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Biomedical subjects

E Nicastri

Publications and source records attributed to E Nicastri.

At least 19 recordsLinked to original sources
PubMed2005

HIV infection among low-risk first lifetime testers in Rome, 1990-2000.

BACKGROUND: HIV spread among low-risk populations through heterosexual intercourse is a major public health concern. This study was aimed at describing prevalence and determinants of HIV infection among Italian low-risk subjects seeking their first lifetime HIV test. PATIENTS AND METHODS: Information collected between January 1990 and December 2000 at a major counseling and testing site in Rome, Italy, was analyzed. Multiple logistic regression odds ratios (OR) and 95% confidence intervals (CI) were computed. RESULTS: Among the 14,313 study subjects, 64 (0.4%) were seropositive for HIV infection. HIV seropositivity increased with age (OR = 4.0, 95% CI: 2.1-7.6 for >/= 40 years vs 18-24), and it seemed to be more common among men (OR = 1.6, lower 95% CI:0.9). There was no evidence of temporal variations, whereas motivations for HIV testing were strongly associated with HIV prevalence. Testing for alarming symptoms (OR = 13.8) or for heterosexual intercourse (OR = 11.0) were associated with a more than 10-fold increased HIV risk. CONCLUSION: Our findings are consistent with data from other industrialized countries and they show a strong association between HIV seropositivity and reason for first-time testing. Moreover, they indicate a stable trend of HIV prevalence among low-risk persons in the last decade. Further studies on time trends in low-risk populations would be useful to evaluate current HIV prevention programs.

Adolescent↗
PubMed2005

Hospital preparedness and management of patients affected by viral haemorrhagic fever or smallpox at the Lazzaro Spallanzani Institute, Italy.

The US cases of anthrax in 2001 and the recent severe acute respiratory syndrome outbreak have heightened the need for preparedness and response to naturally emerging and re-emerging infections or deliberately released biological agents. This report describes the response model of the Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (INMI), Rome, Italy for managing patients suspected of or affected by smallpox or viral haemorrhagic fever (VHF) either in the context of an intentional release or natural occurrence. The INMI is Italy's leading hospital in its preparedness and response plan to bioterrorism-related infectious agents. All single and double rooms of INMI are equipped with negative air pressure, sealed doors, high efficiency particulate air (HEPA) filters and a fully-equipped anteroom; moreover, a dedicated high isolation unit with a laboratory next door for the initial diagnostic assays is available for admission of sporadic patients requiring high isolation. For patient transportation, two fully equipped ambulances and two stretcher isolators with a negative pressure section are available. Biomolecular and traditional diagnostic assays are currently performed in the biosafety level 3/4 (BSL 3/4) laboratories. Continuing education and training of hospital staff, consistent application of infection control practices, and availability of adequate personnel protective equipment are additional resources implemented for the care of highly infectious patients and to maintain the readiness of an appropriately trained workforce to handle large scale outbreaks.

Disease Management↗
PubMed2004

Decrease of replicative capacity of HIV isolates after genotypic guided change of therapy.

A longitudinal study of the replication capacity of HIV strains isolated from 18 patients failing highly active antiretroviral therapy (HAART) was undertaken at the time of genotypic guided change of therapy and after 12 months. Patients were divided in two groups according to the response to therapy: immune responders (12 patients with immune recovery defined as having more than 100 CD4 cells compared to baseline value), and failing patients (six patients without immune recovery). At enrollment no significant difference in terms of CD4 cell count and HIV plasma viremia was detected between the two groups. One year after change of therapy, all patients experienced a decrease in the replication capacity of HIV strains. The HIV replication capacity of the failing and of immune-responder patients decreased from 60% (range 14-96%) to 26.4% (range 0.4-74.5) and from 46.8% (range 15-98%) to 3.6% (range 0.1-26.8%), respectively. At month 12, the difference of HIV replication capacity between the two groups reached a statistical significance (P<0.03). After the change of therapy, an increase in the number of drug resistance mutations in the protease gene was detected in both groups with a higher prevalence of M36I mutation in immune responders. The HIV strains of patients failing HAART showed a progressive impaired replication capacity. The degree of the impairment in viral replication correlated with the viro-immunological discordant response to HAART and with the acquisition of new drug resistant mutations in the protease gene. In patients failing HAART, the impaired replication capacity of HIV strains could justify the persistence of an immune recovery.

