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Rocky Mountain or Brazilian spotted fever, caused by Rickettsia rickettsii, is a fulminant, seasonal, and neglected disease that occurs in focal points of North America and South America. Its rapid detection is essential for the better prognosis and survival rate of infected individuals. However, disease diagnosis still faces challenges as the accuracy of many of the available laboratory tests fluctuates. This review aimed to analyze methods for antibody or antigen detection, their gaps, and their evolution over time. A search was conducted to find all studies in the Pubmed database that described the antibody or antigen detection of R. rickettsii infections. Initially, a total of 403 articles were screened. Of these articles, only 17 fulfilled the pre-established inclusion criteria and were selected. Among the different methods applied, the IFA technique was the one most frequently found in the studies. However, it presented varied results such as a low specificity when using the indirect method. Other techniques, such as ELISA and immunohistochemistry, were also found, although in smaller numbers and with their own limitations. Although some studies showed promising results, there is a pressing need to find new techniques to develop a rapid and effective diagnosis of R. rickettssi infection. [ABSTRACT FROM AUTHOR]

ABSTRACTRickettsia rickettsii (R. rickettsii), the causative agent of Rocky Mountain spotted fever (RMSF), is the most pathogenic member among Rickettsia spp. Previous studies have shown that tripartite motif-containing 56 (TRIM56) E3 ligase-induced ubiquitination of STING is important for cytosolic DNA sensing and type I interferon production to induce anti-DNA viral immunity, but whether it affects intracellular replication of R. rickettsii remains uncharacterized. Here, we investigated the effect of TRIM56 on HeLa and THP-1 cells infected with R. rickettsii. We found that the expression of TRIM56 was upregulated in the R. rickettsii-infected cells, and the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii, while R. rickettsii replication was enhanced in the TRIM56-silenced host cells with the reduced phosphorylation of IRF3 and STING and the increased production of interferon-β. In addition, the mutation of the TRIM56 E3 ligase catalytic site impairs the inhibitory function against R. rickettsii in HeLa cells. Altogether, our study discovers that TRIM56 is a host restriction factor of R. rickettsii by regulating the cGAS-STING-mediated signaling pathway. This study gives new evidence for the role of TRIM56 in the innate immune response against intracellular bacterial infection and provides new therapeutic targets for RMSF.IMPORTANCEGiven that Rickettsia rickettsii (R. rickettsii) is the most pathogenic member within the Rickettsia genus and serves as the causative agent of Rocky Mountain spotted fever, there is a growing need to explore host targets. In this study, we examined the impact of host TRIM56 on R. rickettsii infection in HeLa and THP-1 cells. We observed a significant upregulation of TRIM56 expression in R. rickettsii-infected cells. Remarkably, the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii, while silencing TRIM56 enhanced bacterial replication accompanied by reduced phosphorylation of IRF3 and STING, along with increased interferon-β production. Notably, the mutation of the TRIM56’s E3 ligase catalytic site did not impede R. rickettsii replication in HeLa cells. Collectively, our findings provide novel insights into the role of TRIM56 as a host restriction factor against R. rickettsii through the modulation of the cGAS-STING signaling pathway.

In some regions of the Americas, domestic dogs are the host for the tick vector Rhipicephalus sanguineus, and spread the tick-borne pathogen Rickettsia rickettsii, which causes Rocky Mountain Spotted Fever (RMSF) in humans. Interventions are carried out against the vector via dog collars and acaricidal wall treatments. This paper investigates the optimal control of acaricidal wall treatments, using a prior model for populations and disease transmission developed for this particular vector, host, and pathogen. It is modified with a death term during questing stages reflecting the cost of control and level of coverage. In the presence of the control, the percentage of dogs and ticks infected with Ri. rickettsii decreases in a short period and remains suppressed for a longer period, including after treatment is discontinued. Risk of RMSF infection declines by 90% during this time. In the absence of re-application, infected tick and dog populations rebound, indicating the eventual need for repeated treatment.

Rocky Mountain or Brazilian spotted fever, caused by Rickettsia rickettsii, is a fulminant, seasonal, and neglected disease that occurs in focal points of North America and South America. Its rapid detection is essential for the better prognosis and survival rate of infected individuals. However, disease diagnosis still faces challenges as the accuracy of many of the available laboratory tests fluctuates. This review aimed to analyze methods for antibody or antigen detection, their gaps, and their evolution over time. A search was conducted to find all studies in the Pubmed database that described the antibody or antigen detection of R. rickettsii infections. Initially, a total of 403 articles were screened. Of these articles, only 17 fulfilled the pre-established inclusion criteria and were selected. Among the different methods applied, the IFA technique was the one most frequently found in the studies. However, it presented varied results such as a low specificity when using the indirect method. Other techniques, such as ELISA and immunohistochemistry, were also found, although in smaller numbers and with their own limitations. Although some studies showed promising results, there is a pressing need to find new techniques to develop a rapid and effective diagnosis of R. rickettssi infection.

Background Tick-borne diseases have grown in incidence over recent decades. As a result, diagnostic testing has become more common, often performed as broad antibody-based panels for multiple tick-transmitted pathogens. Rocky Mountain spotted fever (RMSF) is rare in our region yet may cause severe morbidity, leading to diagnostic screening in low-risk patients. We sought to describe trends in RMSF diagnostic testing, rate of IgG seropositivity, and clinical features of those tested. Methods We performed a retrospective chart review of patients ≤21 years old undergoing testing for RMSF and/or with an ICD-9/10 code for RMSF. Patients were categorized by infection likelihood based on clinical and laboratory criteria adapted from Centers for Disease Control and Prevention's (CDC) case definition of spotted fever rickettsioses. Clinical data were collected and analyzed with descriptive statistics. Results One hundred and seventy patients were included. 5.8% met CDC criteria for rickettsial infection, 6.5% had an elevated IgG titer but lacked suggestive symptoms, and 87.6% had a negative IgG titer. Many patients tested were unlikely to have RMSF, including 50% lacking fever, 20% lacking any RMSF "classic triad" symptoms, 13% without acute illness, and 22% tested during months with low tick activity. Convalescent serology was performed in 7.6% of patients and none underwent Rickettsia rickettsii polymerase chain reaction (PCR) testing. Conclusions Diagnostic testing was frequently performed in patients unlikely to have RMSF. We identified many opportunities for improving test utilization. Reserving testing for those with higher pretest probability, performing convalescent serology, and utilizing PCR may improve the accuracy of RMSF diagnosis and reduce clinical challenges stemming from inappropriate testing. [ABSTRACT FROM AUTHOR]

