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.

First description of a clinical case of murine typhus in Campeche, Mexico

Abstract Murine typhus is a flea-borne disease caused by Rickettsia typhi, which was first detected in Mexico in 1927. It was not until 1996 that the first systematized study involving this pathogen was conducted in two coastal states of Mexico. We now report the first confirmed case of murine typhus in the state of Campeche, which occurred in a male patient who exhibited fever, thrombocytopenia, hyperbilirubinemia, and a rash. Furthermore, the patient reported having had previous contact with Rickettsia reservoirs.

Case of Rickettsia typhi-induced Brain Abscess Mimicking Brain Tumor

Murine typhus is one of the most prevalent rickettsial infections in the world, caused by the bacterial genus Rickettsia. Though the disease manifests a relatively benign clinical course with fever, rash, and headache being the 3 classic symptoms, neurological complications may arise in patients that could become permanent. In this case study, a patient with a brain abscess caused by R typhi infection is described. Based upon the recent reemergence of arthropod-borne disease, the findings in this case are significant; R typhi can cause a brain abscess that mimics a brain tumor, which delays the diagnosis and appropriate management of the disease. Murine typhus should always be considered when performing the differential diagnosis of brain abscesses in South Korea.

Caso probable de tifus murino con falla ventilatoria en una adolescente del área urbana de Cali, Colombia / Probable case of murine typhus with respiratory failure in an adolescent from the urban area of Cali, Colombia

El tifus murino es una enfermedad infecciosa de carácter zoonótico causada por Rickettsia typhi . Se presenta el caso de una paciente femenina de 13 años edad, procedente del área urbana de la ciudad de Cali, quien presentó un cuadro febril asociado a taquipnea y exantema maculopapular generalizado en tronco y extremidades. Durante las primeras 48 h en la UCI pediátrica desarrolló rápido deterioro clínico, fiebre persistente, aumento de reactantes de fase aguda, presencia de infiltrados pulmonares intersticiales bilaterales y derrame pleural, requiriendo ventilación mecánica no invasiva. Se inició tratamiento con doxiciclina frente a la sospecha de una posible infección por agentes rickettsiales. Veinticuatro horas más tarde la paciente presentó mejoría clínica, resolución del exantema y retiro de la ventilación no invasiva. Por medio de la prueba de inmunofluorescencia indirecta se evidenciaron títulos de 1:512 frente al grupo del tifus, constatando el diagnóstico probable de tifus murino.

Murine typhus is a zoonotic infectious disease caused by Rickettsia typhi . We report a case of a 13-year old female patient from the urban area of the city of Cali, who presented with fever, associated with tachypnoea and generalised maculopapular exanthema on the trunk and limbs. During the first 48 h in the paediatric ICU, she rapidly deteriorated, with persistent fever, increased acute phase reactants, bilateral interstitial pulmonary infiltrates and pleural effusion requiring noninvasive ventilation. Treatment with doxycycline was initiated due to a suspected infection by rickettsial agents. Twenty-four hours later the patient presented clinical improvement and resolution of the exanthema, thus the non-invasive ventilation was withdrawn. By means of a indirect immunofluorescence test, titres of 1:512 were shown against the typhus group, leading to the probable diagnosis of murine typhus.

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.

Delayed-Onset Complete Atrioventricular Block in a Patient with Murine Typhus Myocarditis / 대한내과학회지

Murine typhus is a flea-borne infectious disease caused by Rickettsia typhi, of which myocarditis is a rare complication in the acute disseminating phase. A 62-year-old female presented with a fever and was diagnosed with murine typhus. She was treated with doxycycline and discharged after complete resolution of the fever. However, recurrent presyncope and exertional dyspnea developed 6-8 weeks later. Complete atrioventricular (AV) block with a wide QRS escape rhythm and a left bundle branch block configuration was documented. Subacute myocarditis was diagnosed based on persistent cardiac troponin-I elevation and typical cardiac magnetic resonance imaging findings. A permanent pacemaker was implanted for symptomatic complete AV block. Few reports of myocarditis in murine typhus have been published. We report a case of murine typhus myocarditis complicated by complete AV block in the late convalescence phase.

