Persistence of anti-West Nile virus-specific antibodies among asymptomatic blood donors in northeastern Italy.

The development and persistence of anti-West Nile Virus (WNV) immunoglobulin G (IgG)- and IgM-specific antibodies were investigated in 68 asymptomatic blood donors (BDs) previously tested as positive between October, 2008, and September, 2009, and living in northeastern Italy. Our study showed that WNV-specific IgG titers became negative (41%) or decreased (33%) in a large percentage of BDs, while they increased in a smaller percentage (10%); 16% of BDs showed no titer variation. Reversion to seronegative status within a short time frame suggests that WNV surveillance should be maintained year after year.

Seroprevalence of West Nile virus-specific antibodies in a cohort of blood donors in northeastern Italy.

IgG and IgM levels against West Nile virus (WNV) were measured in 20,033 serum samples that were obtained between October 2008 to September 2009 from 9913 blood donors in the district of Ferrara, northeastern Italy. As confirmatory test, a microneutralization assay was used to detect the presence of neutralizing antibodies against WNV. Sixty-eight subjects (0.69%) were positive for anti-WNV by immunofluorescence assay. Large differences in the prevalence of antibodies to WNV were noted between towns in the area evaluated.

Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART.

UNLABELLED: Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4(+) T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks) on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002). Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002), served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4(+) and CD8(+) cellular activation (CD38 and HLA-DR) together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4(+) T cells and B cells with reduction of CD8(+) T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4(+) and CD8(+) T cells were accompanied by increases of CD4(+) and CD8(+) T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes were opposite, absent or partial in the OBS population. These findings support the use of Tat immunization to intensify HAART efficacy and to restore immune homeostasis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00751595.

Absence of neuroinvasive disease in a liver transplant recipient who acquired West Nile virus (WNV) infection from the organ donor and who received WNV antibodies prophylactically.

We describe the first case of West Nile virus (WNV) infection in Europe with transmission from donor to recipient following liver transplantation. The infection was detected in the recipient 3 days after transplantation, during the asymptomatic phase. We also report an innovative prophylactic strategy based on infusion of WNV hyperimmune plasma and gamma globulins that could be effective in preventing the appearance of a neuroinvasive disease.

Self-reported history of Pap-smear in HIV-positive women in Northern Italy: a cross-sectional study.

BACKGROUND: The incidence of invasive cervical cancer in HIV-positive women is higher than in the general population. There is evidence that HIV-positive women do not participate sufficiently in cervical cancer screening in Italy, where cervical cancer is more than 10-fold higher in women with AIDS than in the general population. The aim of the present study was to evaluate the history of Pap-smear in HIV-positive women in Italy in recent years. We also examined the sociodemographic, clinical, and organizational factors associated with adherence to cervical cancer screening. METHODS: A cross-sectional study was conducted between July 2006 and June 2007 in Emilia-Romagna region (Northern Italy). All HIV-positive women who received a follow-up visit in one of the 10 regional infectivology units were invited to participate. History of Pap-smear, including abnormal smears and subsequent treatment, was investigated through a self-administered anonymous questionnaire. The association between lack of Pap-smear in the year preceding the interview and selected characteristics was assessed by means of odds ratios (OR) and 95% confidence intervals adjusted for study centre and age. RESULTS: A total of 1,002 HIV-positive women were interviewed. Nine percent reported no history of Pap-smear, and 39% had no Pap-smear in the year prior to the date of questionnaire (last year). The lack of Pap-smear in the last year was significantly associated with age <35 years (OR = 1.4, compared to age > or =45 years), lower education level (OR = 1.3), first HIV-positive test in the last 2 years (OR = 1.4), and CD4 count <200 cells/microl (OR = 1.6). Conversely, when women were advised by a gynecologist rather than other health workers to undergo screening, it significantly increased adherence. Non-significantly higher proportions of lack of Pap-smear in the last year were found in women born in Central-Eastern Europe (OR = 1.8) and Africa (OR = 1.3). No difference in history of Pap-smear emerged by mode of HIV-acquisition or AIDS status.Three hundred five (34%) women reported a previous abnormal Pap-smear, and of the 178 (58%) referred for treatment, 97% complied. CONCLUSIONS: In recent years the self-reported history of Pap-smear in HIV-positive women, in some public clinics in Italy, is higher than previously reported, but further efforts are required to make sure cervical cancer screening is accessible to all HIV-positive women.

