Immunology of human rickettsial diseases.

Among human rickettsial diseases caused by micro-organisms of the genus Rickettsia (Order Rickettsiales; Family Rickettsiaceae), transmitted to human hosts through arthropod vectors, Mediterranean Spotted Fever, or Boutonneuse Fever, and Rocky Mountain Spotted Fever are considered to be important infectious diseases due to continued prevalence in the developed world, and potentially fatal outcome in severe cases. Proliferation of rickettsiae, at the site of the tick bite, results in focal epidermal and dermal necrosis (tache noire). Rickettsiae then spread via lymphatic vessels to the regional lymph nodes, and, via the bloodstream, to skin, brain, lungs, heart, liver, spleen and kidneys. The pathogen invades and proliferates in the endothelial cells of small vessels, target cells of rickettsial infection, destroying them, and spreading the infection to the endothelia of the vascular tree. The damage of the endothelium, and the subsequent endothelia dysfunction, is followed by the activation of acute phase responses, with alteration in the coagulation and in the cytokine network, together with a transient immune dysregulation, characterized by the reduction in peripheral CD4+ T lymphocytes

Relevance of gamma interferon, tumor necrosis factor alpha, and interleukin-10 gene polymorphisms to susceptibility to Mediterranean spotted fever.

The acute phase of Mediterranean spotted fever (MSF) is characterized by dramatic changes in cytokine production patterns, clearly indicating their role in the immunomodulation of the response against the microorganism, and the differences in cytokine production seem to influence the extent and severity of the disease. In this study, the single nucleotide polymorphisms (SNPs) of tumor necrosis factor alpha (TNF-α) -308G/A (rs1800629) and interleukin-10 (IL-10) -1087G/A (rs1800896), -824C/T (rs1800871), and -597C/A (rs1800872) and the gamma interferon (IFN-γ) T/A SNP at position +874 (rs2430561) were typed in 80 Sicilian patients affected by MSF and in 288 control subjects matched for age, gender, and geographic origin. No significant differences in TNF-α -308G/A genotype frequencies were observed. The +874TT genotype, associated with an increased production of IFN-γ, was found to be significantly less frequent in MSF patients than in the control group (odds ratio [OR], 0.18; 95% confidence interval [95% CI], 0.06 to 0.51; P corrected for the number of genotypes [Pc], 0.0021). In addition, when evaluating the IFN-γ and IL-10 genotype interaction, a significant increase of +874AA/-597CA (OR, 5.31; 95% CI, 2.37 to 11.88; Pc, 0.0027) combined genotypes was observed. In conclusion, our data strongly suggest that finely genetically tuned cytokine production may play a crucial role in the regulation of the immune response against rickettsial infection, therefore influencing the disease outcomes, ranging from nonapparent or subclinical condition to overt or fatal disease

Risk factors, atrial fibrillation and thromboembolic events

AIM: The aim of this study was to evaluate the relation between risk factors for atrial fibrillation (AF) and thromboembolic complications. METHODS: We studied 480 patients (mean age: 71.2+/-11.6 years): 240 with paroxysmal AF, 240 with permanent AF. The association between AF and the presence of risk factors, cardiac and systemic disease was observed and the correlation with the occurrence of complications analyzed. RESULTS: Patients with AF had a high prevalence of the following conditions: hypertension, hypertensive heart disease (HHD), coronary artery disease, hyperthyroidism. Thromboembolism was observed in 26.6% of the patients. A correlation between the occurrence of a thromboembolic complication and the presence of one of the following risk factors for thromboembolism was observed: older age, diabetes mellitus, HHD and hyperfibrinogenemia. No correlation was detected between: female sex, arterial hypertension, hypercholesterolemia, smoking, and obesity. Exitus was observed in 7 patients with permanent AF. CONCLUSION: Older age, diabetes mellitus, HHD and hyperfibrinogenemia were strongly associated with the occurrence of thromboembolic complications. Patients with effectively pharmacologically controlled hypertension had not more frequently thromboembolic complications. A strict blood pressure control may prevent thromboembolic complications of AF.AIM: The aim of this study was to evaluate the relation between risk factors for atrial fibrillation (AF) and thromboembolic complications. METHODS: We studied 480 patients (mean age: 71.2+/-11.6 years): 240 with paroxysmal AF, 240 with permanent AF. The association between AF and the presence of risk factors, cardiac and systemic disease was observed and the correlation with the occurrence of complications analyzed. RESULTS: Patients with AF had a high prevalence of the following conditions: hypertension, hypertensive heart disease (HHD), coronary artery disease, hyperthyroidism. Thromboembolism was observed in 26.6% of the patients. A correlation between the occurrence of a thromboembolic complication and the presence of one of the following risk factors for thromboembolism was observed: older age, diabetes mellitus, HHD and hyperfibrinogenemia. No correlation was detected between: female sex, arterial hypertension, hypercholesterolemia, smoking, and obesity. Exitus was observed in 7 patients with permanent AF. CONCLUSION: Older age, diabetes mellitus, HHD and hyperfibrinogenemia were strongly associated with the occurrence of thromboembolic complications. Patients with effectively pharmacologically controlled hypertension had not more frequently thromboembolic complications. A strict blood pressure control may prevent thromboembolic complications of AF