Rhipicephalus sanguineus is a species complex of ticks that vector disease worldwide. Feeding primarily on dogs, members of the complex also feed incidentally on humans, potentially transmitting disease agents such as Rickettsia rickettsii, Rickettsia conorii, and Ehrlichia species. There are two genetic Rh. sanguineus lineages in North America, designated as the temperate and tropical lineages, which had occurred in discrete locations, although there is now range overlap in parts of California and Arizona. Rh. sanguineus in Europe are reportedly more aggressive toward humans during hot weather, increasing the risk of pathogen transmission to humans. The aim of this study was to assess the impact of hot weather on choice between humans and dog hosts among tropical and temperate lineage Rh. sanguineus individuals. Ticks in a two-choice olfactometer migrated toward a dog or human in trials at room (23.5°C) or high temperature (38°C). At 38°C, 2.5 times more tropical lineage adults chose humans compared with room temperature, whereas temperate lineage adults demonstrated a 66% reduction in preference for dogs and a slight increase in preference for humans. Fewer nymphs chose either host at 38°C than at room temperature in both lineages. These results demonstrate that risk of disease transmission to humans may be increased during periods of hot weather, where either lineage is present, and that hot weather events associated with climatic change may result in more frequent rickettsial disease outbreaks.

Introduction: Brazilian spotted fever (BSF) is a neglected zoonotic disease, with compulsory notification, high mortality rates, since adequate diagnosis and treatment usually begin at a late stage. The main etiological agent of BSF is Rickettsia rickettsii, one of the most lethal when compared to others of its kind. The vectors of this organism are the different species of ticks, which contributes to a wide transmission area. Objective: This work aims to analyze the challenges of clinical and laboratorial diagnosis of BSF, addressing epidemiological aspects and describing the signs and symptoms presented by patients affected by the disease in clinical cases described in the scientific literature, with the aim of highlighting the importance of an early clinical diagnosis, as well as exploring alternatives for laboratorial diagnosis that could help reduce the time for correct identification of this zoonosis. Methods: A narrative review was carried out on BSF and its clinical and epidemiological aspects, as well as its laboratory diagnosis methods, consulting the databases of the Scientific Electronic Library Online (SCIELO), Latin American and Caribbean Literature on Health Sciences (LILACS), Virtual Health Library (BVS) and PubMed. The articles were selected through the delimitation of keywords by the Descriptors in Health Sciences (DeCS-BIREME) described in the keywords. Relevant articles were selected, published between 2011 and 2022, written in Spanish, English or Portuguese. Results and Discussion: The laboratory diagnosis of BSF can be performed by Indirect Immunofluorescence Assay (IFA), Enzyme Immunoassay (ELISA), Immunohistochemistry (IHC), Polymerase Chain Reaction (PCR) or Culture with bacterial isolation. Complementary exams include blood count, coagulogram, evaluation of enzymes such as lactic dehydrogenase (LDH), liver transaminases (ALT and AST), creatine kinase (CK) and pancreatic enzymes. The procalcitonin test (PCT) can be useful to select suspected cases, since procalcitonin is an important laboratory marker in systemic bacterial infections and its elevation can guide the clinical diagnosis. Conclusion: Factors such as delay in laboratory diagnosis or inaccuracy in the clinical diagnosis of this neglected disease result in high lethality, which remains a challenge for public health institutions. The present work demonstrated that IFA is considered the gold standard test for laboratory diagnosis, but there are problems such as cross-reactions with other exanthematous diseases, which causes inaccuracy in the results. The data obtained underscore the need to implement new technologies for clinical and laboratory diagnosis in order to speed up the diagnosis and appropriate treatment.

Rickettsia rickettsii is the etiological agent of Rocky Mountain spotted fever, which is an important tick-borne zoonosis and, in Brazil, it causes Brazilian spotted fever, which has high lethality rate. This study aimed to evaluate a synthetic peptide corresponding to a segment of the outer membrane protein A (OmpA) as an antigen in a serological test for the diagnosis of rickettsial infections. The amino acid sequence of the peptide was selected by predicting B cell epitopes using B Cell Epitope Prediction (Immune Epitope Database and Analysis Resource) and Epitopia and OmpA sequences of Rickettsia rickettsii strain 'Brazil' and Rickettsia parkeri strains 'Maculatum 20' and 'Portsmouth'. A peptide with amino acid sequence common to both Rickettsia species was synthesized and arbitrarily named OmpA-pLMC. To evaluate this peptide in enzyme-linked immunosorbent assay (ELISA), serum samples of capybara (Hydrochoerus hydrochaeris), horse (Equus caballus), and opossum (Didelphis albiventris) that had been previously tested by indirect immunofluorescence assay (IFA) for rickettsial infection were separated into IFA-positive and IFA-negative groups and used in the assay. There were no significant differences in ELISA optical density (OD) values between IFA-positive and IFA-negative groups with horse samples. The mean OD values were significantly higher in the IFA-positive capybara serum samples (IFA-pos vs. IFA-neg = 2.389 ± 0.761 vs. 1.760 ± 0.840). However, receiver operating characteristic (ROC) curve analysis did not show significant diagnostic parameters. On the other hand, 12 out of 14 (85.7%) opossum samples of the IFA-positive group showed reactivity in ELISA, and this was significantly higher than of the IFA-negative group (0.7196 ± 0.440 vs. 0.2318 ± 0.098, respectively; 85.7% sensitivity, 100% specificity). Therefore, our results show that OmpA-pLMC has a potential to be used in immunodiagnostic assays to detect spotted fever group rickettsial infections. [ABSTRACT FROM AUTHOR]

