial scan statistic (FlexScan), and Duczmal's simulated annealing (SA) method using two datasets. Furthermore, we utilize the methods to examine clusters of murine typhus cases in South Texas from 1996 to 2006. RESULT: When compared with the SaTScan and FlexScan method, the two new algorithms were more flexible and sensitive in detecting the clusters with arbitrary shapes in the test datasets. Clusters detected by the MLF algorithm are statistically more significant than those detected by the NGG algorithm. However, the NGG algorithm appears to be more stable when there are no extreme cluster patterns in the data. For the murine typhus data in South Texas, a large portion of the detected clusters were located in coastal counties where environmental conditions and socioeconomic status of some population groups were at a disadvantage when compared with those in other counties with no clusters of murine typhus cases. CONCLUSION: The two new algorithms are effective in detecting the location and boundary of spatial clusters with arbitrary shapes. Additional research is needed to better understand the etiology of the concentration of murine typhus cases in some counties in south Texas.

[Experimental study of the inoculative transmission of Rickettsia typhi by gamasid mites (Gamasidae) Ornithonyssus bacoti].

The authors' studies have established that the concentration of Rickettsia typhi may increase about 100-fold in the infected Ornithonyssus bacoti mites. At the time, when on feeding 20 to 200 adult mites on guinea-pigs and albino rats 4 to 36 days after inoculation, they did not transmit Rickettsia typhi on blood sucking.