State of the art: Vest Nile Virus circulation surveillance in Italy and transfusion risk early prevention methods.

After the Chikungunya outbreak in 2007 in Italy, a national Plan for the surveillance of human vector-borne diseases has been implemented and annually updated on the basis of the epidemiological changes based-evidences. The transfusion Authorities cooperates, since 2008, with public health services and veterinary (entomological and ornithological) surveillance systems. In some Italian regions, a common protocol for exchanging data is in place to identify the West Nile Virus (WNV) circulation in birds and mosquitoes: the goal is to anticipate the introduction of WNV-NAT screening in blood donors and, on the other hand, to limit testing only in geographic areas where the virus circulation is actual. The integration of surveillance activities and a multidisciplinary approach made it possible to introduce efficient and preventive measures for reducing the risk of of transmission of WNV trough blood, tissues and organ donation.

The experience of West Nile virus integrated surveillance system in the Emilia-Romagna region: five years of implementation, Italy, 2009 to 2013.

Predicting West Nile virus (WNV) circulation and the risk of WNV epidemics is difficult due to complex interactions of multiple factors involved. Surveillance systems that timely detect virus activity in targeted areas, and allow evidence-based risk assessments may therefore be necessary. Since 2009, a system integrating environmental (mosquitoes and birds) and human surveillance has been implemented and progressively improved in the Emilia-Romagna region, Italy. The objective is to increase knowledge of WNV circulation and to reduce the probability of virus transmission via blood, tissue and organ donation. As of 2013, the system has shown highly satisfactory results in terms of early detection capacity (the environmental surveillance component allowed detection of WNV circulation 3­4 weeks before human cases of West Nile neuroinvasive disease (WNND) occurred), sensitivity (capacity to detect virus circulation even at the enzootic level) and area specificity (capacity to indicate the spatial distribution of the risk for WNND). Strong correlations were observed between the vector index values and the number of human WNND cases registered at the province level. Taking into consideration two scenarios of surveillance, the first with environmental surveillance and the second without, the total costs for the period from 2009 to 2013 were reduced when environmental surveillance was considered (EUR 2.093 million for the first scenario vs EUR 2.560 million for the second). Environmental surveillance helped to reduce costs by enabling a more targeted blood unit testing strategy. The inclusion of environmental surveillance also increased the efficiency of detecting infected blood units and further allowed evidence-based adoption of preventative public health measures.

Impact of nucleic acid amplification technology (NAT) in Italy in the three years following implementation (2001-2003).

The use of NAT technology to screen blood donations in Italy became mandatory on 28 June 2002, but had been available experimentally since 2001. During the transition period, an EIA test to detect hepatitis C core antigen (HCVcoreAg) had also been permitted. Considering the large number of blood transfusion centres in Italy, an initial reorganisation of the biological validation of blood units was necessary, with a partial centralisation of NAT testing. The Gruppo Italiano per lo Studio delle Malattie Trasmissibili con la Trasfusione (Italian Group for the Study of Transfusion-Transmissible Diseases) conducted a national survey evaluating NAT testing, based on an annual collection of data through a questionnaire sent to all centres. In the first three years of the investigation, 219 blood transfusion centres returned the questionnaires. In the period between January 2001 and December 2003, 3,894,894 blood donations were investigated for HCV RNA and 2,186,468 for HIV RNA. Of these, 12 were found to be HCV RNA positive and four HIV RNA positive, with an observed NAT versus antibody-based assay yield of 3.1/106 donations for HCV and 1.8/106 donations for HIV, respectively. Five of the 12 HCV RNA positive and anti-HCV negative donors had abnormal ALT values and their donations would have been discarded even in absence of NAT testing. Thus the final NAT yield for HCV is 1.79/106. The residual risk for HCV or HIV transmission by blood transfusion after NAT implementation is currently estimated to be extremely low in Italy.

Impact of nucleic acid amplification technology (NAT) in Italy in the three years following implementation (2001-2003).

The use of NAT technology to screen blood donations in Italy became mandatory on 28 June 2002, but had been available experimentally since 2001. During the transition period, an EIA test to detect hepatitis C core antigen (HCVcoreAg) had also been permitted. Considering the large number of blood transfusion centres in Italy, an initial reorganisation of the biological validation of blood units was necessary, with a partial centralisation of NAT testing. The Gruppo Italiano per lo Studio delle Malattie Trasmissibili con la Trasfusione (Italian Group for the Study of Transfusion-Transmissible Diseases) conducted a national survey evaluating NAT testing, based on an annual collection of data through a questionnaire sent to all centres. In the first three years of the investigation, 219 blood transfusion centres returned the questionnaires. In the period between January 2001 and December 2003, 3 894 894 blood donations were investigated for HCV RNA and 2 186 468 for HIV RNA. Of these, 12 were found to be HCV RNA positive and four HIV RNA positive, with an observed NAT versus antibody-based assay yield of 3.1/106 donations for HCV and 1.8/106 donations for HIV, respectively. Five of the 12 HCV RNA positive and anti-HCV negative donors had abnormal ALT values and their donations would have been discarded even in absence of NAT testing. Thus the final NAT yield for HCV is 1.79/106. The residual risk for HCV or HIV transmission by blood transfusion after NAT implementation is currently estimated to be extremely low in Italy.

