TRIM56-mediated production of type I interferon inhibits intracellular replication of Rickettsia rickettsii.

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-ß. 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-ß 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.

Acaricidal activity of synthetic spilanthol derivative against ticks of medical and veterinary importance.

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 LC50 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.

Unconventional Rocky Mountain Spotted Fever Presentation From Kentucky: A Compelling Case Report and Literature Review.

Rocky Mountain spotted fever (RMSF) is a potentially lethal tick-borne disease caused by Rickettsia rickettsii, known for its tropism for vascular endothelial cells. Its classic symptoms include fever, headaches, and a rash, but atypical presentations can challenge diagnosis. We present the case of a 71-year-old male with fever, weakness, and hiccups, evolving into confusion. Laboratory findings showed severe hyponatremia, leukocytosis, and abnormal blood parameters. Initial management addressed sepsis and hyponatremia, leading to symptom improvement. Later, a fever of 106.5°F prompted ICU transfer, broad-spectrum antibiotics, and testing for tick-borne diseases. The patient reported tick exposure and received prophylactic doxycycline. Follow-up confirmed the RMSF diagnosis based on serological testing and clinical symptoms. This case highlights the diagnostic challenges posed by atypical RMSF presentations and underscores the importance of early detection and treatment to prevent complications.

Optimal control of a tick population with a view to control of Rocky Mountain Spotted Fever.

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.

Analysis of Rocky Mountain spotted fever cases in Northern Mexico reveals genetic variability of Rickettsia rickettsii and the different distribution of genotypes.

Rickettsioses have been reported in parts of Mexico since the last century, with Rocky Mountain spotted fever (RMSF) being one of the most prevalent in northern states. Unfortunately, fatality rates for RMSF in Mexico are higher than in other countries, like the USA. The reason for this difference in fatality rates is currently unknown and could be associated with a genotype of the bacterium, but no comparative molecular typing has been conducted in Mexico to date. The purpose of this study was to analyze 47 RMSF samples with different outcomes from several states in northern Mexico to know the genetic variability of Rickettsia rickettsii, as well as to reconstruct its phylogeny, for which the following intergenic regions were sequenced: RR0155-rpmB, cspA-ksgA, RR1240-tlc5, and Spo0J-abc T1, as well as the following partial genes: ompA, ompB, and gltA. We identified 8 genotypes with different distribution and prevalence among the states analyzed, as well as a different association with case outcome; these genotypes were clustered in 2 clades and 5 lineages were revealed, some of them probably exclusive from Mexico.

Serologic Testing for Rocky Mountain Spotted Fever in a Low-Incidence Region.

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.

Evaluation of a mimotope of the Rickettsia outer membrane protein A (OmpA) as an antigen in enzyme-linked immunosorbent assay to detect rickettsiosis in capybaras (Hydrochoerus hydrochaeris), horses (Equus caballus), and opossums (Didelphis sp.).

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.

Clinical manifestations of Rickettsia rickettsii in a familial outbreak in Panama.

We report an isolated outbreak of Rickettsia rickettsii in the Ngäbe-Buglé indigenous region, located 750 m (tropical wet) above sea level, in a jungle and mountainous area of Western Panama. Seven members of a family were infected simultaneously, resulting in four deaths. Family outbreaks have been previously described and are responsible for 4-8% of the cases described [1-4]. The simultaneous onset of symptoms in the affected population group is extremely unusual [1,5], but it should not dissuade the clinician from considering the possibility of Rickettsia rickettsii infection.

Rickettsia Vaccine Candidate pVAX1-OmpB24 Stimulates TCD4+INF-γ+ and TCD8+INF-γ+ Lymphocytes in Autologous Co-Culture of Human Cells.

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.

Detection of Rickettsia montanensis in Dermacentor variabilis in Northern Wisconsin.

Background: Spotted fever rickettsiosis is caused by a group of closely related bacteria that includes Rickettsia rickettsii, the etiological agent of Rocky Mountain spotted fever. Recently, Rickettsia montanensis has been reported to cause clinical and subclinical symptoms in both humans and animal models. Materials and Methods: In this study, we collected ticks in Ashland County, located in northern Wisconsin, and tested 16 ticks identified as Dermacentor variabilis for the presence of rickettsial bacteria using PCR techniques. Results: Four positive results identified using gel electrophoresis were then sequenced to determine the rickettsiae species. Of the samples sequenced, three matched for R. montanensis (∼19% of the 16 ticks tested). Conclusion: In this study, we report the presence and prevalence of R. montanensis in northern Wisconsin.

A Vaccine for Canine Rocky Mountain Spotted Fever: An Unmet One Health Need.

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.

Emerging Tick-Borne Pathogens in Central Canada: Recent Detections of Babesia odocoilei and Rickettsia rickettsii.

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.

