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Rickettsia felis , responsible for flea-borne spotted fever, is a rising zoonotic pathogen posing an increasing global threat due to its expanding geographical distribution. The rise in antibiotic-resistant strains of this pathogen underscores the urgent need for new therapeutic interventions. This study employed a comprehensive subtractive proteomics analysis of the R. felis proteome, aiming to identify essential, non-host homologous, and pathogen-specific proteins, which were subsequently evaluated as potential new drug targets. These findings offer valuable insights into the development of therapeutic strategies against rickettsiosis. The analysis revealed 343 proteins that are non-homologous to the host, including 108 essential proteins, 25 unique metabolic pathways, and 11 distinct proteins. Out of these, 10 proteins were druggable in which two associated with virulence, and one related to resistance (succinate dehydrogenase). Through a rigorous screening process and extensive literature review, succinate dehydrogenase emerged as a promising drug target. Protein interaction partners for succinate dehydrogenase were identified using the STRING database. To further assess the functionality of succinate dehydrogenase, structure-based studies were conducted. Approximately 18,000 ZINC compounds were screened, leading to the finding of six potential inhibitors: ZINC67847806, ZINC67982856, ZINC67974679, ZINC67895371, ZINC05668040, and ZINC05670149. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling confirmed that most compounds met the preferred pharmacokinetic properties, except for ZINC67895371 and ZINC67847806, which exhibited positive ames test results, and ZINC05670149, ZINC67895371, and ZINC67847806, showed hepatotoxicity. All compounds were found to be non-sensitizing to the skin. Based on these findings, further experimental validation of ZINC67974679, ZINC67982856, and ZINC05668040 is recommended. [ABSTRACT FROM AUTHOR]

Sha Wen,* Jing-Jing Zeng,* Ying Li Department of Critical Care Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Li, Email liying20020813@163.comAbstract: Rickettsia felis (R. felis) is a Gram-negative obligate intracellular bacterium with a global presence across various hosts, including mammals, humans, and ectoparasites. Herein, we present a case of R. felis infection in a previously healthy 43-year-old male with a history of Clonorchis sinensis and recent corticosteroid use. The identification of R. felis was accomplished through metagenomic next-generation sequencing (mNGS) of the patient’s bronchoalveolar lavage fluid (BALF). This case represents the first documented pulmonary infection caused by R. felis in China, confirmed by mNGS analysis of bronchoalveolar lavage fluid (BALF) and reported from Shenzhen, China.Keywords: mNGS technology, Rickettsia felis, bronchoalveolar lavage fluid, pulmonary infection

Abstract Vector-borne diseases account for nearly 20% of all globally recognised infectious diseases. Within the spectrum of flea-borne pathogens, Bartonella and Rickettsia bacteria are prominent, contributing to the emergence and resurgence of diseases on a global scale. This study investigates the presence of species of Bartonella and Rickettsia harboured by fleas collected from wild rodents in northwestern Argentina (NWA). A total of 28 fleas from three genera and seven species were assessed. DNA of Bartonella and Rickettsia spp. was found in 12 fleas (42.8%). Phylogenetic analysis of concatenated sequences of gltA and rpoB genes showed the presence of Bartonella quintana in eight fleas of two species, Craneopsylla minerva minerva and Polygenis acodontis. Phylogenetic analysis of concatenated sequences of gltA, ompA and ompB genes identified Rickettsia felis in ten fleas of five species, C. m. minerva, P. acodontis, Polygenis bohlsi bohlsi, Polygenis byturus and Tiamastus palpalis. These bacterial species mark the first report in all flea species studied. This study represents the first survey of flea-borne bacteria for NWA. The results provide information to address strategies for the control and prevention of bartonellosis and rickettsiosis that could have an impact on public health in one of the geographical areas of Argentina with the highest incidence of infections transmitted to humans by ectoparasites.

Vector-borne diseases account for nearly 20% of all globally recognised infectious diseases. Within the spectrum of flea-borne pathogens, Bartonella and Rickettsia bacteria are prominent, contributing to the emergence and resurgence of diseases on a global scale. This study investigates the presence of species of Bartonella and Rickettsia harboured by fleas collected from wild rodents in northwestern Argentina (NWA). A total of 28 fleas from three genera and seven species were assessed. DNA of Bartonella and Rickettsia spp. was found in 12 fleas (42.8%). Phylogenetic analysis of concatenated sequences of gltA and rpoB genes showed the presence of Bartonella quintana in eight fleas of two species, Craneopsylla minerva minerva and Polygenis acodontis. Phylogenetic analysis of concatenated sequences of gltA, ompA and ompB genes identified Rickettsia felis in ten fleas of five species, C. m. minerva, P. acodontis, Polygenis bohlsi bohlsi, Polygenis byturus and Tiamastus palpalis. These bacterial species mark the first report in all flea species studied. This study represents the first survey of flea-borne bacteria for NWA. The results provide information to address strategies for the control and prevention of bartonellosis and rickettsiosis that could have an impact on public health in one of the geographical areas of Argentina with the highest incidence of infections transmitted to humans by ectoparasites. [ABSTRACT FROM AUTHOR]

Rickettsia felis, responsible for flea-borne spotted fever, is a rising zoonotic pathogen posing an increasing global threat due to its expanding geographical distribution. The rise in antibiotic-resistant strains of this pathogen underscores the urgent need for new therapeutic interventions. This study employed a comprehensive subtractive proteomics analysis of the R. felis proteome, aiming to identify essential, non-host homologous, and pathogen-specific proteins, which were subsequently evaluated as potential new drug targets. These findings offer valuable insights into the development of therapeutic strategies against rickettsiosis. The analysis revealed 343 proteins that are non-homologous to the host, including 108 essential proteins, 25 unique metabolic pathways, and 11 distinct proteins. Out of these, 10 proteins were druggable in which two associated with virulence, and one related to resistance (succinate dehydrogenase). Through a rigorous screening process and extensive literature review, succinate dehydrogenase emerged as a promising drug target. Protein interaction partners for succinate dehydrogenase were identified using the STRING database. To further assess the functionality of succinate dehydrogenase, structure-based studies were conducted. Approximately 18,000 ZINC compounds were screened, leading to the finding of six potential inhibitors: ZINC67847806, ZINC67982856, ZINC67974679, ZINC67895371, ZINC05668040, and ZINC05670149. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling confirmed that most compounds met the preferred pharmacokinetic properties, except for ZINC67895371 and ZINC67847806, which exhibited positive ames test results, and ZINC05670149, ZINC67895371, and ZINC67847806, showed hepatotoxicity. All compounds were found to be non-sensitizing to the skin. Based on these findings, further experimental validation of ZINC67974679, ZINC67982856, and ZINC05668040 is recommended.

Rickettsiae, which are obligate intracellular bacterial parasites, have a life cycle commonly associated with arthropod vectors and animal hosts. Rodents are recognized as their natural reservoir hosts and play a role in transmitting the bacteria to humans through arthropod vectors. The true extent of rickettsial infections in Vietnam remains underestimated due to a limited understanding of the disease’s epidemiology, resulting in a significant public health burden.The aim of this investigation was to assess the prevalence of Rickettsia in wild-living rodents in Dien Bien, Son La, and Phu Tho provinces of Northern Vietnam between 2020 and 2022.Materials and methods. A total of 396 wild-living rodents were collected from the Northern provinces of Vietnam during 2020–2022. Real-time polymerase chain reaction (PCR) was employed to detect the percentage of Rickettsia-positive specimens. Subsequently, the ompB and 17kDa genes were extracted, amplified, and sequenced from the Rickettsia-positive rodents.Results and discussion. Among the 396 rodents examined, the majority were Rattus norvegicus (56.1%), followed by R. tanezumi (37.4%), R. nitidus (2.5%), and R. germaini (1.8%). R. korodentsensis and R. argentiverter constituted the remaining rodents, accounting for 2.2% of the total. The real-time PCR analysis revealed that 27 blood samples out of the 396 rodent samples collected, tested positive for Rickettsia (6.81%). R. germaini was shown to have the highest positive rate 1/8 (12.5%), followed by R. nitidus 1/10 (10.0%), R. tanezumi 14/149 (9.5%), and R. norvegicus 11/222 (4.9%). No other tick-borne pathogens were detected in any of the provinces. Sequencing of the positive samples as regards the ompB and 17kDa genes revealed the closest relation to R. felis. These findings highlight the potentially high risk of R. felis infection in humans and animals within the studied areas.

