(1/803) Tuberculous meningitis in South African urban adults.
We retrospectively reviewed 56 adults with culture-proven tuberculous meningitis (TBM), investigating clinical signs, cerebrospinal fluid (CSF) findings and outcome. There were 50 patients, aged 18-59 years, 39 with and 11 without human immunodeficiency virus (HIV) infection. Six were aged 60 years or older. Neurological signs of TBM in 18-59-year-olds were unaffected by HIV serostatus while, compared to those > or = 60 years of age, there were more patients with meningism (86.0% vs. 33.3%; p = 0.011) and fewer with seizures (12.0% vs. 50.0%; p = 0.046). The HIV-infected 18-59-year-olds had significantly more extrameningeal tuberculosis compared to the non-HIV-infected (76.9% vs. 9.1%; p = 0.0001) and 23.1% had 'breakthrough' TBM. CSF analysis revealed 12 patients (21.4%) with acellular fluid (more common in those > or = 60 years of age, p = 0.016), of whom three had completely normal CSF. A neutrophil predominance was found in 22 patients (39.3%). Only three patients (5.4%) had a positive CSF smear for acid-fast bacilli. In-hospital mortality occurred in 39 patients (69.1%), was similar in all study groups, and was not related to neurological stage. The diagnosis of TBM can be masked by lack of meningism in the elderly and by atypical CSF findings. (+info)
(2/803) Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women.
BACKGROUND: Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepithelial lesions commonly seen among women infected with human immunodeficiency virus-1 (HIV). We characterized HPV infection in a large cohort of HIV-positive and HIV-negative women participating in the Women's Interagency HIV Study to determine the prevalence of and risk factors for cervicovaginal HPV infection in HIV-positive women. METHODS: HIV-positive (n = 1778) and HIV-negative (n = 500) women were tested at enrollment for the presence of HPV DNA in a cervicovaginal lavage specimen. Blood samples were tested for HIV antibody status, level of CD4-positive T cells, and HIV RNA load (copies/mL). An interview detailing risk factors was conducted. Univariate and multivariate analyses were performed. RESULTS: Compared with HIV-negative women, HIV-positive women with a CD4+ cell count of less than 200/mm3 were at the highest risk of HPV infection, regardless of HIV RNA load (odds ratio [OR] = 10.13; 95% confidence interval [CI] = 7.32-14.04), followed by women with a CD4+ count greater than 200/mm3 and an HIV RNA load greater than 20,000 copies/mL (OR = 5.78; 95% CI = 4.17-8.08) and women with a CD4+ count greater than 200/mm3 and an HIV RNA load less than 20,000 copies/mL (OR = 3.12; 95% CI = 2.36-4.12), after adjustment for other factors. Other risk factors among HIV-positive women included racial/ethnic background (African-American versus Caucasian, OR = 1.64; 95% CI = 1.19-2.28), current smoking (yes versus no; OR = 1.55; 95% CI = 1.20-1.99), and younger age (age < 30 years versus > or = 40 years; OR = 1.75; 95% CI = 1.23-2.49). CONCLUSIONS: Although the strongest risk factors of HPV infection among HIV-positive women were indicators of more advanced HIV-related disease, other factors commonly found in studies of HIV-negative women, including racial/ethnic background, current smoking, and age, were important in HIV-positive women as well. (+info)
(3/803) Human herpesvirus 8 seroprevalence and evaluation of nonsexual transmission routes by detection of DNA in clinical specimens from human immunodeficiency virus-seronegative patients from central and southern Italy, with and without Kaposi's sarcoma.
In order to investigate the seroprevalence of human herpesvirus 8 (HHV-8) infection in central and southern Italy, sera from human immunodeficiency virus (HIV)-seronegative subjects, with and without Kaposi's sarcoma (KS), were analyzed by immunofluorescence assay, using BC-3, a cell line latently infected with HHV-8. High titers of antibody against HHV-8 lytic and latent antigens were detected in all 50 KS patients studied, while in 50 HIV-seronegative subjects without KS, 32 (64%) were found positive for HHV-8 antibodies. Titers in the sera of these patients were lower than those for KS patients. This data suggests that HHV-8 infection is not restricted to KS patients and that the prevalence of HHV-8 infection in the general population may be correlated with differing rates of prevalence of KS in different parts of the world. In view of these findings, possible nonsexual transmission routes were evaluated. Nested PCR was used to test for the presence of HHV-8 DNA in saliva, urine, and tonsillar swabs from KS and non-KS patients. In KS patients, 14 out of 32 tonsillar swabs (43.7%), 11 out of 24 saliva samples (45.8%), and just 2 out of 24 urine samples (8.3%) tested positive for HHV-8 DNA. In the control group, on the contrary, none of the 20 saliva and 20 urine specimens was positive for HHV-8 DNA; only 1 out of 22 tonsillar swabs gave a positive result. This data supports the hypothesis that HHV-8 infects the general population in a latent form. The reactivation of viral infection may result in salivary shedding of HHV-8, contributing to viral spread by nonsexual transmission routes. (+info)
(4/803) Cardiac autoimmunity in HIV related heart muscle disease.
