Fever and Rash.

Infectious causes of fever and rash pose a diagnostic challenge for the emergency provider. It is often difficult to discern rashes associated with rapidly progressive and life-threatening infections from benign exanthems, which comprise the majority of rashes seen in the emergency department. Physicians must also consider serious noninfectious causes of fever and rash. A correct diagnosis depends on an exhaustive history and head-to-toe skin examination as most emergent causes of fever and rash remain clinical diagnoses. A provisional diagnosis and immediate treatment with antimicrobials and supportive care are usually required prior to the return of confirmatory laboratory testing.

Neurological manifestation of Brazilian spotted fever in childhood.

Rocky Mountain Spotted Fever is a rickettsial disease caused by the bacteria Rickettsia rickettsii. In Brazil, the disease is known as Brazilian spotted fever (BSF), being the most significant tick-borne disease in the country. Among the affected patients, only 5% of cases occur in children aged one to nine years. Typical symptoms of the disease are fever, rash, headache and digestive symptoms. Neurological manifestations such as seizures, aphasia and hemiparesis have been described in few patients. This study aimed to describe the case of an infant diagnosed with BSF who presented severe signs of neurological manifestation.

Case Report: Fatal Rickettsiosis in Pregnancy.

Rocky Mountain spotted fever (RMSF) is a tick-borne infection caused by Rickettsia rickettsii. We present a series of two cases of pregnant patients who showed up at the emergency room of a hospital in Nuevo León, Mexico. Both patients lived in environments where R. rickettsii is endemic and they presented with several days of symptoms, including fever. Both patients developed a rash and had stillbirths during their hospital stay. Treatment with doxycycline was delayed, with fatal results in both patients. Diagnosis of RMSF was confirmed via polymerase chain reaction assay postmortem. The need to link epidemiological clues with clinical data is critical in the diagnosis and early treatment of RMSF to prevent maternal deaths.

An impedimetric immunosensor for diagnosis of Brazilian spotted fever in blood plasma.

Brazilian spotted fever (BSF) is a serious disease of medical importance due to its rapid evolution and high lethality. The effectiveness of the treatment mainly depends on the rapid diagnosis, which is currently performed by indirect immunofluorescence and PCR tests, which require high costs and laboratory structure. In order to propose an alternative methodology, we sought to develop an impedimetric immunosensor (IM) based on the immobilization of specific IgY antibodies for IgG anti Rickettsia rickettsii, using blood plasma from capybara (Hydrochoerus hydrochaeris), for characterization, validation and applications of the ready IM. IM selectivity was observed when comparing capybara reagent IgG (IgGcr) readings with non-reagent IgG (IgGnr). A reagent IgG calibration curve was obtained, from which the limits of detection (LOD) and quantification (LOQ) of 1.3 ng mL-1 and 4.4 ng mL-1 were calculated, respectively. The accuracy tests showed that different concentrations of IgGcr showed a maximum deviation of 20.0%, with CI between 90.00% and 95.00%. Intermediate precision tests showed a relative standard deviation of 2.09% for researcher 1 and 2.61% for researcher 2, and the F test showed no significant difference between the recovery values found between the two analysts, since Fcal 1.56 < 5.05 and P-value 0.48 > 0, 05. Therefore, an impedimetric immunosensor was developed to detect anti BSF IgG in capybara blood plasma, which greatly contributes to the improvement of diagnostic tests, cost reduction and ease of execution.

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.

Alerta epidemiológico: alerta acerca do registro de casos de febre maculosa no Estado de São Paulo / Epidemiological alert: alert about the record of cases of spotted fever in the State of São Paulo

Alerta emitido pela Coordenação de Zoonoses da Gerência de Vigilância Epidemiológica de Doenças Transmissíveis (GVEDT) e o Centro de Informações Estratégicas e Resposta em Vigilância (CIEVS Goiás) da Gerência de Emergências em Saúde Pública (GESP) da Superintendência de Vigilância em Saúde (SUVISA) com o objetivo de alertar os profissionais de saúde quanto aos sinais e sintomas devido aos casos recentes de febre maculosa (FM) registrados no estado de São Paulo

Alert issued by the Zoonoses Coordination of the Communicable Diseases Epidemiological Surveillance Management (GVEDT) and the Center for Strategic Information and Surveillance Response (CIEVS Goiás) of the Public Health Emergencies Management (GESP) of the Health Surveillance Superintendence (SUVISA) in order to alert health professionals about the signs and symptoms due to recent cases of spotted fever (FM) registered in the state of São Paulo

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.