Different patterns of HIV-1 DNA after therapy discontinuation.

BACKGROUND: By persisting in infected cells for a long period of time, proviral HIV-1 DNA can represent an alternative viral marker to RNA viral load during the follow-up of HIV-1 infected individuals. In the present study sequential blood samples of 10 patients under antiretroviral treatment from 1997 with two NRTIs, who refused to continue any antiviral regimen, were analyzed for 16-24 weeks to study the possible relationship between DNA and RNA viral load. METHODS: The amount of proviral DNA was quantified by SYBR green real-time PCR in peripheral blood mononuclear cells from a selected group of ten patients with different levels of plasmatic viremia (RNA viral load). RESULTS: Variable levels of proviral DNA were found without any significant correlation between proviral load and plasma HIV-1 RNA levels. Results obtained showed an increase or a rebound in viral DNA in most patients, suggesting that the absence of therapy reflects an increase and/or a persistence of cells containing viral DNA. CONCLUSION: Even though plasma HIV RNA levels remain the basic parameter to monitor the intensity of viral replication, the results obtained seem to indicate that DNA levels could represent an adjunct prognostic marker in monitoring HIV-1 infected subjects.

Risk of failure in patients with 215 HIV-1 revertants starting their first thymidine analog-containing highly active antiretroviral therapy.

OBJECTIVE: To investigate the impact of 215 HIV-1 revertants on the risk of virological failure of the first thymidine analog-containing highly active antiretroviral therapy (HAART). DESIGN: The study included 491 HIV-1 subjects of the Italian Cohort Naive for Antiretrovirals, 405 of whom received a genotypic assay before therapy and had a virological follow-up. METHODS: Pre-treatment genotypic resistance was assessed by sequencing of the whole protease (PR) and reverse transcriptase (RT) region. RESULTS: Three (3.2%) and 13 (3.3%) individuals with recent (n = 95) and chronic (n = 396) HIV-1 infection carried an HIV-1 strain with 215 revertants (215D/C/E/A/V), respectively. In contrast, nucleoside associated mutations were higher in the former (15.8%) compared with the latter group (6.8%) (P = 0.005). A multivariable regression model, considering pre-HAART viral load levels, use of saquinavir-hard gel as the only PI, use of zidovudine, number of other RT and PR mutations, indicated that patients carrying 215 revertants had an increased risk of virological failure compared with those not carrying such mutants (adjusted relative hazard = 2.97 95% confidence interval, 1.11-7.94, P = 0.03). Among patients with 215 revertants, who experienced virological failure, four out of seven showed the emergence of the 215Y resistant mutation. The probability of 215Y occurrence was different between patients carrying 215 revertants compared with those who did not carried these mutants (P = 0.006). CONCLUSIONS: HIV-1 215 revertants with an increased ability for selecting 215Y mutation are associated with a higher risk of virological failure and may lead to the appearance of virus carrying 215Y/F mutation in vivo. These findings suggest that 215 revertant viruses may compromise the efficacy of the first thymidine analog-containing regimen.

Genotypic resistance tests for the management of patients at simplification of highly active antiretroviral therapy.

