Background The pathophysiologic mechanisms of severity of Mediterranean spotted fever (MSF) and the host and microbial risk factors for a fatal outcome are incompletely determined. Methods In a prospective study of 140 patients with documented identification of the causative rickettsial strain admitted to 13 Portuguese hospitals during 1994−2006, univariate and multivariate analyses determined the risk factors for a fatal outcome. Findings Seventy one (51%) patients were infected with Rickettsia conorii Malish strain and 69 (49%) with Israeli spotted fever (ISF) strain. Patients were admitted to ICU (29%), hospitalized as routine inpatients (67%), or managed as outpatients (4%). Deaths occurred in 29 (21%) adults. Fatal outcome was significantly more likely for patients with ISF strain infection, and alcoholism was a risk factor. The pathophysiology of a fatal outcome involved significantly greater incidence of petechial rash, gastrointestinal symptoms, confusion/obtundation, dehydration, tachypnea, hepatomegaly, leukocytosis, coagulopathy, azotemia, hyperbilirubinemia, and elevated hepatic enzymes and creatine kinase. Some but not all these were observed more often in ISF strain-infected patients. Conclusions Although fatalities and similar clinical manifestations occurred with both strains, ISF strain was more virulent than Malish strain. Multivariate analysis revealed that acute renal failure and hyperbilirubinemia were most strongly associated with a fatal outcome.

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Mediterranean spotted fever (MSF), endemically present, is associated with a low mortality and morbidity in Portugal. Etiological agents are Malish and Israeli tick typhus strains of Rickettsia conorii. In the last few years severe forms of MSF have emerged, with patients presenting atypical symptoms, major neurological manifestations, and multiorgan involvement, who have required intensive care facilities. Advanced age, underlying chronic disease, and delay of appropriate treatment are bad prognostic factors. In the acute phase of diagnosis, serological studies are delayed, inconclusive, and often unhelpful. A definitive diagnosis can only be made using isolation or molecular biology which can establish and clearly identify agents. Using evidence-based case reports, clinical and laboratory data were evaluated from patients with severe or fatal MSF observed in Garcia da Orta Hospital-Almada. Of the eight reference cases, four died, three in an acute fulminant stage. Of the survivors, four presented atypical involvement: ocular inoculation, massive gastric hemorrhage, acute respiratory disease (ARDS), and necrotizing vasculitis. Diagnosis by isolation of the agent was made in two cases, by immunohistochemistry in three, and by the indirect fluorescent antibody test (IFA) in three others. Israeli tick typhus and Malish R. conorii strains were isolated once each in fatal cases. In early stages, diagnosis continues to be clinical and patients should start appropriate therapy without delay if clinical suspicion of rickettsiosis arises to prevent poor outcome. Patients ranged in age from 39 to 71 years (mean 60), APACHE II ranged from 15 to 38 points and TISS 28 was between 24 and 46 points. In reported cases severity of disease was not obviously related to the usual comorbidities. Accelerated clinical course may not suggest classical MSF. Another relevant factor was prior prescription of an inappropriate antibiotic that contributed to misleading clinical features. The reported complications and atypical manifestations illustrate well the diversity of this disease.

In Portugal, Mediterranean spotted fever (MSF) is caused by R. conorii Malish and Israeli spotted fever (ISF) strains. It has been suggested that the ISF strain isolated from patients with MSF causes different clinical manifestations compared to those caused by Malish strain, namely the absence of eschar and greater severity. The aim of this study was to analyze the presence or absence of eschar and of fatality in Portuguese patients infected with either Malish or ISF strain. Of 94 patients with a clinical diagnosis of MSF between 1994 to 2004, 47 were infected with Malish strain and 47 with ISF strain. Eschars were reported in 20 patients (49%) infected with Malish strain, and in 17 (39%) with ISF strain. The presence of eschar is not statistically associated to a greater extent with either R. conorii strain (P=0.346). A total of 22 patients died, 9 infected with Malish strain and 13 infected with ISF strain, and no statistically significant difference was found (P=0.330). This study showed that the concepts of absence of the eschar and greater severity in Israeli spotted fever infection should be revised.

Mild/moderate MSF is associated with a strong and balanced intralesional proinflammatory and anti-inflammatory response, with a dominant type 1 immunity, whereas severe MSF is associated with increased expression of chemokine mRNA. Whether these factors are simply correlates of mild and severe MSF or contribute to antirickettsial immunity and pathogenesis remains to be determined.

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In this study, we propose a modified VTE risk score that effectively risk-stratifies a mixed inpatient population during hospital stay. The use of this score may result in improvement of thromboprophylaxis practices in hospitals.

Introduction: Venous thromboembolism (VTE) is the primary cause of preventable death in hospitalized patients in the United States. This is a cross-sectional study with a brief cost analysis of thromboprophylaxis with rivaroxaban and enoxaparin in acutely ill medical inpatients.Methods: The study included a total of 122 patients admitted to a public teaching hospital from December 2019 to January 2021. The sample was equally divided into two groups according to the thromboprophylactic agent prescribed: rivaroxaban or enoxaparin. The primary outcomes included bleeding and symptomatic, ultrasonography-confirmed arterial or venous thrombotic events during or within 90 days after hospitalization. Our secondary outcome was the direct costs of each anticoagulant in US dollars over the 14 months.Results: During hospitalization, two events were detected in the enoxaparin group: minor bleeding with minimum intervention required (1.6%) and a deep vein thrombosis (DVT) case (1.6%) confirmed by ultrasonography. Within 90 days after discharge, two patients, one of each sample (1.6% vs. 1.6%), were readmitted due to confirmed acute arterial occlusion. Concerning financial assessment, the mean unit cost of enoxaparin during the 14 months assessed was 102.14% more expensive than rivaroxaban.Conclusions: Both rivaroxaban and enoxaparin showed equivalence in effectiveness and safety in thromboprophylaxis in medical inpatients, aside from possible financial benefit with the first-mentioned drug.