Cytokines and soluble receptor changes in the transition from primary to early chronic HIV type 1 infection.

We studied determinants of chronic inflammation and/or immune activation in plasma from patients in the transition from primary to early chronic HIV-1 infection. The following parameters were estimated in seven patients over time: plasma concentrations of soluble CD8 (sCD8), tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor type II (sTNFRII), interleukin 6 (IL-6), soluble IL-6 receptor (sIL6R), IL-10, transforming growth factor beta1 (TGF-beta1), along with CD4- and CD8-positive T cell counts, p24 antigenemia, and clinical evaluation. Results showed that concentrations of sCD8, TNF-alpha, and sTNFRII, and peripheral CD8-positive lymphocyte counts, were significantly increased in patients, compared to HIV-negative controls, and showed a trend toward normal values over time. Levels of IL6, sIL6R, IL-10, and TGF-beta1 did not differ from those of controls and did not change over time. Heterogeneity was observed among the patients in terms of CD4-positive T cell depletion, levels of sCD8, concentrations of TNF-alpha/sTNFRII, and clinical outcome. These data indicate that in the transition phase from primary acute to chronic and asymptomatic infection the host immune activation in response to the virus is highly heterogeneous and that the sustained rise in TNF-alpha and its receptor may represent an important therapeutic target in early disease. The persistence of a state of chronic inflammation and/or immune activation could influence the progression of disease independently from CD4-positive T cell counts.

Detection of prognostic factors for oral allergy syndrome in patients with birch pollen hypersensitivity.

To determine why a significant proportion of birch pollen-sensitive patients do not have the oral allergy syndrome (OAS), possible predictive in vivo or in vitro tests for OAS were sought in a large retrospective and prospective follow-up study performed in 283 patients with clinical evidence of birch pollen hypersensitivity. OAS was associated with more severe respiratory symptoms and with higher birch-specific and total IgE levels; moreover, its onset was clearly related to duration of birch pollinosis. The prospective part of this study, performed in 63 patients without OAS, confirmed these findings and highlighted the very high negative predictive value of both skin prick tests with fresh foods and RAST with food allergens. This work suggests that about 15% of patients with birch pollen hypersensitivity are not prone to OAS and that their anti-birch IgE might be directed against determinants that do not crossreact with food allergens.

In vitro production of type 1 and type 2 cytokines by peripheral blood mononuclear cells from high-risk HIV-negative intravenous drug users.

OBJECTIVE: To study type 1 and type 2 cytokine patterns in HIV-negative high-risk intravenous drug users (IVDU). DESIGN: We investigated interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-6 and IL-10 production by phytohaemagglutinin (PHA)-stimulated and unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV-negative high-risk IVDU, HIV-negative controls and HIV-positive subjects. METHODS: Cytokine production was measured in supernatants using enzyme-linked immunosorbent assay (ELISA) in 10 HIV-negative high-risk IVDU, 25 HIV-negative controls, and 12 HIV-positive IVDU. We also determined spontaneous in vitro immunoglobulin (Ig) G and IgM production. RESULTS: HIV-negative high-risk IVDU showed increased IFN-gamma and decreased IL-4, IL-10 and IL-2, although the latter was not significant compared with HIV-negative controls. Further, HIV-negative high-risk IVDU had reduced IgG production and impaired IgM-IgG switch. CONCLUSIONS: The reduced IL-2 and IL-4 production suggest an impaired CD4+ T-cell function in HIV-negative high-risk IVDU. The increased IFN-gamma production along with the decreased type 2 cytokine profile is consistent with the hypothesis that protective immunity against HIV may reside in type 1 responses and cell-mediated immunity.

Modeling incidence rate ratio and rate difference: additivity or multiplicativity of human immunodeficiency virus parenteral and sexual transmission among intravenous drug users. Northern Italy Seronegative Drug Addicts Study.

