Biomedical subjects

E Nicastri

Publications and source records attributed to E Nicastri.

29 records · Page 2Linked to original sources

PubMed1999

Reduction of IFN-gamma and IL-2 production by peripheral lymphocytes of HIV-exposed seronegative subjects.

OBJECTIVES: In order to evaluate the role played by cytokine profile as a co-factor involved in the resistance to HIV infection in couples serodiscordant for HIV, we studied HIV-seronegative subjects with multiple unprotected sexual exposures. DESIGN AND METHODS: Twenty-one HIV-exposed seronegative subjects (HEPS), their 21 HIV-seropositive partners and 10 HIV-seronegative unexposed individuals were studied for T helper (Th) types 1-2 cell pattern and CCR5 receptor. RESULTS: Twelve out of 21 HIV-seropositive partners of HEPS showed a CD4 cell count below 200 lymphocytes/microl. HIV strains were isolated from peripheral blood mononuclear cells (PBMC) in 17 patients (81%): seven subjects with syncytium-inducing strains and 10 with non-syncytium-inducing isolates. Low Th1 cytokine production and high levels of IL-4 were detected in HIV-seropositive subjects. A significant reduction of IL-2 and IFN-gamma expression in the CD4 and CD8 cells of HEPS was found compared with HIV-seronegative unexposed individuals. Similar levels of low IL-4 were present in both HEPS and controls. The partial deletion of a single allele (wild type/delta32) of CCR5 was found in only one HEPS. CONCLUSION: The downregulated Th1 profile we observed in HEPS could be related to a cellular anergy state with a protective role in the transmission rate of HIV. Low levels of IL-2 and IFN-gamma could be involved in a low-grade activation state of CD4 lymphocytes. A decrease of IFN-gamma levels could render macrophage cells incapable of antigen presentation, thus resulting in a reduction of the cell-to-cell spread of infection.

CD4-Positive T-Lymphocytes↗

PubMed1999

High seroprevalence of antibodies to human herpesvirus-8 in Egyptian children: evidence of nonsexual transmission.

BACKGROUND: In western countries, human herpesvirus-8 (HHV-8) appears to be transmitted mainly by sexual contact. To evaluate the role of other transmission routes, especially in developing countries, we estimated the seroprevalence of HHV-8 in Egyptian children, who, if seropositive, would have acquired the virus through a nonsexual route. METHODS: Sera from 196 children (<1-12 years of age), 20 adolescents (13-20 years of age), and 30 young adults (21-25 years of age) attending a vaccination program in Alexandria, Egypt, were studied. Immunofluorescence assays were used to detect antibodies against HHV-8 lytic-phase antigens (anti-lytic) and latent-phase antigens (anti-latent). Antibodies against Epstein-Barr virus viral cap antigen, cytomegalovirus, and HHV-6 were detected by enzyme-linked immunosorbent assays. Seroprevalence of these herpesviruses was calculated after stratifying the subjects by age. RESULTS: Anti-lytic and anti-latent HHV-8 antibodies were detected in 44.7% and 8.5% of the study participants, respectively. The prevalence of anti-lytic antibodies tended to increase with age, exceeding 50% in children older than 6 years; once children reached the age of 10 years, the prevalence tended to stabilize. The seroprevalence of other herpesviruses tended to be higher than that of HHV-8, ranging from approximately 83% to more than 97% in the 9- to 12-year age group. One- to 3-year-old children had higher titers of antilytic HHV-8 antibodies than children in the other age groups. Anti-latent antibodies were more frequently detected in individuals with high anti-lytic antibody titers. CONCLUSIONS: HHV-8 antibodies are highly prevalent in Egyptian children, suggesting that, in developing countries, HHV-8 infection may be acquired early in life through routes other than sexual transmission. The lower seroprevalence of HHV-8 relative to that of the other herpesviruses suggests that HHV-8 is less transmissible than other common herpesviruses.