OBJECTIVE: To assess the frequency of circulating cardiac specific autoantibodies in HIV positive patients with and without echocardiographic evidence of left ventricular dysfunction. SUBJECTS: 74 HIV positive patients including 28 with echocardiographic evidence of heart muscle disease, 52 HIV negative people at low risk of HIV infection, and 14 HIV negative drug users who had all undergone non-invasive cardiac assessment were studied along with a group of 200 healthy blood donors. RESULTS: Cardiac autoantibodies detected by indirect immunofluorescence (serum dilution 1/10) were more common in the HIV positive patients (15%), particularly the HIV heart muscle disease group (21%), than in HIV negative controls (3.5%) (both p < 0.001). By ELISA (dilution 1/320), abnormal anti-alpha myosin autoantibody concentrations were found more often in HIV patients with heart muscle disease (43%) than in HIV positive patients with normal hearts (19%) or in HIV negative controls (3%) (p < 0.05 and p < 0.001, respectively). Anti-alpha myosin autoantibody concentrations were greater in HIV positive patients than in HIV negative controls, regardless of cardiac status ((mean SD) 0.253 (0.155) v 0.170 (0.076); p = 0.003). In particular the mean antibody concentration was higher in the HIV heart muscle disease patients (0.291 (0.160) v 0.170 (0.076); p = 0.001) than in HIV negative controls. On follow up, six subjects with normal echocardiograms but raised autoantibody concentrations had died after a median of 298 days, three with left ventricular abnormalities at necropsy. This compared with a median survival of 536 days for 21 HIV positive patients with normal cardiological and immunological results. CONCLUSIONS: There is an increased frequency of circulating cardiac specific autoantibodies in HIV positive individuals, particularly those with heart muscle disease. The data support a role for cardiac autoimmunity in the pathogenesis of HIV related heart muscle disease, and suggest that cardiac autoantibodies may be markers of the development of left ventricular dysfunction in HIV positive patients with normal hearts. (+info)
(5/803) Comparison between a whole blood interferon-gamma release assay and tuberculin skin testing for the detection of tuberculosis infection among patients at risk for tuberculosis exposure.
A new test that measures interferon-gamma (IFN-gamma) release in whole blood following stimulation with tuberculin has the potential to detect tuberculosis infection using a single blood draw. The IFN-gamma release assay was compared with the standard tuberculin skin test (TST) among 467 intravenous drug users at risk for tuberculosis in urban Baltimore. Among 300 human immunodeficiency virus (HIV)-seronegative patients, the IFN-gamma release assay was positive in 177 (59%), whereas the TST was positive in 71 (24%), for a percent agreement of 59% (kappa=26%). Among 167 HIV-seropositive subjects, the IFN-gamma release assay identified 32 reactors (19%); the TST identified 16 reactors (9.6%), for a percent agreement of 82% (kappa=28%). The IFN-gamma release assay detected more reactors than did the TST, but its agreement with TST was weak. As the TST is an imperfect standard, further evaluation of the IFN-gamma release assay among uninfected persons and persons with culture-confirmed tuberculosis will be useful. (+info)
(6/803) Reduced naive and increased activated CD4 and CD8 cells in healthy adult Ethiopians compared with their Dutch counterparts.