Adult↗
PubMed2003

Hospital infection control in Italy.

In 1998, the National Health Plan identified the reduction of hospital infection (HI) incidence as a priority. This article reviews the main activities set up in Italy on infection control in the hospital setting. In 1983, the first national prevalence survey reported 6.8% and 7.6% prevalence rates of patients with HI and of HIs, respectively. The high point prevalence found in the intensive care units (ICU) (12.5%), prompted a national incidence study in 1985. This study found an incidence of 29.5 HIs per 100 patients in the ICUs: lower respiratory tract infections (LRTI) were the most common HIs (47.8%), followed by urinary tract infections (UTI) (19.9%) and blood stream infections (BSI) (4.8%). A 1999 survey showed that in 463 Italian hospitals only 40.5% had protocols on the use of disinfectants, 32.3% on sterilization, 30.8% on occupational risk management, 18.3% on isolation measures, 17.7% on hand-washing, 14.3% on antibiotic prophylaxis in surgery, 9.4% on the prevention of surgical site infections and 8.5% on the management of CVC. A national forum to consider surveillance systems using standardized definitions and methodologies is urgently needed.

Bacteremia↗
PubMed2003

Prevalence of nosocomial infections in 15 Italian hospitals: first point prevalance study for the INF-NOS project.

BACKGROUND: The aim of our study was to assess the magnitude of nosocomial infections (NI) in 15 Italian hospitals. PATIENTS AND METHODS: A multicenter point prevalence study of NI was carried out in October 2001 among eight medical, surgical and intensive care units in hospitals with more than 400 beds, after a pilot phase performed in April 2001. RESULTS: Of the 2,165 surveyed patients, 163 had a total of 179 NIs. The global prevalence rate of patients with NI and of NI was respectively 7.5% (95% CI 6.4-8.6) and 8.3% (95% CI 7.1-9.4), ranging from 5.5% (95% CI 4.2-6.8) in medical wards to 34.2% (95% CI 25.7-42.7) in intensive care units (ICUs). The NI prevalence was higher in: hospitals that did not have an infection control committee (ICC) compared to hospitals with an ICC (10.3%, 95% CI 6.4-10.1 versus 7.2, 95% CI 6.0-8.3, p = 0.08); university hospitals compared with non-teaching hospitals (9.4%, 95% CI 4.5-14.2 versus 7.4%, 95% CI 6.3-8.5, p = 0.4) and; hospitals with 1,000 or more beds compared to lower volume hospitals (9.5%, 95% CI 7.3-11.7 versus 6.6%, 95% CI 5.3-7.8, p = 0.02). The most prevalent infections found were lower respiratory tract infections, urinary tract infections and surgical-site infections, representing 38.0%, 20.1% and 12.8%, respectively, of all NI. Among 1,674 patients without any infection, 575 (34.3%) of them had been undergoing antibiotic treatment at the time of the survey. CONCLUSION: The high rate of NI, particularly in ICUs, and the high number of improper procedures emphasize the need to develop clinically-oriented guidelines, tailor active infection control programs and implement an active ICU surveillance system.

Bacteremia↗
PubMed2001

Clearance of human herpesvirus 8 from blood and regression of leukopenia-associated aggressive classic Kaposi's sarcoma during interferon-alpha therapy: a case report.