Adolescent↗

PubMed1999

Serum IgG antibodies to human herpesvirus-6 (HHV-6) do not predict the progression of HIV disease to AIDS. Italian Seroconversion Study group.

OBJECTIVES: To evaluate if different levels of human herpesvirus 6 (HHV-6) antibodies can predict HIV disease progression. DESIGN: Longitudinal study of individuals with a documented date of HIV seroconversion. SETTING: Clinical centers located throughout Italy. PATIENTS: Individuals who serconverted for HIV between 1983 and 1995 in Italy. METHODS: Sera were tested for IgG antibodies to HHV-6 using a commercial enzyme immunoassay. A serum sample with an optical density (OD) > or =242 (i.e. the mean value of 10 negative controls +4x standard deviation) was considered as HHV-6 positive; the progression of HIV disease was evaluated estimating the relative hazards (RH) of AIDS (by Cox models) for individuals with higher levels vs. lower levels of HHV-6 antibodies or considering levels of antibodies based on 10% increase of the distribution (deciles). Rates of CD4 decline fitting linear regression were also estimated. RESULTS: A total of 381 persons were followed for a median time of 4 years (range: 0.15-9 years) following the date of collection of the serum sample. The median OD value of HHV-6 antibodies was 306, with an interquartile range of 241-440 and a range of 48-2330. A slight inverse correlation was found between HHV-6 antibody levels and age of the individual at the time of serum collection (Spearman rank correlation coefficient, -0.16; p = 0.0013). No association was found between HHV-6 and CD4 level or between HHV-6 and CD8 level at the date of serum collection. The unadjusted RH of progression to AIDS was 0.63 (95% CI: 0.42-0.96) for HHV-6 positive individuals vs. HHV-6 negative; when adjusting for possible confounders (CD4, age, pre-AIDS HIV-related pathologies at the date of sera collection, and previous anti-herpes treatment), the RH of AIDS increased to 0.80 (95% CI: 0.51-1.23). No particular association with HIV disease progression was found when using the deciles of the distribution of HHV-6 antibodies. The median CD4 cell loss was 5.0x10(6) cells/l per month among HHV-6 positive individuals and 5.7x10(6) cells/l per month among the others. CONCLUSIONS: The presence of high levels of HHV-6 antibodies does not seem to predict the clinical or immunologic progression of HIV disease.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Saquinavir delays the emergence of zidovudine resistance in HIV-1 seropositive patients treated with combination therapy.

During a randomized double-blind study to assess the antiviral activity of saquinavir (SQV) alone or in combination with zidovudine (ZDV), the emergence of phenotypic resistance was evaluated in 44 patients treated with SQV (13 subjects), ZDV (14 subjects), and SQV plus ZDV (17 subjects). A significant (P< 0.05) lower CD4+ cell count and higher HIV RNA copy number at entry were found in six patients who developed resistant viral strain (3 to ZDV and 3 to SQV) during the first 4 months of treatment. After 1 year, drug-resistant strains (12 to ZDV and 14 to SQV) were isolated in 26 out of 37 patients. A significant higher number of patients treated with ZDV alone (10/13) harbored ZDV-resistant strains compared to patients treated by combination therapy (2/13); whereas more than 50% of patients had SQV-resistant strains aside from treatment. Early SQV-resistant strains were isolated in a limited number of patients treated with SQV alone (3/13). The rates of emergence of resistant strains during ZDV or SQV monotherapies are comparable. Combination therapy may delay the emergence of phenotypic resistance to either drugs in the short term and to ZDV, but not to SQV, at least after 1 year.

Anti-HIV Agents↗

PubMed1997

Correlation between changes in plasma HIV RNA levels and in plasma infectivity in response to antiretroviral therapy.

