Browsing by Author "Bacellar, F"
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- Host- and microbe-related risk factors for and pathophysiology of fatal Rickettsia conorii infection in Portuguese patients.Publication . Sousa, R; França, A; Nóbrega, SD; Belo, A; Amaro, M; Abreu, T; Poças, J; Proença, P; Vaz, J; Torgal, J; Bacellar, F; Ismail, N; Walker, DBACKGROUND: The pathophysiologic mechanisms that determine the severity of Mediterranean spotted fever (MSF) and the host-related and microbe-related risk factors for a fatal outcome are incompletely understood. METHODS: This prospective study used univariate and multivariate analyses to determine the risk factors for a fatal outcome for 140 patients with Rickettsia conorii infection admitted to 13 Portuguese hospitals during 1994-2006 with documented identification of the rickettsial strain causing their infection. RESULTS: A total of 71 patients (51%) were infected with the Malish strain of Rickettsia conorii, and 69 (49%) were infected with the Israeli spotted fever (ISF) strain. Patients were admitted to the intensive care unit (40 [29%]), hospitalized as routine inpatients (95[67%]), or managed as outpatients (5[4%]). Death occurred in 29 adults (21%). A fatal outcome was significantly more likely for patients infected with the ISF strain, and alcoholism was a risk factor. The pathophysiology of a fatal outcome involved significantly greater incidence of petechial rash, gastrointestinal symptoms, obtundation and/or confusion, dehydration, tachypnea, hepatomegaly, leukocytosis, coagulopathy, azotemia, hyperbilirubinemia, and elevated levels of hepatic enzymes and creatine kinase. Some, but not all, of these findings were observed more often in ISF strain-infected patients. CONCLUSIONS: Although fatalities and similar clinical manifestations occurred among both groups of patients, the ISF strain was more virulent than the Malish strain. Multivariate analysis revealed that acute renal failure and hyperbilirubinemia were most strongly associated with a fatal outcome.
- 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 rickettsiosisPublication . Sousa, R; Ismail, N; Nóbrega, SD; França, A; Amaro, M; Anes, M; Poças, J; Coelho, R; Torgal, J; Bacellar, F; Walker, DBACKGROUND: 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 tryptopha 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.