Biomedical subjects
Publications and source records attributed to V Vullo.
We describe two cases of human immunodeficiency virus-infected patients with visceral leishmaniasis in whom no clinical and parasitological disease relapses were observed after liposomal amphotericin B therapy combined with potent antiretroviral treatment.
This study describes the sexual behaviours of women living with HIV, and assesses differences by history of drug use. Its general aim is to contribute in the design of programmes to help people with HIV/AIDS (PWH/A) adopt and maintain safe sexual behaviours. A self-administered questionnaire on sexual and drug use behaviours was distributed to study participants. Between 1997 and 1999, 573 women with HIV infection naive to antiretroviral therapies completed the questionnaire (of whom 234 reported a history of injection drug use (IDU) and were enrolled in the study. Non-IDU women reported fewer sexual partners, both in their lifetime and in the preceding month, than IDU women: 19% of IDU and 4% of non-IDU women reported more than 25 lifetime sexual partners (p < 0.001). Interestingly, 83% of non-IDU women were infected by their regular partners: these women reported the lowest number of sexual partners. No difference emerged between IDU and non-IDU women in terms of number of sexual intercourse in the two weeks preceding the interview or in terms of condom use in the last intercourse (reported, overall, by 54% of these 573 women). Among women who had sex partners at the time of interview, more non-IDU (65%) than IDU (43%) women reported HIV-positive partners (p < 0.001). Overall, these findings stress a marked heterogeneity in the levels of past and recent sexual promiscuity according to history of drug use. It suggests the need to differentiate and individualize messages about self-protection and behaviours that may prevent further spread of HIV infection.
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Matrix metalloproteinases (MMPs) have been identified as mediators of brain injury in HIV-associated neurological diseases. The activity of the 72 kDa gelatinase A (MMP-2) and 92 kDa gelatinase B (MMP-9) was detected by zymography in the cerebrospinal fluid (CSF) of 138 HIV-infected patients (40 with AIDS dementia, 83 with brain opportunistic infections and 15 neurologically asymptomatic), 26 HIV-seronegative individuals with inflammatory neurological diseases (IND) and 12 HIV-seronegative subjects with noninflammatory neurological diseases (NIND). MMP-2 was present in all CSF samples from HIV-seropositive and HIV-seronegative individuals, including those of subjects with NIND. On the contrary, MMP-9 was absent in the CSF of NIND controls, whereas the activity of this MMP was found in the 77 - 100% of CSF samples from HIV-infected patients, including those with HIV dementia, central nervous system (CNS) opportunistic infections or neurologically asymptomatic subjects. The highest levels of MMP-9 were found in the CSF of patients with cryptococcosis, cytomegalovirus encephalitis and tuberculous meningitis and were comparable with those found in the CSF of HIV-negative patients with multiple sclerosis or meningitis. A significant correlation between CSF MMP-9 activity and CSF cell count was found only in patients with HIV dementia. The increased CSF activity of MMPs capable to degrade components of the extracellular matrix of blood-brain barrier may contribute to the transendothelial migration of virus-infected cells into the CNS and development of HIV-associated neurologic damage.
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.
OBJECTIVE: To investigate the effect of highly active antiretroviral treatment (HAART) on neutrophil and monocyte function in patients with moderately advanced HIV-1 infection. DESIGN: Eighteen HIV-1-infected patients with CD4 T cell counts below 350/microl, no concomitant active infection, and no previous use of protease inhibitors were treated with indinavir or ritonavir and two reverse-transcriptase inhibitors and were followed up for 9 months. Ten age- and sex-matched healthy subjects were included as controls. METHODS: The functional activity of neutrophils and monocytes was measured by assessing chemotaxis towards a bacterial peptide, killing activity against Candida albicans, and oxidative burst as measured by chemiluminescence production. RESULTS: Neutrophils and monocytes from the treatment group exhibited a significantly diminished baseline chemotactic and fungicidal activity compared with healthy controls (P < 0.001). After starting HAART, there was a significant improvement in chemotaxis and fungicidal activity of phagocytic cells (P < 0.001). Values of chemotaxis reached normal ranges in 13 out of 18 patients (72%) for neutrophils and eight out of 18 (44%) for monocytes, whereas phagocyte killing was rarely restored to normal values (3/18 cases for monocytes and 0/18 for neutrophils). The administration of HAART was also associated with significantly increased phagocyte chemiluminescence production in response to phorbol-12-myristate 13-acetate or opsonized C. albicans (P < 0.01). CONCLUSION: The functional improvement of two critical components of innate antimicrobial immunity, such as neutrophils and monocytes, may contribute to the improved cell-mediated immune responses against opportunistic infections in HAART-treated patients.
