Giustina Vitale

MARKERS OF INFLAMMATION AND INFECTION INFLUENCE THE OUTCOME OF PATIENTS WITH BASELINE ASYMPTOMATIC CAROTID LESIONS: A 5-YEAR FOLLOW UP STUDY

BACKGROUND AND PURPOSE It is still in debate whether the evaluation of markers of infection and inflammation may be of importance for cerebrovascular and cardiovascular prevention, and we aimed to investigate this field in a prospective 5-year clinical follow-up study in patients with early stages of atherosclerosis. METHODS We studied 668 subjects divided in 3 groups according to the results of carotid ultrasound examination: (1) normal subjects, if intima-media thickness (IMT) was <0.9 mm; (2) with IMT, if IMT was between 0.9 and 1.5 mm; and (3) with asymptomatic carotid plaque, if IMT was >1.5 mm. Traditional cardiovascular risk factors were investigated, and laboratory analysis included measurement of plasma lipids, fibrinogen, C-reactive protein, IgG antibodies for helicobacter pylori (HP), cytotoxic HP, cytomegalovirus, and chlamydia pneumoniae. RESULTS Cerebrovascular or cardiovascular events were registered in 18% of patients during the follow-up, and at multivariate analysis we found that the high levels of fibrinogen (P<0.0001) and C-reactive protein (P=0.014), the seropositivity to cytotoxic HP (P=0.001) and chlamydia pneumoniae (P=0.026), the presence of IMT or asymptomatic carotid plaque (P<0.0001), and the total burden of infections (P<0.0001) were the variables predictive of the clinical events. CONCLUSIONS Beyond traditional cardiovascular risk factors, markers of inflammation and infections seem to significantly influence the occurrence of cerebrovascular and cardiovascular events in patients with baseline asymptomatic carotid lesions.

New Insight into Immunity and Immunopathology of Rickettsial Diseases

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecular Rickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene expression. The roles of innate and adaptive immune responses are discussed, and potential new targets for therapies to block host-pathogen interactions and pathogen virulence mechanisms are considered.

Immunopathology of leishmaniasis: an update.

Leishmaniasis represents a severe, increasing, public health problem. The perspective of its control is highly dependent on research progress, on therapeutic manipulations of the immune system, and on vaccine development. There is a correlation between the clinical outcome of Leishmania infection and the cytokine response profile. While a protective immune response against Leishmania has been clearly identified to be related to the influence of a type-1 response and IFN-γ production, the precise role of T helper (TH) 2 cytokines in non-healing infections requires further exploration. IL-4 and IL-13 (TH2 cytokines) can promote disease progression in cutaneous leishmaniasis, whereas IL-4 would appear to enhance protective type-1 responses in visceral leishmaniasis. Thus, the TH1/TH2 paradigm of resistance/susceptibility to intracellular parasites is probably an oversimplification of a more complicated network of regulatory/counter regulatory interactions. Moreover, the presence of antigen specific regulatory T cell subsets may provide an environment that contributes to the balance between TH1 and TH2 cells. Finally, the involvement of CD8+ T cells has been described, but the modality of their function in this kind of infection has not been so far elucidated.

Hypogonadism and Hormone Replacement Therapy on Bone Mass of Adult Women with Thalassemia Major

We studied bone mass and metabolism in 30 adult women (age 28.5 ± 1.3) with thalassemia major (TM) and evaluated whether prolonged hormone replacement therapy (HRT) was able to optimize bone accrual. TM patients had reduced bone mass, increased bone turnover and lower serum gonadotropin and estradiol levels compared with 10 normal women of similar age. A significant correlation was found between bone mass and sex hormone levels. Six TM patients with normal ovarian function had normal bone turnover markers and modestly low bone mass (lumbar spine −1.29 ± 0.31; femoral neck −0.60±0.21; Z-score). The other 24 TM women were hypogonadic and had significantly lower bone mass for age (lumbar spine −2.35 ± 0.2, femoral neck −1.83 ± 0.2) and increased bone turnover relative to eugonadal women. Of the hypogonadal patients, 13 had taken HRT since age 15 ± 1 years, but their bone mass and turnover markers were not different than untreated hypogonadal patients. In conclusion, while hypogonadism negatively affects bone mass acquisition in adult TM women, HRT at the standard replacement doses is not sufficient to secure optimal bone accrual.