Clinical features of four atypical pediatric cases of endemic typhus with pneumonia / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze clinical manifestations, treatment and prognosis of 4 cases with endemic typhus.</p><p><b>METHOD</b>The clinical data of four endemic typhus patients in prognosis were retrospectively analyzed. These four atypical cases of endemic typhus with pneumonia were treated in our department from October 2011 to March 2012. They were all male, with an age range of 15 months to 7 years. The four patients had long history, mild respiratory symptom and no improvement was found after treatment with cephalosporins. There were no evidences of bacterial, viral, or fungal infections and we thought they might have infection with other pathogen. Three were from rural areas. Routine blood tests, Weil-Felix reaction, blood smear (Giemsa staining) , and indirect immunofluorescence assay were performed.</p><p><b>RESULT</b>Blood smear and IFA tests showed evidences for endemic typhus. The clinical presentations were atypical, the patients had no headache, but all had fever, rash, and pneumonia of varying severity. None of the patients had a severe cough, but bronchial casts were observed in one case. Recurrent fever was reported in three cases. Physical examinations showed no eschars, but one patient had a subconjunctival hemorrhage, and one had skin scratches, cervical lymphadenopathy, pleural effusion, pericardial effusion, and cardiac dilatation. Two patients had remarkably increased peripheral blood leukocyte counts; both these patients also had high alanine aminotransferase (ALT) levels and one had a high C-reactive protein (CRP) level. Weil-Felix testing was negative or the OX19 titer was low. The peripheral blood smear (Giemsa stain) showed intracellular pathogens in all four cases. After combined therapy with doxycycline and macrolide antibiotics, all four patients recovered well.</p><p><b>CONCLUSION</b>The endemic typhus children often come from rural areas. The clinical presentations were atypical, they usually have no headache, but have fever (often Periodic fever) , rash, and pneumonia of varying severity in these four cases. Combined therapy with doxycycline and macrolide antibiotics was effective in all four patients.</p>

Ectoparasites of rodents captured in Bandar Abbas, Southern Iran

Rodents play important role as hot of ectoparasites and reservoir of different zoonotic diseases. The aim of this study was to asses the infestation of commensal rodents with ectoparasites in Bandar Abbas, a port city located in the northern part of the Persian Gulf in Iran. Rodents were captured using live traps during the study period in year 2007. after transferring the rodents to the laboratory, they were identified and then their ectoparasites were collected and mounted for species identification using appropriate systematic keys. A total of 77 rodents were identified including Rattus norvegicus [74%], R. rattus [16.9%], Mus musculus [7.8%] and one hamster. Among all rodents, 40.3% were found infested with ectoparasites. A total of 6 ectoparasites were collected comprising flea, lice, mite and tick. Two species fleas; Xenopsylaa cheopis and X. astia were identified with higher index of X. astia. Two genera of ticks including Hyalomma sp. And Rhipicephalus sp. Were identified. Laelaps nuttalli was the only mite found. The Polyplax spinulosa was considered as lice ectoparasite. Among all arthropods collected, flea and lice had the most and the least frequency, respectively. Nearly all rodent species were infested with Xenopsylla. These fleas are important due to their role in plague and murine ty-phus transmission. Ticks are important due to their role in CCHF [Crimean-Cong Hemorrhagic Fever], theileriosis, babesiosis, anaplasmosis and ehrlichiosis transmission. Monitoring of ectoparaiste infestation is important for preparedness and early warning preparation for possible control of arthropod-borne diseases

The Pathologic Splenic Rupture of a Patient with Scrub Typhus: A Case Report

A pathologic splenic rupture is rare, occurring primarily in a spleen affected by infective, hematological, and neoplastic disease. To the best of our knowledge, no prior reports of a pathologic splenic rupture due to scrub typhus exist. Intrasplenic pseudoaneurysms and focal infarctions are visible on an initial CT scan. Moreover, the spontaneous splenic rupture occurred a week later. We report a case of nontraumatic-splenic rupture in a patient with scrub typhus.