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Human herpesvirus-8 (HHV-8) has been associated with Kaposi's sarcoma, multicentric Castleman's disease and primary effusion lymphoma. Kaposi's sarcoma and multicentric Castleman's disease patients may develop body cavity effusions that, unlike primary effusion lymphoma, are poorly characterized. To better define these effusions, pleural and peritoneal fluids derived from 12 human immunodeficiency virus-seropositive and one seronegative patients affected by Kaposi's sarcoma or multicentric Castleman's disease were analyzed by a combination of morphologic, immunophenotypic, and DNA analyses, including polymerase chain reaction amplification of HHV-8, Epstein-Barr virus, and immunoglobulin heavy-chain (IgH) gene sequences. In addition, HHV-8 serologic status was assessed by using an immunofluorescence assay. All patients were adult men with high antibody titers to HHV-8; 11 of the 13 patients were homosexual/bisexual. Effusions revealed monocyte/macrophage-rich infiltration (10 patients) or large-cell lymphoma with CD45(+)/non-T/non-B phenotype (three of 13 patients); polymerase chain reaction analysis showed the presence of HHV-8 sequences (nine of 13 patients), germline IgH (seven of 12 patients) or clonal IgH rearrangements (four of 12 patients), and rarely Epstein-Barr virus sequences (two of 12 patients). In the setting of HHV-8 infection, two effusion types may occur. One fulfills the criteria for HHV-8-positive PEL (lymphoma-morphology, HHV-8-DNA(+), IgH rearrangement). The other seems more reminiscent of an HHV-8-associated nonneoplastic process (monocyte-macrophage morphology, HHV-8-DNA(+/-), germline IgH). Interestingly, a single case of the latter effusion type harbored a B-cell monoclonal proliferation, which suggests the hypothesis that a prelymphomatous effusion may precede overt body cavity lymphoma.
Diversity of virulence-associated antigens of Rhodococcus equi was detected among thirteen strains isolated from AIDS patients on two continents. One out of four Brazilian isolates presented the virulence-associated antigen of 15- to 17-kDa, and the other three isolates had the 20-kDa virulence-associated antigen. In contrast, only three out of nine Italian isolates were positive for virulence-associated antigens - two for the 15- to 17-kDa antigen and one for the 20-kDa antigen. In four other Italian strains, one or more other low-molecular-weight antigens were identified. Because of R. equi variability and host immune dysfunction, no characteristic antibody profile was detected among patients, although the presence of specific antibodies in serum samples suggested prognostic value: good patient outcome and recovery from pneumonia were correlated with R. equi antibody detection, whereas the lack or disappearance of specific antibodies, mainly those to low-molecular-weight antigens, was correlated with disease progression and patient death. These results confirmed the nonobligatory presence of the well-known virulence-associated antigens for the pathogenicity of R. equi in humans, and also the diversity of R. equi strains isolated from AIDS patients, which may be related to the geographic origin of the isolates or may be a consequence of the route of R. equi transmission in different countries. Some mechanisms underlying the results obtained are discussed, suggesting immune complex formation during the progress of the disease.
