Significance of persistence of antibodies against Leishmania infantum in Sicilian patients affected by acute visceral leishmaniasis.

The background of this article is as follows: Few data are available about the persistence of serum-specific IgG antibodies to L. infantum after acute VL. The objective of this article is to evaluate the persistence of antibodies against L. infantum in patients healed from acute VL, and the kinetic of the same antibodies observed in 2 cases of VL relapse and 2 cases of resistance to therapy. The methods which we used to obtain our objective are the following: 55 apparently immunocompetent, HIV-negative patients were examined for antibodies to L. infantum by IFAT over 14 years period, and we got the following results: Serum-specific IgG antibodies titers decrease slowly, but constantly. In the patients with a diagnosis of VL relapse, the kinetic of antibodies was characterized by an initial reduction, and a subsequent antibody levels rapidly increase, while in the patients with a clinical and parasitological diagnosis of VL not responding to specific therapy, we demonstrated persistent high level of antibodies to L. infantum. Finally, we conclude that specific antibodies to L. infantum might persist for many years, and decrease slowly, but steadily. The persistence of these specific antibodies is not related to poor therapeutic response or prognosis, but an acute increase in their levels might be a sentinel of a VL relapse, while persistence of high antibody levels could suggest a resistance to therapy.

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-alpha) -308G/A (rs1800629) and interleukin-10 (IL-10) -1087G/A (rs1800896), -824C/T (rs1800871), and -597C/A (rs1800872) and the gamma interferon (IFN-gamma) 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-alpha -308G/A genotype frequencies were observed. The +874TT genotype, associated with an increased production of IFN-gamma, 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-gamma and IL-10 genotype interaction, a significant increase of +874AA/-597CA (OR, 5.31; 95% CI, 2.37 to 11.88; P(c), 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.

Fever of unknown origin in a Mediterranean survey from a division of internal medicine: report of 91 cases during a 12-year-period (1991-2002).

Despite the availability of all advanced diagnostic tools, fever of unknown origin (FUO) remains a diagnostic challenge for physicians. The objective was to define, through a retrospective study, the categories of the diseases of Sicilian patients admitted at the Department of Clinical Medicine and Emerging Diseases, University of Palermo, Italy, for classical FUO. Using the registration system for patients admitted from 1991 to 2002, 508 charts of patients admitted because of fever were reviewed. Of these, only 91 patients fulfilled the criteria for classical FUO. The origin of FUO was diagnosed in 62 (68.1%) patients. Infection was the most common cause of FUO with 29 cases (31.8% of total of FUO), neoplasms accounted for 13 cases (14.2%), collagen vascular disease for 11 cases (12.0%), and miscellaneous for 9 cases (9.8%). Undiagnosed FUO were 29 (31.8%) and, of them, 22 cases were followed-up for 2 years. A definite diagnosis could be established only in 8 cases, 13 subjects completely recovered and 4 of them died. In the 73.4% of cases, the FUO have been the result of misleading factors in the diagnostic approaches as made by the physician. The results of our study are similar to those already reported by other authors in other populations, with infections as first, neoplasm as second, and collagen vascular diseases as third most important causes of FUO. In our study the prognosis for undiagnosed FUO cases was good, but a definite diagnosis could be established only in few cases. Therefore, further multicentric, prospective studies of good design are required.

Asymptomatic carotid lesions and aging: Role of hypertension and other traditional and emerging risk factors.

BACKGROUND: We evaluated the prevalence of intima-media thickening (IMT) and asymptomatic carotid plaque (ACP) in a group of subjects with or without traditional and/or emerging risk factors (RF). METHODS: There were 631 subjects (313 male and 318 female) aged between 19 and 97 years, asymptomatic for cerebro- and cardiovascular diseases. The following measurements were used: anamnesis, physical examination, height and sitting blood pressure. Biochemistry variables were also considered: total cholesterol, HDL-C, LDL-C, triglycerides, fibrinogen, high sensitive C-reactive protein, IgG antibodies for Helicobacter pylori (HP), cytotoxic HP, cytomegalovirus and Chlamydia pneumoniae. Finally, an echo color Doppler examination of the carotid arteries was performed. We subdivided the population studied in normotensive and hypertensive subjects and evaluated in each group the frequency of IMT and ACP in relation to age. RESULTS: We showed that IMT + ACP was significantly more frequent in patients >65 years in comparison with those <65 years (80.6 vs. 52.1%, p < 0.005) and in hypertensive patients in comparison to normotensive, independent of coexistence of other cardiovascular risk factors (71 vs. 48%, p < 0.005). Another interesting result of our study is a significant presence of IMT and ACP in subjects with emerging but without traditional RF than in subjects with traditional but without emerging RF. CONCLUSIONS: IMT and ACP of carotid arteries are significantly more frequent in patients >65 years vs. those <65 years and in hypertensive patients in comparison to controls. Finally, we have found that the seropositivity of infection and the presence of higher levels of marker of inflammation were correlated with carotid lesion.

Presence of Rickettsia conorii subsp. israelensis, the causative agent of Israeli spotted fever, in Sicily, Italy, ascertained in a retrospective study.

A retrospective analysis by molecular-sequence-based techniques was performed to correctly identify the etiological agent of 24 Mediterranean spotted fever cases occurring in Western Sicily, Italy, from 1987 to 2001. Restriction analysis of a 632-bp PCR-amplified portion of the ompA gene allowed presumptive identification of five clinical isolates as belonging to Rickettsia conorii subsp. israelensis, the etiological agent of Israeli spotted fever (ISF). The remaining 19 rickettsial isolates were Rickettsia conorii subsp. conorii, the only pathogenic rickettsia of the spotted fever group reported in Italy until the present. Sequence analysis of the ompA gene confirmed the identification of all the R. conorii subsp. israelensis isolates and demonstrated that rickettsiosis caused by R. conorii subsp. israelensis can be traced back to 1991 in Sicily. The recorded clinical data of the five ISF patients support the idea that these strains could correlate to more-severe forms of human disease. Three of five patients experienced severe disease, and one of them died.