Copyright of Minas Gerais Medical Journal / Revista Médica de Minas Gerais is the property of Associacao Medica de Minas Gerais and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: In recent years, promising vaccination strategies against rickettsiosis have been described in experimental animal models and human cells. OmpB is considered an immunodominant antigen that is recognized by T and B cells. The aim of this study was to identify TCD4+INF-γ+ and TCD8+INF-γ+ lymphocytes in an autologous system with macrophages transfected with the vaccine candidate pVAX1-OmpB24. Lymphocytes and monocytes from 14 patients with Rickettsia were isolated from whole blood. Monocytes were differentiated into macrophages and transfected with the plasmid pVAX1-OmpB24 pVax1. Isolated lymphocytes were cultured with transfected macrophages. IFN-γ-producing TCD4+ and TCD8+ lymphocyte subpopulations were identified by flow cytometry, as was the percentage of macrophages expressing CD40+, CD80+, HLA-I and HLA-II. Also, we analyzed the exhausted condition of the T lymphocyte subpopulation by PD1 expression. Macrophages transfected with pVAX1-OmpB24 stimulated TCD4+INF-γ+ cells in healthy subjects and patients infected with R. typhi. Macrophages stimulated TCD8+INF-γ+ cells in healthy subjects and patients infected with R. rickettsii and R. felis. Cells from healthy donors stimulated with OmpB-24 showed a higher percentage of TCD4+PD1+. Cells from patients infected with R. rickettsii had a higher percentage of TCD8+PD-1+, and for those infected with R. typhi the larger number of cells corresponded to TCD4+PD1+. Human macrophages transfected with pVAX1-OmpB24 activated TCD4+IFN-γ+ and CD8+IFN-γ+ in patients infected with different Rickettsia species. However, PD1 expression played an important role in the inhibition of T lymphocytes with R. felis. [ABSTRACT FROM AUTHOR]

An epidemic of Rocky Mountain spotted fever (RMSF) is ongoing in Mexicali, México. We visited 100 neighborhoods with diagnosed human cases and 100 control neighborhoods to evaluate knowledge of the epidemic; obtain data on the spatial distribution of dogs, canine seroprevalence and active infection, tick infestations, and presence of rickettsial DNA in ticks; and evaluate risk factors for human cases, seropositivity, and tick infestation within an unbiased study design. The majority (80%) of residents had heard of RMSF, but only 48% used acaricides in the home or on dogs. Case neighborhoods and those with high canine seroprevalence tended to be on the city periphery or in the agricultural valley. No dogs were polymerase chain reaction (PCR) positive for Rickettsia rickettsii, and the overall seroprevalence was 65% (titers from 64 to 1,024). PCR prevalence in ticks was 0.70%, confirmed by DNA sequencing as R. rickettsii; neighborhood prevalence ranged from 0.7% to 6.1%. Twelve percent of dogs had high tick burdens, and all ticks were Rhipicephalus sanguineus. Epidemiologically significant risk factors were ground covering for a neighborhood having a human case; dogs having poor body condition and weighing < 10 kg for canine seropositivity; dogs living at the home for the number of ticks in the environment; and being near canals, having trash on the patio, and a dog being thin for tick burdens on dogs. A One Health approach is crucial to understanding RMSF and brown dog ticks.

Abstract A three‐year‐old boy presented with fever, maculopapular rash involving palms and soles, and hyponatremia two weeks following a tick bite. Empiric doxycycline that he was on was discontinued following negative initial rickettsial serology based on the non‐endemicity of Rocky Mountain spotted fever (RMSF) in Northeast Ohio. He demonstrated high inflammatory markers and met the criteria for hemophagocytic lymphohistiocytosis (HLH). With a working diagnosis of macrophage activation syndrome secondary to presumed systemic‐onset juvenile idiopathic arthritis (soJIA), he received HLH‐directed therapy. Rising antibody titers in convalescent sera established the diagnosis of RMSF. The patient recovered completely with HLH directed therapy and re‐institution of doxycycline. This is the first pediatric case report of Rickettsia rickettsii induced HLH demonstrating a favorable outcome despite modified therapy.

Background: The spread of emerging tick-borne pathogens has steadily increased in Canada with the widespread establishment of tick vectors and vertebrate hosts. At present, Borrelia burgdorferi, the bacterium causing Lyme disease, is the most common tick-borne pathogen in Canada and primarily transmitted by Ixodes scapularis. A low prevalence of other emerging tick-borne pathogens, such as Anaplasma phagocytophilum, Babesia species, Borrelia miyamotoi, and Francisella tularensis have also been detected through surveillance efforts in Canada. Although Rickettsia rickettsii has been historically detected in Haemaphysalis leporispalustris in Canada, the current prevalence and geographic extent of this pathogen is unknown. Material and Methods: In this study, we assessed the presence and prevalence of several emerging tick-borne pathogens in ticks and hosts collected through tick dragging and small mammal trapping in Central Canada. Results: Nested PCR testing detected three pathogen species in ticks, with Babesia odocoilei and B. burgdorferi in I. scapularis in addition to R. rickettsii in H. leporispalustris. Three pathogen species were detected in small mammals by nested PCR including B. odocoilei in Blarina brevicauda, Babesia microti in Peromyscus leucopus, and a Hepatozoon species in P. leucopus and Peromyscus maniculatus. B. burgdorferi and Babesia species were the pathogens most often detected in our samples, suggesting they are widely distributed across Central Canada. We also detected B. odocoilei and R. rickettsii beyond their known geographic distribution. Conclusions: Our results provide evidence that emerging tick-borne pathogens may be present outside defined risk areas identified by current surveillance efforts in Canada. As a result, emerging tick-borne pathogens introduced by the dispersal of infected ticks by migratory birds or maintained by hosts and vectors through cryptic transmission cycles may go undetected. More comprehensive testing including all tick life stages and additional tick-borne pathogens will help detect the spread and potential risk of emerging or re-emerging tick-borne pathogens for human and wildlife populations throughout Canada. [ABSTRACT FROM AUTHOR]