Historical geographic overlap of human rickettsiosis with animal reservoirs in Juiz de Fora, Minas Gerais, Brazil / Sobreposição geográfica histórica da riquetsiose humana com reservatórios animais em Juiz de Fora, Minas Gerais, Brasil

Background and objectives: we investigated the existence of a historical geographic overlap between the location of spotted fever group rickettsiosis human cases, a disease caused by the gram-negative bacterium Rickettsia sp., and that of mammalian reservoirs, specifically domestic horses and capybaras, in the urban perimeter of the city of Juiz de Fora, Minas Gerais, Brazil. Methods: cases of human rickettsiosis that occurred during a period of 17 years (2003-2020) were geolocated and the distribution of cases in time and geographic space was assessed using 1st and 2nd order geospatial association indicators. We also analyzed the overlap between the locations of human rickettsiosis cases and the area of occurrence of domestic horses and capybaras. Results: men were diagnosed more often than women, but a large proportion of affected women died. The results indicate an aggregation of human rickettsiosis cases in time (cases tend to occur close to each other at each epidemic event) and in geographic space (cases are concentrated in a specific geographic region of the urban perimeter). Human cases seem to be more associated with city regions with: i) higher local frequency of domestic horses and not capybaras; ii) lower rates of family development. Conclusion: it is suggested that, in the local epidemiological scenario, domestic horses appear to be the main sources of the rickettsia infecting humans, not capybaras.(AU)

Justificativa e objetivos: foi investigada a existência de uma sobreposição geográfica histórica entre a localização dos casos de riquetsiose humana do grupo da febre maculosa, um grupo de doenças causadas pela bactéria Gram-negativa Rickettsia sp., e dos reservatórios mamíferos, especificamente cavalos domésticos e capivaras, no perímetro urbano do município de Juiz de Fora, Minas Gerais, Brasil. Métodos: foram geolocalizados os casos de riquetsiose humana ocorridos durante um período de 17 anos (2003-2020), sendo avaliada a distribuição dos casos no tempo e espaço geográfico através de indicadores de associação geoespacial de 1a e 2a ordem. Também analisamos a superposição dos locais dos casos de riquetsiose humana com a área de ocorrência de cavalos domésticos e capivaras. Resultados: homens foram diagnosticados mais frequentemente que as mulheres, mas grande proporção das mulheres acometidas faleceu. Os resultados indicam uma agregação dos casos de riquetsiose humana no tempo (os casos tendem a ocorrer próximos entre si a cada evento epidêmico) e no espaço geográfico (os casos se concentram em uma região geográfica específica do perímetro urbano). Os casos humanos aparentam ser mais associados às regiões da cidade com: i) maior frequência local de cavalos domésticos e não das capivaras; ii) menores índices de desenvolvimento familiar. Conclusão: sugere-se que, no cenário epidemiológico local, são os cavalos domésticos que aparentam ser as principais fontes da riquétsia infectando os humanos, não as capivaras.(AU)

Justificación y objetivos: investigamos la existencia de una superposición geográfica histórica entre la localización de casos de rickettsiosis exantemáticas humana, enfermedad causada por la bacteria gramnegativa Rickettsia sp., y la de mamíferos reservorios, específicamente caballos domésticos y capibaras, en el perímetro urbano de la ciudad de Juiz de Fora, Minas Gerais, Brasil. Métodos: se geolocalizaron los casos de rickettsiosis humana ocurridos durante un período de 17 años (2003-2020), y se evaluó la distribución de casos en el tiempo y espacio geográfico utilizando indicadores de asociación geoespacial de 1er y 2do orden. También analizamos la superposición entre las ubicaciones de los casos de rickettsiosis humana y el área de ocurrencia de los caballos domésticos y capibaras. Resultados: los hombres fueron diagnosticados con más frecuencia que las mujeres, pero una gran proporción de mujeres afectadas fallecieron. Los resultados indican una agregación de casos de rickettsiosis humana en el tiempo (los casos tienden a ocurrir cerca uno del otro en cada evento epidémico) y en el espacio geográfico (los casos se concentran en una región geográfica específica del perímetro urbano). Los casos humanos parecen estar más asociados con regiones urbanas con: i) mayor frecuencia local de caballos domésticos y no de capibaras; ii) menores tasas de desarrollo familiar. Conclusión: se sugiere que, en el escenario epidemiológico local, los caballos domésticos parecen ser las principales fuentes de la rickettsia que infecta a los humanos, no los capibaras.(AU)

Secondary hemophagocytic lymphohistiocytosis associated with Rocky Mountain spotted fever in a toddler: A case report.

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.

Rickettsia rickettsii infection as an unusual cause of pediatric retinitis: A case report.

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.

Socio-ecological determinants of rickettsial seroprevalence in a rural community of Yucatán, Mexico.