Epidemiologie investigation on murine typhus in Hongta areas of Yuxi city, Yunnan province of China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To identify epidemic status of murine typhus in Hongta areas of Yuxi city and to provide evidence for control and prevention of the disease.</p><p><b>METHODS</b>Serologic survey was conducted among residents and rodents. Isolation of Rickettsia moseri was performed.</p><p><b>RESULTS</b>The overall infection rate among general population was 28.92% (96/332) with geometric meantiter (GMT) as 10.83 and there was no difference between males and females (26.71%, 43/161 vs. 30.99%, 53/171, P > 0.05). Significant differences were found between age groups (P < 0.05) with positive rates of 29.63% (8/27), 18.06% (13/72), 39.62% (42/106), 27.50% (22/80) and 23.40% (11/47) among age groups 0-6, 7-18, 19-39, 40-59 and over 60, respectively. The overall rate of infection in mouse was 44.95% (89/198) with GMT as 30.30. Five isolates of R. moseri from mouse specimen, three from fleas plus one case of murine typhus were diagnosed. Rattus norvegicus and Rattus flavipectus were the predominant species of rodent animals (99.49%, 197/198) and Xenopsylla cheopis was the major species of vector (74.26%, 303/408). Flea index and mouse density were 2.06 and 11.13% respectively.</p><p><b>CONCLUSION</b>High infection rates on R. moseri were demonstrated in rodents and residents as well as high risk of murine typhus outbreak might occur in these areas.</p>

Tifus murino en el Cairo- Valle ¿Brote o condición endémica emergente? / Murine typhus in el Cairo, Valle ¿outbreak or emerging diseases?

Introducción: En el Municipio de El Cairo Valle se reportó un brote de Tifus Murino, el cual habitualmente no se diagnostica en la región. Métodos: Se presenta una serie de casos obtenidos del Sitema de Vigilancia Epidemiológica del Municipio de El Cairo, administrado por el Hospital Municipal. Resultados: Se reportan 34 casos nuevos de Tifus Murino, que como característicasespeciales fueron predominantemente femeninos, y población adulta. Conclusión: El brote fue controlado con la oportuna intervención del Comité de Vigilancia Epidemiológica del Municipio y coordinado por diferentesinstituciones.

Molecular epidemic survey on co-prevalence of scrub typhus and marine typhus in Yuxi city, Yunnan province of China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human rickettsioses are worldwide zoonoses and it is not easy to differentiate them from other infectious diseases because of their atypical manifestation. In recent years the number of patients with fever of unknown causes from Hongta District CDC, Yuxi city of Yunnan Province has been increasing significantly in the summer. Diagnosis of scrub typhus was made by local clinicians. In order to ascertain the disease, we undertook a laboratory investigation for such patients from August 18 to 26, 2005.</p><p><b>METHODS</b>Active surveillance was conducted by Hongta District CDC Yuxi city of Yunnan Province from 2002 to 2004 and basic data were obtained from cases confirmed according to clinical definitions. Average incidences and town-level incidences were calculated during the study periods. Blood samples were analyzed by PCR and serological test. Based on the groEL gene sequences a paired general outer primers (Gro-1 and Gro-2) targeting typhus, spotted fever as well as scrub typhus and two paired inner primers (SF1, SR2 and TF1, TR2) for typhus together with spotted fever and scrub typhus, respectively, were designed to perform a multiplex-nested PCR. Serological assay was carried out by indirect immunofluorescence assay with 7 different rickettsial antigens, i.e., R.mossori, R.sibirica, R.conorii, O.tsutsugamushi, B.quintana, B.henselae and Coxilella burnetii phase II Ag.</p><p><b>RESULTS</b>Epidemiological surveillance showed that from 2002 to 2004, the average incidences of the scrub typhus or scrub typhus with murine typhus were 222.1/10(5), 204.3/10(5) and 109.6/10(5), respectively. Of 13 blood samples taken during acute stage of illness, 6 showed the amplified products for scrub typhus and the sequenced products showed 100%, 99%, 99%, 99%, 99%, 99% similarity to O.tsutsugamushi Karp but they shared the same deduced amino acid sequences, which indicated 100% identity with the heat shock protein of the O.tsutsugamushi Karp strain. Five yielded PCR products for murine typhus and their corresponding nucleotide sequences exhibited 100%, 100%, 99%, 99% and 99% similarity to R. mossori Wilmington and the analyses of predicted amino acid sequences indicated 100%, 100%, 98%, 98% and 98% identity with the heat shock protein of R. mossori Wilmington strain. Of the 8 PCR positive patients, 3 showed a co-infection of scrub typhus with murine typhus. All the 13 serum samples from febrile patients were positive against O. tsutsugamushi and 8 of them were positive against R. mossori. All of the 8 paired specimens had four-fold elevation of antibody against O. tsutsugamushi, and seroconversion for typhus was demonstrated in 3 paired serum samples. Another finding in the study was that a high seropositive prevalence (76.9%) of Q fever was detected.</p><p><b>CONCLUSION</b>It's confirmed that co-prevalence of scrub typhus with murine typhus are occurring in Yuxi city of Yunnan province, China. Other rickettsial diseases also need to be investigated in these areas.</p>

