HIV-2 and natural protection against HIV-1 infection.
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Biomedical subjects
Publications and source records attributed to S Z Wiktor.
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To characterize human immunodeficiency virus (HIV) risk practices among men with tuberculosis, and to determine what factors are associated with HIV infection in this population, we conducted a case-control analysis of data collected during enrollment in a prospective cohort study in the two large tuberculosis treatment centers of Abidjan, Côte d'Ivoire. Demographic information and data on risk factors for HIV infection, including history of sex with female sex workers (FSWs) and history of sexually transmitted diseases (STDs), were collected on 490 HIV-infected and 239 HIV-uninfected men diagnosed with pulmonary tuberculosis between 1989 and 1992. HIV-infected men were significantly more likely than uninfected men to have had sex with FSWs in their lifetime [83 versus 63%, odds ratio (OR) 2.9, 95% confidence internal (CI) 2.0-4.2], genital ulcer disease in the past 5 years (38 versus 15%, OR 3.4, 95% CI 2.2-5.2), urethritis in the past 5 years (44 versus 23%, OR 2.6, 95% CI 1.8-3.8), and sex with FSWs in the past year (43 versus 25%, OR 2.3, 95% CI 1.6-3.3); no difference was found in the proportion with at least one non-FSW partner in the past year (84 versus 79%, OR 1.3, 95% CI 0.9-2.0). Among all men, 74% never used condoms, and only 1.4% always used condoms. In a multivariate analysis, sex with FSWs, genital ulcer disease, urethritis, and lack of circumcision were all significantly associated with HIV. This study demonstrates the critical roles of commercial sex, STDs, and condom neglect in fueling the HIV/AIDS epidemic in Abidjan, and illustrates the urgent need for widespread HIV education both in the general population and in men with tuberculosis.
OBJECTIVES: To compare the radiologic manifestations of pulmonary tuberculosis in HIV-1-infected, HIV-2-infected, and HIV-negative patients; and to assess the impact of HIV-related immunosuppression on the radiologic manifestations of pulmonary tuberculosis. METHODS: We compared chest radiographs from consecutive HIV-1-positive, HIV-2-positive and seronegative patients with pulmonary tuberculosis. Differentiation between HIV-1 and HIV-2 antibodies was based on a synthetic peptide-based enzyme immunoassay. A subset of patients had CD4+ lymphocyte levels estimated by flow cytometry; in these patients, abnormalities on chest radiographs were analysed in relation to the severity of CD4+ lymphocyte depletion. RESULTS: HIV-1-infected patients were significantly more likely to have extrapulmonary tuberculosis than were HIV-2-infected or HIV-negative patients (20% vs 8% and 9%). Among patients with pulmonary tuberculosis, no differences were observed in the rates of specific abnormalities on chest radiographs between HIV-1- and HIV-2-infected patients; both HIV-1- and HIV-2-infected patients had a higher frequency of pleural effusion than did HIV-negative patients (8% and 9% vs 4%). Among HIV-infected patients with CD4+ counts of > or = 400/mm3, 200-399/mm3, and < 200/mm3, respectively, the proportions with non-cavitary infiltrates and hilar adenopathy increased significantly (33% to 44% to 58%, and 0% to 14% to 20%), while the proportion with cavitary lesions decreased significantly (63% to 44% to 29%). CONCLUSIONS: The radiologic manifestations of pulmonary tuberculosis in HIV-infected patients varied significantly over the spectrum of immune deficiency. HIV-infected patients with tuberculosis and relatively high CD4+ counts showed only slight differences from HIV-negative persons. HIV-1-positive patients had a higher frequency of extrapulmonary tuberculosis at presentation than those infected with HIV-2. Radiographic abnormalities were broadly similar in HIV-2-infected and HIV-1-infected patients. Clinicians and radiologists must be alert to the altered radiologic spectrum of pulmonary tuberculosis in immunosuppressed HIV-infected patients.