Rhodococcus equi (formerly Corynebacterium equi) are known to be highly virulent, intermediate in virulence, or avirulent correlated with specific virulence-associated antigens identified immunochemically by different molecular weights. The association of virulence antigens with infection of AIDS patients by this organism has not been sufficiently evaluated in Brazil or Italy. The objective of the present study was to search for virulence-associated antigens of 15-to 17-kD and 20-kD in Rhodococcus equi strains isolated from patients with rhodococcal infection and AIDS. Four Brazilian and 9 Italian strains were studied. All isolates were analyzed by gel electrophoresis followed by immunoblotting using specific monoclonal antibodies to identify virulence-associated antigens. The results obtained on gel electrophoresis analyses showed complexing of R. equi components with proteins of molecular weights ranging from 10-to 150-kD. By immunoblotting, a wide diversity in R. equi virulence-associated antigens was detected: 1 of the 4 Brazilian isolates and 2 Italian isolates had the 15-to 17-kD virulence-associated antigen, 3 Brazilian isolates and 1 Italian isolate had the 20-kD virulence-associated antigen, and the other Italian isolates had no virulence-associated antigens. These results indicate that the pathogenicity of R. equi strains for humans does not depend only on the presence of these well established virulence-associated antigens.
OBJECTIVE: Nerve growth factor (NGF) is an autocrine survival factor for memory B lymphocytes. As functional B-cell deregulation is present during HIV infection, NGF serum levels were measured in HIV-infected patients and compared with the patients' clinical features. DESIGN: Sera from 48 consecutive HIV-infected patients and matched healthy controls were retrospectively and blindly analysed. Sera from seven patients with classical Kaposi's sarcoma (KS) were subsequently included in the study. The effects of NGF on spindle-shaped cells from KS lesions (KS cells) were also investigated. METHODS: NGF titration was performed by enzyme-linked immunosorbent assay (ELISA) and human herpesvirus 8 (HHV-8) antibody testing by immunofluorescent assay (IFA). NGF receptors were assessed by Western blot analysis. Cell growth assays were performed by cell counting. RESULTS: Very high median NGF serum levels were detected in all seven patients with AIDS-related KS (2500 pg/ml) compared with HIV-infected patients without KS (40 pg/ml), as well as in all seven classical KS patients (550 pg/ml) compared with healthy controls (20 pg/ml). In HIV-infected patients, NGF serum levels were significantly related to KS (P=0.0038) by stepwise multiple regression analysis, and HHV-8 seropositivity was significantly associated with KS (P=0.045) and to NGF levels (P=0.001) by logistic regression analysis. KS cells did not produce NGF but expressed both NGF receptors and presented increased proliferation rate after exogenous NGF addition. CONCLUSIONS: These results strongly suggest that increased NGF levels, possibly related to HHV-8 infection, may be involved in KS progression.
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The concentrations of the chemokines IL-8, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) were measured in 120 CSF samples from 23 patients with pyogenic meningitis and from 11 patients with tuberculous meningitis (TBM) and in 10 CSF from subjects with non-infectious neurological diseases. The chemokine concentrations in patients with meningitis were significantly higher than in control subjects (P<0.0001). The highest CSF levels were found for IL-8 (median 2917 pg/ml) and MCP-1 (median 2557 pg/ml), whereas those of MIP-1alpha were less significantly elevated (median 24 pg/ml) (P<0.0001). Patients with pyogenic meningitis had higher levels of IL-8 and MCP-1 than those with TBM (P<0.0001). In serial samples from patients with pyogenic meningitis IL-8 levels declined before MCP-1 and MIP-alpha. In the case of TBM, IL-8, MCP-1 and MIP-1alpha decreased more gradually during treatment and were detectable in the CSF for several weeks, without any characteristic time course of elimination. These data indicate that patients with pyogenic meningitis and TBM show different chemokine profiles in CSF. The distinct chemokine pattern could be responsible for a differential attraction and activation of leucocytes in the CSF which is reflected in differences in the inflammatory response and clinical course of pyogenic meningitis and TBM.