An Unsuspected Case of Rocky Mountain Spotted Fever: A Lesson to Keep a Broad Differential.

Rocky Mountain spotted fever (RMSF), a tick-borne illness, can cause serious illness or death even in a healthy individual. Unfortunately, this illness can be difficult to diagnose as symptoms are nonspecific and oftentimes mimic benign viral illnesses. Delayed diagnosis can be detrimental as the timing of antibiotic administration is critical to prevent associated morbidity and mortality. A careful travel and social history can sometimes provide clues to make the diagnosis. Being aware of lesser-known objective findings such as hyponatremia, neurologic derangements, transaminitis, and thrombocytopenia may help raise suspicion for the disease. This is a case of a 72-year-old woman who presented with nonspecific symptoms and hyponatremia without known tick exposure. She was eventually diagnosed with RMSF. The timing of her presentation corresponded with a surge in COVID-19 infections throughout her area of residence, which further complicated her presentation and contributed to a delayed diagnosis.

Emerging Spotted Fever Rickettsioses in the United States.

Spotted fever rickettsioses are important causes of emerging infectious disease in the United States and elsewhere. Rocky Mountain Spotted Fever, caused by R. rickettsii causes a febrile, acute illness in dogs. Because it circulates in peripheral blood in low copy number and because of the acute nature of the disease, dogs may test PCR and seronegative at the time of presentation. Therefore, therapy with doxycycline must be initiated and continued based on the clinician's index of suspicion. Combining PCR with serologic testing, repeat testing of the same pre-antimicrobial blood sample, and testing convalescent samples for seroconversion facilitates diagnosis. The prognosis can be excellent if appropriate antimicrobial therapy is begun in a timely fashion. It is well established that dogs are sentinels for infection in people in households and communities. Whether R. rickettsii causes illness in cats is not well established. The role of other spotted fever group rickettsia in causing illness in dogs and cats is being elucidated. Veterinarians should keep in mind that novel and well characterized species of SFG Rickettsia are important causes of emerging infectious disease. Veterinarians can play an important role in detecting, defining, and preventing illness in their canine patients and their human companions.

Fatal Brazilian spotted fever in a healthy military man during field training in Rio de Janeiro city, southeastern Brazil.

Brazilian spotted fever, a zoonotic disease transmitted by ticks, is caused by Rickettsia rickettsii. We report a fulminant case of this zoonosis in a healthy 46-year-old military man in the urban region of Rio de Janeiro city, in October, 2021. Ticks and capybaras (Amblyomma sculptum, Hydrochoerus hydrochaeris, respectively) were identified in the military fields, pointing to the participation of this large synanthropic rodent, recognized as an efficient amplifier host of Rickettsia rickettsii in Brazil. As the military population is considered a risk group for spotted fever, it is necessary to alert health professionals to the importance of the early detection of the disease and its adequate management, mainly in populations that are particularly at risk of exposure to ticks, in order to avoid fatal outcomes.

Knowledge, Attitudes, and Practices on Rocky Mountain Spotted Fever among Physicians in a Highly Endemic Region-Mexicali, Mexico.

