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.

Does Paging Clinicians about Tick-Borne Disease Serological Results Impact Clinical Care? A Retrospective Analysis of 70 Cases in North Carolina.

Delayed treatment of Rocky Mountain spotted fever is associated with increased morbidity and mortality. Because the diagnosis cannot be established from a single serological test, guidelines recommend empirical antibiotic initiation in suspect patients. We evaluated a policy used by UNC Health of paging clinicians when acute testing for Rickettsia returned with a titer ≥1:256. Our objective was to assess the potential effect of paging on routine treatment practices. Notably, we found that a high proportion of cases (N = 28, 40%) were not prescribed antibiotics until the results were available. The vast majority of these cases did not have evidence of compatible symptoms or disease progression. These findings suggest that paging may have prompted unnecessary treatment. Overall, the policy, which has now been discontinued, appears to have had limited benefit. Efforts are urgently needed to improve adherence to testing and treatment guidelines.

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 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.

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.

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.

Knowledge, Attitudes, and Practices Related to Rocky Mountain Spotted Fever in Hermosillo, México.

Rocky Mountain spotted fever (RMSF) is a serious disease in northwest Mexico, particularly in low-income communities. This study aimed to evaluate RMSF-related knowledge, attitudes, and practices in an endemic urban area with a high burden of the disease. A cross-sectional study design using a non-probabilistic household survey was conducted with 400 residents in Hermosillo, Mexico. Primary themes assessed included dog and tick-related exposure, RMSF knowledge, healthcare-seeking behavior, sociodemographic data, and household information. The majority (59%) of those surveyed had heard about RMSF, although only 36% of RMSF-aware respondents knew any RMSF symptoms. Among RMSF-aware respondents, 26% did not know or were unsure of prevention strategies. Individuals in the low socioeconomic status (SES) stratum were less likely to have heard about RMSF (odds ratio [OR]: 0.39; 95% CI: 0.25-0.59), use dog collars or any other product to avoid ticks (OR: 0.40; 95% CI: 0.17-0.99), or check their dogs for ticks (OR: 0.25; 95% CI: 0.09-0.74). The likelihood of observing high numbers of free-roaming dogs in their neighborhood was four times higher in the low SES stratum (OR: 4.19; 95% CI: 2.10-8.38) than in the high SES stratum. These findings emphasize the need for an integrative community approach to improve early recognition of symptoms and knowledge of prevention strategies, particularly in low SES neighborhoods.

Síndrome Dress relacionada ao uso de Alopurinol: relato de caso / Dress Syndrome related to the use of allopurinol: case report

A síndrome DRESS é uma reação adversa a medicamentos pouco conhecida dentro da prática clínica, porém com grande potencial de letalidade devido a combinação de manifestações cutâneas e envolvimento de múltiplos órgãos. Objetivo: identificar possíveis reações adversas graves e incomuns secundárias ao uso de medicações usadas frequentemente na prática clínica. Métodos: Trata-se de um relato de caso construído com base em levantamento de dados do prontuário do paciente e análise a partir de um referencial teórico para comprovação de sua relevância na prática clínica. Resultado: Enfatizou-se a importância de um reconhecimento precoce dessa condição, a fim de evitar desfechos graves

The DRESS syndrome is an adverse drug reaction that is unsual in clinical practice, but with a high potential for lethality, due to the combination of cutaneous manifestations and involvement of multiple organs. Objective: identify possible serious and unusual adverse reactions secondary to the use of medications frequently used in clinical practice. Methods: This is a case report built on the basis of data collection from the patient's medical record and analysis from a theoretical framework to prove its source in clinical practice. Outcome: The importance of early recognition of this condition was emphasized, in order to avoid serious outcomes

Clinical characteristics of Rocky Mountain spotted fever in the United States: A literature review.

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.

Susceptibility of Rickettsia rickettsii to Tigecycline in a Cell Culture Assay and Animal Model for Rocky Mountain Spotted Fever.

Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii, is a severe tick-borne infection endemic to the Americas. Oral doxycycline is effective, but during severe life-threatening disease, intravenous therapy is recommended. Unfortunately, intravenous formulations of doxycycline are not always available. Therefore, we aimed to determine the susceptibility of R. rickettsii to an alternative parenteral agent, tigecycline, in vitro and in vivo. To determine the minimum inhibitory concentration of tigecycline, R. rickettsii-inoculated Vero cells were incubated with medium containing tigecycline. At various time points, monolayers were collected and R. rickettsii was quantified via real-time polymerase chain reaction (PCR). The growth of R. rickettsii was inhibited in the presence of ≥ 0.5 µg/mL of tigecycline. To determine the effectiveness of tigecycline in vivo, guinea pigs were inoculated with R. rickettsii. Five days after inoculation, they were treated twice daily with subcutaneous tigecycline 3.75 mg/kg or subcutaneous doxycycline 5 mg/kg. Treated animals improved, whereas untreated controls remained ill. Tissues were collected for quantitative PCR-determined bacterial loads on day 8. Median bacterial loads in the tigecycline group were less than those in untreated animals: liver (0 versus 2.9 × 104 copies/mg), lung (0 versus 8.3 × 103 copies/mg), skin (2.6 × 102 versus 2.2 × 105 copies/mg), spleen (0 versus 1.3 × 104 copies/mg), and testes (0 versus 1.0 × 105 copies/mg, respectively). There were no significant differences in the bacterial loads between doxycycline-treated versus tigecycline-treated guinea pigs. These data indicate that tigecycline is effective against R. rickettsii in cell culture and in an animal model of RMSF.