We evaluated the degree of correlation between the variation of different HIV-1 viral load measures in response to antiretroviral therapy. A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for plasma HIV-RNA, and HIV plasma infectivity titration, were performed on prospective samples obtained from 86 antiretroviral-naive patients with symptomatic infection and CD4+ < 300/mm3, enrolled in a randomized double-blind trial of the HIV protease inhibitor saquinavir (SQV) in combination with zidovudine (ZDV). Subjects were stratified according to plasma virus infectivity and examined for correlations between distinct response categories with respect to CD4 count and HIV RNA copy number changes. Infectious virus could be titrated in 72% of patients at baseline. A significant reduction (< 1 log10) in HIV plasma infectivity titer was observed during the study in 69% of these patients. The reduction in plasma infectivity was a good predictor of sustained CD4+ cell increases and of sustained decrease in HIV RNA plasma copies. A decrease of at least 0.5 log10 in HIV RNA copy number was observed in 82% of the treated patients. A good correlation was found between HIV plasma infectivity titer and plasma HIV RNA copy number variations (p < 0.001). However, 10 of 17 patients with unchanged plasma infectivity titer showed a significant reduction in HIV RNA copies. While a good correlation was found between plasma infectivity and RNA plasma copies variations, only a minor correlation was found between CD4+ cell count variation and plasma infectivity titer variation. However, reduction in plasma infectivity was a very good predictor of high CD4 changes.

Anti-HIV Agents↗

PubMed1997

HIV phenotype switching during antiretroviral therapy: emergence of saquinavir-resistant strains with less cytopathogenicity.

OBJECTIVES: The aim of the study was to investigate changes in virological characteristics of HIV strains isolated from 38 HIV-seropositive subjects during antiretroviral therapy. DESIGN AND METHODS: Patients with a CD4+ cell count < or = 300 x 10(6)/l were treated with zidovudine (12 individuals) and saquinavir (10 individuals) alone or in combination (16 individuals). CD4+ cell count, viral load, HIV biological phenotype and drug resistance were evaluated during the study period. RESULTS: After 52 weeks, 28 subjects (74%) harboured drug-resistant strains. In patients with a syncytium-inducing (SI) strain, a decline of CD4+ cell count and an increase of viral load were observed aside from the emergence of drug resistance. Conversely, at the emergence of antiretroviral resistance, an immunological and virological deterioration was observed only in patients who had a non-syncytium-inducing (NSI) strain. During the study, a phenotype switching of HIV isolates was detected in eight (21%) patients and a temporal correspondence between the appearance of phenotype switching and the emergence of drug resistance was found in seven cases. Three patients harbouring saquinavir-resistant strains showed a switch from SI to NSI variants associated with a moderate increase in CD4+ cell count. CONCLUSIONS: The emergence of resistant strains during antiretroviral therapy may be associated with the selection of viral strains with less cytopathogenicity, while it could become a poor prognostic sign in patients with NSI isolates.

Anti-HIV Agents↗

PubMed1997

Increase in neutralizing antibody titer against sequential autologous HIV-1 isolates after 16 weeks saquinavir (Invirase) treatment.

The humoral immune response to HIV infection plays an important role in determining disease progression. Few and discordant results correlate changes in neutralizing antibody (NtAb) titer with antiretroviral treatment. The NtAb titer against autologous-HIV was evaluated in 33 patients treated with the protease inhibitor saquinavir (SQV, Invirase) and zidovudine (ZDV) alone or in combination. Ten out of 33 (30%) patients showed a significant increase (4-fold or greater) in NtAb titer from baseline in response to the initiation of therapy. A significant correlation (P = 0.007) was found between an increase in NtAb titer and treatment with SQV alone (5 subjects) or in combination (5 subjects). A significant decrease in NtAb titer was detected in 7 patients, 5 of whom were treated with ZDV alone. After one year of therapy a significant decrease in HIV-RNA copy number (> 0.5 log) with respect to baseline value was detected only in patients treated with SQV alone or in combination. Patients with increased NtAb titer showed a significantly reduced HIV-RNA copy number and increased CD4+ cell count at week 16 of treatment which were sustained up to week 52. These data suggest that treatment with SQV can improve neutralizing activity against autologous virus as well as bring about a significant and sustained reduction in viral load.