A sero-epidemiological survey of asymptomatic cases of boutonneuse fever in western Sicily

963 sera from contacts, persons from various localities, and blood donors were examined with a commercially produced kit for micro-immunofluorescence for the presence of antibodies to Rickettsia conorii. 10.6% of sera were serologically positive. The higher rates of positivity were observed in sera of contacts (19%) and persons from Mussomeli (20%) and Ustica (18.4%), the lower rates in blood donors from Palermo (3.5%). These results support the view that there is an occupational risk factor related to a rural environment.

Presence of Rickettsia conorii subsp. israelensis, the Causative Agent of Israeli Spotted Fever, in Sicily, Italy, Ascertained in a Retrospective Study

ABSTRACT 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.

Leishmaniasis in travelers: a literature review.

Leishmaniasis is a vector-borne protozoan infection whose clinical spectrum ranges from asymptomatic infection to fatal visceral leishmaniasis. Over the last decades, an increase in imported leishmaniasis cases in developed, non-endemic countries, have been pointed-out from a review of the international literature. Among the possible causes are increasing international tourism, influx of immigrants from endemic regions and military operations. The main area for the acquisition of cutaneous leishmaniasis, especially for adventure travelers on long-term trips in highly-endemic forested areas, is represented from South America, whereas popular Mediterranean destinations are emerging as the main areas to acquire visceral variant. Leishmaniasis should be considered in the diagnostic assessment of patients presenting with a compatible clinical syndrome and a history of travel to an endemic area, even if this occurred several months or years before. Adventure travelers, researchers, military personnel, and other groups of travelers likely to be exposed to sand flies in endemic areas, should receive counseling regarding leishmaniasis and appropriate protective measures.

Cryptic Leishmania infantum infection in Italian HIV infected patients

BackgroundVisceral leishmaniasis (VL) is a protozoan diseases caused in Europe by Leishmania (L.) infantum. Asymptomatic Leishmania infection is more frequent than clinically apparent disease. Among HIV infected patients the risk of clinical VL is increased due to immunosuppression, which can reactivate a latent infection. The aims of our study were to assess the prevalence of asymptomatic L. infantum infection in HIV infected patients and to study a possible correlation between Leishmania parasitemia and HIV infection markers.MethodsOne hundred and forty-five HIV infected patients were screened for the presence of anti-Leishmania antibodies and L. infantum DNA in peripheral blood. Statistical analysis was carried out by using a univariate regression analysis.ResultsAntibodies to L. infantum were detected in 1.4% of patients. L. infantum DNA was detected in 16.5% of patients. Significant association for PCR-Leishmania levels with plasma viral load was documented (p = 0.0001).ConclusionIn our area a considerable proportion of HIV infected patients are asymptomatic carriers of L. infantum infection. A relationship between high HIV viral load and high parasitemic burden, possibly related to a higher risk of developing symptomatic disease, is suggested. PCR could be used for periodic screening of HIV patients to individuate those with higher risk of reactivation of L. infantum infection.

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‐γ 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.

Interleukin‐15, as Interferon‐gamma, Induces the Killing of Leishmania infantum in Phorbol‐Myristate‐Acetate‐Activated Macrophages Increasing Interleukin‐12

The potential leishmanicidal activity of interleukin‐15 (IL‐15) was examined while priming with the cytokine phorbol‐myristate‐acetate (PMA)‐activated macrophages and infecting them with Leishmania infantum parasites. The activation of macrophage cultures with IL‐15 determined a significant anti‐leishmanial activity, comparable with that induced by interferon‐gamma (IFN‐γ). The killing of Leishmania in macrophages primed with IL‐15, as well as with IFN‐γ, was followed by an increase in the IL‐12 synthesis. The neutralization of IL‐15 or IFN‐γ, by specific monoclonal antibodies (MoAb) caused a significant reduction in leishmanicidal activity. Furthermore, in PMA‐activated macrophages, the neutralization of IL‐12 production by a specific anti‐IL‐12 MoAb reduced leishmanicidal activity induced by IL‐15 and IFN‐γ. Data indicate that IL‐15 could have a role as an activator of leishmanicidal activity, directly or indirectly, by inducing IL‐12 production.