Monocytes/macrophages from human immunodeficiency virus (HIV)-infected patients had a defect in their ability to kill Rhodococeus equi in vitro, as compared with healthy HIV-seronegative individuals. Virulent and avirulent R. equi strains isolated from humans and horses showed no significant intracellular replicative differences within both HIV-positive and -negative monocytes/macrophages. Infection with R. equi induced the production of nitric oxide (NO) by monocytes/macrophages from healthy individuals, but not by cells from HIV-positive patients. The NO formation was significantly inhibited by L-NG-monomethyl arginine and arginase. However. neither competitive inhibition of NO synthesis from L-arginine with L-NMMA nor depletion of arginine with arginase altered the killing activity of human monocytes/macrophages against R. equi, thus suggesting that L-arginine:NO pathway is not required for the intracellular antirhodococcal mechanisms of human monocytes/macrophages.
The capability of heat-killed Rhodococcus equi organisms to induce in vitro release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8 from normal human mononuclear cells as well as the secretion kinetics of these inflammatory cytokines over a 48 h period were evaluated. Results show that normal human mononuclear cells are efficiently triggered to secrete TNF-alpha, IL-6 and IL-8 following R. equi stimulation according to a different kinetics. In particular, release of IL-B was already maximally expressed after 2 h of stimulation, while TNF-alpha amounts progressively increased in a time-dependent fashion. Finally, IL-6 secretion reached peak levels as soon as 18 h of incubation. Taken together, these data point out that monocyte-derived cytokines may play an important role in the immunological control of R. equi infection in immunocompetent people.
The level of tumor necrosis factor (TNF)-alpha, soluble TNF receptors p75 (sTNFR-75) and sTNFR-55, interferon (IFN)-gamma, and interleukin (IL)-10 and IL-12 were measured in 59 cerebrospinal fluid (CSF) samples from 15 patients with tuberculous meningitis (TBM). TBM was associated with elevated concentrations of TNF-alpha, sTNFR-75, sTNFR-55, IFN-gamma, and IL-10, while CSF IL-12 was undetectable in all TBM patients. A significant correlation between cytokines and CSF adenosine deaminase activity was also found. The levels of TNF-alpha did not decrease over time, being still detectable in the CSF 16 months after starting antibiotic therapy, whereas IFN-gamma along with anti-inflammatory mediators sTNFR-75, sTNFR-55, and IL-10 remained elevated in the CSF for 4-8 months. The chronic release of cytokines in the CSF compartment was related neither to the TBM stage nor to the clinical outcome of the disease, thus suggesting the presence of a continuous activity of the inflammatory process at the site of infection.
Thirteen cases of Chlamydia pneumoniae infection in patients seropositive for the human immunodeficiency virus (HIV) are described. The occurrence, the clinical spectrum, and the significance of the infection during HIV disease are compared with data reported in the literature. Chlamydia pneumoniae infection was established by a serologic micro-immunofluorescence test using standard diagnostic criteria. In four cases the results of serological tests were confirmed by direct immunofluorescence on respiratory specimens. Five patients developed focal pneumonia but recovered completely after specific antibiotic treatment. Three patients developed severe and diffuse interstitial pulmonary involvement, two of whom died of acute respiratory failure. Five patients developed upper respiratory tract infection. Using 39 pair-matched HIV-seropositive subjects as controls, the cases of infection were found to be significantly associated with a previously diagnosed pulmonary disease. Upon retrospective analysis of 319 consecutive cases of pneumonia among HIV-infected patients, Chlamydia pneumoniae was the sole agent detected in eight (2.5%) cases, and Chlamydia pneumoniae together with other infectious agents was detected in seven (2.2%) cases. Chlamydia pneumoniae is a possible cause of severe respiratory infection in Italian HIV-infected immunocompromised patients, and its presence must be suspected when patients do not respond to therapy with beta-lactam agents or to anti-Pneumocystis carinii treatment.
A case of an Italian AIDS patient who developed both meningitis and cerebral mass lesion as a final relapse of disseminated histoplasmosis is reported. Central nervous system (CNS) involvement occurred while the patient was receiving both amphotericin B and itraconazole as maintenance therapy, thus indicating the difficulty of eradicating histoplasmosis in patients with AIDS.