Jie Wang,1,* Hong Zhou,2,* Zan Dong,3 Jing Wang,1 Rui Wang,1 Yuanlin Guan4 1Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 2Graduate School, the First Clinical School of Medicine, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Neurology, Yuncheng Central Hospital, Yuncheng, 044000, People’s Republic of China; 4Department of Scientific Affairs, Hugobiotech Co, Ltd, Beijing, 100176, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Wang, Department of Neurology, First Hospital of Shanxi Medical University, No. 85 of Jiefang South Road, Taiyuan, Shanxi, 030000, People’s Republic of China, Tel +8613753198116, Email luwanglu2012@163.comBackground: Rickettsia felis is a kind of zoonotic pathogen. Rickettsia felis infections of the central nervous system are rare with only a few cases reported worldwide. The early diagnosis of R. felis is difficult due to its nonspecific clinical features and laboratory tests. Here, we report two meningitis cases caused by R. felis using metagenomic next-generation sequencing (mNGS).Methods: The clinical data of patients with meningitis who were diagnosed to have R. felis through cerebrospinal fluid culture, nuclear magnetic imaging, mNGS detection from January 2019 to December 2019 in The First Clinical Hospital of Shanxi Medical University, were retrospectively analyzed, and their clinical characteristics and disease regression findings were summarized.Case Presentation: The first case was a female patient aged 23 years who was admitted to our hospital presenting with symptoms of headache, fever, and weakness in both lower limbs. Upon examination of spinal imaging, myelitis was diagnosed. However, routine examination and culture of cerebrospinal fluid did not identify the pathogen responsible. Subsequently, metagenomic second-generation sequencing (mNGS) revealed that the infection was caused by R. felis. The patient responded well to standard treatment and showed signs of recovery. The second case was a male patient aged 29 years who was admitted to our hospital with a headache and fever that had persisted for 4 days within a month. Routine examination and culture of the cerebrospinal fluid did not reveal any identifiable pathogens. However, metagenomic second-generation sequencing (mNGS) determined that the patient had a Rickettsial infection likely transmitted by a cat. The patient showed significant improvement after 14 days of doxycycline treatment. Tests for herpes simplex virus, cytomegalovirus, Epstein-Barr virus and tubercle bacillus nucleic acid in the CSF and blood were negative.Therefore mNGS of the cerebrospinal fluid was used, which identified the pathogen as R. felis. One case was diagnosed as subacute meningitis with immune-associated myelitis and the other as subacute meningitis.Conclusion: mNGS of cerebrospinal fluid can be used as a fast and effective method to identify intracranial R. felis infections.Keywords: Rickettsia felis, meningitis, myelitis, metagenomic next-generation sequencing, case report

Objective To report a case of neurosyphilis complicated with Rickettsia felis infection, and summarize the clinical manifestations, cerebrospinal fluid (CSF) and imaging characteristics. Methods and Results A 33⁃year⁃old male with a disease course of more than 3 months was admitted to Beijing Tiantan Hospital, Capital Medical University on October 12, 2022, who had kept a cat at home for more than 10 years. The main clinical manifestations were seizure, cognitive function decline, and low fever in the last one month. Serum Treponema syphilis (TP) antibody, Treponema Pallidum Hemagglutination Assay (TPHA), Toluidine Red Unheated Serum Test (TRUST) were positive. CSF test showed increased white blood cell count and protein, positive oligoclonal band, 24h intrathecal IgG synthesis rate and IgG index. Head MRI showed T2WI and FLAIR hyperintensity in bilateral medial temporal lobe and hippocampus atrophy, evident on the right side. There were 229 Rickettsia felis sequences and 2TP sequences detected in CSF metagenomic next⁃generation sequencing (mNGS). After his medical history was asked again, he was infected with syphilis 7 years ago, and his serum and CSF were positive for TP antibody. The comprehensive clinical and imaging findings were consistent with the characteristics of neurosyphilis, and the fever was consistent with the characteristics of Rickettsia felis infection. He was diagnosed as neurosyphilis complicated with Rickettsia felis infection, who improved after penicillin and doxycycline treatment. Conclusions Neurosyphilis complicated with Rickettsia felis infection is clinically rare. mNGS can help with early diagnosis. Early anti⁃infective therapy can improve the prognosis.

Infection with members of the order Rickettsiales (the genera Rickettsia, Anaplasma, Orientia, and Ehrlichia) is known to cause hemophagocytic lymphohistiocytosis (HLH). The literature is scant on flea-borne typhus (FBT) being implicated in this process. We present a case of autopsy-proven HLH caused by FBT in a 71-year-old diabetic female who was initially suspected of having diabetic ketoacidosis who rapidly suffered decompensated multi-organ failure. Although she was suspected of having FBT and HLH pre-mortem, due to her rapid progression to multi-organ failure, she was transitioned to comfort care by her family five days after admission. A literature search yielded five other cases of HLH secondary to FBT, which are analyzed in this review. The literature on HLH occurring with infection due to other members of the order Rickettsiales is also surveyed.

Rickettsia is an important pathogenic entity among tick-borne diseases (TBD), which are considered serious emerging public health problems globally. In India, though the widespread distribution of ticks and TBD has been documented, its real burden remains underreported. In a preliminary attempt, rickettsial surveillance was carried out in ticks collected from Sirumalai, Eastern Ghats in Tamil Nadu, India by using pathogen genome-based phylogenetic inferences generated through multi-locus sequence typing (MLST), targeting the genes 16s rRNA, OmpA, OmpB, and gltA by nested PCR. The laboratory evidence confirms the circulation of Rickettsia in Haemaphysalis intermedia species collected from this area. Analysis of the four gene sequences detected demonstrates their closest identity to the spotted fever group (SFG) available in the GenBank database. Further, multiple sequence alignment with other sequences derived from the GenBank database showed close relatedness to Rickettsia conorii subsp. raoultii (16s rDNA-99.32%, OmpA-93.38%, OmpB-97.39%, and gltA-98.57%) and Rickettsia felis (16s rDNA 99.54%, OmpA-100%, OmpB-100% and gltA-99.41%). With this genomic evidence, the circulation of rickettsial pathogens in the pools of H. intermedia ticks infesting livestock in the Sirumalai foothill area has been demonstrated and to complement the microscopic identification of the tick species, DNA barcodes were generated for H. intermedia using the mitochondrial cytochrome c oxidase subunit I gene (COI). Nevertheless, R. raoultii and R. felis were found to be the aetiological agents of tick-borne lymphadenopathy and flea-borne spotted fever in human cases, respectively, further study on the determination of their diversity, distribution, clinical relevance, and potential risk to the local community in these areas is highly warranted. [ABSTRACT FROM AUTHOR]

Homeless encampments are a persistent feature in the city of Oakland, California. Unsanitary conditions in these camps can contribute to large populations of Norway rats and associated vector-borne disease. Alameda County Vector Control Services District has developed a surveillance program for safe and efficient data collection in these encampments. This program includes outreach to residents, effective live-trap ping, ectoparasite collection, vector species suppression, and coordinating with other agencies. The District’s operations around Oakland’s pilot “Tuff Shed” homeless shelter strategy are presented as a case study for Norway rat and Oriental rat flea risk assessment and control.