Early childhood infection with human T cell lymphotropic virus type I (HTLV-I) has been suggested to be involved in the pathogenesis of infective dermatitis and adult T cell leukemia/lymphoma. Since only a very small percentage of HTLV-I-infected children develop disease later in life, identification of early interim markers for persons at risk for developing disease would enable monitoring and might provide insight into the pathophysiology of the various diseases associated with HTLV-I infection. A cross-sectional study analyzed T cell subsets in 35 HTLV-I-seronegative and 16 HTLV-I-seropositive Jamaican children 11-31 months old. HTLV-I seropositivity was associated with an increase in the mean percentage of CD4 cells expressing HLA-DR, a marker for T cell activation (P = .02). This increase was positively correlated with duration of infection (r = .74, P = .009). These data demonstrate perturbation of regulatory cells of the immune system in HTLV-I-infected children.
Human T lymphotropic virus type I (HTLV-I) is a human retrovirus etiologically linked to adult T cell leukemia and the progressive chronic neurologic disease HTLV-I-associated myelopathy/tropical spastic paraparesis. Described is a method that measures the production of interleukin-2 from HTLV-I synthetic peptide-stimulated peripheral blood lymphocytes (PBL) of HTLV-I-infected persons. The peptides correspond to immunogenic regions of the HTLV-I Env and Tax proteins. Significantly, this assay demonstrated T cell responses to these HTLV-I peptides from coded PBL samples in 7 of 19 HTLV-I-seronegative polymerase chain reaction-negative persons known to have been exposed to HTLV-I but in none of 16 matched controls without risk factors for exposure (P = .007). The implications of this finding are discussed.
To determine the prevalence of firearm ownership and storage practices in New Mexico, we did a random-digit-dialing survey of New Mexico residents in October 1991. Of 200 households surveyed, 79 (40%) had 1 or more firearms in the home. Rural households were more likely than urban households to have firearms (44% versus 30%), and households with annual incomes of greater than $25,000 were more likely to have a firearm than households with incomes of $25,000 or less (41% versus 33%). Household firearm ownership did not vary with the presence of young (< 15 years old) children (38% with children versus 41% without). Handguns were generally owned for self-protection, and rifles were owned for hunting. Of households with firearms, 24% stored them unsafely (unlocked and loaded or unloaded but with ammunition nearby), including 21% of households with young children. Of the households with handguns only, 40% stored these firearms unsafely compared with 13% of those with rifles only. The prevalence of gun ownership in New Mexico is similar to that reported in national surveys; handguns are stored less safely than rifles; and the presence of young children in the home does not appear to improve firearm storage safety.
Mapping the geographic distribution of human T-lymphotrophic virus types 1 and 2 (HTLV-I and -II) has been complicated because conventional serologic approaches cannot distinguish between these 2 viruses. To more precisely define the epidemiology of HTLV-I and HTLV-II, we evaluated a convenience sample of 4,832 HTLV-I immunoblot results from over 140,000 samples screened for HTLV-I, collected in 16 countries for 35 separate studies. An algorithm that compares reactivity against p19 and p24, 2 gag (HTLV-I core) proteins, was employed to characterize the immunoblots: type I, p19 stronger than p24 (presumptive HTLV-I), type 2, p24 stronger than p19 (presumptive HTLV-II), or indeterminate (p19 and p24 weakly positive or p19 weakly positive in the presence of p21e). Geographic areas could be grouped into 4 patterns. Patterns A (> 75% type I) and B (> 75% type 2) were usually observed where the specific type of HTLV or its characteristic diseases had been found. Pattern C (mixed type 1 and 2 pattern) was observed predominantly in intravenous-drug-using and other populations in which both virus types have been reported. Pattern D (> 10% indeterminate), suggests the presence of non-specific reactivity, perhaps resulting from exposure to non-virus-related antigens or an HTLV-related virus. HTLV-I predominates in southern Japan, the South Pacific, parts of West Africa, and in Afro-populations of the Western hemisphere. HTLV-II clusters in Native American populations and among intravenous drug users. Pattern-D areas in Africa and Venezuela might prove to be fertile in the search for new and variant HTLV virus types.