A Suspected Case of Rocky Mountain Spotted Fever in an Adult Horse in the Southeastern United States.

A 20-year-old Paint gelding was evaluated for fever of unknown origin. History and clinical signs were consistent with potential tick-borne disease. Samples were collected and submitted for tick-borne disease panel, herpes virus, complete blood count, and serum biochemistry. Based on physical examination findings and vaccination history, the gelding was treated for suspected tick-borne disease with oxytetracycline (8 mg/kg intravenously BID) for 5 days, followed by doxycycline (10 mg/kg PO BID) for an additional 5 days. Although titers to Borrelia burgdorferi, Anaplasma phagocytophilum, and Neorickettsia risticii on Days 4 and 8 were negative, the Rickettsia rickettsii titer went from 1:1,600 on Day 4 to 1:800 on Day 8, 1:100 on Day 21, and was seronegative by Day 38. Although complete blood polymerase chain reaction for Rickettsia rickettsii was negative, the clinical and serologic features of this case are extremely consistent with clinical cases of Rocky Mountain Spotted Fever (RMSF) described in both dogs and humans. Therefore, we submit this case report to document suspected clinical infection of an adult horse in the southeastern United States with Rickettsia rickettsii, the causative agent of RMSF. Other relevant differentials (i.e., Rickettsia parkeri, Theileria equi, and Babesia caballi) are also discussed.

The Rickettsioses: A Practical Update.

Rickettsia are small, obligately intracellular, gram-negative bacilli. They are distributed among a variety of hematophagous arthropod vectors and cause illness throughout the world. Rickettsioses present as an acute undifferentiated febrile illness and are often accompanied by headache, myalgias, and malaise. Cutaneous manifestations include rash and eschar, which both occur at varying incidence depending on the infecting species. Serology is the mainstay of diagnosis, and the indirect immunofluorescence assay is the test of choice. Reactive antibodies are seldom present during early illness, so testing should be performed on both acute-phase and convalescent-phase sera. Doxycycline is the treatment of choice.

Medical knowledge related to Rocky Mountain spotted fever in Sonora, Mexico.

Background: Rocky Mountain spotted fever (RMSF) is a tick-borne disease with a high case-fatality rate unless diagnosed promptly and treated timely with doxycycline. Physician knowledge about presentation and treatment can improve outcomes of RMSF in endemic regions, such as Sonora in northern Mexico, where RMSF has caused 1348 non-fatal cases and 247 deaths from 2003 to 2016. Methods: A cross-sectional study was conducted with 343 physicians working in medical facilities in Sonora, Mexico. A 25-item questionnaire explored physician knowledge of clinical, epidemiological and preventive aspects of RMSF. Results: Only 62% of physicians agreed that doxycycline should be used as the first choice treatment for children under 8 years with suspected RMSF. Additionally, 40% of primary care physicians correctly identified the time to initiate doxycycline, and 32% correctly identified the case-fatality rate of untreated RMSF in all patients. Conclusions: Inadequate medical knowledge may adversely affect how patients infected with Rickettsia rickettsii are diagnosed and treated. Educational programs that improve the risk perception and medical knowledge about RMSF should be targeted at physicians most likely to have initial contact with diseased patients.

Comparative genomic analysis of Rickettsia rickettsii for identification of drug and vaccine targets: tolC as a proposed candidate for case study.

BACKGROUND: Antibiotic resistance is increasing rapidly in pathogenic organisms, creating more complications for treatment of diseases. Rocky Mountain spotted fever (RMSF) is a neglected tropical disease in humans caused by Rickettsia rickettsii for which no effective therapeutic is available. Subtractive genomics methods facilitate the characterization of non-homologous essential proteins that could be targeted for the discovery of potential therapeutic compounds against R. rickettsii to combat RMSF. Present study followed an in-silico based methodology, involving scanning and filtering the complete proteome of Rickettsia rickettsii by using several prioritization parameters in the search of potential candidates for drug development. Further the putative targets were subjected to series of molecular dockings with ligands obtained from PDB ligand database to identify suitable potential inhibitors. The comparative genomic analysis revealed 606 non-homologous proteins and 233 essential non-homologous proteins of R. rickettsii. The metabolic pathway analysis predicted 120 proteins as putative drug targets, out of which 56 proteins were found to be associated with metabolic pathways unique to the bacteria and further subcellular localization analysis revealed that 9 proteins as potential drug targets which are secretion proteins, involved in peptidoglycan biosynthesis, folate biosynthesis and bacterial secretion system. As secretion proteins are more feasible as vaccine candidates, we have selected a most potential target i.e. tolC, an outer membrane efflux protein that belongs to type I secretion system and has major role in pathogen survival as well as MDR persistence. So for case study, we have modelled the three dimensional structure of tolC (tunnel protein). The model was further subjected to virtual screening and in-silico docking. The study identified three potential inhibitors having PDB Id 19V, 6Q8 and 39H. Further we have suggested that the above study would be most important while considering the selection of candidate targets and drug or vaccine designing against R. rickettsii.

Rocky Mountain Spotted Fever.

The tick-borne disease Rocky Mountain spotted fever (RMSF) can have deadly outcomes unless treated appropriately, yet nonspecific flu-like symptoms complicate diagnosis. Occupational health nurses must have a high index of suspicion with symptomatic workers and recognize that recent recreational or occupational activities with potential tick exposure may suggest RMSF.