Objective To report a case of neurosyphilis complicated with Rickettsia felis infection, and summarize the clinical manifestations, cerebrospinal fluid (CSF) and imaging characteristics. Methods and Results A 33-year-old male with a disease course of more than 3 months was admitted to Beijing Tiantan Hospital, Capital Medical University on October 12, 2022, who had kept a cat at home for more than 10 years. The main clinical manifestations were seizure, cognitive function decline, and low fever in the last one month. Serum Treponema syphilis (TP) antibody, Treponema Pallidum Hemagglutination Assay (TPHA), Toluidine Red Unheated Serum Test (TRUST) were positive. CSF test showed increased white blood cell count and protein, positive oligoclonal band, 24 h intrathecal IgG synthesis rate and IgG index. Head MRI showed T2WI and FLAIR hyperintensity in bilateral medial temporal lobe and hippocampus atrophy, evident on the right side. There were 229 Rickettsia felis sequences and 2 TP sequences detected in CSF metagenomic next-generation sequencing (mNGS). After his medical history was asked again, he was infected with syphilis 7 years ago, and his serum and CSF were positive for TP antibody. The comprehensive clinical and imaging findings were consistent with the characteristics of neurosyphilis, and the fever was consistent with the characteristics of Rickettsia felis infection. He was diagnosed as neurosyphilis complicated with Rickettsia felis infection, who improved after penicillin and doxycycline treatment. Conclusions Neurosyphilis complicated with Rickettsia felis infection is clinically rare. mNGS can help with early diagnosis. Early anti-infective therapy can improve the prognosis. [ABSTRACT FROM AUTHOR]

Infection with members of the order Rickettsiales (the genera Rickettsia, Anaplasma, Orientia, and Ehrlichia) is known to cause hemophagocytic lymphohistiocytosis (HLH). The literature is scant on flea-borne typhus (FBT) being implicated in this process. We present a case of autopsy-proven HLH caused by FBT in a 71-year-old diabetic female who was initially suspected of having diabetic ketoacidosis who rapidly suffered decompensated multi-organ failure. Although she was suspected of having FBT and HLH pre-mortem, due to her rapid progression to multi-organ failure, she was transitioned to comfort care by her family five days after admission. A literature search yielded five other cases of HLH secondary to FBT, which are analyzed in this review. The literature on HLH occurring with infection due to other members of the order Rickettsiales is also surveyed. [ABSTRACT FROM AUTHOR]

Chiggers are larval ectoparasites of the Trombiculidae that can transmit pathogens to their hosts. In this study, chiggers collected from birds in Brazil were morphologically identified as Blankaartia sinnamaryi, Eutrombicula batatas, Eutrombicula daemoni, Eutrombicula goeldii, Eutrombicula tinami, and Parasecia gilbertoi. For these specimens, a beginning attempt at molecular identification were also provided, as well as, were genetically screened to detect bacterial pathogens. The species B. sinnamaryi and E. tinami were positive for Rickettsia felis-like and ‘Candidatus Rickettsia colombianensi’-like, respectively. For the other agents (Anaplasmataceae, Borrelia spp. and Orientia tsutsugamushi), the tests were negative. This is the first report of ‘Ca. R. colombianensi’-like and the second record of R. felis-like in chigger collected on birds from Brazil. [ABSTRACT FROM AUTHOR]

Canine vector-borne pathogens (CVBPs) comprise a group of disease agents mainly transmitted by ticks, fleas, mosquitoes and sand flies. In this study, we assessed the presence of CVBPs in an Afro-descendent community (Quilombola) of northeastern, Brazil. Dog blood samples (n = 201) were collected and analyzed by rapid test for the detection of antibodies against Leishmania spp., Anaplasma spp., Ehrlichia spp. and Borrelia burgdorferi sensu lato (s.l.), and antigens of Dirofilaria immitis. In addition, polymerase chain reactions were performed for Anaplasmataceae, Babesia spp., Hepatozoon spp., Rickettsia spp. and B. burgdorferi s.l. Overall, 66.7% of the dogs scored positive to at least one pathogen at serological and/or molecular methods. Antibodies against Ehrlichia spp. were the most frequently detected (57.2%; n = 115/201), followed by Anaplasma spp. (8.5%; n = 17/201), Leishmania spp. (8.5%; n = 17/201) and B. burgdorferi s.l. (0.5%; n = 1/201). For D. immitis, 11 out of 201 (5.5%) animals scored positive. At the molecular analysis, 10.4% (n = 21/201) of the samples scored positive for Babesia spp./Hepatozoon spp., followed by Anaplasmataceae (5.0%; n = 10/201) and Rickettsia spp. (3.0%; n = 6/201). All samples were negative for B. burgdorferi s.l. Our data demonstrated the presence of CVBPs in the studied population, with a high seropositivity for Ehrlichia spp. In addition, considering the detection of zoonotic pathogens in dogs and their relationship with people from Quilombola communities, effective control strategies are advocated for minimizing the risk of infection in this socially vulnerable human population and their pets. [ABSTRACT FROM AUTHOR]

We identified four flea-borne spotted fever cases caused by Rickettsia felis in a retrospective survey of 182 patients with fever of unknown origin (FUO) in China between 2021 and 2022. The clinical signs and symptoms of the patients were similar to those of other rickettsioses, including fever, rash, and liver and kidney dysfunction. All four patients in the present study developed pneumonia or lung lesions after R. felis infection. The cases of R. felis infection, a neglected infectious disease, were sporadic in multiple provinces of the country. The high prevalence (2.14%, 4/187) of R. felis among patients with FUO highlights the risk posed by this pathogen to public health in China. [ABSTRACT FROM AUTHOR]

Background: Rickettsia felis is emergent in tropical areas. Despite its high morbidity, its natural history has not yet been fully determined. We investigated the role of the common household booklouse, Liposcelis bostrychophila, recently found to harbor R. felis.Methods: Blood samples from 372 febrile patients from Senegalese villages, as well as nasal and skin samples from 264 asymptomatic individuals, were tested for cat flea-associated and booklice-associated strains of R. felis. Dust samples from beds were collected to isolate booklice and R. felis. Mice were infected with aerosol of R. felis strain from naturally infected booklice.Results: Forty febrile patients (11%) were infected by R. felis, including 26 (7%) by the booklice-associated strain. Nine nasal samples (3.4%) and 28 skin samples (10.6%) contained R. felis, including 7 and 24, respectively, with the booklice-associated strain. The presence of live L. bostrychophila was observed in 32 dust samples (16.8%); R. felis was identified in 62 dust samples (32.5%). Several mice samples were positive for R. felis; interstitial lymphohistiocytic infiltrates were identified in lungs.Conclusions: Liposcelis bostrychophila may be a reservoir of R. felis. The booklice-associated strain is pathogenic in mammals, causing pneumonia. Human infection may be acquired via inhalation of infected booklice particles. [ABSTRACT FROM AUTHOR]

Introducción. Las rickettsiosis son enfermedades zoonóticas transmitidas por artrópodos que cumplen el papel de vectores y reservorios, y cuyos síntomas son inespecíficos, por lo que su diagnóstico clínico es difícil. La inmunofluorescencia indirecta (IFI) es el método de referencia para el diagnóstico. En Colombia, ha resurgido el interés por su estudio por los casos de rickettsiosis detectados en el norte del departamento de Caldas a partir del 2001. Objetivo. Establecer la frecuencia de anticuerpos y la seroconversión contra Rickettsia spp. en pacientes atendidos en instituciones de salud del departamento de Caldas, Colombia, entre 2016 y 2019. Materiales y métodos. Se hizo un estudio de diseño cuantitativo, observacional y descriptivo, con una muestra no probabilística de 175 pacientes atendidos en diferentes municipios de Caldas, a quienes se les realizó IFI para la detección de anticuerpos en fase aguda y convaleciente contra Rickettsia rickettsii, R. typhi y R. felis. Resultados. El promedio de edad de los pacientes fue de 31 años. Los municipios con mayor proporción de seropositivos fueron Belalcázar, Chinchiná, Filadelfia, La Dorada, La Merced y Manizales. El 66 % tenía mascotas y el 12 % reportó picaduras por artrópodos. Los signos y síntomas más frecuentes fueron cefalea (69,7 %), artromialgia (60 %), y fiebre (58,2 %). La seroprevalencia por IgG fue de 60 % para R. rickettsii, 47,9 % para R. typhi y 24 % para R. felis. Ocho pacientes presentaron seroconversión. Conclusión. Se encontró evidencia de la circulación de rickettsias del grupo de las fiebres manchadas y del grupo del tifus asociada con casos humanos en el departamento de Caldas.