Anti-HIV Agents↗

PubMed1993

Antimicrobial susceptibilities of enterococci isolated from hospitalized patients.

One hundred and one isolates of Enterococcus species isolated recently from hospitalized patients were evaluated in vitro for antibiotic susceptibility. Teicoplanin and mideplanin were the most active agents, followed by ramoplanin, vancomycin, ciprofloxacin, ampicillin, and imipenem. High-level resistance to gentamicin (MIC > 500 micrograms/ml) and/or streptomycin (MIC > 2,000 micrograms/ml) was found in 60 isolates. High-level resistance to ampicillin (MIC > or = 16 micrograms/ml) was found in 17 isolates. MBC studies revealed that ramoplanin possesses significant bactericidal activity.

Anti-Bacterial Agents↗

PubMed1992

High-level aminoglycoside resistance among enterococci: evaluation of an agar screen susceptibility test.

Seventy-five enterococci from infected (63 isolates) and colonized (12 isolates) patients hospitalized in various divisions of the Policlinico Umberto I, University of Rome, were in vitro studied for high-level resistance (HLR) to gentamicin (HLRG) and streptomycin (HLRS) with adoption of a standard broth dilution and an agar screen test. The employed procedures provided equal results for 100% of the 75 isolates. Of these, 21 (28%) showed HLRG and 43 (57%) HLRS. Combined HLRG and HLRS were found in 18 (24%) isolates, whereas HLRS or HLRG alone were found in 25 (33%) and 3 (4%) isolates respectively. It is concluded that HLR to aminoglycosides may represent a major problem in Italian institutions. Along with other established procedures, the agar screen test employed in the study may be used to detect this antibiotic resistance in enterococci.

Drug Resistance, Microbial↗

PubMedDate not supplied

Five human immunodeficiency virus type 1 phenotypic variants with different MT-2 cell tropisms correlate with prognostic markers of disease.

OBJECTIVES: We correlated virologic and immunologic parameters of disease progression with cytopathogenicity of HIV isolates. STUDY DESIGN/METHODS: Human immunodeficiency virus type 1 (HIV-1) isolates from 207 patients with CD4+ cell counts < 500/mm3 were examined for biologic phenotype in MT-2 cells. We used a cross-sectional study design. RESULTS: Three subtypes of syncytium-inducing (SI) strains with different times of appearance of syncytia formation in cell culture and two subtypes of non-syncytium-inducing (NSI) isolates, with (NSI/MT2+) or without (NSI/MT2-) replicative capacity in MT-2 cells, were identified. Early SI strains were associated with the lowest CD4+ cell counts and the highest levels of viral load, and NSI/MT2- isolates correlated with the highest CD4+ cell counts and the lowest viral loads. Patients with late SI and NSI/MT2+ strains showed minimal differences in immunologic and virologic markers. CONCLUSIONS: Five HIV phenotypic variants that correlate significantly (P < 0.001) with markers of disease progression were identified.

CD4 Lymphocyte Count↗

PubMedDate not supplied

Determinants of emerging and re-emerging infectious diseases.

In the 1960s and 1970s, many public health experts assumed that infectious diseases could at long last be conquered as had occurred with smallpox. In the last two decades, reports warned that infectious diseases were clearly not a problem of the past. They could not be considered as a unique or isolated event of wild and faraway regions, but penetrated every corner of the globe. Emerging infectious diseases have been recently described as clinically distinct conditions whose incidence in humans has increased regionally or worldwide within the past two decades. Emergence may be due to the introduction of new agents to or the recognition of an existing disease that has gone undetected, and re-emergence may describe the re-appearance of known diseases after a decline in incidence. In this article a global, multidisciplinary and integrated approach in different fields of demography, epidemiology, economy, ecology, anthropology and environment at science has been considered to describe the different determinants responsible for the emergence and re-emergence of infectious diseases.

Biological Evolution↗