Outbreaks of life-threatening Rocky Mountain spotted fever in humans and dogs associated with a canine-tick maintenance cycle constitute an important One Health opportunity. The reality of the problem has been observed strikingly in Mexico, Brazil, Colombia, and Native American tribal lands in Arizona. The brown dog tick, Rhipicephalus sanguineus sensu lato, acquires the rickettsia from bacteremic dogs and can maintain the bacterium transtadially to the next tick stage. The subsequent adult tick can then transmit infection to a new host, as shown by guinea pig models. These brown dog ticks maintain spotted fever group rickettsiae transovarially through many generations, thus serving as both vector and reservoir. Vaccine containing whole-killed R. rickettsii does not stimulate sufficient immunity. Studies of Rickettsia subunit antigens have demonstrated that conformationally preserved outer-membrane autotransporter proteins A and B are the leading vaccine candidates. The possibility of a potentially safe and effective live attenuated vaccine has only begun to be explored as gene knockout methods are applied to these obligately intracellular pathogens. [ABSTRACT FROM AUTHOR]

Since 2008, a large epidemic of Rocky Mountain spotted fever has been emerging among humans and dogs in Mexicali, adjacent to the United States in Baja California, Mexico. We molecularly confirmed the causative agent; this information can be used to study the origin and dynamics of the epidemic.

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.

Copyright of Saúde Coletiva is the property of MPM Comunicacao and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Epidemic levels of Rocky Mountain spotted fe­­­ver (RMSF) have persisted in Mexicali, Mexico, since the initial outbreak was first reported in December 2008. We compared clinical and epidemiologic data of cases in Mexicali during 2009–2019 between patients with an IgG titer reactive with Rickettsia rickettsii bacteria by indirect immunofluorescence antibody (IFA) assay and those who demonstrated DNA of R. rickettsii in a whole blood sample when tested by PCR. We identified 4,290 patients with clinical and epidemiologic features compatible with RMSF; of these, 9.74% tested positive by IFA and 8.41% by PCR. Overall, 140 patients died (10-year case-fatality rate 17.97%). Substantial differences in the frequency of commonly recognized clinical characteristics of RMSF were identified between PCR-positive and IFA-positive cases. The Mexicali epidemic is unique in its size and urban centralization. Cases confirmed by PCR most accurately reflect the clinical profile of RMSF.

Purpose: To report a case of infectious pediatric retinitis attributed to Rocky Mountain spotted fever which is rarely reported in the United States. Observations: A previously healthy 14-year-old male return traveler from Mexico was admitted to the pediatric ICU with septic shock and a diffuse rash. He subsequently complained of blurry vision and was found to have evidence of retinitis on exam. Infectious workup revealed high titers of rickettsial IgM and IgG antibodies. He was treated successfully with 14 days doxycycline and followed up in clinic with improvement in his visual complaints and retinitis. Conclusions and importance: Rickettsioses are worldwide endemic zoonotic infections caused by Gram negative obligate intracellular bacteria and spread to humans by infected ticks. Rickettsial infections, including Rocky Mountain spotted fever caused by Rickettsia rickettsii, are a cause of infectious retinitis, and atypical and zoonotic infections should remain on the differential diagnosis for patients presenting with rash, systemic illness, and visual complaints, even if the patient's travel or exposure history do not immediately suggest a likely rickettsial infection. In general, the ocular manifestations of rickettsial infection improve with systemic doxycycline treatment of the underlying infection.

The ANESPSAT, a synthetic spilanthol derivative, and its nanoformulation were evaluated against Rhipicephalus microplus and Amblyomma sculptum ticks. ANESPSAT activity was compared with spilanthol and derivatives (ANESPE and others). The compound was synthesized in a gram-scale by a 2-step process, comprising a direct ester amidation and a Horner-Wadsworth- Emmons reaction. The nanoemulsions were produced by coarse homogenization followed by high-energy ultrasonication, in which hydrodynamic diameter, polydispersity index, and zeta potential remained stable. The spilanthol-eugenol hybrid derivatives did not show significant acaricidal activity. ANESPE killed 83% of the R. microplus larvae at 30 mg.mL−1, while ANESPSAT killed 97% at 0.5 mg.mL−1, showing to be the most active compound. Spilanthol and ANESPSAT had similar high mortality rates for tick larvae, with LC 50 values of 0.10 and 0.14 mg.mL−1 for R. microplus larvae, and 0.04 and 0.48 mg.mL−1 for A. sculptum larvae, respectively. The efficacy of spilanthol was lower against R. microplus engorged females when compared with ANESPSAT, which was highly effective (>98%) against R. microplus engorged females. The nanoemulsion with ANESPSAT was effective against tick females, preventing egg laying and achieving 100% efficacy at 2.5 mg.mL−1. Spilanthol had only 59% efficacy at 10 mg.mL−1. The results suggest that ANESPSAT, a natural product derivative, could be used in novel formulations for tick management that might be safer and environmentally friendly. • First report of acaricidal activity of spilanthol derivative against ticks. • The spilanthol-eugenol hybrids have no acaricidal activity on ticks. • The ANESPE had lower acaricidal activity than ANESPSAT on ticks. • ANESPSAT was effective against Amblyomma sculptum and Rhipicephalus microplus. • The nanoemulsion with ANESPSAT was effective against engorged cattle tick females. [ABSTRACT FROM AUTHOR]