Rickettsial diseases have seen a re-emergence in the Americas in the last few decades, with concerning morbidity, mortality and economic implications that result from loss of productivity, income, curbs in liberal trade agreements, and reduction in agricultural practices. The aim of this study is to determine the socioecological determinants and seroprevalence for Rickettsia typhi and Rickettsia rickettsii among residents of Teabo, a rural community of Yucatán, Mexico. Sociodemographic data and serum samples were obtained from 180 consenting participants. Antibody titers for R. typhi and R. rickettsii were determined by indirect immunofluorescence assay (IFA). Participants also submitted tick samples collected from their residential area. We conducted logistic regression models to evaluate the association between exposure variables and seroprevalence. Rhipicephalus sanguineus s.l. (37%; n = 65), and Amblyomma cajennense Fabricius (17%; n = 29) were the predominant tick species in peri-domestic areas. Out of the 180 participants, there was significantly higher seroprevalence of R. typhi (n = 77; 46%) compared to R. rickettsii [n = 27, 15%, (p < 0.05)]. Pearson's chi-square test of independence revealed significant differences in R. rickettsii seroprevalence by gender (X2 [n = 175, df = 4, (p < 0.001)] = 180.26), level of education, (X2 [n = 180, df = 4, (p < 0.001)] = 44.0), and by tick species found in residential area, (X2 [n = 180, df = 4, (p = 0.050)] = 9.48). After adjusting for other variables in a logistic regression model, for each unit increase in the number of dogs present in the residential area, there was a 27% increase in the odds of human seroprevalence for R. typhi IgG (AOR = 1.27, 95% CI: 1.01-1.63). Compared to study participants living in residential areas with a 'low' height of vegetation, those living in residential areas with a 'medium' height of vegetation had 2.5 times greater odds of human seroprevalence for R. typhi IgG (AOR = 2.51, 95% CI: 1.19-5.40). Potentially modifiable existing factors in the peri-domestic area may constitute a high-risk source of seroprevalence for rickettsial antibodies among residents of the rural community of Teabo, Yucatán, Mexico.

Does Tigecycline Have a Place in Therapy for Rickettsial Infection of the Central Nervous System?

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.

Frecuencia de anticuerpos y seroconversión frente a Rickettsia spp. en pacientes atendidos en instituciones de salud del departamento de Caldas, Colombia, 2016-2019 / Frequency of antibodies and seroconversion against Rickettsia spp in patients consulting health institutions in the department of Caldas, Colombia, 2016-2019

Resumen | 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.

Abstract | Introduction: Rickettsioses are zoonotic diseases transmitted by arthropods acting as vectors and reservoirs. Disease symptoms are nonspecific and, therefore, their clinical diagnosis is difficult. Indirect immunofluorescence (IFA) is the gold standard assay for diagnosis. The interest for conducting studies on these pathologies has resurfaced in Colombia since 2001; besides, previous studies have evidenced cases of rickettsiosis in the north of the department of Caldas. Objective: To establish the frequency of antibodies and seroconversion against Rickettsia spp. In patients consulting health institutions in Caldas, Colombia, from 2016 to 2019. Materials and methods: We conducted a quantitative, observational, and descriptive study on a non-probabilistic sample of 175 patients with symptoms compatible with rickettsiosis who consulted in different municipalities of Caldas, Colombia; IFA was performed to detect antibodies in the acute and convalescent phases against Rickettsia rickettsii, Rickettsia typhi, and Rickettsia felis. Results: The average age of the patients was 31 years. The municipalities with the highest proportion of seropositive cases were Belalcázar, Chinchiná, Filadelfia, La Dorada, La Merced, and Manizales; 66% of patients owned pets and 12% reported arthropod bites. The most frequent signs and symptoms were headache (69.7%), arthromyalgia (60%), and fever (58.2%). IgG seroprevalence was 60% for R. rickettsii, 47.9% for R. typhi, and, and 24% for R. felis. Eight patients presented seroconversion. Conclusion: We found evidence of the circulation of Rickettsia species from the spotted fever group and the typhus group associated with human cases in Caldas.

Impact of a Severe Rocky Mountain Spotted Fever Case on Treatment Practices at an Academic Institution Within a Nonendemic Area.

INTRODUCTION: Rocky Mountain spotted fever (RMSF) is a bacterial disease associated with morbidity and mortality when untreated. The primary study objectives are to describe clinician diagnostic and treatment practices in a nonendemic area after the occurrence of an unrecognized severe pediatric presumed RMSF case (index case). We hypothesized that inpatient diagnostic testing frequency and initiation of empiric treatment will increase after the index case. METHODS: We performed a retrospective chart review of patients aged less than 18 y evaluated for RMSF at Penn State Hershey Children's Hospital between 2010 and 2019. We divided the study population into 2 groups (preindex and postindex) and evaluated patient characteristics, RMSF testing completion, and timing of doxycycline administration. RESULTS: Fifty-four patients (14 [26%] preindex and 40 [74%] postindex) were included. Age (median [25th percentile, 75th percentile]) decreased from 14.5 y (8.6, 16) preindex to 8.3 y (3.6, 14) postindex. Twelve (86%) preindex and 31 (78%) postindex patients received empiric doxycycline (P=0.70). Four years after the index case, a decrease in empiric and urgent initiation of doxycycline administration was noted. One case of severe RMSF was diagnosed 4 y after the index case. CONCLUSIONS: Our study found that inpatient RMSF testing increased after the index case, but not all patients received empiric treatment. This may represent an underappreciation of RMSF severity even after a recent devastating case. We suggest that when severe rare but possibly reversible diseases, such as RMSF occur, all clinicians are educated on the diagnostic and treatment approach to reduce the morbidity and mortality risk.