Rickettsia is an important pathogenic entity among tick-borne diseases (TBD), which are considered serious emerging public health problems globally. In India, though the widespread distribution of ticks and TBD has been documented, its real burden remains underreported. In a preliminary attempt, rickettsial surveillance was carried out in ticks collected from Sirumalai, Eastern Ghats in Tamil Nadu, India by using pathogen genome-based phylogenetic inferences generated through multi-locus sequence typing (MLST), targeting the genes 16s rRNA, OmpA, OmpB, and gltA by nested PCR. The laboratory evidence confirms the circulation of Rickettsia in Haemaphysalis intermedia species collected from this area. Analysis of the four gene sequences detected demonstrates their closest identity to the spotted fever group (SFG) available in the GenBank database. Further, multiple sequence alignment with other sequences derived from the GenBank database showed close relatedness to Rickettsia conorii subsp. raoultii (16s rDNA-99.32%, OmpA-93.38%, OmpB-97.39%, and gltA-98.57%) and Rickettsia felis (16s rDNA 99.54%, OmpA-100%, OmpB-100% and gltA-99.41%). With this genomic evidence, the circulation of rickettsial pathogens in the pools of H. intermedia ticks infesting livestock in the Sirumalai foothill area has been demonstrated and to complement the microscopic identification of the tick species, DNA barcodes were generated for H. intermedia using the mitochondrial cytochrome c oxidase subunit I gene (COI). Nevertheless, R. raoultii and R. felis were found to be the aetiological agents of tick-borne lymphadenopathy and flea-borne spotted fever in human cases, respectively, further study on the determination of their diversity, distribution, clinical relevance, and potential risk to the local community in these areas is highly warranted.

Background Flea-borne rickettsioses have been limitedly explored in the Indian sub-Himalayan belt, including the North Eastern Region (NER) of India. This study investigates the presence of rickettsiae hosts and their probable pathogens in the disease-endemic hilly state of the NER of India. Methods Entomological surveys were carried out in disease-reporting localities in a hilly state in India. Fleas collected from domesticated animals were processed for detection of a Rickettsia -specific 17-kDa gene. Results Sequence analysis revealed Rickettsia felis in six flea pools (40%), Candidatus Rickettsia senegalensis in two pools (13.3%) and Rickettsia asembonensis in one pool (6.6%). Conclusions Our findings suggest Ctenocephalides felis, Ctenocephalides canis and Pulex irritans as potential carriers of R. felis and R. felis –like organisms in India. [ABSTRACT FROM AUTHOR]

Maria A Caravedo Martinez,1 Alejandro Ramírez-Hernández,2 Lucas S Blanton1 1Department of Internal Medicine – Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA; 2Department of Pathology, University of Texas Medical Branch, Galveston, TX, USACorrespondence: Lucas S Blanton 301 University Boulevard, Galveston, TX, 77555-0435, USATel +1 (409) 747-0236Fax +1 (409) 772-6527Email lsblanto@utmb.eduAbstract: Murine typhus and flea-borne spotted fever are undifferentiated febrile illnesses caused by Rickettsia typhi and Rickettsia felis, respectively. These organisms are small obligately intracellular bacteria and are transmitted to humans by fleas. Murine typhus is endemic to coastal areas of the tropics and subtropics (especially port cities), where rats are the primary mammalian host and rat fleas (Xenopsylla cheopis) are the vector. In the United States, a cycle of transmission involving opossums and cat fleas (Ctenocephalides felis) are the presumed reservoir and vector, respectively. The incidence and distribution of murine typhus appear to be increasing in endemic areas of the US. Rickettsia felis has also been reported throughout the world and is found within the ubiquitous cat flea. Flea-borne rickettsioses manifest as an undifferentiated febrile illness. Headache, malaise, and myalgia are frequent symptoms that accompany fever. The incidence of rash is variable, so its absence should not dissuade the clinician to consider a rickettsial illness as part of the differential diagnosis. When present, the rash is usually macular or papular. Although not a feature of murine typhus, eschar has been found in 12% of those with flea-borne spotted fever. Confirmatory laboratory diagnosis is usually obtained by serology; the indirect immunofluorescence assay is the serologic test of choice. Antibodies are seldom present during the first few days of illness. Thus, the diagnosis requires acute- and convalescent-phase specimens to document seroconversion or a four-fold increase in antibody titer. Since laboratory diagnosis is usually retrospective, when a flea-borne rickettsiosis is considered, empiric treatment should be initiated. The treatment of choice for both children and adults is doxycycline, which results in a swift and effective response. The following review is aimed to summarize the key clinical, epidemiological, ecological, diagnostic, and treatment aspects of flea-borne rickettsioses.Keywords: Rickettsia typhi, murine typhus, endemic typhus, flea-borne typhus, Rickettsia felis, flea-borne spotted fever, rickettsiosis

Pediculus humanus is an obligate bloodsucking parasite of humans that has two ecotypes, the head louse and the body louse, which share an intimate history of coevolution with their human host. In the present work, we obtained and analysed head and body lice collected from Mbuti pygmies living in the Orientale province of the Democratic Republic of the Congo. Cytochrome b DNA analysis was performed in order to type the six known lice clades (A, D, B, F, C and E). The results revealed the presence of two mitochondrial clades. Clade D was the most frequent (61.7% of 47), followed by clade A (38.3% of 47). Sixteen haplotypes were found in 47 samples, of which thirteen were novel haplotypes, indicating an unusually high genetic diversity that closely mirrors the diversity of their hosts. Moreover, we report for the first time the presence of the DNA of R. felis in three (6.4% of 47) head and body lice belonging to both clades A and D. Additional studies are needed to clarify whether the Pediculus lice can indeed transmit this emerging zoonotic bacterium to their human hosts. [ABSTRACT FROM AUTHOR]

Abstract Background The main vector and reservoir host of Rickettsia felis, an emerging human pathogen causing flea-borne spotted fever, is the cat flea Ctenocephalides felis. While cats have not been found to be infected with the organism, significant percentages of dogs from Australia and Africa are infected, indicating that they may be important mammalian reservoirs. The objective of this study was to determine the presence of R. felis DNA in the blood of domestic dogs and cats in the USA. Methods Three previously validated PCR assays for R. felis and DNA sequencing were performed on blood samples obtained from clinically ill domestic cats and dogs from 45 states (2008–2020) in the USA. The blood samples had been submitted for the diagnosis of various tick-borne diseases in dogs and feline infectious peritonitis virus, feline immunodeficiency virus, and Bartonella spp. in cats. Phylogenetic comparisons were performed on the gltA nucleotide sequences obtained in the study and those reported for R. felis and R. felis-like organisms. Results Low copy numbers of R. felis DNA (around 100 copies/ml whole blood) were found in four cats (4/752, 0.53%) and three dogs (3/777, 0.39%). The very low levels of infection in clinically ill animals is consistent with R. felis being an unlikely cause of disease in naturally infected dogs and cats. The low copy numbers we found emphasize the requirement for very sensitive PCRs in prevalence studies. Conclusions The low prevalence of naturally infected PCR-positive cats is further evidence that cats are unlikely to be important reservoirs of R. felis. Similarly, the low prevalence in dogs suggests they are not important reservoirs in the USA. Investigations should continue into the role other mammalian species may be playing in the epidemiology of R. felis infections.