Background: In recent years, promising vaccination strategies against rickettsiosis have been described in experimental animal models and human cells. OmpB is considered an immunodominant antigen that is recognized by T and B cells. The aim of this study was to identify TCD4+INF-γ+ and TCD8+INF-γ+ lymphocytes in an autologous system with macrophages transfected with the vaccine candidate pVAX1-OmpB24. Lymphocytes and monocytes from 14 patients with Rickettsia were isolated from whole blood. Monocytes were differentiated into macrophages and transfected with the plasmid pVAX1-OmpB24 pVax1. Isolated lymphocytes were cultured with transfected macrophages. IFN-γ-producing TCD4+ and TCD8+ lymphocyte subpopulations were identified by flow cytometry, as was the percentage of macrophages expressing CD40+, CD80+, HLA-I and HLA-II. Also, we analyzed the exhausted condition of the T lymphocyte subpopulation by PD1 expression. Macrophages transfected with pVAX1-OmpB24 stimulated TCD4+INF-γ+ cells in healthy subjects and patients infected with R. typhi. Macrophages stimulated TCD8+INF-γ+ cells in healthy subjects and patients infected with R. rickettsii and R. felis. Cells from healthy donors stimulated with OmpB-24 showed a higher percentage of TCD4+PD1+. Cells from patients infected with R. rickettsii had a higher percentage of TCD8+PD-1+, and for those infected with R. typhi the larger number of cells corresponded to TCD4+PD1+. Human macrophages transfected with pVAX1-OmpB24 activated TCD4+IFN-γ+ and CD8+IFN-γ+ in patients infected with different Rickettsia species. However, PD1 expression played an important role in the inhibition of T lymphocytes with R. felis.

This brief report documents the safety and efficacy of high-dose tigecycline as a salvage-therapy in in a case series of five patients with serious central nervous system (CNS) rocky mountain spotted fever (RMSF). These severily ill patients were unable to take any oral drug therapy, parenteral doxycycline was unavailable and absorption of oral doxycycline was a concern in these critically ill patients. As far as we know, we report the successfull use of tigecycline for the treatment of rickettsial meningitis for the first time in Italy. We suggest more studies on tigecycline in severe CNS infections from Rickettsia species and multi-drug resistant bacteria, especially the use of tigecycline at higher than standard doses in these life-threathening infectious diseases. [ABSTRACT FROM AUTHOR]

Brazilian Spotted Fever (BSF) is a potentially lethal, tick-borne disease, caused by the bacterium Rickettsia rickettsii. This study investigated the circulation of bacteria of the genus Rickettsia in dogs and ticks in the urban and rural areas of Itu, a BSF-endemic area in southeastern Brazil. During 2017–2018, blood serum samples were obtained from 289 domestic dogs. Through an indirect immunofluorescence assay with antigens of R. rickettsii, R. parkeri, and R. bellii, 21.8% (63/289) of the dogs reacted serologically to at least one Rickettsia species, with endpoint titres ranging from 64 to 2048. A total of 877 ticks were collected from the dogs, being 404 (2 Amblyomma sculptum, 5 A. aureolatum, 1 Amblyomma ovale and 396 R. sanguineus s.l.) tested for the presence of rickettsial DNA by molecular analyses, R. rickettsii was identified in 3 R. sanguineus s.l. from dogs. Our results provide serological and molecular evidence of R. rickettsii infection between dogs and ticks in a BSF-endemic area, where Amblyomma ticks have been previously implicated as vectors of the disease agent, R. rickettsii, to humans, however the role of R. sanguineus s.l. as a vector of R. rickettsii for humans in Brazil cannot be neglected. [ABSTRACT FROM AUTHOR]

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and objectives: Rocky Mountain spotted fever (RMSF) is a rapidly progressive and potentially fatal tickborne disease caused by Rickettsia rickettsii. Despite current recommendations and information on the severity of RMSF, studies show that delayed recognition and treatment continues to occur. Methods: A literature search was performed on cases published in English between 1990–2017. The frequencies for demographic, clinical, and treatment variables was calculated. Results: A total of 340 cases from 34 articles were included. Data on rash were available for 322 patients, and 261 (80%) noted rash. Mortality was 4% (2) in those who received doxycycline within the first five days of illness, and 35% (18) when treatment was delayed beyond Day five. Twenty-four (16%) reported chronic sequelae, including speech impairment (7, 5%) and ataxia (5, 3%). Interpretation and conclusion: These data highlight the importance of early treatment, and add to our understanding of long-term sequelae. Early recognition by providers will facilitate appropriate treatment and reduction in morbidity and mortality.

Abstract Rickettsia spp. bacteria are responsible for tick-borne diseases worldwide, mostly maintained by rickettsial amplifiers capybaras in Brazilian endemic areas. The campus of the University of São Paulo, in southeastern Brazil, is an area endemic for Brazilian spotted fever (BSF), with high density of capybaras and Amblyomma spp., along with confirmed human cases. Besides capybaras, the university has also an in-campus high population of sheltered and free-roaming cats. Accordingly, the aim of this study was to determine the prevalence and characteristics associated with Rickettsia rickettsii, Rickettsia parkeri and Rickettsia felis exposure among cats in a BSF-endemic area. Out of 51 cats sampled, 23/35 shelter (65.7%) and 5/16 free-roaming (31.2%) were positive (titers ≥ 64) for at least one Rickettsia species. Ticks species were present in 3/16 free-roaming cats (18.8%), consisting of Amblyomma spp., nymphs of Amblyomma sculptum and adult Rhipicephalus sanguineus sensu lato. Despite sharing the capybaras environment, the seropositivity among the free-roaming and shelter cats was lower than owned cats in other endemic areas. Whether equally or less exposed to rickettsial infection, compared with owned cats in endemic areas, free-roaming and shelter cats may be used as environmental sentinels for human exposure to rickettsiae in such areas.