Abundance and distribution of Xenopsylla cheopis on small mammals collected in West Java, Indonesia during rodent-borne disease surveys.

During February 2004 and September 2005, Xenopsylla cheopis were collected from small mammal hosts during rodent-bone disease surveys in Jakarta and Bandung, Indonesia. During 4 trap nights in Jakarta, 4 rodent species (Rattus exulans, Rattus norvegicus, Rattus tanezumi and Mus musculus) and one shrew species (Suncus murinus) were collected. Rattus tanezumi had the highest X. cheopis load (128 X. cheopis from 84 R. tanezumi) but R. norvegicus had the highest flea index, 1.8. In Bandung, over 6 trap nights 3 rodent species were collected (R. norvegicus, R. tanezumi and M. musculus) and the shrew, S. murinus, were collected. Rattus norvegicus had the highest number of X. cheopis collected (407 X. cheopis from 181 R. norvegicus) but R. tanezumi had the highest flea index, 3.5. During both surveys, X. cheopis was the species of flea collected.

Study on serum transcobalamin II in patients with murine typhus.

We measured the serum transcobalamin II in murine typhus- infected patients (n = 16) admitted to the Hospital for Tropical Diseases in 1996-1997, compared with healthy controls (n = 60). The results showed that the transcobalamin II (TCII) and total serum unsaturated vitaminB12 binding capacity (UBBC) in patients with murine typhus (2,126.5 pg/ml, range 1,262-4,568 and 3,771.5 pg/ml, range 1,576-6,763 pg/ml) were statistically significantly higher than normal subjects (987.5 pg/ml, range 678-2,000 pg/ml and 1,402 pg/ml, range 932-2,470 ml) (p<0.001). Serum TCII levels in patients (63%) were elevated during the febrile period and returned to normal post-treatment. These findings suggest that patients with murine typhus had stimulation of reticulo-endothelial system, spleen, mesenteric lymph nodes, liver and skin and then released TCII into the blood circulation. The elevation in TCII may be used for confirming a diagnosis of murine typhus.

Seroprevalence of Rickettsia japonica on an Island Where a Korean Patient with Japanese Spotted Fever was First Identified

BACKGROUND: Spotted fever group rickettsiosis occurs worldwide and includes various causative organisms depending on the region and clinical features. In Korea, previous studies have shown that several kinds of spotted fever rickettsiae have been identified in ticks, and in stored sera obtained from febrile patients. Previously, it was difficult to correlate the results of serologic or molecular biologic tests with the clinical or epidemiological features of this disease in humans. In 2004, the first Korean patient with Japanese spotted fever (JSF) was identified on Mueui Island, Incheon, Korea. To estimate the prevalence of JSF and to compare the incidence of JSF with those of other infectious diseases endemic to Korea, we performed a serosurvey of Japanese spotted fever and other rickettsiosis (scrub typhus and murine typhus), hemorrhagic fever with renal syndrome and leptospirosis on the island where the patient had been living. MATERIALS AND METHODS: In October 2004, we performed a seroprevalence survey of Mueui Island where nearly 300 persons resided. There were 91 persons who participated in the survey and answered the questionnaire. The participants included 30 healthy subjects receiving a check up at the Health Promotion Center at Inha University Hospital, and 30 patients with rheumatoid factor as control groups for the serologic tests. RESULTS: Of the 91 residents, only one person showed a positive reaction to R. japonica at a titer of 1:80. IgG antibodies against O. tsutsugamushi were positive at a titer of 1:32 in 3 persons, and those against R. typhi were at 1:32 in 1 person and at 1:64 in 2 persons. Serum IgG antibodies to Hantan virus were positive at a dilution of 1:64 in 2 persons and those to leptospira were negative. All 30 healthy persons and 30 patients with rheumatoid factor in the control group showed negative results in 1:40 diluted sera. CONCLUSION: This study demonstrates that the seroprevalence of R. japonica is not as high in Korea as it is in Japan. Further studies should be performed in a large number of patients, including residents of other islands and the Korean peninsula.