CD4+ CCR5+ and CD4+ CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis.

The potential involvement of apoptosis in the pathogenesis of visceral leishmaniasis (VL) was examined by studying spontaneous and Leishmania antigen (LAg)-induced apoptosis using cryopreserved peripheral blood mononuclear cells (PBMC) of Sicilian patients with VL. Results indicate that monocytes and T lymphocytes from acute VL patients show a significantly higher level of apoptosis compared with that observed in healed subjects. The percentage of apoptotic cells was higher in monocytes than in T lymphocytes. T cells involved in programmed cell death (PCD) were mainly of the CD4(+) phenotype. In particular, the T helper 1-type (Th1) subset, as evaluated by chemokine receptor-5 (CCR5) expression, is involved in this process. Cell death in Th1-type uses a CD95-mediated mechanism. Furthermore, Th1-type CCR5(+) cells are prone to cell suicide in an autocrine or paracrine way, as attested by enhanced expression of CD95L in acute VL patients. The reduction in Th1-type cells by apoptosis was confirmed by the decrease in interferon-gamma secretion. In conclusion, apoptosis of monocytes, CD4(+) and CD4(+) CCR5(+) T cells could be involved in the failure of cell mediated immunity that is responsible for severe immune-depression in VL.

[Bartonellosis]. / Bartonellosi.

In the last years the number of Bartonella species significantly raised, often with an epidemiological profile of emergent disease. B. bacilliformis is the etiological agent of Carrion's disease. B. clarridgeiae has been associated, together with B. henselae, to Cat-Scratch Disease (CSD), whereas B. elizabethae to endocarditis and B. grahamii to neuroretinitis. B. henselae has been associated to CSD and, in patients with immunodeficiency, together with B. quintana, to bacillary angiomatosis, to peliosis and to endocarditis. B. quintana is the etiological agent of "trench fever", in its "classical" and "urban" form. B. vinsonii subsp. arupensis and subsp. berkhoffii have been associated to bacteremia and endocarditis. The diagnosis foresees pathological examination of the lesions, germ isolation and use of specific serological test and of polymerase chain reaction. Prognosis is, generally, favourable. Therapy foresees the use of numerous antibacterial agents, like: penicillins, cephalosporins, aminoglycosides, tetracyclines, macrolides, quinolones, trimethoprim-sulfomethoxazole and rifampicin.

Comparison of anti-transglutaminase ELISAs and an anti-endomysial antibody assay in the diagnosis of celiac disease: a prospective study.

BACKGROUND: Most studies of anti-transglutaminase (anti-tTG) assays have considered preselected groups of patients. This study compared the sensitivity, specificity, and predictive value of an immunofluorescence method for anti-endomysial antibodies (EmAs) and two anti-tTG ELISAs, one using guinea pig tTG (gp-tTG) and the other human tTG (h-tTG) as antigen, in consecutive patients investigated for suspected celiac disease (CD). METHODS: We studied 207 consecutive patients (99 men, 108 women; age range, 17-84 years) who underwent intestinal biopsy for suspected CD. Patients presented with one or more of the following: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia, alternating bowel habits, constipation, pain in the joints, and dermatitis. At entry to the study, an intestinal biopsy was performed and a serum sample was taken for IgA EmAs, anti-gp-tTG, and anti-h-tTG. RESULTS: Intestinal histology showed that 24 patients had partial or total villous atrophy; in these patients the diagnosis of CD was confirmed by follow-up. The remaining 183 patients had villous/crypt ratios that were within our laboratory's reference values and were considered controls. Serum EmAs, anti-gp-tTG, and anti-h-tTG were positive in all 24 CD patients; in the control group, none were positive for serum EmAs, but 15 of 183 (8.2%) were positive for anti-gp-tTG, and 6 of 183 (3.3%) were positive for anti-h-tTG. Sensitivity was 100% for all assays, whereas specificity was 100% for the EmA, 92% for the anti-gp-tTG, and 97% for the anti-h-tTG assay. The negative predictive value was 100% for all assays; the positive predictive value was 100% for the EmA, 80% [95% confidence interval (CI), 65-95%] for the anti-h-tTG (P = 0.03 vs EmA) and 60% (95% CI, 44-76%) for the anti-gp-tTG assay (P = 0.0002 vs EmA). Areas (95% CIs) under the ROC curves were 0.987 (0.97-1.0) for anti-h-tTG and 0.965 (0.94-0.99) for anti-gp-tTG. Most of the patients testing false positive for anti-tTG had Crohn disease or chronic liver disease. CONCLUSIONS: Although both anti-tTG ELISAs showed optimum sensitivity, their lack of specificity yielded positive predictive values significantly lower than those for the EmA assay.

[Three cases of bartonellosis (cat scratch disease)]. / Su tre casi di bartonellosi (malattia da graffio di gatto).

In the last years the number of Bartonella species has conspicuously increased, with better clinical and diagnostic definitions of the different related illnesses. We report, in the present article, 3 cases of cat-scratch disease, a particular bartonellosis mainly caused by Bartonella henselae which is transmitted by the cat. After an incubation period, cat-scratch disease clinically manifests as a regional lymphoadenitis, with the appearance of a small cutaneous lesion at the site of inoculation of the germ. The pathogenetic agent is susceptible to a number of antibacterial agents, such as penicillin, cephalosporins, aminoglycosides, tetracyclines, macrolides, quinolones, trimethoprim combined with sulphamethoxazole and rifampicin. The prognosis is usually favorable.