The analysis concerns data from the Northern Italian Seronegative Drug Addicts Study, a multicenter longitudinal study about the incidence of human immunodeficiency virus infection in intravenous drug users from Milan and other areas of northern Italy between 1987 and 1991. Different measures of parenteral and heterosexual exposure effects were estimated by fitting multiplicative models for rate ratio and additive models for both rate ratio and rate difference into a Poisson regression model for grouped cohort data. In areas of high human immunodeficiency virus prevalence among intravenous drug users, the adjusted rate ratio under a multiplicative structure was 6.2 (95% likelihood-based confidence interval (LCI) 2.9-14.4) for parenteral and 2.9 (95% LCI 1.3-6.1) for sexual transmission. Under the additive model, the rate ratio was 7.8 (95% LCI 3.4-20.2) for parenteral and 9.2 (95% LCI 2.2-29.7) for sexual transmission, and the rate difference per 100 person-years was 9.8 (95% LCI 5.3-15.6) for parenteral and 10.5 (95% LCI 1.8-24.2) for sexual transmission (controlled for each other). Because of the small sample size, a clear discrimination between models could not be reached. However, in spite of the greater risk associated with parenteral transmission under a multiplicative model, the additive model suggests that the relative impact of measures aimed at inducing condom use is similar to that which would be obtained by measures aimed at stopping syringe sharing.

Estimation of cardiovascular risk: total cholesterol versus lipoprotein profile.

The complete lipoprotein profile is thought to give more information about the individual risk of coronary heart disease than total cholesterol alone. Although total cholesterol has a low sensitivity in the correct assessment of the risk of coronary heart disease, it may be of value in screening programs because of its low cost. In this study of 5,335 subjects, total cholesterol gave a different assessment of coronary heart disease risk (United States National Cholesterol Education Program guidelines) in 25% of subjects than the complete lipoprotein profile. Differences in risk assignment were mainly accounted for by high- and low-density lipoprotein-cholesterol (Friedewald equation). The calculated low-density lipoprotein-cholesterol was highly correlated with the value measured with a mixed ultracentrifugation and precipitation procedure. However, calculated values gave estimates of coronary heart disease risk which were 20% different from those from measure values. In 200 subjects in whom the lipoprotein profile was assessed three times in 1 year, the total cholesterol low-density lipoprotein-cholesterol varied by more than 30 mg/dl (0.78 mmol/l) in 52% and 50%, respectively, triglycerides by more than 30 mg/dl (0.34 mmol/l) in 75%, and high-density lipoprotein-cholesterol by more than 15 mg/dl (0.39 mmol/l) in 34%. Compared with the mean of the measurements, the single measurement of total cholesterol misclassified 48% of subjects, low-density lipoprotein-cholesterol 60%, high-density lipoprotein-cholesterol 12%, and 28%. We conclude that total cholesterol alone may be misleading in the assignment of coronary heart disease risk. Calculation of low-density lipoprotein-cholesterol, although less accurate than desirable, is the only way of evaluating this in clinical practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of idiopathic hemochromatosis in Italy: study of 1301 blood donors.

Idiopathic hemochromatosis (IH) was considered a rare hereditary disease until population studies in the U.S.A. and Northern Europe indicated an unexpectedly high frequency. In this study we estimated the prevalence of IH in Italy by testing 1301 presumably healthy blood donors. Transferrin saturation (TS) and serum ferritin (SF) levels were used as screening methods. The subjects with TS greater than 50% and/or SF greater than 300 micrograms/l in men and greater than 160 micrograms/l in women were given a complete medical and laboratory examination and those with evidence of iron overload were asked to undergo liver biopsy. Five male donors but no female donors presented increased iron indexes. Diagnosis of homozygous IH in two of them was confirmed by liver biopsy, indicating a prevalence of the disease in this population of 0.2%; that is a gene frequency of 4.5% and a heterozygote frequency of 9%. Since our study might underestimate the true prevalence of the disease because blood donors are at high risk of iron depletion, IH could be one of the most frequent hereditary diseases in Italy. Large-scale screening of young adults based on TS and SF determinations should be proposed for early diagnosis and treatment.

Alpha thalassaemia in an Italian population.

The incidence of alpha-thalassaemia in an Italian population has been determined by a survey of random cord bloods for the presence of Hb Bart's. 144 out of 4730 (3%) had detectable amounts of Hb Bart's. Furthermore, alpha-globin gene analysis of 100 random cord bloods showed that five out of 100 had the common type of alpha-thalassaemia caused by a single alpha-globin gene deletion (-alpha). The molecular basis of alpha-thalassaemia was also determined in a selected group of 34 newborns with detectable levels of Hb Bart's. 25 of these cases had the -alpha 3.7 deletion type of alpha-thalassaemia and nine had nondeletion types of alpha-thalassaemia in four of which the molecular defect was detectable directly by restriction enzyme analysis.

[Plasmodium falciparum malaria transmitted through human contact in a group of drug addicts]. / Malaria da Plasmodium falciparum trasmessa per contagio interumano in un gruppo di tossicomani.

The Authors describe a case of malaria from P. falciparum occurred in a group of young drug-addicts. Noteworthy is the fact that such a way of transmission did never occur before in Italy. Current concepts in treatment of malaria are briefly reviewed.