Seroprevalence of Rickettsia japonica on an Island Where a Korean Patient with Japanese Spotted Fever was First Identified

BACKGROUND: Spotted fever group rickettsiosis occurs worldwide and includes various causative organisms depending on the region and clinical features. In Korea, previous studies have shown that several kinds of spotted fever rickettsiae have been identified in ticks, and in stored sera obtained from febrile patients. Previously, it was difficult to correlate the results of serologic or molecular biologic tests with the clinical or epidemiological features of this disease in humans. In 2004, the first Korean patient with Japanese spotted fever (JSF) was identified on Mueui Island, Incheon, Korea. To estimate the prevalence of JSF and to compare the incidence of JSF with those of other infectious diseases endemic to Korea, we performed a serosurvey of Japanese spotted fever and other rickettsiosis (scrub typhus and murine typhus), hemorrhagic fever with renal syndrome and leptospirosis on the island where the patient had been living. MATERIALS AND METHODS: In October 2004, we performed a seroprevalence survey of Mueui Island where nearly 300 persons resided. There were 91 persons who participated in the survey and answered the questionnaire. The participants included 30 healthy subjects receiving a check up at the Health Promotion Center at Inha University Hospital, and 30 patients with rheumatoid factor as control groups for the serologic tests. RESULTS: Of the 91 residents, only one person showed a positive reaction to R. japonica at a titer of 1:80. IgG antibodies against O. tsutsugamushi were positive at a titer of 1:32 in 3 persons, and those against R. typhi were at 1:32 in 1 person and at 1:64 in 2 persons. Serum IgG antibodies to Hantan virus were positive at a dilution of 1:64 in 2 persons and those to leptospira were negative. All 30 healthy persons and 30 patients with rheumatoid factor in the control group showed negative results in 1:40 diluted sera. CONCLUSION: This study demonstrates that the seroprevalence of R. japonica is not as high in Korea as it is in Japan. Further studies should be performed in a large number of patients, including residents of other islands and the Korean peninsula.

A Case of Acute Renal Failure Resulting from Murine Typhus Infection Induced Acute Tubulointerstitial Nephritis / 대한신장학회잡지

Murine typhus is an infectious disease caused by Rickettsia typhi, an intracellular parasite that lives in the cytoplasm of host cells. Rickettsia typhi infection can induce lymphohistiocytic vasculitis leading to pulmonary, cardiovascular, central nervous system and renal complications. We experienced a case of acute renal failure resulting from acute tubulointerstitial nephritis associated with murine typhus infection. A 67 year old man was transferred from local hospital due to fever, confusion, oliguria with renal failure. Laboratory finding showed elevated liver enzyme with hypoalbuminemia and progressive azotemia. Despite supportive care, his azotemia progressed with anuria and acute hemodialysis was started. Kidney biopsy showed acute tubulointerstitial nephritis with vasculitis and indirect immunofluorecent antibody to murine typhus was 1: 3, 200. Doxycyclin was started and his renal function recovered. We report a case of acute renal failure resulting from murine typhus infection induced acute tubulointerstitial nephritis.

Murine (endemic) typhus in Brazil: case report and review

O tifo murino tem sido reconhecido com freqüência crescente em todo o mundo e vem se tornando um relevante diagnóstico diferencial de quadros febris. No Brasill, o tifo murino nunca mereceu grande atenção. Descrevemos um caso clínico e fazemos revisão da literatura que sugere que a doença poderia ser mais prevalente no sudeste brasileiro do que reconhecido até então.