Pediculus humanus is an obligate bloodsucking parasite of humans that has two ecotypes, the head louse and the body louse, which share an intimate history of coevolution with their human host. In the present work, we obtained and analysed head and body lice collected from Mbuti pygmies living in the Orientale province of the Democratic Republic of the Congo. Cytochrome b DNA analysis was performed in order to type the six known lice clades (A, D, B, F, C and E). The results revealed the presence of two mitochondrial clades. Clade D was the most frequent (61.7% of 47), followed by clade A (38.3% of 47). Sixteen haplotypes were found in 47 samples, of which thirteen were novel haplotypes, indicating an unusually high genetic diversity that closely mirrors the diversity of their hosts. Moreover, we report for the first time the presence of the DNA of R. felis in three (6.4% of 47) head and body lice belonging to both clades A and D. Additional studies are needed to clarify whether the Pediculus lice can indeed transmit this emerging zoonotic bacterium to their human hosts.

Opossums and cat fleas have been epidemiologically linked to flea-borne rickettsial disease transmission in residential backyards of Orange County, California. In 2013, a study was initiated to better elucidate the life history of opossums and their role as vectors of disease and hosts for both internal and external parasites. The study population consisted of adult opossums collected year-round from flea-borne rickettsial disease exposure sites, and moribund opossums submitted by wildlife rehabilitators in Orange County. Carcasses were examined for ectoparasites and necropsied, which included the removal and collection of endoparasites, organ tissues, feces, and urine. Reproductive life history data suggested one brood of young per year, with an average litter size of 7 (n = 9, range 2-11). Average adult weight was 2.49 kg (range 1.30-4.41 kg). Cat fleas were present on each opossum with an average of 96 fleas per opossum (n = 82, range 2-725). Thirty of 33 cat flea pools tested PCR-positive for one of the following bacteria: Rickettsia felis (53%), R. typhi (3%), the R. felis-like organisms, Candidatus Rickettsia senegalensis (28%) and Ca. Rickettsia asemboensis (3%), or Bartonella vinsonii subsp. arupensis (1.5%). Sticktight fleas (Echidnophaga gallinacea), the only other flea detected, were present on less than 6% of opossums, and ticks were not detected on any carcasses (n = 83). Endoparasitic nematodes Cruzia americana and Physaloptera turgida were present in each stomach and cecum, and Didelphostrongylus hayesior or Heterstongylus heterostrongylus was noted in lung samples of opossums (n = 83). Salmonella spp. were detected in 52% of fecal samples (n = 50), with subsequent typing of strains indicating the presence of human pathogens in all but three of the samples (n = 26). Blood and spleen samples were negative for Bartonella spp., Brucella spp., and Yersinia pestis (n = 33). Sera were negative for Leptospira-specific antibodies and Leptospira DNA was not detected in urine (n = 83). Results from this multi-agency study show that the presence of opossums in the backyard environment put Orange County residents and their pets at risk of flea-borne bartonella and rickettsial diseases and salmonellosis.

More than 500 human cases of flea-borne typhus have been reported from Los Angeles and Orange Counties over the past 20 years. Only West Nile virus exceeds flea-borne typhus as an important vector-borne disease in these counties. Despite this, flea-borne typhus garners insignificant public attention compared to West Nile virus. In Los Angeles County alone there were 121 human cases of flea-borne typhus from 2000 to 2009, and 292 human cases from 2010 to 2015. Results from previous studies in Los Angeles and Orange Counties identified a suburban cycle of flea-borne typhus transmission involving backyard wildlife, pets, and the cat flea Ctenocephalides felis. Prior studies and recent observations in Los Angeles County showed that the flea burden of opossums and feral cats is onerously high, and the cat flea is the main vector of the pathogens (Rickettsia typhi and R. felis) responsible for human typhus. The rise of cases in recent years has been accompanied by policy changes in public and private animal control groups that manage nuisance animals in Los Angeles and Orange Counties. Instead of trapping and removing strays and supporting a policy of not feeding wild or stray animals, some governmental agencies and private organizations prefer trap, neuter, and release (TNR) programs and support rehabilitating/relocating feral animals. We believe these policy changes have contributed to the increased incidence of human typhus.

Rickettsia felis (R. felis) infection is a cause of unspecified encephalitis. However, the incidence has been underestimated due to the intracellular features of the pathogen and insufficient understanding of its clinical picture. This study reported a case of R. felis infection in a 26-year-old female who only manifested with certain neurological symptoms. With a lack of specific systemic inflammatory symptoms, the diagnosis was initially misdiagnosed as a brain glioma. However, a brain tissue biopsy showed prominent perivascular inflammatory infiltrations, which indicated inflammatory disease. Spinal fluid metagenomic next-generation sequencing (mNGS) was taken after ruling out other common infectious and autoimmune diseases. The results suggested R. felis infection, which was also supported by Weil-Felix reaction in the serum. After the diagnosis was corrected as R. felis encephalitis, the patient was successfully treated with doxycycline and had a good prognosis at the 1-year follow-up.

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Bed bugs, common blood-feeding pests, have received limited attention regarding their potential involvement in emerging pathogen transmission. This study aimed to investigate the main vector-borne bacteria within bed bugs collected from Tunisian governorates and to genetically characterize the identified species. Molecular screening was conducted on field-collected bed bug samples, targeting zoonotic vector-borne bacteria from the Anaplasmataceae family, as well as the genera Rickettsia , Ehrlichia , Bartonella , and Borrelia. A total of 119 Cimex lectularius specimens were collected and grouped into 14 pools based on sampling Tunisian sites. Using genus-specific PCR assays, DNA of Rickettsia and Ehrlichia spp. was detected in a single pool. Sequencing and BLAST analysis of the obtained partial ompB and dsb sequences from positive samples revealed 100% similarity with those of Ehrlichia canis and Rickettsia felis available in GenBank. Obtained partial sequences showed phylogenetic similarity to R. felis and E. canis isolates found in dogs and ticks from American and European countries. To the best of our knowledge, this study is the first to investigate bed bugs in Tunisia and to report the worldwide identification of R. felis and E. canis DNA in the common bed bug, C. lectularius. These findings highlight the need for further research to explore the potential role of bed bugs in the epidemiology of these vector-borne bacteria. • The study revealed the detection of Rickettsia and Ehrlichia spp. DNA in a single pool of Cimex lectularius. • The analysis of Dsb and ompB partial sequences showed 100% similarity with those of E. canis and R. felis found in GenBank. • Phylogenetic analysis revealed similarity to R. felis and E. canis found in dogs and ticks from American and European countries. • Further research is needed to explore the potential role of bed bugs in the epidemiology of these vector-borne bacteria. [ABSTRACT FROM AUTHOR]

Abstract Background Flea-borne spotted fever is a zoonosis caused by Rickettsia felis, a Gram-negative obligate intracellular bacterium. The disease has a worldwide distribution including western and eastern sub-Saharan Africa where it is associated with febrile illness in humans. However, epidemiology and the public health risks it poses remain neglected especially in developing countries including Zambia. While Ctenocephalides felis (cat fleas) has been suggested to be the main vector, other arthropods including mosquitoes have been implicated in transmission and maintenance of the pathogen; however, their role in the epidemiological cycle remains to be elucidated. Thus, the aim of this study was to detect and characterize R. felis from animal hosts and blood-sucking arthropod vectors in Zambia. Methods Dog blood and rodent tissue samples as well as cat fleas and mosquitoes were collected from various areas in Zambia. DNA was extracted and screened by polymerase chain reaction (PCR) targeting genus Rickettsia and amplicons subjected to sequence analysis. Positive samples were further subjected to R. felis-specific real-time quantitative polymerase chain reactions. Results Rickettsia felis was detected in 4.7% (7/150) of dog blood samples and in 11.3% (12/106) of rodent tissue samples tested by PCR; this species was also detected in 3.7% (2/53) of cat fleas infesting dogs, co-infected with Rickettsia asembonensis. Furthermore, 37.7% (20/53) of cat flea samples tested positive for R. asembonensis, a member of spotted fever group rickettsiae of unknown pathogenicity. All the mosquitoes tested (n = 190 pools) were negative for Rickettsia spp. Conclusions These observations suggest that R. felis is circulating among domestic dogs and cat fleas as well as rodents in Zambia, posing a potential public health risk to humans. This is because R. felis, a known human pathogen is present in hosts and vectors sharing habitat with humans.