To assess possible differences in immune status, proportions and absolute numbers of subsets of CD4+ and CD8+ T cells were compared between HIV- healthy Ethiopians (n = 52) and HIV- Dutch (n = 60). Both proportions and absolute numbers of naive CD4+ and CD8+ T cells were found to be significantly reduced in HIV Ethiopians compared with HIV- Dutch subjects. Also, both proportions and absolute numbers of the effector CD8+ T cell population as well as the CD4+CD45RA-CD27- and CD8+CD45RA-CD27- T cell populations were increased in Ethiopians. Finally, both proportions and absolute numbers of CD4+ and CD8+ T cells expressing CD28 were significantly reduced in Ethiopians versus Dutch. In addition, the possible association between the described subsets and HIV status was studied by comparing the above 52 HIV- individuals with 32 HIV+ Ethiopians with CD4 counts > 200/microliter and/or no AIDS-defining conditions and 39 HIV+ Ethiopians with CD4 counts < 200/microliter or with AIDS-defining conditions. There was a gradual increase of activated CD4+ and CD8+ T cells, a decrease of CD8+ T cells expressing CD28 and a decrease of effector CD8+ T cells when moving from HIV- to AIDS. Furthermore, a decrease of naive CD8+ T cells and an increase of memory CD8+ T cells in AIDS patients were observed. These results suggest a generally and persistently activated immune system in HIV- Ethiopians. The potential consequences of this are discussed, in relation to HIV infection. (+info)
(7/803) CD4 depletion in HIV-infected haemophilia patients is associated with rapid clearance of immune complex-coated CD4+ lymphocytes.
The predominant immunological finding in HIV+ haemophilia patients is a decrease of CD4+ lymphocytes during progression of the disease. Depletion of CD4+ lymphocytes is paralleled by an increase in the proportion of immune complex-coated CD4+ cells. We examined the hypothesis that the formation of immune complexes on CD4+ lymphocytes is followed by rapid clearance of immune complex-coated CD4+ lymphocytes from the circulation. In this study, the relationship of relative to absolute numbers of immune complex-loaded CD4+ blood lymphocytes and their association with viral load were studied. Two measurements of relative and absolute numbers of gp120-, IgG- and/or IgM-loaded CD4+ lymphocytes were analysed in HIV+ and HIV- haemophilia patients, with a median interval of approx. 3 years. Immune complexes on CD4+ lymphocytes were determined using double-fluorescence flow cytometry and whole blood samples. Viral load was assessed using NASBA and Nuclisens kits. Whereas the proportion of immune complex-coated CD4+ lymphocytes increased with progression of the disease, absolute numbers of immune complex-coated CD4+ lymphocytes in the blood were consistently low. Relative increases of immune complex-coated CD4+ blood lymphocytes were significantly associated with decreases of absolute numbers of circulating CD4+ lymphocytes. The gp120 load on CD4+ blood lymphocytes increased in parallel with the viral load in the blood. These results indicate that immune complex-coated CD4+ lymphocytes are rapidly cleared from the circulation, suggesting that CD4+ reactive autoantibodies and immune complexes are relevant factors in the pathogenesis of AIDS. Relative increases of immune complex-positive cells seem to be a consequence of both an increasing retroviral activity as well as a stronger loading with immune complexes of the reduced number of CD4+ cells remaining during the process of CD4 depletion. The two mechanisms seem to enhance each other and contribute to the progressive CD4 decrease during the course of the disease. (+info)
(8/803) Protective role of beta-chemokines associated with HIV-specific Th responses against perinatal HIV transmission.
To examine the protective role of cellular immunity in the vertical transmission of HIV, we analyzed HIV-specific IL-2 and CTL responses, as well as beta-chemokine expression in HIV-infected and uninfected infants of HIV+ mothers. Our results showed that HIV envelope (env) peptide-specific IL-2 responses associated with beta-chemokine production were detectable at birth in the majority of uninfected infants of HIV+ mothers. The responses falling to background before the infants were 1 yr old were rarely associated with HIV-specific CTL activity. Conversely, HIV-specific Th and CTL cellular responses were absent at birth in HIV-infected infants. Infants with AIDS-related symptoms exhibited undetectable or very low levels of HIV-specific cellular immunity during the first year of life, whereas those with a slowly progressive disease showed evidence of such immunity between their second and ninth month. The latter group of infected infants tested negative for plasma HIV RNA levels shortly after birth, suggesting lack of intrauterine exposure to HIV. The presence of HIV-specific Th responses at birth in uninfected newborns of HIV+ mothers, but absence of such activities in HIV-infected infants without evidence of intrauterine HIV infection, suggests that in utero development of HIV-specific Th responses associated with beta-chemokines could mediate nonlytic inhibition of infection during vertical transmission of HIV. (+info)