To study mother-to-child transmission of HTLV-I in Jamaica, we screened antenatal patients in Kingston, Jamaica, from 1983 to 1985. Of 2,329 women, 81 (3.5%) were HTLV-I seropositive. Two to three years later, 36 seropositive mothers were recontacted, and blood was drawn from them and their children. All sera were tested for HTLV-I antibodies, and mother's sera were additionally tested for HTLV-I whole-virus antibody titer, syncytium-inhibition neutralizing antibody titer, and titers to six synthetic peptides from the HTLV-I envelope glycoprotein gp46. Seventeen of 74 (23%) [95% confidence interval (CI) 15-34%] children were seropositive. HTLV-I transmission was associated with breast-feeding duration > 6 months [relative risk (RR) 3.2; CI 0.4-22.1], maternal age > 30 years (RR 2.8; CI 1.0-7.8), and higher maternal whole-virus antibody titer (RR 3.3; CI 1.3-8.5). After controlling for higher whole-virus antibody titer, transmission remained associated with higher titer of neutralizing antibody and higher titer of antibody to the peptide sp4a1, corresponding to amino acids 196-209 of the gp46 envelope glycoprotein. We conclude that mother-to-child transmission of HTLV-I in Jamaica is associated with longer duration of breast-feeding, older age, and higher HTLV-I antibody titer, in particular to a certain immunogenic portion of the gp46 envelope glycoprotein.
Patients attending sexually transmitted disease (STD) clinics in Baltimore (n = 4880) and New Orleans (n = 1054) were surveyed in 1987 to estimate the prevalence of human T lymphotropic virus (HTLV)-I/II infection. In Baltimore, 0.4% (95% confidence interval [CI], 0.2-1.1) were HTLV-I/II-seropositive and 4.9% were human immunodeficiency virus (HIV-1)-positive. In New Orleans, 1.8% (CI, 1.2-2.9) of sera were HTLV-I/II-seropositive and 5.1% were HIV-1-seropositive. In both cities, HTLV-I/II prevalence increased significantly with age, and the New Orleans age- and sex-adjusted HTLV-I/II prevalence was significantly higher than that of Baltimore (P less than .001). In Baltimore, almost all HTLV-I/II seropositivity was associated with a history of parenteral drug use or sexual contact with partners who were drug users or male homosexuals. In addition, individuals in both cities who were seropositive for HIV-1 or syphilis were significantly more likely to be HTLV-I/II-seropositive.
Antibodies to herpes simplex virus type 2 (HSV-2), antibodies to hepatitis B virus (HBV) core antigen (anti-HBc), and VDRL antibodies (serologic evidence of syphilis) were evaluated in women known to be infected with human immunodeficiency virus type 1 (HIV-1) (n = 95) or human T lymphotropic virus type I (HTLV-I) (n = 45) and controls (n = 89). HIV-1-seropositive women were more likely than controls to have antibodies to HSV-2 (88% vs. 54%; P less than .001), anti-HBc (67% vs. 43%; P = .008), and VDRL antibodies (21% vs. 8%; P = .02). Similarly, HTLV-I-seropositive women were more likely than controls to have antibodies to HSV-2 (82% vs. 54%; P = .003) and anti-HBc (67% vs. 43%; P = .008). There was no evidence that HIV-1 or HTLV-I predisposed to chronic hepatitis B virus infection. The stronger associations between HIV-1 and HTLV-I with HSV-2 than the associations with syphilis or HBV are consistent with the hypothesis that recurrent disruptions of mucous membranes caused by HSV-2 infections predispose to sexual transmission of HIV-1 and HTLV-I.
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We measured lymphocyte proliferation in the absence of antigenic stimulation in 45 HTLV-II infected, 9 HTLV-I infected, and 19 HTLV-I seronegative intravenous drug users (IVDU). Lymphocyte proliferation was higher in IVDUs infected with HTLV-II than in seronegative IVDUs but lower than among those infected with HTLV-I. Higher rates of proliferation were also associated with needle sharing, CD4+ and IL2R+ lymphocyte counts, and HTLV-I antibody titres.