Witness for the prosecution: There is a growing interest in exploring simpler protease inhibitor (PI)-sparing regimens that could improve patients' quality of life and adherence, provide relief from adverse events and, at the same time, preserve virological and immunological success. Simplified maintenance studies have used switch regimens with equivalent antiretroviral efficacy to PI-containing highly active antiretroviral therapy (HAART), replacing the PI with non-nucleoside reverse transcriptase inhibitors (NNRTI) such as efavirenz and nevirapine or with a 3 nucleoside-based maintenance regimen. As simplification strategies apply to patients with undetectable viral load, the conventional methods to measure viral resistance on plasma RNA cannot be applied. The only possibility relies on the determination of mutations within the integrated HIV-DNA in peripheral blood mononuclear cells. A careful anamnestic examination is therefore the only tool the caregiver has to direct his choices. In this respect and in our opinion it would be wise not to simplify treatment with abacavir in those patients who underwent a previous suboptimal therapy with lamivudine or thymidine analogues. Witness for the defence: The antiretroviral therapy that includes PI and 2 nucleoside analogue reverse transcriptase inhibitors (NRTI) was the first HAART in HIV infection: this combination results in a reduction of the risk of progression to AIDS and death, but it shows many problems caused by high tablet volume, dietary restrictions, multiple daily dosing and development of toxicity. Simplifying antiretroviral treatment regimens would increase patients' adherence and minimize toxicity.

Emotional stress, psychosocial variables and coping associated with hepatitis C virus and human immunodeficiency virus infections in intravenous drug users.

BACKGROUND: The increasing health problem of hepatitis C virus (HCV) infection has only recently attracted the attention of psychosocial research, especially among subjects at higher risk (e.g. intravenous drug users; IDUs). The aim of the present study was to compare emotional stress symptoms, psychosocial variables (i.e. social support, external locus of control and emotional repression) and coping strategies in HCV-seropositive, human immunodeficiency virus (HIV)-seropositive and HCV/HIV-noninfected IDUs. METHODS: IDUs followed by the Infectious Diseases Outpatient clinic were enrolled in the study over a period of 1 year. HCV-positive (n = 62) and HIV-positive (n = 76) IDUs and HCV/HIV-seronegative IDUs (n = 152) completed the Brief Symptom Inventory, the Social Provision Scale, the Locus of Control scale and the affective inhibition scale of the Illness Behavior Questionnaire. Coping with illness among HCV-positive and HIV-positive subjects was assessed through a modified version of the Mental Adjustment to Cancer Scale. RESULTS: No significant differences were found between the samples with respect to individual and interpersonal variables. HCV-positive subjects showed higher scores on several psychological stress dimensions (i.e. obsessive-compulsive, phobic anxiety, paranoid ideation, psychoticism) and lower scores on fighting spirit, hopelessness and anxious preoccupation towards illness than HIV-positive patients. HCV-positive and HCV/HIV-seronegative IDUs reported comparable scores on most of the psychological measures. CONCLUSIONS: The findings indicate that routine assessment of psychosocial variables and coping mechanisms should be integrated into all HCV and HIV services, especially those dedicated to treatment of patients with substance abuse, as a vulnerable segment of the population at risk for life-threatening physical illness such as HCV and HIV infections.

[Vector-borne diseases. Recent advances in the diagnosis, treatment and prevention]. / Patologie a trasmissione vettoriale.

Vector borne diseases are infections transmitted by arthropods. The vector can mechanically spread the infectious disease or give hospitality to microrganisms for their biological cycle. The etiologic agents of these infections are viruses as yellow fever and Dengue, protozoans as plasmodium of malaria, Leishmania spp., bacteria as Borrelia burgdorferi, Rickettsia spp. or worms as lymphatic filariasis. They are emerging infectious diseases for the epidemiological changes of our national territory (ex. Lyme disease) but especially for the significant increase of the imported forms. Malaria is the more important infection for its clinical management but also for its remote possibility of a further transmission in Italy. In this review are illustrated the recent progresses in the diagnosis, treatment and prevention of the main vector borne infections that the clinical physicians may frequently observe. It is very important to know these diseases because an adequate preparation and continuous updating are necessarily required.