Rocky Mountain spotted fever (RMSF) is a potentially fatal tickborne disease caused by the bacterium, Rickettsia rickettsii and transmitted primarily by the brown dog tick (Rhipicephalus sanguineus) in the southwestern United States and Mexico. RMSF can be rapidly fatal if not treated early with doxycycline, making healthcare worker awareness and education critical to reduce morbidity and mortality. During 2008-2019, Mexicali experienced a RMSF epidemic with 779 confirmed cases, and an 11-year case-fatality rate of 18% (N = 140). A cross-sectional study was conducted with 290 physicians and physicians-in-training across 12 medical facilities in Mexicali. They were asked to complete a 23-item questionnaire to assess knowledge, attitudes, and practices for clinical, epidemiologic, and preventive aspects of RMSF. Half of participants were female, the largest age group was aged 25 to 44 (47%), and median time in practice was 6 years (interquartile rate: 1-21.5). Less than half (48%) surveyed were confident where diagnostic testing could be performed, and two-thirds did not regularly order serology (67%) or molecular diagnostic (66%) tests for RMSF when a patient presented with fever. Sixty-four percent knew doxycycline as first-line treatment of children < 8 years with suspected RMSF. When comparing healthcare workers with < 6 years of experience to those with ≥ 6 years, more experience was associated with greater confidence in where to have diagnostic testing performed (prevalence odds ratio [prevalence odds ratios [pOR]] = 2.3; P = 0.004), and frequency of ordering laboratory tests (serology, pOR = 3.3; P = 0.002; polymerase chain reaction, pOR = 3.9; P = 0.001). Continued education, including information on diagnostic testing is key to reducing morbidity and mortality from RMSF.

Case Report: Rocky Mountain Spotted Fever with Adrenalectomy and a Hard-to-Find Tick.

BACKGROUND Rocky Mountain spotted fever (RMSF) is a potentially fatal infectious disease caused by the gram-negative intracellular bacterium Rickettsia rickettsii. The classic triad includes fever, rash, and history of tick exposure; however, the triad presents in only 3% to 18% of cases at the initial visit, and the tick bite is often painless and overlooked. RMSF can present with other manifestations, including hyponatremia, lymphopenia, thrombocytopenia, and coagulopathy. Some of these manifestations can be overlooked if they overlap with manifestations of a patient's pre-existing conditions. CASE REPORT A 43-year-old woman with RMSF presented with fever and treatment-resistant hyponatremia before developing a rash. Initially, the cause of her hyponatremia was attributed to adrenal insufficiency and dehydration. After appropriate treatments with hormone replacement therapy and intravenous hydration, her laboratory values remained relatively unchanged. A rash later appeared with an atypical RMSF pattern, warranting a detailed integumentary examination, which uncovered the culprit tick in an unusual location. After starting doxycycline, the patient's signs and symptoms, including her sodium level, improved. CONCLUSIONS We conclude that the diagnosis of RMSF is an empiric diagnosis based on clinical signs, symptoms, and appropriate epidemiologic settings for tick exposures. However, typical clinical signs do not always display at presentation. Other manifestations that a patient's pre-existing conditions can simultaneously cause should not be overlooked and should be examined holistically with other signs, symptoms, laboratory values, and physical examinations. Early treatment with doxycycline is encouraged as evidence strongly suggests that early treatment is correlated with lower mortality.

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.

Clinical features of patients with Rocky Mountain spotted fever, dengue and chikungunya infection.

INTRODUCTION: Clinical distinction between arbovirus infections and those caused by rickettsia is crucial to initiate appropriate medical treatment. OBJECTIVE: To compare the differences between Rocky Mountain spotted fever (RMSF) and other vector-borne diseases (dengue and chikungunya) with similar clinical presentation, and to identify data that could aid rapid diagnosis of these diseases. METHODS: We evaluated sociodemographic, clinical and laboratory data of 399 patients from five hospitals and clinics of Sonora, Mexico, between 2004 and 2016, with laboratory-confirmed diagnosis of RMSF, dengue, or chikungunya. RESULTS: The RMSF group had the highest lethality (49/63 deaths, 77.8 %), followed by the chikungunya group (3/161, 1.9 %) and the dengue group (3/161, 1.9 %). Clinical differences included the presence of rash, edema, and pruritus; in addition, differences in multiple biomarkers such as platelets, hemoglobin, indirect bilirubin, and serum sodium levels were documented. CONCLUSION: Rash on the palms and soles, edema and absence of pruritus, together with high levels of direct bilirubin and severe thrombocytopenia could be useful indicators to differentiate patients at RMSF advanced stages from those with dengue and chikungunya.

