Intralesional expression of mRNA of interferon- gamma , tumor necrosis factor- alpha , interleukin-10, nitric oxide synthase, indoleamine-2,3-dioxygenase, and RANTES is a major immune effector in Mediterranean spotted fever rickettsiosis.

BACKGROUND: The mechanisms of immunity to Rickettsia conorii that have been elucidated in mouse models have not been evaluated in human tissues. METHODS: In this study, quantitative real-time polymerase chain reaction was used to determine the levels of expression of inflammatory and immune mediators in skin-biopsy samples collected from 23 untreated patients with Mediterranean spotted fever (MSF). RESULTS: In all 23 patients, the levels of intralesional expression of mRNA of tumor necrosis factor (TNF)- alpha , interferon (IFN)- gamma , interleukin (IL)-10, RANTES, and indoleamine-2,3-dioxygenase (IDO), an enzyme involved in limiting rickettsial growth by tryptophan degradation, were higher than those in control subjects; 6 of the 23 patients had high levels of inducible nitric oxide synthase (iNOS), a source of microbicidal nitric oxide. Positive correlations between TNF- alpha , IFN- gamma , iNOS, IDO, and mild/moderate MSF suggest that type 1 polarization plays a protective role. Significantly higher levels of intralesional expression of IL-10 mRNA were inversely correlated with levels of intralesional expression of IFN- gamma mRNA and TNF- alpha mRNA. The mRNA-expression level of the chemokine RANTES was significantly higher in patients with severe MSF. CONCLUSION: 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.

Mediterranean spotted fever in Portugal: risk factors for fatal outcome in 105 hospitalized patients.

Mediterranean spotted fever (MSF) is the most important tick-borne disease in Portugal. It is a notifiable disease and during 1989-2000 the annual incidence rate in Portugal was 9.8/10(5) inhabitants. Although recognized as a benign acute disease and treated mainly with ambulatory procedures, some cases are severe and fatalities have increased in the last few years. In 1997, MSF mortality became more evident in Beja, a Portuguese southern district, with a case fatality rate of 32.3% in hospitalized patients. Analysis of 55 variables regarding epidemiologic, clinical, laboratory, and therapeutic data of fatal and nonfatal MSF cases were compared to identify risk factors in 105 patients hospitalized in Beja District Hospital, between 1994 and 1998. It was statistically significant that the patients dying in 1997 were younger than those in other years. The risk of dying is statistically significant in those who presented with diabetes, vomiting, dehydration, and uremia. The interval between the onset of symptoms to administration of anti-rickettsial therapy was the same for all patients. Therapy delay, reported by some authors to be associated with mortality of MSF, was not a risk factor in our study. The patients who died in 1997 died faster than those in other years. The variables studied could not explain the higher mortality rates observed in our study. Although one may speculate that the pathogenic strain of Israeli tick typhus, isolated in 1997, could be responsible for this increase of fatality rate, inherited patient factors might also be strongly associated with mortality.

[Epidemiologic features of Mediterranean spotted fever in Portugal]. / Sobre a realidade da febre escaro-nodular em Portugal.

Mediterranean spotted fever (MSF) is a tick-borne rickettsial disease. It is endemic in Portugal and Ricardo Jorge recognized it in 1930. Rhipicephalus sanguineus is the main vector and reservoir of the disease. In Portugal the etiologic agents are two strains of Rickettsia conorii complex: R. conorii Malish and "Israeli tick typhus". MSF is clinically characterized by a vasculitis process with the classical clinical triad of fever, rash, and lesion at the site of tick bite. Although the majority MSF cases are considered benign, last years some districts presented more severe cases than expected. The reported incidence of MSF in Portugal for 1989 to 2000 was 9.8/10(5) inhabitants, the highest incidence compared to other mediterranean countries. Alentejo was the region who presents the highest incidence with 31/10(5) inhabitants. Nevertheless, Bragança was the district which appears with greater number of cases, 62/10(5) inhabitants. The highest annual incidence rate reported was among children, peaking in those 1-4 years of age with 60.2/10(5) inhabitants. Observation of mortality rates have shown that Beja district have the highest mortality rates for MSF in Portugal, but in 1997 in this district, mortality have unexpected values with 7.6 deaths per 100,000 inhabitants have occurred. Although is an obligatory notifiable disease, high number of underreported cases are detected.