Spotted fever group (SFG) rickettsiae are obligatory intracellular bacteria that cause disease in humans and other animals. Ixodid ticks are the principal vectors of SFG rickettsiae. The present study aimed to determine the prevalence and species identity of SFG rickettsiae in ticks and horses from urban and rural areas of western Cuba using PCR assays. Tick samples, collected from 79 horses, consisted of 14 Amblyomma mixtum adults, 111 Dermacentor nitens adults and 19 pools of D. nitens nymphs (2–5 individuals/pool). The PCR results revealed the presence of Rickettsia spp. in 64% of the A. mixtum adults, 16% of the D. nitens adults, and 11% of the pooled samples of D. nitens nymphs. In contrast, Rickettsia spp. was not detected in any of the 200 horse blood samples included in this study. DNA sequence data of the rickettsial 17 kDa antigen gene showed that Rickettsia amblyommatis was present in A. mixtum; and Rickettsia felis in D. nitens. This is the first report of R. felis in D. nitens in Cuba. The present study extends our knowledge of the potential vector spectrum and distribution of SFG rickettsiae pathogens in western Cuba. [ABSTRACT FROM AUTHOR]

Small Indian mongooses (SIMs, Herpestes auropunctatus) have invasively inhabited over 60 islands worldwide. They have been confirmed as a reservoir of rabies, leptospirosis, and salmonellosis; however, their role in the epidemiology of other zoonoses is little known. On St. Kitts, as well as other islands, SIMs harbor Ctenocephalides felis, which can vector several zoonotic diseases. In this study, SIMs were examined for fleas, and the collected fleas analyzed by PCR and DNA sequencing for Bartonella henselae, Rickettsia felis, Yersinia pestis, and Dipylidium caninum. Of the 87 SIMs, 75 (86.2%) harbored C. felis. C. felis recovered from nine (10.3%), one (1.1%), and one (1.1%) of the SIMs was positive for B. henselae, R. felis, and D. caninum, respectively. These data indicate that SIMs serve as an additional reservoir of B. henselae and R. felis, which should be taken into consideration in control and prevention of these rapidly emerging zoonoses. [ABSTRACT FROM AUTHOR]

Abstract Rickettsia felis is an obligate intracellular bacterium capable of infecting ticks, fleas, lice, and other arthropods. This bacterium is classified as a member of the Transitional Group (TRG) Rickettsia. It is known the evidence of R. felis mutualistic and obligatory relationship with some eukaryote organisms. However, there aren’t scientific accounts of R. felis and moths of the order Lepidoptera association. The current work reports the first identification of the bacteria R. felis in Phereoeca sp. For that, a polymerase chain reaction (PCR) assay using gltA, ompA, and ompB genes was used. The nucleotide sequences showed 100% of identity with other Rickettsia felis sequences. The genus-level identification of the moth larvae was performed by morphological taxonomic keys and PCR analysis of the cytochrome oxidase I (COI) gene. The nucleotide sequenced showed 94.94% similarity with the species Phereoeca praecox. However, with the low number of sequences deposited in the databases, the species was classified as Phereoeca sp. The results suggest that R. felis may develop in an organism without blood-feeding behavior (Lepidoptera), as it has been demonstrated for booklice (Psocoptera). Further investigation is necessary in order to confirm pathogenic or mutualistic association with moths.

Flea-borne typhus has emerged as an important vector-borne disease in Los Angeles and Orange Counties, California, with over 400 human cases having been reported since the mid-1980s. In Orange County alone, 127 human cases have been investigated by the Orange County Vector Control District since 2006. Results from a collaborative study with the Centers for Disease Control and Prevention from 2006-2008 identified the suburban cycle of flea-borne typhus transmission (backyard wildlife/pets – fleas – humans) in Los Angeles and Orange counties. Free-ranging feral and companion cats and the Virginia opossum were identified as the primary host animals of the cat flea, the insect vector responsible for maintenance and transmission of the etiologic agents, Rickettsia typhi and R. felis, for disease in humans. Although the causes of the increase in human flea-borne typhus cases are not well-defined, this rise has been accompanied by changes in how public and privately-sponsored animal control groups manage nuisance animal populations in the affected southern California counties. Instead of elimination through euthanasia of unwanted feral cats and non-native opossums, rehabilitation, relocation, and “no-trap” policies have become the preferred practice of local animal control agencies. The public health obligation for which governmental animal control agencies were created must be re-emphasized as one way of preventing further outbreaks of flea-borne typhus infections in Orange County and the surrounding California counties.

Fleas are carriers for many largely understudied zoonotic, endemic, emerging, and re-emerging infectious disease agents, but little is known about their prevalence and role as a vector in Africa. The aim of this study was to determine the diversity of fleas and the prevalence of infectious agents in them collected from human dwellings in western Kenya. A total of 306 fleas were collected using light traps from 33 human dwellings; 170 (55.56%) were identified as Ctenocephalides spp., 121 (39.54%) as Echidnophaga gallinacea, 13 (4.25%) as Pulex irritans, and 2 (0.65%) as Xenopsylla cheopis. Of the 306 individual fleas tested, 168 (54.9%) tested positive for rickettsial DNA by a genus-specific quantitative real-time PCR (qPCR) assay based on the 17-kDa antigen gene. Species-specific qPCR assays and sequencing revealed presence of Rickettsia asembonensis in 166 (54.2%) and Rickettsia felis in 2 (0.7%) fleas. Borrelia burgdorferi, normally known to be carried by ticks, was detected in four (1.3%) flea DNA preparations. We found no evidence of Yersinia pestis, Bartonella spp., or Orientia spp. Not only were Ctenocephalides spp. the most predominant flea species in the human dwellings, but also almost all of them were harboring R. asembonensis. [ABSTRACT FROM AUTHOR]