Rickettsia rickettsii ( R. rickettsii ), the causative agent of Rocky Mountain spotted fever (RMSF), is the most pathogenic member among Rickettsia spp. Previous studies have shown that tripartite motif-containing 56 (TRIM56) E3 ligase-induced ubiquitination of STING is important for cytosolic DNA sensing and type I interferon production to induce anti-DNA viral immunity, but whether it affects intracellular replication of R. rickettsii remains uncharacterized. Here, we investigated the effect of TRIM56 on HeLa and THP-1 cells infected with R. rickettsii . We found that the expression of TRIM56 was upregulated in the R. rickettsii -infected cells, and the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii , while R. rickettsii replication was enhanced in the TRIM56-silenced host cells with the reduced phosphorylation of IRF3 and STING and the increased production of interferon-β. In addition, the mutation of the TRIM56 E3 ligase catalytic site impairs the inhibitory function against R. rickettsii in HeLa cells. Altogether, our study discovers that TRIM56 is a host restriction factor of R. rickettsii by regulating the cGAS-STING-mediated signaling pathway. This study gives new evidence for the role of TRIM56 in the innate immune response against intracellular bacterial infection and provides new therapeutic targets for RMSF., Importance: Given that Rickettsia rickettsii ( R. rickettsii ) is the most pathogenic member within the Rickettsia genus and serves as the causative agent of Rocky Mountain spotted fever, there is a growing need to explore host targets. In this study, we examined the impact of host TRIM56 on R. rickettsii infection in HeLa and THP-1 cells. We observed a significant upregulation of TRIM56 expression in R. rickettsii -infected cells. Remarkably, the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii , while silencing TRIM56 enhanced bacterial replication accompanied by reduced phosphorylation of IRF3 and STING, along with increased interferon-β production. Notably, the mutation of the TRIM56's E3 ligase catalytic site did not impede R. rickettsii replication in HeLa cells. Collectively, our findings provide novel insights into the role of TRIM56 as a host restriction factor against R. rickettsii through the modulation of the cGAS-STING signaling pathway., Competing Interests: The authors declare no conflict of interest.

Background and Objectives:Rickettsia rickettsii is a pathogen that is known to cause spotted fever, a zoonosis that is endemic in several regions of the Americas. However, no systematic review and meta-analysis has been conducted to estimate the prevalence of this rickettsial disease in the Americas. Therefore, the objective of this study was to estimate the prevalence of R. rickettsii in ticks in the Americas. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and data were retrieved from four electronic databases: MEDLINE/PubMed, SciELO, ScienceDirect, and Directory of Open Access Journals. The pooled prevalence and heterogeneity were determined using a random-effects model and using Cochran's Q test and I2 index, respectively. Publication bias was assessed using a funnel plot and Egger's method. Results: The pooled prevalence of R. rickettsii in ticks was highest in Colombia (17.00%; confidence interval [95% CI]: 7.01–30.24), followed by Mexico (9.89%; 95% CI: 2.03–22.74), Panama (2.76%; 95% CI: 0.45–6.93), Brazil (2.03%; 95% CI: 0.66–4.14), and the United States (0.50%; 95% CI: 0.15–1.05). The tick species most frequently infected by R. rickettsii were Rhipicephalus sanguineus sensu lato (6.23%; 95% CI: 2.79–10.92) and Amblyomma mixtum (4.36%; 95% CI: 0.25–13.14). Interpretation and Conclusion: It can be suggested that studies aiming to identify the potential vectors of R. rickettsii should be conducted more intensively to better understand the epidemiology of spotted fever in the Americas. [ABSTRACT FROM AUTHOR]

Outbreaks of life-threatening Rocky Mountain spotted fever in humans and dogs associated with a canine-tick maintenance cycle constitute an important One Health opportunity. The reality of the problem has been observed strikingly in Mexico, Brazil, Colombia, and Native American tribal lands in Arizona. The brown dog tick, Rhipicephalus sanguineus sensu lato, acquires the rickettsia from bacteremic dogs and can maintain the bacterium transtadially to the next tick stage. The subsequent adult tick can then transmit infection to a new host, as shown by guinea pig models. These brown dog ticks maintain spotted fever group rickettsiae transovarially through many generations, thus serving as both vector and reservoir. Vaccine containing whole-killed R. rickettsii does not stimulate sufficient immunity. Studies of Rickettsia subunit antigens have demonstrated that conformationally preserved outer-membrane autotransporter proteins A and B are the leading vaccine candidates. The possibility of a potentially safe and effective live attenuated vaccine has only begun to be explored as gene knockout methods are applied to these obligately intracellular pathogens.

Epidemic levels of Rocky Mountain spotted fe­­­ver (RMSF) have persisted in Mexicali, Mexico, since the initial outbreak was first reported in December 2008. We compared clinical and epidemiologic data of cases in Mexicali during 2009–2019 between patients with an IgG titer reactive with Rickettsia rickettsii bacteria by indirect immunofluorescence antibody (IFA) assay and those who demonstrated DNA of R. rickettsii in a whole blood sample when tested by PCR. We identified 4,290 patients with clinical and epidemiologic features compatible with RMSF; of these, 9.74% tested positive by IFA and 8.41% by PCR. Overall, 140 patients died (11-year case-fatality rate 17.97%). Substantial differences in the frequency of commonly recognized clinical characteristics of RMSF were identified between PCR-positive and IFA-positive cases. The Mexicali epidemic is unique in its size and urban centralization. Cases confirmed by PCR most accurately reflect the clinical profile of RMSF. [ABSTRACT FROM AUTHOR]

Amblyomma aureolatum ticks are vectors of Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever in Brazil. Maintenance of R. rickettsii in nature depends on horizontal transmission along tick generations. Although such transmission is known to occur when uninfected and infected ticks feed simultaneously on susceptible animals (co-feeding systemic transmission), we investigated co-feeding nonsystemic transmission, which was based on R. rickettsii–infected and –uninfected A. aureolatum ticks feeding simultaneously on guinea pigs immune to R. rickettsii. Our acquisition and transmission infestations demonstrated that horizontal transmission of R. rickettsii by co-feeding ticks on immune hosts with no systemic infection did not occur when uninfected larvae fed distantly from infected nymphs but did occur in a few cases when uninfected larvae fed side-by-side with infected nymphs, suggesting that they shared the same feeding site. The co-feeding nonsystemic transmission type might have no epidemiologic importance for Rocky Mountain spotted fever.