INTRODUCCIÓN: La distinción clínica entre infecciones arbovirales y las provocadas por rickettsias es crucial para iniciar el tratamiento médico apropiado. OBJETIVO: Comparar las diferencias entre fiebre manchada de las montañas rocosas (FMMR) y otras enfermedades transmitidas por vector (dengue y chikungunya) con presentación clínica similar e identificar los datos que pudieran ayudar al diagnóstico rápido de esas enfermedades. MÉTODOS: Se evaluaron datos sociodemográficos, clínicos y de laboratorio de 399 pacientes de cinco hospitales y clínicas en Sonora, México, entre 2004 y 2016, con el diagnóstico confirmado por laboratorio de FMMR, dengue o chikungunya. RESULTADOS: El grupo con FMMR presentó la mayor letalidad (49/63 muertes, 77.8 %), seguido por el de chikungunya (3/161, 1.9 %) y el de dengue (3/161, 1.9 %). Las diferencias clínicas consistieron en la presencia de exantema, edema y prurito; además, se documentaron diferencias en múltiples biomarcadores como plaquetas, hemoglobina, bilirrubina indirecta y niveles de sodio sérico. CONCLUSIÓN: El exantema en palmas y plantas, edema y ausencia de prurito, aunados a niveles altos de bilirrubina directa y trombocitopenia severa pudieran ser indicadores útiles para diferenciar a pacientes con FMMR en etapas avanzadas de aquellos con dengue y chikungunya.

Serological evidence of Rickettsia in horses from a semi-arid Brazilian region.

Brazilian spotted fever (BSF) is a common tick-borne disease caused by Rickettsia rickettsii. Horses are the primary hosts of the main vector, Amblyomma sculptum, and are considered efficient sentinels for circulation of Rickettsia. Therefore, the aim of this study was to detect antibodies reactive to R. rickettsii antigens in horses from a non-endemic area in the north-central region of Bahia state, Brazil. Blood samples and ticks were collected from 70 horses from the municipalities of Senhor do Bonfim, Antônio Gonçalves, Pindobaçu, and Campo Formoso. The sera obtained were tested by an indirect immunofluorescence assay to detect anti-Rickettsia antibodies. Overall, 5.7% (4/70) of the horses reacted to R. rickettsii antigens. Ticks were collected from 18.6% (13/70) of the horses and were identified as A. sculptum and Dermacentor nitens. Despite being a non-endemic area, seropositive animals were identified in our study, suggesting circulation of rickettsial agents in the region. This is the first serological survey of this agent in horses from the north-central region of Bahia, and further studies are needed to understand the epidemiology of BSF in these locations.

Características clínicas de los pacientes con fiebre manchada de las Montañas Rocosas, infección por dengue y chikungunya / Clinical features of patients with Rocky Mountain spotted fever, dengue and chikungunya infection

Resumen Introducción: La distinción clínica entre infecciones arbovirales y las provocadas por rickettsias es crucial para iniciar el tratamiento médico apropiado. Objetivo: Comparar las diferencias entre fiebre manchada de las Montañas Rocosas (FMMR) y otras enfermedades transmitidas por vector (dengue y chikungunya) con presentación clínica similar e identificar los datos que pudieran ayudar al diagnóstico rápido de esas enfermedades. Métodos: Se evaluaron datos sociodemográficos, clínicos y de laboratorio de 399 pacientes de cinco hospitales y clínicas en Sonora, México, entre 2004 y 2016, con el diagnóstico confirmado por laboratorio de FMMR, dengue o chikungunya. Resultados: El grupo con FMMR presentó la mayor letalidad (49/63 muertes, 77.8 %), seguido por el de chikungunya (3/161, 1.9 %) y el de dengue (3/161, 1.9 %). Las diferencias clínicas consistieron en la presencia de exantema, edema y prurito; además, se documentaron diferencias en múltiples biomarcadores como plaquetas, hemoglobina, bilirrubina indirecta y niveles de sodio sérico. Conclusión: El exantema en palmas y plantas, edema y ausencia de prurito, aunados a niveles altos de bilirrubina directa y trombocitopenia severa pudieran ser indicadores útiles para diferenciar a pacientes con FMMR en etapas avanzadas de aquellos con dengue y chikungunya.