The feline population is extensive in urban areas worldwide, comprising stray and domestic cats. Cats, acting as reservoirs, can transmit various zoonotic organisms to humans, which can cause significant public health issues. We evaluated the seroprevalence of zoonotic pathogens in stray cats in an urban area of northeast Spain (the city of Zaragoza) to assess potential risks to human health. A total of 88 sampled cats (52 females and 36 males) underwent antibody evaluation using the indirect immunofluorescence technique. Seroprevalence rates were determined for IgG antibodies to Bartonella henselae (36.3%), Toxoplasma gondii (31.8%), Rickettsia felis (14.7%), Rickettsia typhi (9%), and Leishmania infantum (10.2%). Our results confirmed the presence in stray cats of antibodies against all those pathogens, indicating that they all circulate in the feline population in Zaragoza. Male cats exhibited a higher predisposition to T. gondii, whereas females showed an increased likelihood of contracting B. henselae. This difference may be attributed to distinct behaviors according to sex. Our findings underscore the importance of maintaining and intensifying surveillance coupled with preventive measures against zoonotic pathogens in cats. They highlight the need for comprehensive control strategies designed to mitigate public health risks associated with feline populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract Background Flea-borne spotted fever (FBSF) caused by Rickettsia felis is an arthropod-borne zoonosis. This study aimed to determine the prevalence, primary species and genotype(s) of R. felis infecting fleas from dogs and cats. Results All fleas were identified as Ctenocephalides felis felis. All rickettsial DNA detected in fleas was identified as being 100% homologous to R. felis URRWXCal2, with positivity within tropical, subtropical and temperate regions noted at 6.7%, 13.2% and 15.5%, respectively. Toy/small breed dogs were found to be at a lower odds of harboring R. felis-positive fleas compared with large breed dogs on univariate analysis, while DMH and pedigree breed cats were at a lower odds compared to DSH cats. Cooler minimum temperature ranges of between 15 to 20 °C and between 8 to 15 °C increased the odds of R. felis positivity in fleas, as did a constrained maximum temperature range of between 27 to 30 °C on multivariable analysis. Conclusions Environmental temperature may play a part in influencing R. felis prevalence and infectivity within its flea host. Regional climatic differences need to be considered when approaching public health risk mitigation strategies for FBSF.

Murine typhus and flea-borne spotted fever are undifferentiated febrile illnesses caused by Rickettsia typhi and Rickettsia felis, respectively. These organisms are small obligately intracellular bacteria and are transmitted to humans by fleas. Murine typhus is endemic to coastal areas of the tropics and subtropics (especially port cities), where rats are the primary mammalian host and rat fleas (Xenopsylla cheopis) are the vector. In the United States, a cycle of transmission involving opossums and cat fleas (Ctenocephalides felis) are the presumed reservoir and vector, respectively. The incidence and distribution of murine typhus appear to be increasing in endemic areas of the US. Rickettsia felis has also been reported throughout the world and is found within the ubiquitous cat flea. Flea-borne rickettsioses manifest as an undifferentiated febrile illness. Headache, malaise, and myalgia are frequent symptoms that accompany fever. The incidence of rash is variable, so its absence should not dissuade the clinician to consider a rickettsial illness as part of the differential diagnosis. When present, the rash is usually macular or papular. Although not a feature of murine typhus, eschar has been found in 12% of those with flea-borne spotted fever. Confirmatory laboratory diagnosis is usually obtained by serology; the indirect immunofluorescence assay is the serologic test of choice. Antibodies are seldom present during the first few days of illness. Thus, the diagnosis requires acute- and convalescent-phase specimens to document seroconversion or a four-fold increase in antibody titer. Since laboratory diagnosis is usually retrospective, when a flea-borne rickettsiosis is considered, empiric treatment should be initiated. The treatment of choice for both children and adults is doxycycline, which results in a swift and effective response. The following review is aimed to summarize the key clinical, epidemiological, ecological, diagnostic, and treatment aspects of flea-borne rickettsioses. [ABSTRACT FROM AUTHOR]

Rickettsia felis is an obligate intracellular Gram‐negative bacterium which causes flea‐borne spotted fever in humans. In the past decades, R. felis has been detected worldwide in Ctenocephalides felis fleas and various other arthropods. However, due to its shared symptoms with other common vector‐borne diseases, human infection is prone to be underestimated or misdiagnosed, especially in the malaria‐endemic areas including sub‐Saharan Africa, where confirmatory laboratory diagnoses are not usually available. In this study, a 'One Health' approach was adopted to explore potential vector‐borne and zoonotic pathogens in the Democratic Republic of Sao Tome and Principe (DRSTP), an island nation in the Gulf of Guinea. By collaborating with local veterinarians, 1,187 fleas were collected from 95 domestic dogs across the country and later identified as Ct. felis using taxonomic keys. A cytochrome oxidase gene‐based phylogenetic analysis revealed that all collected fleas belonged to a single haplotype and were identical to isolates from Ivory Coast and Brazil that clustered into a clade of tropical distribution. Additional samples of 14 chigoe fleas (Tunga penetrans) were collected from the surrounding environment of the dogs' resting spots. Rickettsia felis infection in fleas was examined by molecular methods targeting the citrate synthase (gltA)‐ and outer membrane protein A (ompA)‐coding genes as well as the R. felis‐specific pRF plasmid. The bacterial DNA was detected in 21.01% (146/695) of cat fleas but none of the chigoe fleas. Microimmunofluorescence assay was then performed to assess pathogen exposure of the residents. Of 240 dried blood spots from participants with dog contacts, 8 (3.33%) exhibited R. felis antibodies. Our findings demonstrated the presence of R. felis in DRSTP. Further extensive epidemiological studies regarding its prevalence and its role in causing febrile illness while the nation is entering pre‐elimination stage of malaria will be carried out. [ABSTRACT FROM AUTHOR]

The cat flea Ctenocephalides felis is the main vector of Bartonella henselae and Bartonella clarridgeiae, the causative agents of cat‐scratch disease (CSD) and the spotted‐fever agent Rickettsia felis. In spite of their worldwide distribution, there are no data on the occurrence of CSD‐causing Bartonella species or the prevalence of Rickettsia species in the Canary Islands, Spain. Therefore, the aim of our study was to screen cat and dog fleas for both pathogens. A total of 128 C. felis from cats and dogs were screened for Bartonella and Rickettsia by PCR. Bartonella henselae (2.3%) and B. clarridgeiae (3.9%) were found in fleas infesting cats, whereas R. felis was identified in both cat (36.6%) and dog (40.7%) fleas. Further, co‐infections were observed. This work constitutes the first finding of CSD‐causing Bartonella species and the first study on the prevalence of R. felis in fleas from domestic animals in the Canary Islands. These results indicate public health importance, as associated infections could be misdiagnosed in the Archipelago despite their clinical relevance. Establishing human and animal routine diagnosis procedures for these pathogens along with improving vector control in shelters is necessary in order to prevent the spread of the infections among animals. [ABSTRACT FROM AUTHOR]

Background: The main vector and reservoir host of Rickettsia felis, an emerging human pathogen causing flea-borne spotted fever, is the cat flea Ctenocephalides felis. While cats have not been found to be infected with the organism, significant percentages of dogs from Australia and Africa are infected, indicating that they may be important mammalian reservoirs. The objective of this study was to determine the presence of R. felis DNA in the blood of domestic dogs and cats in the USA. Methods: Three previously validated PCR assays for R. felis and DNA sequencing were performed on blood samples obtained from clinically ill domestic cats and dogs from 45 states (2008–2020) in the USA. The blood samples had been submitted for the diagnosis of various tick-borne diseases in dogs and feline infectious peritonitis virus, feline immunodeficiency virus, and Bartonella spp. in cats. Phylogenetic comparisons were performed on the gltA nucleotide sequences obtained in the study and those reported for R. felis and R. felis-like organisms. Results: Low copy numbers of R. felis DNA (around 100 copies/ml whole blood) were found in four cats (4/752, 0.53%) and three dogs (3/777, 0.39%). The very low levels of infection in clinically ill animals is consistent with R. felis being an unlikely cause of disease in naturally infected dogs and cats. The low copy numbers we found emphasize the requirement for very sensitive PCRs in prevalence studies. Conclusions: The low prevalence of naturally infected PCR-positive cats is further evidence that cats are unlikely to be important reservoirs of R. felis. Similarly, the low prevalence in dogs suggests they are not important reservoirs in the USA. Investigations should continue into the role other mammalian species may be playing in the epidemiology of R. felis infections. [ABSTRACT FROM AUTHOR]