A two decades-long epidemic of Rocky Mountain spotted fever in northern México reached the U.S. border city of Tijuana in 2021. Cases were near the city periphery in marginalized areas, some lacking infrastructure such as streets or utilities. We worked in the three census areas where human cases were reported and in 12 additional control Áreas Geoestadisticas Básicas. There were dogs, the primary tick host and Rickettsia rickettsii reservoir, in 76% of homes, with 2.2 owned dogs per home on average, approximately equal numbers of roaming dogs were seen, and 46.2% of owned dogs were allowed to roam in the street. Sixty-eight percent of people had heard of Rocky Mountain spotted fever (RMSF), and 35% self-reported tick infestation, including 19% of homes without dogs. Ticks appeared to move among houses of adjacent neighbors. Of 191 examined dogs, 61.8% were tick-infested, with 6-fold increased odds if they were allowed to roam. Although no dogs were Rickettsia polymerase chain reaction-positive, we found one R. rickettsii- and 11 Rickettsia massiliae-infected ticks. The rickettsial IgG seroprevalence by immunofluorescence antibody assay was 76.4%, associated with unhealthy body condition, adults, dogs with >10 ticks, more dogs being seen in the area, and dogs being permitted in the street. Insufficient medical and canine management resources have contributed to a case fatality rate of RMSF that has exceeded 50% in areas. High canine seroprevalence suggests risks to people and dogs; unfortunately, herd immunity is impeded by high turnover in the canine population owing to the birth of puppies and high death rates. Binational One Health workers should monitor disease spread, enact canine population management and tick eradication, and provide prevention, diagnostic, and treatment support.

Background: Rocky Mountain Spotted Fever (RMSF) is a disease with a high mortality rate, caused by Rickettsia rickettsii, a bacteria transmitted to humans by infected ticks. In 2008 there was a Rocky Mountain Spotted Fever (RMSF) outbreak in the city of Mexicali, México, resulting in an increased mortality rate amongst the area population. Methods: Case-series study of patients admitted to the General Hospital of Mexicali between 2014 and 2019 with a confirmed diagnosis of RMSF. Mortality was compared dividing the population on those ?20 and younger than ?21 years of age. Results: A total of 129 patients’ records during a 5-year period whose diagnosis was RMSF confirmed with PCR were included. Mortality was compared among patients admitted who were younger than ?20 years of age with that among patients who were older than ?20 years of age (61 versus 68 respectively), the latter being higher with an OR 4.2 (p

Abstract The purpose of this study was to do a serological survey on three rickettsial species: Rickettsia rickettsii and Rickettsia parkeri, two species of the spotted fever group (SFG) that are considered to be great importance for public health; and Rickettsia bellii, a species of unknown pathogenicity that infects a variety of human-biting ticks. Serum samples from 273 dogs were tested using the indirect immunofluorescence assay (IFA). A total of 52 samples (19.04%) were seropositive for at least one of the three Rickettsia spp. antigens. Thirty-eight (73.07%), twelve (23.07%) and one (1.92%) of these dogs showed homologous reactions to R. bellii, R. rickettsii and R. parkeri, respectively. Our results showed that the seroprevalence of Rickettsia spp. was relatively low. However, the positive serological tests indicated that these dogs had become infected by these agents at some point in their lives. Lastly, our study adds to the previous knowledge on the epidemiology of rickettsiosis in the state of Goiás by doing the first record of detection of anti-R. rickettsii, R. parkeri and R. bellii antibodies by IFA among dogs, thus indicating that these agents may be circulating in the dog population analyzed.

Abstract Rickettsia rickettsii is the causative agent of Brazilian spotted fever (BSF), for which humans and dogs are both susceptible. Dogs are sentinels in serological surveys, however, canine disease is rarely reported. Therefore, we aimed to evaluate natural infection by spotted fever group (SFG) Rickettsia spp. in dogs and ticks collected from domiciles close to forest fragments, featuring domestic–wildlife interface areas. Samples from 115 dogs and 135 ixodids were assessed by polymerase chain reactions (PCR) targeting the gltA gene for Rickettsia spp. and the ompA gene for the SFG rickettsial species. One dog (0.87%; 1/115) was positive for R. rickettsii. This dog presented nonspecific laboratory and clinical abnormalities (thrombocytopenia, hyperproteinemia, lymph node enlargement, emaciation, anorexia, and lethargy). Rickettsia parkeri was identified in 2.96% (4/135) of the ticks (Amblyomma sculptum, A. aureolatum, and Rhipicephalus sanguineus). This study confirmed the presence of SFG bacteria in non-endemic and preserved locations, where domestic and wild populations interact. We reinforce the fact that the dog is susceptible to natural R. rickettsii infection. Although this is a rare finding, preventive measures should be taken against BSF in the studied areas. Finally, R. parkeri infection is possibly being demonstrated in A. sculptum for the first time.

The Guarapiranga Dam region, in the metropolitan area of São Paulo, has been an endemic area for Brazilian spotted fever (BSF), a tick-borne disease caused by the bacterium Rickettsia rickettsii. In this particular area, R. rickettsii is known to be transmitted to humans by Amblyomma aureolatum, a typical dog tick that is not associated with horses. In other BSF-endemic areas, R. rickettsii transmission is associated with Amblyomma sculptum, a tick species that typically infest capybaras and horses. The Guarapiranga Dam bears abundant populations of capybaras and horses; however, since nothing is known about a possible cycle of transmission of R. rickettsii by A. sculptum in this area, this study evaluated such transmission by performing a serosurvey of horses living in the Guarapiranga Dam region. A total of 206 equids living in the margins of the Guarapiranga Dam were serologically tested for antibodies reactive to five Rickettsia species, four of the spotted fever group (R. rickettsii, R. parkeri, R. amblyommatis, R. rhipicephali) and one basal group species, R. bellii. Overall, 171 (83%) equids reacted positively to at least one Rickettsia species. A total of 160 (78%), 123 (60%), 80 (39%), 72 (35%), and 71 (34%), equid sera reacted to R. bellii, R. rickettsii, R. parkeri, R. rhipicephali, and R. amblyommatis, respectively, with endpoint titers ranging from 64 to 1024 for R. bellii, and 64 to 512 for the remaining four Rickettsia species. Endpoint titers to R. bellii (median: 256) was significantly higher (P