A human immunodeficiency virus-negative woman with severe classic Kaposi's sarcoma, idiopathic leukopenia, and massive spread of human herpesvirus 8 (HHV-8) in circulating cells showed stable disease remission in response to systemic interferon-alpha treatment that was accompanied by increased CD3(+) and CD4(+) T cell numbers and complete clearance of HHV-8 from the circulation. These results suggest a direct relationship between HHV-8 clearance from blood and regression of Kaposi's sarcoma and are consistent with the in vitro inhibitory effects of interferon-alpha on HHV-8 infection.

Antiviral Agents↗
PubMed2001

Human immunodeficiency virus-1 specific and natural cellular immunity in HIV seronegative subjects with multiple sexual exposures to virus.

The probability of HIV infection by sexual contact, although it varies greatly, appears to be lower than that of infection by other routes of exposure. The aim of this study was to evaluate immunological determinants involved in protection against HIV infection in subjects with multiple and repeated sexual exposures to the virus. Twenty-two subjects were studied for CD8+ cell anti-HIV suppression activity and serum neutralizing activity against the HIV strain of their own partners, beta-chemokine production, and natural killer cell activity. CD8+ cell anti-HIV activity and neutralizing activity of sera were found in 13 (76%) and 12 (70.5%) out of 17 HIV-1 negative subjects, respectively. Six individuals had a relevant immune response against HIV: three subjects with a high CD8+ cell antiviral suppression activity and three individuals with sera neutralizing activity titer >1:10. These last three subjects had the highest beta-chemokine levels, a very prolonged period of multiple sexual intercourse (>6 years) and a seropositive partner with a high viral load. A partial reduction of neutralizing activity titer was observed when pre-incubating the sera with anti-beta-chemokine neutralizing antibodies. A spontaneous natural killer cell activity was suppressed in the majority of HIV-1 negative subjects with sexual exposure in comparison with normal individuals. The protection from sexual HIV transmission appears to be the result of a network of different humoral and cellular factors.

Adult↗
PubMed2001

Failure of stavudine-lamivudine combination therapy in antiretroviral-naive patients with AZT-like HIV-1 resistance mutations.

To analyze the clinical relevance of AZT resistance mutations in AZT-naive patients, 56 HIV-1 seropositive patients treated for 18 months with stavudine/lamivudine (27 patients) or AZT/lamivudine (29 patients) were studied. AZT-like resistance mutations were found in 13 out of 29 (44%) patients treated with AZT/lamivudine and in 11 out of 27 (40%) patients treated with stavudine/lamivudine. No stavudine or multi-drug resistance mutations were detected. After 26 months of treatment more than 60% of patients showed a virological failure. Among 10 patients failing treatment with stavudine/lamivudine, 9 had AZT-like resistance mutations. The phenotypic test, performed on HIV-1 strains isolated from six of these nine patients, showed a resistance to AZT in five isolates and to stavudine in two isolates. The genotypic pattern of the latter two isolates showed the combined mutations M184V plus R211K and L214F. AZT-like resistance mutations in AZT-naive patients seem to correlate with a virological failure during long-term stavudine therapy.

Anti-HIV Agents↗
PubMed2001

Catheter-related bloodstream infections in HIV-infected patients.

Bloodstream infections (BSI) constitute a significant public health problem and represent an important cause of morbidity and mortality in hospitalized patients, with an approximate incidence of one episode per hundred hospital admissions. Studies on BSI in HIV+ patients have identified central venous catheters (CVC) as a risk factor, with an attributable mortality rate of 10-20%. The long-term CVC-related infection risk appeared to be 5 to 10-fold higher with respect to the infection rates among HIV- patients. CVC associated infection rate ranges from 1.3 to 12 infections per 1,000 catheter-days. Staphylococcus aureus is the most common etiologic agent causative of CVC-related BSI, likely the result of the high skin and nasal carriage of this organism among HIV+ patients, mostly intravenous drug users. Coagulase-negative staphylococci are also frequently identified as cause of CVC-related BSI, likely the result of breaches in infection control measures and in antiseptic technique during CVC management. Treating bacteremia without catheter removal would be optimal, but the reported efficacy of systemic antibiotic therapy alone is only 25-32%. Conversely, recent studies have shown that, using an antibiotic-lock procedure, up to 90% of HIV-infected and uninfected patients achieved complete eradication of catheter-related BSIs without catheter removal. Clinical trials using new materials such as covalently linked heparin on the CVC surface, electrically charged CVC, novel topical agents that interfere with bacterial colonization, antiadhesin molecules and agents that block the gene expression involved in the biofilm formation, are all needed to reduce the high catheter-related infection risk among HIV+ patients.