Abstract Introduction: Clinical distinction between arbovirus infections and those caused by rickettsia is crucial to initiate appropriate medical treatment. Objective: To compare the differences between Rocky Mountain spotted fever (RMSF) and other vector-borne diseases (dengue and chikungunya) with similar clinical presentation, and to identify data that could aid rapid diagnosis of these diseases. Methods: Sociodemographic, clinical and laboratory data of 399 patients from five hospitals and clinics of Sonora, Mexico, with laboratory-confirmed diagnosis of RMSF, dengue, or chikungunya between 2004 and 2016 were evaluated. Results: The RMSF group had the highest lethality (49/63 deaths, 77.8 %), followed by the chikungunya group (3/161, 1.9 %) and the dengue group (3/161, 1.9 %). Clinical differences included the presence of rash, edema, and pruritus; in addition, differences in multiple biomarkers such as platelets, hemoglobin, indirect bilirubin, and serum sodium levels were documented. Conclusion: Rash on the palms and soles, edema and absence of pruritus, together with high levels of direct bilirubin and severe thrombocytopenia could be useful indicators to differentiate patients at RMSF advanced stages from those with dengue and chikungunya.

Isolate-Dependent Differences in Clinical, Pathological, and Transcriptional Profiles following In Vitro and In Vivo Infections with Rickettsia rickettsii.

Rickettsia rickettsii, the etiological agent of Rocky Mountain spotted fever (RMSF), a life-threatening tick-borne disease that affects humans and various animal species, has been recognized in medicine and science for more than 100 years. Isolate-dependent differences in virulence of R. rickettsii have been documented for many decades; nonetheless, the specific genetic and phenotypic factors responsible for these differences have not been characterized. Using in vivo and in vitro methods, we identified multiple phenotypic differences among six geographically distinct isolates of R. rickettsii, representing isolates from the United States, Costa Rica, and Brazil. Aggregate phenotypic data, derived from growth in Vero E6 cells and from clinical and pathological characteristics following infection of male guinea pigs (Cavia porcellus), allowed separation of these isolates into three categories: nonvirulent (Iowa), mildly virulent (Sawtooth and Gila), and highly virulent (Sheila SmithT, Costa Rica, and Taiaçu). Transcriptional profiles of 11 recognized or putative virulence factors confirmed the isolate-dependent differences between mildly and highly virulent isolates. These data corroborate previous qualitative assessments of strain virulence and suggest further that a critical and previously underappreciated balance between bacterial growth and host immune response could leverage strain pathogenicity. Also, this work provides insight into isolate-specific microbiological factors that contribute to the outcome of RMSF and confirms the hypothesis that distinct rickettsial isolates also differ phenotypically, which could influence the severity of disease in vertebrate hosts.

A Space-Time Permutation Scan Statistic for Evaluating County-Level Tickborne Disease Clusters in Indiana, 2009-2016.

The purpose of this study was to identify age group, gender, rural-urban differences, and spatiotemporal clusters of tickborne disease diagnoses in Indiana. We analyzed retrospective surveillance data for Lyme disease, ehrlichiosis, Rocky Mountain spotted fever, typhus/rickettsial diseases, and tularemia diagnosed in Indiana from 2009 to 2016. We used chi-square cross tabulation to test gender, age group, and county classification (rural, rural-mixed, urban) differences in tickborne disease. We used the Kruskal-Wallis test with a post hoc Conover test to identify differences in summated tickborne disease by county classification. Finally, we used retrospective space-time permutation models in SaTScan to test the hypothesis of complete spatiotemporal randomness of tickborne disease. We found more Lyme disease diagnoses among Indiana residents 44 years of age or younger compared with those over 44 years. Conversely, more ehrlichiosis, Rocky Mountain spotted fever, and tularemia were reported in Indiana residents aged over 44 years of age. An analysis of summated tickborne disease by county showed significantly higher diagnosis reported in urban counties, compared with rural and rural-mixed counties. Finally, 2 significant clusters of summated tickborne disease were observed in south-central Indiana in 2014 and in western Indiana from 2010 to 2011. The detection of tickborne disease clusters, coupled with the finding that significant differences exist in the diagnosis of tickborne diseases between urban, rural, and rural-mixed counties in Indiana, suggests a need for continued surveillance of the counties observed within these clusters.