Introduction: Rocky Mountain spotted fever is a highly lethal infectious disease, particularly if specific treatment with doxycycline is given belatedly. Objective: To describe the clinical profile of fatal Rocky Mountain spotted fever cases in hospitalized patients in the state of Sonora, México. Materials and methods: We conducted a cross-sectional study on a series of 47 deaths caused by Rickettsia rickettsii from 2013 to 2016. The diagnosis of Rocky Mountain spotted fever was confirmed in a single blood sample by polymerase chain reaction (PCR) or by a four-fold increase in immunoglobulin G measured in paired samples analyzed by indirect immunofluorescence. Clinical and laboratory characteristics were compared stratifying subjects into two groups: pediatric and adult. Results: There were no differences in clinical characteristics between groups; petechial rash was the most frequent sign (96%), followed by headache (70%) and myalgia (67%). Although that doxycycline was administered before the fifth day from the onset of symptoms, death occurred in 55% of patients. In clinical laboratory, thrombocytopenia, and biomarkers of liver acute failure and acute kidney failure were the most frequent. Conclusion: Rocky Mountain spotted fever remains as one of the most lethal infectious diseases, which may be related not only to the lack of diagnostic suspicion and delayed administration of doxycycline, but to genotypic characteristics of Rickettsia rickettsii that may play a role in the variability of the fatality rate that has been reported in other geographical regions where the disease is endemic.

Two clinical cases of Rocky Mountain spotted fever in children with different clinical course are presented. One patient had a satisfactory evolution, since the specific treatment was initiated within the first five days of initiating the symptoms; while the other patient had a fatal outcome, with necrosis and gangrene in lower extremities. In both cases, diagnosis was confirmed by skin biopsy using the technique of Pinkerton. [ABSTRACT FROM AUTHOR]

The systematics of several ticks species (Acari: Ixodidae) remains controversial. Many species, including those of the Amblyomma cajennense complex and Rhipicephalus sanguineus s.l., are given special attention since they are cryptic species complexes and are also important in human and veterinary medicine. The A. cajennense complex was recently reorganized into six valid species, among which Amblyomma patinoi and Amblyomma mixtum have been confirmed in Colombia. On the other hand, the taxonomic status of R. sanguineus s.l. is controversial since it is a cosmopolitan cryptic species complex with a high reproductive capacity and a broad range of hosts (including man). To address this challenge, the germ cells of male ticks display a diverse morphology that offers novel opportunities for taxonomy. This study describes the events of spermatogenesis in A. mixtum and R. sanguineus s.l. individuals collected during active feeding on domestic hosts in the department of Caldas, Colombia. The individuals were identified using dichotomous keys and through PCR amplification of a fragment of the mitochondrial 16S ribosomal DNA gene. The male reproductive systems of A. mixtum and R. sanguineus s.l. were fixed in 2.5% glutaraldehyde for 48 h and dehydrated in increasing dilutions of ethanol. The samples were then embedded and mounted in historesin to obtain sections of 3 μm that were stained with hematoxylin-eosin (HE), photographed, and visualized through optical microscopy. The results show that the morphology of mature germ cells displays excellent diagnostic traits that can be used for tick taxonomy. [ABSTRACT FROM AUTHOR]

Background: Since 2000, the reported prevalence of tick-borne spotted fever rickettsiosis has increased considerably. We compared the level of antibody reactivity among healthy blood donors from 2 widely separated regions of the United States and evaluated the impact of antibody prevalence on public health surveillance in one of these regions.Methods: Donor serum samples were evaluated by indirect immunofluorescence antibody assay to identify immunoglobulin G (IgG) antibodies reactive with Rickettsia rickettsii. The Georgia Department of Public Health (GDPH) analyzed characteristics of cases from 2016 surveillance data to evaluate the utility of laboratory surveillance for case assessment.Results: Of the Georgia donors (n = 1493), 11.1% demonstrated antibody titers reactive with R. rickettsii at titers ≥64, whereas 6.3% of donors from Oregon and Washington (n = 1511) were seropositive. Most seropositive donors had a titer of 64; only 3.1% (n = 93) of all donors had titers ≥128. During 2016, GDPH interviewed 243 seropositive case patients; only 28% (n = 69) met inclusion criteria in the national case definition for spotted fever rickettsiosis.Conclusions: These findings suggest that a single IgG antibody titer is an unreliable measure of diagnosis and could inaccurately affect surveillance estimates that define magnitude and clinical characteristics of Rocky Mountain spotted fever and other spotted fever rickettsioses. [ABSTRACT FROM AUTHOR]

There is a paucity of data on human exposure to tick-borne pathogens in the western United States. This study reports prevalence of antibodies against three clinically important tick-borne pathogens (Borrelia burgdorferi, Anaplasma phagocytophilum, and Rickettsia spp.) among 249 people in five counties in northern California. Individuals from Humboldt County were recruited and answered a questionnaire to assess risk of exposure to tick-borne pathogens. Samples from other counties were obtained from a blood bank and were anonymized. Seventeen (6.8%) samples were seropositive for antibodies against at least one pathogen: five for A. phagocytophilum, eight for B. burgdorferi, and four for Rickettsia spp. Women and people aged 26–35 had higher seroprevalence compared to other demographic groups. Santa Cruz County had no seropositive individuals, northern Central Valley counties had three seropositive individuals (all against A. phagocytophilum), and Humboldt County had 14 (all three pathogens), a significant, four-fold elevated risk of exposure. The Humboldt County questionnaire revealed that a bird feeder in the yard was statistically associated with exposure to ticks, and lifetime number of tick bites was associated with increasing age, time watching wildlife, and time hiking. Three-quarters of respondents were concerned about tick-associated disease, 81.0% reported experiencing tick bites, and 39.0% of those bitten reported a tick-borne disease symptom, including skin lesions (76.4%), muscle aches (49.1%), joint pain (25.5%), or fever (23.6%). Despite high levels of concern, many individuals who had been bitten by a tick were not tested for a tick-borne pathogen, including those with consistent symptoms. We highlight the need for further research and dissemination of information to residents and physicians in Northern California regarding tick-associated disease, so that appropriate medical attention can be rapidly sought and administered. [ABSTRACT FROM AUTHOR]

We report a fatal case of Rocky Mountain spotted fever (RMSF) in a man in Brazil without recent history of tick bites or environmental exposure. He received an accidental needlestick while working as a nurse. The nurse and his patient died. Both cases were confirmed as RMSF by molecular methods.