55 HTLV-I (human T-cell lymphotropic virus) and 45 HTLV-II carriers, confirmed by HTLV-type specific polymerase chain reaction (PCR), were distinguished by western blot assays with recombinant HTLV I or II envelope glycoproteins. Recombinant protein (RP) B1 contains aminoacids 166-201 from HTLV-I exterior glycoprotein gp46 and was reactive with HTLV-I samples only. RP-IIB, which contains aminoacids 96-235 from HTLV-II exterior glycoprotein gp52, was reactive with all HTLV-II samples. 39 patients (86.6%) had high reactivity by densitometry. Of 55 HTLV-I samples, 35 (65.5%) had antibody reactivity to RP-IIB, but only 1 (1.8%) had high reactivity by densitometry. RP B1 and IIB western blot assays may replace the PCR test in diagnosis of HTLV infection.
During the 7th annual follow-up of our cohort of homosexual men in 1989, we tested the hypotheses that infection with human immunodeficiency virus (HIV) may enhance the expression of human papilloma virus (HPV) and that the development of anal epithelial abnormality is related to a biologic interaction between these two viruses. Overall, 41 (39%) of the 105 men had anal swabs positive for one or more genotypes of HPV 6/11, 16/18 or 31/33/35. Twenty-three (53%) of the 43 HIV-positive subjects harbored HPV compared to 18 (29%) of the 64 HIV-negative subjects (p = 0.012), including higher prevalence rates for HPV genotypes 16/18 (p = 0.01), 6/11 (p = 0.007), and 31/33/35 (p = 0.07). Multivariate logistic regression analysis of the HIV-positive subjects showed low CD4+ cell counts to be an independent risk factor for detection of HPV (p = 0.04) and in particular for HPV genotypes 31/33/35 (p = 0.02) and 6/11 (p = 0.07). In contrast, similar analysis of the HIV-negative subset showed that a positive antibody test for syphilis was associated with HPV (p = 0.03). Anal epithelial abnormalities were found in 13 (14%) of 92 technically adequate cytologic smears and were strongly associated with detection of any HPV genotypes by the dot-blot method (p = 0.01), and in particular with HPV genotypes 6/11 (p = 0.001). None of 15 subjects with HPV detected only by PCR had anal epithelial abnormality. We propose a viral interaction model, in which HIV-related immune deficiency allows reactivation of HPV, with a subsequent or concomitant appearance of epithelial abnormality.
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Three hundred seventy-seven prostitutes from Kinshasa, Zaire, were enrolled in a study to determine associated risk factors for human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic virus type I (HTLV-I) infection. Twelve samples (3.2%) were seropositive for HTLV-I; results for HIV-1 (101 [26.8%]) are reported elsewhere. HTLV-I prevalence increased with age, and seven of the seropositive women originated from the Equateur region, a remote area in northwestern Zaire. The prevalence among women from Equateur (7.2%) was higher than that of women from all other regions (1.8%, P = .02). Presence of HTLV-I antibodies was not associated with frequency or type of sex practice. In a subsequent study, 350 serum samples were obtained from a variety of subjects in the Equateur region in 1986. Nineteen (5.4%) showed antibodies to HTLV-I. These data and a recent report of a cluster of patients with tropical spastic paraparesis from this region suggest that HTLV-I is endemic in the Equateur region of Zaire.
The identification and isolation of unique and immunogenic recombinant epitopes for human T cell lymphotrophic virus (HTLV) type I might allow the development of an antibody-based assay to differentiate between HTLV-I and HTLV-II infections. To test the feasibility of this approach, an HTLV-I envelope epitope was isolated by immunoscreening of a lambda gt11 recombinant HTLV-I DNA library with a human monoclonal antibody to HTLV-I. This recombinant epitope. MTA-4, when tested with sera from HTLV-I- or HTLV-II-infected individuals, was reactive with all HTLV-I and nonreactive with all HTLV-II antisera. These results indicate that MTA-4 is a unique and immunodominant epitope on HTLV-I and confirm the usefulness of human-derived monoclonal antibodies in an experimental approach to dissect the human humoral response to a viral pathogen.