Introduction: Rickettsioses are zoonotic diseases caused by pathogenic bacteria of the genus Rickettsia and transmitted to man by means of arthropod vectors such as ticks, fleas, mites and lice. Historically, Caldas Department has reported a significant number of cases of murine typhus to the Colombian national health surveillance system, and consequent studies of flea-borne rickettsiosis identified the circulation of Rickettsia typhi and Rickettsia felis in multiple municipalities. Our aim was to genotype species of Rickettsia detected in fleas collected from domestic and wild mammals in Caldas. Methodology: Flea samples were taken by convenience sampling from dogs, cats and wild mammals (rodents and marsupials) in 26 municipalities. Specimens were classified by current taxonomic keys and pooled for DNA extraction and molecular screening for Rickettsia spp. by PCR amplification of gltA, htrA and sca5 genes. Positive samples were genotyped by enzyme digestion (htrA) and sequencing. Results: A total of 1388 flea samples were collected. Rickettsia DNA was amplified in 818 (gltA), 883 (htrA) and 424 (sca5) flea pools. Alignment analysis with available Rickettsia DNA sequences showed greater similarity with R. asembonensis (gltA) and with R. felis (sca5 and htrA). Restriction pattern was compatible with R. felis. R. typhi was not identified. Conclusion: The present study confirms the presence and high prevalence of R. asembonensis and R. felis in fleas from domestic and wild animals in different municipalities from Caldas Department. [ABSTRACT FROM AUTHOR]

This survey is aimed at investigation of species composition of fleas removed from small terrestrial mammals captured in rural, suburban, and urban types of habitat and molecular screening of the presence and diversity of Rickettsia species in collected ectoparasites. In total, 279 fleas (Siphonaptera) belonging to 9 species of 2 families, Ceratophyllidae and Hystrichopsyllidae, were collected from 115 (46%) out of 250 trapped small mammals of eight species (Apodemus agrarius, Apodemus flavicollis, Apodemus uralensis, Myodes glareolus, Microtus arvalis, Microtus subterraneus, Crocidura leucodon, and Sorex minutus). Rickettsia spp. were found in 2.5% (7/279) of tested fleas, namely in Ctenophthalmus agyrtes, Ctenophthalmus solutus, Ctenophthalmus uncinatus, Megabothris turbidus, and Amalareus penicilliger. Rickettsia felis, Rickettsia helvetica, and unidentified Rickettsia species were detected in fleas infesting small mammals in Eastern Slovakia. The results of the study suggest that some species of rickettsiae have a different range of arthropod vectors. [ABSTRACT FROM AUTHOR]

Ticks and fleas are arthropods widely distributed around the world involved in the transmission of various vector-borne diseases (VBDs), including Brazilian Spotted Fever (BSF), Baggio-Yoshinari Syndrome and the plague, with outstanding consequences for the public health. The aim of this study was to investigate the presence of Rickettsia spp., Borrelia spp. and Yersinia pestis in arthropods collected from dogs, cats and horses living in the state of Pernambuco, Northeastern Brazil. From January 2017 to April 2019, ectoparasites were collected, morphologically identified and molecularly analysed through PCR and sequencing. In total 401 specimens were collected from 86 animals, being 68% (n = 273) and 32% (n = 128) from rural and urban areas, respectively. The most commonly detected species were the ticks Dermacentor nitens, Amblyomma sculptum, Rhipicephalus sanguineus sensu lato (s.l.), Rhipicephalus microplus, and Amblyomma ovale, and the fleas Ctenocephalides felis and Ctenocephalides canis. DNA of Rickettsia felis was detected in D. nitens collected from horses, and C. felis, and R. sanguineus s.l. collected from dogs. All samples scored negative for Borrelia spp. and Y. pestis DNA. This study provides valuable data on ectoparasite fauna from domestic animals and identifies the circulation of a zoonotic pathogen (i.e., R. felis) in the population of the arthropods assessed. Therefore, preventive measures should be adopted in order to reduce the risk of occurrence of neglected VBD caused by this pathogen in animal and human hosts. [ABSTRACT FROM AUTHOR]

Rickettsia felis is an obligate intracellular bacterium that is being increasingly recognized as an etiological agent of human rickettsial disease globally. The agent is transmitted through the bite of an infected vector, the cat flea, Ctenocephalides felis, however there is to date, no consensus on the pathogen's vertebrate reservoir, required for the maintenance of this agent in nature. This study for the first time, demonstrates the role of the domestic dog (Canis familiaris) as a vertebrate reservoir of R. felis. The ability of dogs to sustain prolonged periods of rickettsemia, ability to remain asymptomatically infected with normal haematological parameters and ability to act as biological vehicles for the horizontal transmission of R. felis between infected and uninfected fleas provides indication of their status as a mammalian reservoir of this emerging zoonosis. [ABSTRACT FROM AUTHOR]

Rickettsiae may cause febrile infections in humans in tropical and subtropical regions. From Madagascar, no molecular data on the role of rickettsioses in febrile patients are available. Blood samples from patients presenting with fever in the area of the capital Antananarivo were screened for the presence of rickettsial DNA. EDTA (ethylenediaminetetraacetic acid) blood from 1020 patients presenting with pyrexia > 38.5 °C was analyzed by gltA-specific qPCR. Positive samples were confirmed by ompB-specific qPCR. From confirmed samples, the gltA amplicons were sequenced and subjected to phylogenetic analysis. From five gltA-reactive samples, two were confirmed by ompB-specific qPCR. The gltA sequence in the sample taken from a 38-year-old female showed 100% homology with R. typhi. The other sample taken from a 1.5-year-old infant was 100% homologous to R. felis. Tick-borne rickettsiae were not identified. The overall rate of febrile patients with molecular evidence for a rickettsial infection from the Madagascan study site was 0.2% (2/1020 patients). Flea-borne rickettsiosis is a rare but neglected cause of infection in Madagascar. Accurate diagnosis may prompt adequate antimicrobial treatment.

Rural areas usually show a higher prevalence of rickettsial infection than urban areas. However, information on the rickettsial infection status in urban settings (e.g., built-up areas and city parks) is still limited, particularly in the Bangkok metropolitan area. In this study, we performed a molecular rickettsial survey of spleen samples of small mammals caught in public parks and built-up areas of Bangkok. Out of 198 samples, the Rattus rattus complex was found to be most prevalent. The amplification of rickettsial gltA fragment gene (338 bp) by nested PCR assay revealed positive results in four samples, yielding a low prevalence of infection of 2.02%. DNA sequencing results confirmed that three samples were matched with Rickettsia typhi, and one was identified as R. felis. It is noteworthy that this is the first report of the occurrence of R. felis DNA in rodents in Southeast Asia.

Purpose: Flea-borne rickettsioses, collectively referred to as a term for etiological agents Rickettsia felis , Rickettsia typhi , and RFLOs ( R. felis -like organisms), has become a public health concern around the world, specifically in the United States. Due to a shared arthropod vector (the cat flea) and clinical signs, discriminating between Rickettsia species has proven difficult. While the effects of microbial coinfections in the vector can result in antagonistic or synergistic interrelationships, subsequently altering potential human exposure and disease, the impact of bacterial interactions within flea populations remains poorly defined. Methods: In this study, in vitro and in vivo systems were utilized to assess rickettsial interactions in arthropods. Results: Coinfection of both R. felis and R. typhi within a tick-derived cell line indicated that the two species could infect the same cell, but distinct growth kinetics led to reduced R. felis growth over time, regardless of infection order. Sequential flea coinfections revealed the vector could acquire both Rickettsia spp. and sustain coinfection for up to 2 weeks, but rickettsial loads in coinfected fleas and feces were altered during coinfection. Conclusion: Altered rickettsial loads during coinfection suggest R. felis and R. typhi interactions may enhance the transmission potential of either agent. Thus, this study provides a functional foundation to disentangle transmission events propelled by complex interspecies relationships during vector coinfections.