Blood-Borne Pathogens↗
PubMed2001

Correlation between enzyme-linked immunosorbent assay and immunofluorescence assay with lytic antigens for detection of antibodies to human herpesvirus 8.

The purpose of this study was to evaluate, in Kaposi's sarcoma patients, the correlation between antibody titers to the lytic antigens of human herpesvirus 8, as assessed by immunofluorescence assay, and values obtained by an enzyme immunoassay. The methods showed a stringent correlation, r = 0.625 (P<0.001).

AIDS-Related Opportunistic Infections↗
PubMed2001

Neutralizing antibodies against autologous human immunodeficiency virus Type 1 isolates in patients with increasing CD4 cell counts despite incomplete virus suppression during antiretroviral treatment.

Antiretroviral-treated human immunodeficiency virus (HIV) type 1-seropositive individuals can remain clinically stable for a long period of time with an increasing CD4 cell count irrespective of incomplete viral suppression. We evaluated the role of neutralizing antibody (NtAb) activity in the etiopathogenesis of this viro-immunological disconnection (defined as an increasing CD4(+)-cell count despite a persistent, detectable viral load during antiretroviral therapy) in 33 patients failing therapy with two analogue nucleoside reverse transcriptase inhibitors. An HIV NtAb titer of >/=1:25 was detected in specimens from 16 out of 33 (48%) patients. A significant correlation was found between NtAb titers and CD4(+)-cell counts (P = 0.001; r = 0.546) but not with HIV RNA levels in plasma. Five patients with a viro-immunological disconnection had an NtAb titer of >1:125, statistically higher than the NtAb titers for the remaining 28 patients with both virologic and immunologic failure (P < 0.0001). The HIV-specific humoral immune response could play a role during antiretroviral treatment to improve immunological function despite an incomplete suppression of viral load.

Adult↗
PubMed2000

Cellular proviral HIV-DNA decline and viral isolation in naïve subjects with <5000 copies/ml of HIV-RNA and >500 x 10(6)/l CD4 cells treated with highly active antiretroviral therapy.

OBJECTIVE: To evaluate the decay rate of cellular proviral HIV-DNA and viral replication in patients receiving highly active antiretroviral therapy (HAART) in the very early phase of infection. METHODS: Thirty-four patients treated with HAART and retrospectively selected for progressive decline of plasma viraemia up to undetectable levels (< 20 copies/ml), were stratified according to CD4+ cell count and plasma viraemia at base line: > 500 x 10(6) cells/l with < 5000 copies/ml (group 1) or with > 5000 copies/ml (group 2), > 5000 copies/ml with 300-500 x 10(6) cells/l (group 3) or with < 300 x 10(6) cells/l (group 4). Plasma HIV-RNA and proviral HIV-DNA were analysed at baseline and after 1, 2, 3, 6, 9 and 12 months of treatment. RESULTS: After 1 year of treatment, a significant decrease of proviral DNA titre was observed in all patients and a decrease > 1 log was achieved in 24 of 29 subjects of the first three groups. The more pronounced decay of HIV-DNA (half-life 28 weeks) up to < 50 HIV-DNA copies/10(6) CD4+ cells was detected in patients of group 1. At the year's endpoint, five patients (four in group 1 and one in group 2) had < 20 HIV-DNA copies. However, HIV strains sensitive to antiretroviral drugs were isolated from peripheral lymphocytes of 16 out of 34 patients. CONCLUSION: In patients with undetectable plasma viraemia after 1 year of HAART, the highest reduction of proviral DNA up to < 50 copies/10(6) CD4+ cells was obtained only in subjects in the early asymptomatic phase of infection. Nevertheless, a replication-competent virus can be detected in all phases of antiretroviral therapy.

