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)
(2/3131) Coalescent estimates of HIV-1 generation time in vivo.
The generation time of HIV Type 1 (HIV-1) in vivo has previously been estimated using a mathematical model of viral dynamics and was found to be on the order of one to two days per generation. Here, we describe a new method based on coalescence theory that allows the estimate of generation times to be derived by using nucleotide sequence data and a reconstructed genealogy of sequences obtained over time. The method is applied to sequences obtained from a long-term nonprogressing individual at five sampling occasions. The estimate of viral generation time using the coalescent method is 1.2 days per generation and is close to that obtained by mathematical modeling (1.8 days per generation), thus strengthening confidence in estimates of a short viral generation time. Apart from the estimation of relevant parameters relating to viral dynamics, coalescent modeling also allows us to simulate the evolutionary behavior of samples of sequences obtained over time. (+info)
(3/3131) Cytokine profile induced by Cryptosporidium antigen in peripheral blood mononuclear cells from immunocompetent and immunosuppressed persons with cryptosporidiosis.
The proliferative response of peripheral blood mononuclear cells (PBMC) to a crude extract from Cryptosporidium parvum (CCE) was studied in persons who acquired cryptosporidiosis in the same outbreak (15 immunocompetent subjects with prior cryptosporidiosis and 22 human immunodeficiency virus [HIV]-positive persons with various levels of immunosuppression and active cryptosporidiosis) and in individual patients (8 HIV-positive patients with active cryptosporidiosis and 15 HIV-positive persons without history of cryptosporidiosis). PBMC from HIV-positive persons showed less proliferation to CCE and mitogens than did PBMC from immunocompetent subjects with prior cryptosporidiosis, independent of CD4 cell count. In immunocompetent subjects, cytokine gene expression was consistent with cytokine production, whereas in HIV-positive subjects it was not. The production of interferon-gamma in CCE-stimulated PBMC from both immunocompetent and HIV-positive subjects with cryptosporidiosis and the lack of interferon-gamma in CCE-stimulated PBMC from HIV-positive subjects without cryptosporidiosis indicate that C. parvum mainly induces a Th1 response. (+info)
(4/3131) 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)
(5/3131) Voluntary newborn HIV-1 antibody testing: a successful model program for the identification of HIV-1-seropositive infants.
Harlem Hospital in New York City has one of the highest HIV-1 newborn seroprevalence rates in the United States. We report the results of a program introduced in 1993 and designed to identify HIV-1-seropositive (HIV+) newborns at birth. All new mothers, independent of risk, received HIV counseling that emphasized the medical imperative to know the infant's HIV status as well as their own. Consent was obtained to test the infant; discarded cord blood samples were tested by enzyme-linked immunosorbent assay (ELISA), and when positive, Western Blot confirmation. We compared the number of HIV+ infants identified through voluntary testing with the number reported by the anonymous New York State Newborn HIV Seroprevalence Study. In 1993, 97.8% (91 of 93) of the number of HIV+ infants identified by the anonymous testing were identified through voluntary maternal and newborn testing programs. Eighty-five HIV+ infants were identified before nursery discharge: 50% (42/85) through newborn testing; 14% (12/85) through prenatal testing; 13% (11/85) presented to care knowing their status; 23% (20/85) were known because of a previous HIV+ child. Six additional HIV+ children were diagnosed after hospital discharge (mean age, 5.5 months; range 1.5 through 17 months); four presented with symptomatic disease. The optimal time for identification of the HIV+ pregnant woman is before or during pregnancy, but when this does not occur, voluntary newborn testing can identify many HIV+ infants who would otherwise be discharged undiagnosed from the nursery. (+info)
(6/3131) 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)
(7/3131) 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)
(8/3131) Tissue specific HPV expression and downregulation of local immune responses in condylomas from HIV seropositive individuals.
OBJECTIVE: To study the effect of tissue specific human papillomavirus (HPV) expression and its effect on local immunity in condylomas from HIV positive individuals. METHODS: Biopsy specimens of eight penile and eight perianal condylomas from HIV seropositive individuals were analysed. Expression of viral genes (HIV-tat and HPV E7 and L1) was determined by RT-PCR. The status of local immunity also was determined by RT-PCR by measuring CD4, CD8, CD16, CD1a, HLA-DR, and HLA-B7 mRNA levels in the tissues. Differentiation was determined by measuring involucrin, keratinocyte transglutaminase, as well as cytokeratins 10, 16, and 17. Proliferation markers such as PCNA and c-myc were also determined. RESULTS: The transcription pattern of HPV in perianal condylomas, which preferentially expressed the early (E7) gene, was different from that of penile condylomas, which primarily expressed the late (L1) gene. This transcription pattern is in good correlation with the keratinisation and differentiation patterns of the two epithelia: perianal biopsies preferentially expressed K16 and K17 while penile warts mainly expressed K10, markers of parakeratotic and orthokeratotic epithelia, respectively. Perianal biopsies also showed a higher degree of proliferation (PCNA and c-myc). Interestingly, transcription of HIV-tat was also higher in perianal than in penile biopsies. A high degree of local immunodeficiency was observed in perianal biopsies--that is, levels of CD4, CD16, and CD1a mRNAs were significantly lower. A negative correlation between CD1a (Langerhans cells) levels and HPV E7 levels was established. HPV E7 levels positively correlated with HIV-tat levels. Perianal tissues demonstrated more CD1a depression and tat associated HPV upregulation. CONCLUSION: HIV influences the expression of HPV genes resulting in local immunosuppression that might lead to an inappropriate immune surveillance of viral infection. Also, tissue type is an important factor in controlling viral transcription in a differentiation dependent manner. These findings may explain the higher rate of dysplasia and neoplasia in the perianal area. (+info)