Adult↗
PubMed1999

Does HHV-8 have a protective role on the development of HIV encephalopathy? Italian HIV-Seroconversion Study.

OBJECTIVE: To evaluate risk factors for HIV encephalopathy and whether Kaposi's sarcoma (KS) and coinfection with human herpesvirus 8 (HHV-8) protect against this disease in a cohort of HIV seroconverters. METHODS: Individuals with known dates of HIV seroconversion belonging to different HIV exposure categories (intravenous drug users, homosexual men, heterosexual contacts) were recruited by 17 clinical centers throughout Italy. Antibodies to HHV-8 lytic antigens were detected in a subgroup of participants using an immunofluorescence assay. Risk factors for HIV encephalopathy were evaluated using Cox proportional models. The association between KS or HHV-8 infection and HIV encephalopathy was evaluated using standard statistical techniques. RESULTS: During the study period, 485 of the 1,520 participants developed acquired immunodeficiency syndrome, 38 of whom developed HIV encephalopathy. HHV-8 serologic status was determined for 390 participants. Male gender, injecting drug use, and low CD4 T-cell count were associated with HIV encephalopathy; none of the 63 participants with KS developed this disease. The risk of HIV encephalopathy did not differ significantly by HHV-8 serologic status. CONCLUSIONS: HIV encephalopathy was found to be associated with male gender and intravenous drug use. The risk increased at lower CD4 T-cell counts. Although HIV encephalopathy occurred less frequently in patients with KS, no association with HHV-8 infection was found.

AIDS Dementia Complex↗
PubMed1999

Human herpesvirus 8 seropositivity and risk of Kaposi's sarcoma and other acquired immunodeficiency syndrome-related diseases.

BACKGROUND: The incidence of Kaposi's sarcoma (KS) is increased severalfold in individuals infected with human immunodeficiency virus-1 (HIV). Human herpesvirus 8 (HHV8) has also been implicated in KS. We investigated several factors that may determine the onset of KS, particularly HHV8 infection in individuals after becoming seropositive for HIV. METHODS: We studied 366 individuals belonging to different HIV-exposure categories (i.e., homosexual activity, intravenous drug use, and heterosexual contact) for whom a negative HIV serologic test and then a positive HIV serologic test were available within a 2-year period. HHV8 antibody testing was performed by use of an immunofluorescence assay on the first serum sample available after the first positive HIV test. Actuarial rates of progression of KS and of other acquired immunodeficiency syndrome (AIDS)-defining diseases were estimated by use of time-to-event statistical methods. All statistical tests were two-sided. RESULTS: Twenty-one of the 366 study participants developed AIDS-related KS, and 83 developed AIDS without KS. One hundred forty (38.3%) participants had detectable anti-HHV8 antibodies. The actuarial progression rate to KS among persons co-infected with HIV/HHV8 was nearly 30% by 10 years after HIV seroconversion. Increasing HHV8 antibody titers increased the risk of developing KS (for seronegative versus highest titer [1:125 serum dilution], adjusted relative hazard [RH] = 51.82; 95% confidence interval [CI] = 6.08-441.33) but not of other AIDS-defining diseases (adjusted RH = 1.14; 95% CI = 0.72-1.80). HHV8-seropositive homosexual men compared with HHV8-seropositive participants from other HIV-exposure categories showed an increased risk of KS that approached statistical significance (adjusted RH = 6.93; 95% CI = 0.88-54.84). CONCLUSIONS: Approximately one third of individuals co-infected with HIV/HHV8 developed KS within 10 years after HIV seroconversion. Progression to KS increased with time after HIV seroconversion. Higher antibody titers to HHV8 appear to be related to faster progression to KS but not to other AIDS-defining diseases.

AIDS-Related Opportunistic Infections↗